Publications

Publications

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188
Brucka, M.; Sheberstov, K.; Jeannerat, D. “Homonuclear decoupling in the 13C indirect dimension of HSQC experiments for 13C-enriched compounds”, Magn. Reson. Chem. 2018, in press.

The two most compelling methods for broadband homonuclear decoupling currently available, Zangger-Sterk (ZS) and PSYCHE, were successfully adapted and tested on the 13C isotope. When applied during the indirect carbon dimension of the HSQC experiment, they both entirely eliminated the extended carbon-carbon multiplet structures observed in this dimension of a non-decoupled HSQC spectrum of 13C-enriched cholesterol. The optimized selective pulse modulated using novel non-equidistant scheme for multi-site refocusing (ZS) and the small flip angle saltire chirps (PSYCHE) both proved to be robust and efficient in providing decoupled spectra with a sensitivity of about 25% that of the non-decoupled HSQC spectra with improved quality compared to earlier results.

187
Jarolímová, Z.; Bosson, J.; Labrador, G. M.; Lacour, J.; Bakker, E. “Ion Transfer Voltammetry at Thin Films Based on Functionalized Cationic [6]Helicenes”, Electroanalysis 2018, in press.

We describe a new family of molecular ion-to-electron redox probes based on cationic diaza, azaoxa, and dioxa [6]helicenes and their derivatives. Their unique structure combines, in a single framework, two privileged families of molecules – helicenes and triaryl methyl carbenium moieties. These cationic [6]helicenes exhibit reversible and reproducible oxidation/reduction behavior and facilitate the ion transfer into thin layer sensing films composed of bis(2-ethylhexyl)sebacate (DOS), polyurethane (PU), sodium tetrakis 3.5-bis(trifluoromethyl)phenyl borate, sodium ionophore X and diaza+(C8)2Br2 for cation transfer. Cyclic voltammetry is used to interrogate the thin films. The cationic response can be tuned by adjusting the membrane loading. Addition of lipophilic cation exchanger into the membrane film results in transfer waves of Gaussian shape for cations. A peak separation of 60 mV and peak width of 110 mV are near the theoretical values for a surface confined process. While Nernstian shifts of the peak potentials with analyte concentration is obtained for membranes based on cationic [6]helicenes and doped with sodium-selective ionophore X, this ionophore was found to promote a gradual loss of redox active species from the ionophore-based membranes into the sample solution.

186
Fakis, M.; Beckwith, J.; Seintis, K.; Martinou, E.; Nançoz, C.; Karakostas, N.; Petsalakis, I. D.; Pistolis, G.; Vauthey, E. “Energy Transfer and Charge Separation Dynamics in Photoexcited Pyrene-Bodipy Molecular Dyads”, Phys. Chem. Chem. Phys. 2018, in press.

The photophysical properties of two pyrene-bodipy molecular dyads, composed of a phenyl-pyrene (Py-Ph) linked to the meso position of a bodipy (BD) molecule with either H-atoms (BD1) or ethyl groups (BD2) at the 2, 6 positions, are investigated by stationary, nanosecond and femtosecond spectroscopy. The properties of these dyads (Py-Ph-BD1 and Py-Ph-BD2) are compared to those of their constituent chromophores in two solvents namely 1,2 dichloroethane (DCE) and acetonitrile (ACN). Stationary spectroscopy reveals a weak coupling among the subunits in both dyads. Excitation of the Py subunit eads to emission that is totally governed by the BD subunits in both dyads pointing to excitation energy transfer (EET) from the Py to BD chromophore. Femtosecond fluorescence and transient absorption spectroscopy reveal that EET takes place within 0.3-0.5 ps and is mostly independent of the solvent and the type of the BD subunit. The EET lifetime is in reasonable agreement with that predicted by Förster theory. After EET has taken place, Py-Ph-BD1 in DCE and Py-Ph-BD2 in both solvents decay mainly radiatively to the ground state with 3.5 - 5.0 ns lifetimes which are similar to those of the individual BD chromophores. However, the excited state of Py-Ph-BD1 in ACN is quenched having a lifetime of 1 ns. This points to the opening of an additional non-radiative channel of the excited state of Py-Ph-BD1 in this solvent, most probably charge separation (CS). Target analysis of the TA spectra has shown that the CS follows an inverted kinetics and is substantially slower than the recombination of the charge-separated state. Occurrence of CS with Py-Ph-BD1 in ACN is also supported by energetic considerations. The above results indicate that only a small change in the structure of the BD units incorporated in the dyads, significantly affects the excited state dynamics leading either to a dyad with long lifetime and high fluorescence quantum yield or to a dyad with an intramolecular CS ability.

185
Vasylevskyi, S.; Regeta, K.; Ruggi, A.; Petoud, S.; Piguet, C.; Fromm, K. “Cis- and Trans-9,10-di(1H-imidazol-1-yl)-anthracene based coordination polymers of ZnII and CdII: synthesis, crystal structures and luminescence properties”, Dalton Trans. 2018, in press.

New functional coordination polymers based on the semi-flexible 9,10-di(1H-imidazol-1-yl)-anthracene ligand (L) with ZnII and CdII, namely {[Zn(μ2-L)2](ClO4)2·m(MeOH)·n(DCM)}n (1), {[Zn(μ2-L)2](BF4)2·m(MeOH)·n(DCM)}n (2), {[Zn(μ2-L)2(p-Tos)2]·mDCM·nMeOH}n (3), {[Cd(μ2-L)2(p-Tos)2]·mDCM}n (4) {[Cd(μ2-L)2(p-Tos)2]·mMeOH·nDioxane}n (5) and {[Zn(μ2-L)2(CF3CO2)2]·2Dioxane}(6) were obtained. Dissolving of L in polar solvent mixtures MeOH-DCM (4:1) or MeOH-Dioxane (1:1) with ZnII and CdII salts resulted in the formation of complexes 1–2, 5 adopting a cis-conformation of the imidazole groups in respect to anthracene. In less polar mixtures of solvents such as MeOH-DCM (1:4) trans-L is observed leading to the coordination polymers 3–4 with ZnII and CdII. In an intermediate solvent mixture such as MeOH-Dioxane (1:4), the cis- and trans-conformation coexist as exemplified in the complex 6 with ZnII. In the solid state, complexes 1–5 assemble as supramolecular 2-D coordination polymers with (4,4) topology, while 6 forms a tridimensional porous network with cds topology. All compounds reveal strong blue emission in solid state at room temperature.

184
Zdrachek, E.; Bakker, E. “Describing Ion Exchange at Membrane Electrodes for Ions of Different Charge”, Electroanalysis 2018, in press.

It is well-documented in the literature that the Nikolsky-Eisenman equation cannot accurately describe the equilibrium of ion exchange at membrane electrodes for ions of different charge. Despite this, unfortunately, it is still widely used owing to the complexity of the more rigorous formalism developed by Bakker et al. in 1994. Here, different available approaches are presented in a unified manner and compared. This includes two different approximations that are equally appropriate for cases of low level of interference where the extent of ion-exchange is comparatively small, one of which is introduced here for the first time. The comparison also considers the permutated form of the Nikolsky-Eisenman equation, where the primary ion is treated as the interfering ion and vice versa. As the permutated form gives a deviation from the thermodynamic model that is opposite that of the regular Nikolsky-Eisenman equation, the two can be combined to give a semi-empirical equation that is surprisingly close to the thermodynamic model and that comprises a single equation for any charge combination. The different choices presented here may be helpful to solve more complex theoretical problems, as for example in the modeling of the time dependence of the electrode response by numerical simulation where the interfacial step condition is a unique and difficult feature of the calculation.

183
Smith, A. M.; Maroni, P.; Borkovec, M. “Attractive Non-DLVO Forces Induced by Adsorption of Monovalent Organic Ions”, Phys. Chem. Chem. Phys. 2018, in press.

Direct force measurements between negatively charged colloidal particles were carried out with the atomic force microscope (AFM) in aqueous solutions containing monovalent organic cations, namely tetraphenylarsonium (Ph4As+), 1-hexyl-3-methylimidazolium (HMIM+), and 1-octyl-3-methylimidazolium (OMIM+). These ions adsorb to the particle surface, and induce a charge reversal. The forces become attractive at the charge neutralization point, but they are stronger than van der Waals forces. This additional and unexpected attraction decays exponentially with a decay length of few nanometers, and is strikingly similar to the one previously observed in the presence of multivalent ions. This attractive force probably originates from coupled spontaneous charge fluctuations on the respective surfaces as initially suggested by Kirkwood and Shumaker.

182
Dereka, B.; Rosspeintner, A.; Stężycki, R.; Ruckebusch, C.; Gryko, D. T.; Vauthey, E. “Excited-State Symmetry Breaking in a Quadrupolar Molecule Visualized in Time and Space”, J. Phys. Chem. Lett. 2017, 8, 6029-6034.

The influence of the length of the push–pull branches of quadrupolar molecules on their excited-state symmetry breaking was investigated using ultrafast time-resolved IR spectroscopy. For this, the excited-state dynamics of an A-π-D-π-A molecule was compared with those of an ADA analogue, where the same electron donor (D) and acceptor (A) subunits are directly linked without a phenylethynyl π-spacer. The spatial distribution of the excitation was visualized in real time by monitoring C≡C and C≡N vibrational modes localized in the spacer and acceptor units, respectively. In nonpolar solvents, the excited state is quadrupolar and the excitation is localized on the π-D-π center. In medium polarity solvents, the excitation spreads over the entire molecule but is no longer symmetric. Finally, in the most polar solvents, the excitation localizes on a single D-π-A branch, contrary to the ADA analogue where symmetry breaking is only partial.

181
Chang, D.; Kim, K. T.; Lindberg, E.; Winssinger, N. “Accelerating Turnover Frequency in Nucleic Acid Templated Re-actions”, Bioconjugate Chem. 2017, in press.

Nucleic acid templated reactions have attracted attention as an important technology to sense oligonucleotides and to translate nucleic acid-based instructions into diverse outputs. Great progresses have been made in accelerating the reaction in order to improve signal amplification, reaching rates where substrate turn-over rather than chemical reaction is rate limiting. Herein we explore the utility of architectures inspired by three-way junction that yield a cleavage of a strand thus accelerating substrate turn-over. We demonstrate that such design can overcome product inhibition in templated reactions and operate close to the rate of hybridization.

180
Vishe, M.; Lathion, T.; Pascal, S.; Yushchenko, O.; Homberg, A.; Brun, E.; Vauthey, E.; Piguet, C.; Lacour, J. “Excimer-Based On-Off Bis(pyreneamide) Macrocyclic Chemosensors”, Helv. Chim. Acta 2017, in press.

A series of bis(pyreneamide) macrocycles, synthesized in two steps from THF, THP, oxepane and 1,4-dioxane, are tested as chemosensors for a large range of mono-, di- and trivalent cations. In their native states, these macrocycles exhibit a strong excimer fluorescence that is quenched upon the addition of the metal ions (alkaline, alkaline earth, p-, d-, and f-block metals). UV-Vis spectrophotometric titrations, cyclic voltammetry, excimer fluorescence quenching and transient absorption spectroscopy experiments helped characterize the On-Off changes occurring upon binding and demonstrate that the highest stability constants are obtained with divalent cations Ca2+ and  Ba2+ specifically.

179
Sayers, J.; Payne, R. J.; Winssinger, N. “Peptide nucleic acid-templated selenocystine–selenoester ligation enables rapid miRNA detection”, Chem. Sci. 2018, in press.

The development of a rapid and chemoselective selenocystine–selenoester peptide ligation that operates at nanomolar reactant concentrations has been developed by utilising PNA templation. Kinetic analysis of the templated peptide ligation revealed that the selenocystine–selenoester reaction was 10 times faster than traditional native chemical ligation at cysteine and to our knowledge is the fastest templated ligation reaction reported to date. The efficiency and operational simplicity of this technology is highlighted through the formation of hairpin molecular architectures and in a novel paper-based lateral flow assay for the rapid and sequence specific detection of oligonucleotides, including miRNA in cell lysates.

178
Salassa, G.; Sels, A.; Mancin, F.; Burgi, T. “Dynamic Nature of Thiolate Monolayer in Au25(SR)18 Nanoclusters”, ACS Nano 2017, in press.

Thiolate monolayer, protecting gold nanocluster, is the principal responsible of their chemicalbehavior and their interaction with the environment. Understanding the parameters that influence the sta-bility and reactivity of the monolayer will enable its precise and controlled functionalization. Here we present a protocol for the investigation of the monolayer reactivity in Au25(SR)18 based on MALDI mass spectrometry and NMR spectroscopy. Thiol ex-change reaction between cluster and thiol molecules has been inves-tigated showing how this reaction is affected by the thiol affinity for Au25. Furthermore, inter-cluster thiol exchange has been clarified for the first time to occur during collisions between particles with-out thiol-release to the solution. Importantly, the rate of direct thiol exchange between clusters is comparable to the one for ligand exchange with free thiols. However, the thermodynamic driving force of the two reactions is different, since only the latter involves free thiol species.

177
Duchêne, L.; Kühnel, R.-S.; Stilp, E.; Cuervo Reyes, E.; Remhof, A.; Hagemann, H.; Battaglia, C. “A stable 3 V all-solid-state sodium–ion battery based on a closo-borate electrolyte”, Energy Environ. Sci. 2017, 10, 2609-2615.

We report on a particularly stable 3 V all-solid-state sodium–ion battery built using a closo-borate based electrolyte, namely Na2(B12H12)0.5(B10H10)0.5. Battery performance is enhanced through the creation of an intimate cathode–electrolyte interface resulting in reversible and stable cycling with a capacity of 85 mA h g−1 at C/20 and 80 mA h g−1 at C/5 with more than 90% capacity retention after 20 cycles at C/20 and 85% after 250 cycles at C/5. We also discuss the effect of cycling outside the electrochemical stability window and show that electrolyte decomposition leads to faster though not critical capacity fading. Our results demonstrate that owing to their high stability and conductivity closo-borate based electrolytes could play a significant role in the development of a competitive all-solid-state sodium–ion battery technology.

176
Beckwith, J. S.; Rosspeintner, A.; Licari, G.; Lunzer, M.; Holzer, B.; Fröhlich, J.; Vauthey, E. “Specific Monitoring of Excited-State Symmetry Breaking by Femtosecond Broadband Fluorescence Upconversion Spectroscopy”, J. Phys. Chem. Lett. 2017, 8, 5878-5883.

Most quadrupolar molecules designed for large two-photon absorption cross section have been shown to undergo symmetry breaking upon excitation to the S1 state. This was originally deduced from their strong fluorescence solvatochromism and later visualized in real time using transient infrared spectroscopy. For molecules not containing clear IR marker modes, however, a specific real-time observation of the symmetry breaking process remains lacking. Here we show that this process can be resolved using broadband fluorescence upconversion spectroscopy by monitoring the instantaneous emission transition dipole moment. This approach is illustrated with measurements performed on two quadrupolar molecules, with only one of them undergoing excited-state symmetry breaking in polar solvents.

175
Zdrachek, E.; Bakker, E. “Time-Dependent Determination of Unbiased Selectivity Coefficients of Ion-Selective Electrodes for Multivalent Ions”, Anal. Chem. 2017, in press.

A new method for the determination of unbiased low selectivity coefficients for two of the most prevalent cases of multivalent ions (zi = 2, zj = 1 and zi = 1, zj = 2) was theoretically and experimentally substantiated. The method is based on eliminating the primary ion concentration near the membrane by extrapolating the linearized time-dependencies of selectivity coefficients determined by the separate solutions method (KijPot(SSM))) as a function of t^-1/3 or t^-1/6, depending on the charge combination of the two ions, to infinite time. The applicability of the method is demonstrated for ionophore-based Mg2+-, Ca2+- and Na+-selective electrodes. It is shown that the high level of primary ion impurities in the salts of interfering ions can significantly limit the efficiency of the technique, as demonstrated with salts of different purity levels.

174
Liu, C.; Zhang, J.; Lawson Daku, L. M.; Gosztola, D.; Canton, S. E.; Zhang, X. “Probing the Impact of Solvation on Photoexcited Spin Crossover Complexes with High-Precision X-ray Transient Absorption Spectroscopy”, J. Am. Chem. Soc. 2017, 139, 17518-17524.

Investigating the photoinduced electronic and structural response of bistable molecular building blocks incorporating transition metals in solution phase constitutes a necessary stepping stone for steering their properties toward applications and performance optimizations. This work presents a detailed X-ray transient absorption (XTA) spectroscopy study of a prototypical spin crossover (SCO) complex [FeII(mbpy)3]2+ (where mbpy = 4,4′-dimethyl-2,2′-bipyridine) with an [FeIIN6] first coordination shell in water (H2O) and acetonitrile (CH3CN). The unprecedented data quality of the XTA spectra together with the direct fitting of the difference spectra in k space using a large number of scattering paths enables resolving the subtle difference in the photoexcited structures of an FeII complex in two solvents for the first time. Compared to the low spin (LS) 1A1 state, the average Fe–N bond elongations for the photoinduced high spin (HS) 5T2 state are found to be 0.181 ± 0.003 Å in H2O and 0.199 ± 0.003 Å in CH3CN. This difference in structural response is attributed to ligand–solvent interactions that are stronger in H2O than in CH3CN for the HS excited state. Our studies demonstrate that, although the metal center of [FeII(mbpy)3]2+ could have been expected to be rather shielded by the three bidentate ligands with quasi-octahedral coordination, the ligand field strength in the HS excited state is nevertheless indirectly affected by solvation effects that modifies the charge distribution within the Fe–N covalent bonds. More generally, this work highlights the importance of including solvation dynamics in order to develop a generalized understanding of the spin-state switching at the atomic level.

173
Klein-Júnior, L.; Cretton, S.; Allard, P.-M.; Genta-Jouve, G.; dos Santos Passos, C.; Salton, J.; Bertelli, P.; Pupier, M.; Jeannerat, D.; Vander Heyden, Y.; Gasper, A. L.; Wolfender, J.-L.; Christen, P.; Henriques, A. T. “Targeted Isolation of Monoterpene Indole Alkaloids from Palicourea sessilis”, J. Nat. Prod. 2017, 80, 3032-3037.open archive unige:99707 pdf full text [restricted access]

Phytochemical investigation of the alkaloid extract of Palicourea sessilis by LC-HRMS/MS using molecular networking and an in silico MS/MS fragmentation approach suggested the presence of several new monoterpene indole alkaloids. These compounds were isolated by semipreparative HPLC, and their structures confirmed by means of HRMS, NMR, and ECD measurements as 4-N-methyllyaloside (3), 4-N-methyl-3,4-dehydrostrictosidine (4), 4β-hydroxyisodolichantoside (6), and 4α-hydroxyisodolichantoside (7), as well as the known alkaloids alline (1), N-methyltryptamine (2), isodolichantoside (5), and 5-oxodolichantoside (8). In addition, the acetylcholinesterase inhibitory activity of the compounds was evaluated up to 50 μM.

172
Babel, L.; Guénée, L.; Besnard, C.; Eliseeva, S. V.; Petoud, S.; Piguet, C. “Cooperative loading of multisite receptors with lanthanide containers: an approach for organized luminescent metallopolymers”, Chem. Sci. 2018, in press.

Metal-containing (bio)organic polymers are materials of continuously increasing importance for applications in energy storage and conversion, drug delivery, shape-memory items, supported catalysts, organic conductors and smart photonic devices. The embodiment of luminescent components provides a revolution in lighting and signaling with the ever-increasing development of polymeric light-emitting devices. Despite the unique properties expected from the introduction of optically and magnetically active lanthanides into organic polymers, the deficient control of the metal loading currently limits their design to empirical and poorly reproducible materials. We show here that the synthetic efforts required for producing soluble multi-site host systems Lk are largely overcome by the virtue of reversible thermodynamics for mastering the metal loading with the help of only two parameters: (1) the affinity of the luminescent lanthanide container for a single binding site and (2) the cooperative effect which modulates the successive fixation of metallic units to adjacent sites. When unsymmetrical perfluorobenzene-trifluoroacetylacetonate co-ligands (pbta) are selected for balancing the charge of the trivalent lanthanide cations, Ln3+, in six-coordinate [Ln(pbta)3] containers, the explored anti-cooperative complexation processes induce nearest-neighbor intermetallic interactions  twice as large as thermal energy at room temperature (RT = 2.5 kJ mol−1). These values have no precedent when using standard symmetrical containers and they pave the way for programming metal alternation in luminescent lanthanidopolymers.

171
Hopfgartner, G. “Book Review – Wilfried M. A. Niessen and Ricardo A. Correra C.: Interpretation of MS-MS mass spectra of drugs and pesticides”, Anal. Bioanal. Chem. 2017, 409, 6935-6936.

The present book is a needed contribution in the field of tandem mass spectrometry of low molecular weight compounds in particular for the fragmentation of even electron ions formed by popular soft ionization techniques such as electrospray. The five chapters provide comprehensive insights of MS/MS spectra acquisition, characterization and interpretation. It is a unique resource to any scientist using LC-MS/MS for qualitative and quantitative analysis of drugs and pesticides.

170
Fuchs, K.; Kiss, A.; Bize, P. E.; Duran, R.; Denys, A.; Hopfgartner, G.; Borchard, G.; Jordan, O. “Mapping of drug distribution in the rabbit liver tumor model by complementary fluorescence and mass spectrometry imaging”, J. Controlled Release 2018, in press.

This study describes the use of fluorescence imaging and mass spectrometry imaging, for imaging the anti-angiogenic drug sunitinib, used to treat liver cancer. These techniques allowed for the assessment of local delivery of the unlabeled therapeutic drug. More specifically, the spatial distribution of the drug and its metabolites after local administration was investigated, and drug levels in tumor and liver tissue over time were quantified.

For this purpose, sunitinib-eluting microspheres were locoregionally injected into the tumor feeding arteries of rabbits bearing liver tumors. In adjacent areas of tumor and non-targeted contralateral liver tissue, sunitinib distribution was mapped around beads in occluded vessels 7, 12, 13 and 14 days after embolization by means of the two imaging methods. Presence of sunitinib metabolites was assessed by mass spectrometry imaging.

Sunitinib was found around microspheres in the tumor at day 7, 12, and 13. The drug was retained by the necrotic tumor tissue, resulting in homogeneously distributed and high levels of up to 40 μg/g tissue in a 1.5 mm radius around the beads. The drug was almost completely eliminated from the contralateral liver tissue. Several of the drug's metabolites, including its primary active metabolite SU12662, were detected in the tumor tissue over 13 days.

Sunitinib diffused from the beads and was retained at high, therapeutic levels during 13 days. This was confirmed independently by complementary fluorescence and mass spectrometry imaging, which served as tools to confirm effective drug delivery after hepatic transarterial administration in situ.

Compound: Sunitinib: PubChem CID 5329102.

169
Bassolino, G.; Nançoz, C.; Thiel, Z.; Bois, E.; Vauthey, E.; Rivera-Fuentes, P. “Photolabile coumarins with improved efficiency through azetidinyl substitution”, Chem. Sci. 2018, in press.

Azetidinyl substituents have been recently used to improve the fluorescence quantum yield of several classes of fluorophores. Herein, we demonstrate that other useful photochemical processes can be modulated using this strategy. In particular, we prepared and measured the quantum yield of photorelease of a series of 7-azetidinyl-4-methyl coumarin esters and compared it to their 7-diethylamino and julolidine-fused analogues. The efficiency of the photorelease reactions of the azetidinyl-substituted compounds was 2- to 5-fold higher than the corresponding diethylamino coumarins. We investigated the origin of this effect in model fluorophores and in the photoactivatable esters, and found that H-bonding with the solvent seems to be the prominent deactivation channel inhibited upon substitution with an azetidinyl ring. We anticipate that this substitution strategy could be used to modulate other photochemical processes with applications in chemical biology, catalysis and materials science.

168
Gooding, J. J.; Bakker, E.; Kelley, S.; Long, Y.; Sailor, M.; Tao, N. “Editorial: Should There Be Minimum Information Reporting Standards for Sensors?”, ACS Sens. 2017, 2, 1377-1379.

167
Egea, J.; Fabregat, I.; Frapart, Y.; Ghezzi, P.; Görlach, A.; Kietzmann, T.; Kubaichuk, K.; Knaus, U.; Lopez, M.; Olaso-Gonzalez, G.; Petry, A.; Schulz, R.; Vina, J.; Winyard, P.; Abbas, K.; Ademowo, O.; Afonso, C.; Andreadou, I.; Antelmann, H.; Antunes, F.; Aslan, M.; Bachschmid, M.; Barbosa, R.; Belousov, V.; Berndt, C.; Bernlohr, D.; Bertrán, E.; Bindoli, A.; Bottari, S.; Brito, P.; Carrara, G.; Casas, A.; Chatzi, A.; Chondrogianni, N.; Conrad, M.; Cooke, M.; Costa, J.; Cuadrado, A.; My-Chan Dang, P.; De Smet, B.; Debelec-Butuner, B.; Dias, I.; Dunn, J.; Edson, A.; El Assar, M.; El-Benna, J.; Ferdinandy, P.; Fernandes, A.; Fladmark, K.; Förstermann, U.; Giniatullin, R.; Giricz, Z.; Görbe, A.; Griffiths, H.; Hampl, V.; Hanf, A.; Herget, J.; Hernansanz-Agustín, P.; Hillion, M.; Huang, J.; Ilikay, S.; Jansen-Dürr, P.; Jaquet, V.; Joles, J.; Kalyanaraman, B.; Kaminskyy, D.; Karbaschi, M.; Kleanthous, M.; Klotz, L.; Korac, B.; Korkmaz, K.; Koziel, R.; Kračun, D.; Krause, K.; Křen, V.; Krieg, T.; Laranjinha, J.; Lazou, A.; Li, H.; Martínez-Ruiz, A.; Matsui, R.; McBean, G.; Meredith, S.; Messens, J.; Miguel, V.; Mikhed, Y.; Milisav, I.; Milković, L.; Miranda-Vizuete, A.; Mojović, M.; Monsalve, M.; Mouthuy, P.; Mulvey, J.; Münzel, T.; Muzykantov, V.; Nguyen, I.; Oelze, M.; Oliveira, N.; Palmeira, C.; Papaevgeniou, N.; Pavićević, A.; Pedre, B.; Peyrot, F.; Phylactides, M.; Pircalabioru, G.; Pitt, A.; Poulsen, H.; Prieto, I.; Rigobello, M.; Robledinos-Antón, N.; Rodríguez-Mañas, L.; Rolo, A.; Rousset, F.; Ruskovska, T.; Saraiva, N.; Sasson, S.; Schröder, K.; Semen, K.; Seredenina, T.; Shakirzyanova, A.; Smith, G. L.; Soldati, T.; Sousa, B. C.; Spickett, C. M.; Stancic, A.; Stasia, M. J.; Steinbrenner, H.; Stepanić, V.; Steven, S.; Tokatlidis, K.; Tuncay, E.; Turan, B.; Ursini, F.; Vacek, J.; Vajnerova, O.; Valentová, K.; Van Breusegem, F.; Varisli, L.; Veal, E. A.; Yalçın, A. S.; Yelisyeyeva, O.; Žarković, N.; Zatloukalová, M.; Zielonka, J.; Touyz, R. M.; Papapetropoulos, A.; Grune, T.; Lamas, S.; Schmidt, H. H. H. W.; Di Lisa, F.; Daiber, A. “Corrigendum to “European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)”  [Redox Biol. 13 (2017) 94–162]”, Redox Biol. 2017, 14, 694-696.

The authors regret that they have to correct the acknowledgement of the above mentioned publication as follows:

This article/publication is based upon work from COST Action BM1203 (EU-ROS), supported by COST (European Cooperation in Science and Technology) which is funded by the Horizon 2020 Framework Programme of the European Union. COST (European Cooperation in Science and Technology) is a funding agency for research and innovation networks. Our Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. For further information see www.cost.eu.

The authors would like to apologise for any inconvenience caused.

166
Dereka, B.; Svechkarev, D.; Rosspeintner, A.; Tromayer, M.; Liska, R.; Mohs, A. M.; Vauthey, E. “Direct Observation of a Photochemical Alkyne-Allene Reaction and of a Twisted and Rehybridized Intramolecular Charge-Transfer State in a Donor-Acceptor Dyad”, J. Am. Chem. Soc. 2017, 139, 16885-16893.

The excited-state dynamics of an aniline-triazine electron donor-acceptor dyad with an alkyne spacer has been investigated using a combination of ultrafast broadband mid-IR and visible transient absorption and fluorescence spectroscopies. The transient IR data reveal the occurrence of an efficient alkyne to allene isomerization of the spacer with a time constant increasing from a few hundreds of femtoseconds to a few picoseconds with solvent viscosity. This process is faster than the vibrational cooling of the Franck-Condon excited state, indicative of non-equilibrium dynamics. The transient electronic absorption and fluores-cence data evidence that this transformation is accompanied by a charge separation between the donor and the acceptor sub-units. The allene character of the spacer implies an or-thogonal orientation of the donor and acceptor moieties, similar to that proposed for Twisted Intramolecular Charge Transfer (TICT) states. Such states are often invoked in the excited-state dynamics of donor-acceptor dyads, but their involvement could never be unambiguously evidenced spec-troscopically. The alkyne-allene isomerization does not only involve a torsional motion but also a bending of the molecule due to the sp to sp2 rehybridization of one of the alkyne car-bon atoms. This twisted and rehybridized ICT (‘TRICT’) state decays back to the planar and linear alkyne ground state on a time scale decreasing from a few hundreds to ten pico-seconds upon going from weakly to highly polar solvents. The different solvent dependencies reveal that the dynamics of the allene build-up are controlled by the structural chang-es, whereas the decay is limited by the charge-recombination step.

165
Reinhardt, J. K.; Klemd, A. M.; De Mieri, M.; Smiesko, M.; Bürgi, T.; Gründemann, C.; Hamburger, M. “Absolute configuration of sesquiterpene lactones with potent immunosuppressive activity”, Thieme 2017, 4, S1-S202.

In a screening of Artemisia argyi (Asteraceae) and subsequent HPLC-based activity profiling canin (1) and the seco-tanapartholides 2 and 3 (stereoisomers) were identified as compounds with potent immunosuppressive activity in vitro. These isoprenoids were first discovered in 1969 and 1982, respectively, and have been extensively studied in the past for various biological activities[1]. Although many studies have been published examining their molecular structure and relative configuration by means of NMR and X-ray[2], the absolute configuration remained unresolved. We here established the absolute configuration of compounds 1-3 by a combination of electronic circular dichroism spectroscopy (ECD) and vibrational circular dichroism spectroscopy (VCD).

ECD spectra of 1 – 3 were measured and compared to spectra calculated ab initio for different possible stereoisomers. Thereby, the commonly described relative stereoisomer of canin (1) was established as (1R,2S,3R,4S,5S,6S,7S,10R)-canin. For compounds 2 and 3 the ECD data lowered the number of possible configurational isomers to four stereoisomers. The absolute configuration was finally established by VCD. Compound 2 was identified as (4R,5R,6S,7S)-seco-tanapartholide, and 3 as (4S,5S,6S,7S)-seco-tanapartholide. The combination of ECD and VCD can thus be considered as a powerful approach in resolving the absolute configuration of conformationally flexible molecules.

164
Li, Z.; Rosspeintner, A.; Hu, P.; Zhu, G.; Hu, Y.; Xiong, X.; Peng, R.; Wang, M.; Liu, X.; Liu, R. “Silyl-based initiators for two-photon polymerization: from facile synthesis to quantitative structure–activity relationship analysis”, Polym. Chem. 2017, 8, 6644-6653.

Exploring new initiation functionalities is critical for the design of efficient photoinitiators applied in two-photon polymerization. In this paper, we present a facile and effective synthesis strategy to construct silyl-based two-photon initiators (2PIs) containing nitro groups as electron acceptors, alkylamines as electron donors and double bonds as conjugation bridges. Steady-state absorption, time-resolved fluorescence, and ns-transient absorption were employed to quantitatively investigate the photo-physics and -chemistry of the 2PIs. The results showed that the photophysical and photochemical behavior of these 2PIs is marginally affected by the introduction of a silyl group, but strongly depends on solvent polarity. The nonlinear absorption spectra over a broad spectral range were determined via two-photon-induced fluorescence, revealing maximum two-photon cross sections of ∼90 GM. In two-photon polymerization structuring tests, the 2PIs can be employed to build fine 3D microstructures with a resolution of ∼280 nm. The acrylate formulations containing novel 2PIs exhibit a comparable threshold energy and ideal processing windows as commercial photoresists IP-L, which have been specifically designed for Nanoscribe's laser lithography systems.

163
Richter, B.; Ravnsbæk, D.; Sharma, M.; Stratmann, A. S.; Hagemann, H.; Jensen, T. R. R. “Fluoride substitution in LiBH4; destabilization and decomposition”, Phys. Chem. Chem. Phys. 2017, 19, 30157-30165.

Fluoride substitution in LiBH4 is studied by investigation of LiBH4-LiBF4 mixtures (9:1 and 3:1). Decomposition was followed by in-situ synchrotron radiation X-ray diffraction (in-situ SR-PXD), thermogravimetric analysis and differential scanning calorimetry with gas analysis (TGA/DSC-MS) and in-situ infrared spectroscopy (in-situ FTIR). Upon heating, fluoride substituted LiBH4 forms (LiBH4-xFx) and decomposition occurs, releasing diborane and solid decomposition products. The decomposition temperature is reduced more than fourfold relative to the individual constituents, with decomposition commencing at T / °C = 80 °C. The degree of fluoride substitution is quantified by sequential Rietveld refinement and shows a selective manner of substitution. In-situ FTIR experiments reveal formation of bands originating from LiBH4-xFx. Formation of LiF and observation of diborane release implies that the decomposing materials have a composition that facilitates formation of diborane and LiF, i.e. LiBH4-xFx (LiBH3F). An alternative approach for fluoride substitution was performed, by addition of Et3N∙3HF to LiBH4, yielding extremely unstable products. Spontaneous decomposition indicates fluoride substitution to have occurred. From our point of view, this is the most significant destabilization effect seen for borohydride materials so far.

162
Benz, S.; Mareda, J.; Besnard, C.; Sakai, N.; Matile, S. “Catalysis with Chalcogen Bonds:  Neutral Benzodiselenazole Scaffolds with High-Precision Selenium Donors of Variable Strength”, Chem. Sci. 2017, 8, 8164-8169.open archive unige:99706 pdf full text [free access]

The benzodiselenazoles (BDS) introduced in this report fulfill, for the first time, all the prerequisites for non-covalent high-precision chalcogen-bonding catalysis in the focal point of conformationally immobilized σ holes on strong selenium donors in a neutral scaffold. Rational bite-angle adjustment to the long Se–C bonds was the key for BDS design. For the unprecedented BDS motif, synthesis of 12 analogs from o-xylene, crystal structure, σ hole variation strategies, optoelectronic properties, theoretical and experimental anion binding as well as catalytic activity are reported. Chloride binding increases with the depth of the σ holes down to KD = 11 μM in THF. Catalytic activities follow the same trend and culminate in rate enhancements for transfer hydrogenation of quinolines beyond 100 000.

161
Gopaldass, N.; Fauvet, B.; Lashuel, H.; Roux, A.; Mayer, A. “Membrane scission driven by the PROPPIN Atg18”, EMBO J. 2017, 36, 3097-3267.

Sorting, transport, and autophagic degradation of proteins in endosomes and lysosomes, as well as the division of these organelles, depend on scission of membrane‐bound tubulo‐vesicular carriers. How scission occurs is poorly understood, but family proteins bind these membranes. Here, we show that the yeast PROPPIN Atg18 carries membrane scission activity. Purified Atg18 drives tubulation and scission of giant unilamellar vesicles. Upon membrane contact, Atg18 folds its unstructured CD loop into an amphipathic α‐helix that inserts into the bilayer. This allows the protein to engage its two lipid binding sites for PI3P and PI(3,5)P2. PI(3,5)P2 induces Atg18 oligomerization, which should concentrate lipid‐inserted α‐helices in the outer membrane leaflet and drive membrane tubulation and scission. The scission activity of Atg18 is compatible with its known roles in endo‐lysosomal protein trafficking, autophagosome biogenesis, and vacuole fission. Key features required for membrane tubulation and scission by Atg18 are shared by other PROPPINs, suggesting that membrane scission may be a generic function of this protein family.

160
Galli, V.; Sebastian, R.; Moutel, S.; Ecard, J.; Perez, F.; Roux, A. “Uncoupling of dynamin polymerization and GTPase activity revealed by the conformation-specific nanobody dynab”, eLife 2017, 23, 3483.

Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (Antonny et al., 2016): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us to follow the GTPase activity of dynamin-1 in real-time. We show that in fibroblasts, dynamin GTP hydrolysis occurs as stochastic bursts, which are randomly distributed relatively to the peak of dynamin assembly. Thus, dynamin disassembly is not coupled to GTPase activity, supporting that the GTP energy is primarily spent in constriction.

159
Cuartero, M.; Acres, R. G.; Jarolímová, Z.; Bakker, E.; Crespo, G. A.; De Marco, R. “Electron Hopping Between Fe 3 d States in Ethynylferrocene-doped Poly(Methyl Methacrylate)-poly(Decyl Methacrylate) Copolymer Membranes”, Electroanalysis 2018, in press.

Synchrotron radiation-valence band spectroscopy (SR-VBS) has been utilized in a study of redox molecule valence states implicated in the electron hopping mechanism of ethynylferrocene in unplasticized poly(methyl methacrylate)-poly(decyl methacrylate) [PMMA-PDMA] membranes. In this communication, it is revealed that, at high concentrations of ethynylferrocene, there are observable Fe 3d valence states that are likely linked to electron hopping between ferrocene moieties of neighbouring redox molecules. Furthermore, electrochemically induced stratification of ethynylferrocene in an oxidized PMMA-PDMA membrane produces a gradient of Fe 3d states toward the buried interface at the glassy carbon/PMMA-PDMA membrane enabling electron hopping and electrochemical reactivity of dissolved ethynylferrocene across this buried film.

158
Hopfgartner, G. “Editorial: What makes a good review from an editor’s perspective?”, Anal. Bioanal. Chem. 2017, 409, 6721-6722.

157
Cuartero, M.; Pankratova, N.; Cherubini, T.; Crespo, G. A.; Massa, F.; Confalonieri, F.; Bakker, E. “In Situ Detection of Species Relevant to the Carbon Cycle in Seawater with Submersible Potentiometric Probes”, Environ. Sci. Technol. Lett. 2017, 4, 410-415.open archive unige:97906 pdf full text [restricted access]

We report on the development of a submersible probe for the simultaneous potentiometric detection of carbonate, calcium, and pH in seawater. All-solid-state electrodes incorporating nanomaterials provide an adequate response time (–1), reproducibility (calibration parameter deviation of <0.7%), and accuracy (deviation of <8% compared to reference techniques) for real-time monitoring of seawater using a flow system. The functioning of the deployable prototype was checked in an outdoor mesocosm and via long-term monitoring in Genoa Harbor. The electrodes worked properly for 3 weeks, and the system demonstrated the capability to autonomously operate with routines for repetitive measurements, data storage, and management. In situ profiles observed in Genoa Harbor and Arcachon Bay were validated using on site and ex situ techniques. The validation of in situ-detected carbonate is a challenge because both re-equilibration of the sample with atmospheric CO2 and the use of apparent thermodynamic constants for speciation calculations lead to some differences (<20% deviation). The submersible probe is a promising tool for obtaining rapid and trustworthy information about chemical levels in marine systems. Moreover, the fluidic approach allows for the integration of other ion sensors that may require sample pretreatment.

156
Zare, D.; Suffren, Y.; Nozary, H.; Hauser, A.; Piguet, C. “Controlling Lanthanide Exchange in Triple-Stranded Helicates: A Way to Optimize Molecular Light-Upconversion”, Angew. Chem. Int. Ed. 2017, 56, 14612-14617.open archive unige:98963 pdf full text [restricted access]

The kinetic lability of hexadentate gallium-based tripods is sufficient to ensure thermodynamic self-assembly of luminescent heterodimetallic [GaLn(L3)3]6+ helicates on the hour time scale, where Ln is a trivalent 4f-block cation. The inertness is however large enough for preserving the triple-helical structure when [GaLn(L3)3]6+ is exposed to lanthanide exchange. The connection of a second gallium-based tripod further slows down the exchange processes to such an extent that spectroscopically active [CrErCr(L4)3]9+ can be diluted into closed-shell [GaYGa(L4)3]9+ matrices without metal scrambling. This feature is exploited for pushing molecular-based energy transfer upconversion (ETU) at room temperature.

155
Loizides-Mangold, U.; Perrin, L.; Vandereycken, B.; Betts, J. A.; Walhin, J.-P.; Templeman, I.; Chanon, S.; Weger, B. D.; Durand, C.; Robert, M.; Paz Montoya, J.; Moniatte, M.; Karagounis, L. G.; Johnston, J. D.; Gachon, F.; Lefai, E.; Riezman, H.; Dibner, C. “Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro”, Proc. Natl. Acad. Sci. USA 2017, 114, E8565-E8574.open archive unige:98893 pdf full text [restricted access]

Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest–activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophospholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlated with transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.

154
Hohendahl, A.; Talledge, N.; Galli, V.; Shen, P. S.; Humbert, F.; De Camilli, P.; Frost, A.; Roux, A. “Structural inhibition of dynamin-mediated membrane fission by endophilin”, eLife 2017, 14, 331.

Dynamin, which mediates membrane fission during endocytosis, binds endophilin and other members of the Bin-Amphiphysin-Rvs (BAR) protein family. How endophilin influences endocytic membrane fission is still unclear. Here, we show that dynamin-mediated membrane fission is potently inhibited in vitro when an excess of endophilin co-assembles with dynamin around membrane tubules. We further show by electron microscopy that endophilin intercalates between turns of the dynamin helix and impairs fission by preventing trans interactions between dynamin rungs that are thought to play critical roles in membrane constriction. In living cells, overexpression of endophilin delayed both fission and transferrin uptake. Together, our observations suggest that while endophilin helps shape endocytic tubules and recruit dynamin to endocytic sites, it can also block membrane fission when present in excess by inhibiting inter-dynamin interactions. The sequence of recruitment and the relative stoichiometry of the two proteins may be critical to regulated endocytic fission.

153
Radiom, M.; Maroni, P.; Borkovec, M. “Influence of Solvent Quality on the Force Response of Individual Poly(styrene) Polymer Chains”, ACS Macro Lett. 2017, 6, 1052-1055.

Single molecule mechanics of poly(styrene) polymer chains is investigated in different organic solvents with atomic force microscopy (AFM). The acquired force–extension profiles can be well fitted with a modified freely jointed chain (FJC) model. The model describes the force–extension profiles in terms of an apparent Kuhn length and an elasticity constant. The elasticity constant is found to be the same for all different solvents investigated. Best fit of the force–extension profiles with the FJC model reveals that the Kuhn length varies systematically with solvent quality. In fact, one can establish a good correlation between the Kuhn length and the Flory–Huggins interaction parameter. The increase in the Kuhn length with increasing solvent quality reflects the larger extent of swelling of the polymer in good solvents.

152
López-Andarias, J.; Frontera, A.; Matile, S. “Anion-π Catalysis on Fullerenes”, J. Am. Chem. Soc. 2017, 139, 13296-13299.open archive unige:97267 pdf full text [restricted access]

Anion−π interactions on fullerenes are about as poorly explored as the use of fullerenes in catalysis. However, strong exchange-correlation contributions and the localized π holes on their surface promise unique selectivities. To elaborate on this promise, tertiary amines are attached nearby. Dependent on their positioning, the resulting stabilization of anionic transition states on fullerenes is shown to accelerate disfavored enolate addition and exo Diels–Alder reactions enantioselectively. The found selectivities are consistent with computational simulations, particularly concerning the discrimination of differently planarized and charge-delocalized enolate tautomers by anion−π interactions. Enolate−π interactions on fullerenes are much shorter than standard π–π interactions and anion−π interactions on planar surfaces, and alternative cation−π interactions are not observed. These findings open new perspectives with regard to anion−π interactions in general and the use of carbon allotropes in catalysis.

151
Borrajo-Calleja, G. M.; Bizet, V.; Besnard, C.; Mazet, C. “Mechanistic Investigation of the Pd-Catalyzed Intermolecular Carboetherification and Carboamination of 2,3-Dihydrofuran: Similarities, Differences, and Evidence for Unusual Reaction Intermediates”, Organometallics 2017, 36, 3553-3563.open archive unige:97266 pdf full text [restricted access]

The mechanism of the Pd-catalyzed intermolecular syn carboetherification and syncarboamination of 2,3-dihydrofuran was investigated experimentally. Crystallographic, spectroscopic, and spectrometric methods have shed light on the nature of a number of catalytically competent palladium complexes. Several oxidative addition complexes as well as their cationic derivatives have been characterized by X-ray diffraction analyses. In the latter, the complexes derived from 2-bromophenol displayed an unorthodox η6 binding mode of the privileged Buchwald-type dialkylbiarylphosphine ligands. The hemilabile character of this interaction was found to facilitate coordination of the polarized olefinic substrate, as evidenced by NMR spectroscopy. In contrast, coordination of the pendant sulfonyl group in the cationic complexes derived from 2-bromo-N-sulfonylated anilines prevented direct binding of 2,3-dihydrofuran. Deprotonation of these species induced aggregation of monomeric units through various weak noncovalent interactions to generate trinuclear palladium clusters. The reversibility of this process was probed by conducting crossover experiments. The nature of the alkali ion was found to strongly influence the selectivity of the assembly phenomenon. Examination of the importance of the nucleophilicity in these intermolecular reactions revealed that the switch between syn carbofunctionalization and Heck arylation of 2,3-dihydrofuran certainly arose from a zwitterionic intermediate common to both catalytic manifolds. The understanding of these reactions gained through this study should certainly favor the design of novel Pd-catalyzed transformations for related systems.

150
Liu, L.; Cotelle, Y.; Bornhof, A.-B.; Besnard, C.; Sakai, N.; Matile, S. “Anion-π Catalysis of Diels-Alder Reactions”, Angew. Chem. Int. Ed. 2017, 56, 13066-13069.open archive unige:97331 pdf full text [restricted access]

Among concerted cycloadditions, the Diels–Alder reaction is the grand old classic, which is usually achieved with acid catalysis. In this report, hydroxypyrones, oxa-, and thiazolones are explored because they provide access to anionic dienes. Their [4+2] cycloaddition with cyclic and acyclic dienophiles, such as maleimides and fumarates, affords bicyclic products with four new stereogenic centers. Bifunctional anion–π catalysts composed of amine bases next to the π surface of naphthalenediimides (NDIs) are shown to selectively stabilize the “open”, fully accessible anionic exo transition state on the π-acidic aromatic surface. Our results also include reactivities that are hard to access with conventional organocatalysts, such as the exo-specific and highly enantioselective Diels–Alder reaction of thiazolones and maleimides with complete suppression of the otherwise dominant Michael addition. With increasing π acidity of the anion–π catalysts, the rates, chemo-, diastereo-, and enantioselectivities increase consistently.

149
Halbert, S.; Poblador Bahamonde, A. I. “Computational Study of the Cu-Free Allylic Alkylation Mechanism with Grignard Reagents: Role of the NHC Ligand”, Eur. J. Org. Chem. 2017, 5935-5941.open archive unige:98198 pdf full text [restricted access]

The mechanism of the Cu-free allylic alkylation catalysed by NHC-ligand with Grignard reagents was explored with the hybrid B3PW91 DFT method. The bonding nature of the active Mg-species, which was validated on the 13C chemical shift, was found to be highly ionic. In particular a strong nucleophilic Mg-R (R=CH3) bond was explained by the activation of the NHC Lewis base ligand on Mg. The effect of the ethereal solvent was examined using explicit dimethyl ether solvent and Density-based Solvation Model. The adequate representation of solvation is required to properly reproduce the formation of the supposed active species. The mechanism of the allylic alkylation emphasizes the bifunctional role of Mg center by activating the nucleophile and the nucleofuge promoting an SN2-type mechanism. The NHC ligand bonded to Mg is crucial and activates the Mg-R bond favoring the C-C bond formation in the reaction.

148
Kumpulainen, T.; Rosspeintner, A.; Dereka, B.; Vauthey, E. “Influence of Solvent Relaxation on Ultrafast Excited-State Proton Transfer to Solvent”, J. Phys. Chem. Lett. 2017, 8, 4516-4521.open archive unige:97922 pdf full text [restricted access]

A thorough understanding of the microscopic mechanism of excited-state proton transfer (ESPT) and the influence of the solvent environment on its dynamics are of great fundamental interest. We present here a detailed investigation of an ESPT to solvent (DMSO) using time-resolved broadband fluorescence and transient absorption spectroscopies. All excited-state species are resolved spectrally and kinetically using a global target analysis based on the two-step Eigen-Weller model. Reversibility of the initial short-range proton transfer producing excited contact ion pairs (CIP*) is observed unambiguously in fluorescence and must be explicitly considered to obtain the individual rate constants. Close inspection of the early dynamics suggests that the relative populations of the protonated form (ROH*) and CIP* are governed by solvent relaxation that influences the relative energies of the excited states. This constitutes a breakdown of the Eigen-Weller model, although the overall agreement between the data and the analysis using classical rate equations is excellent.

147
Prager, S.; Zech, A.; Wesolowski, T. A.; Dreuw, A. “Implementation and Application of the Frozen Density Embedding Theory with the Algebraic Diagrammatic Construction Scheme for the Polarization Propagator up to Third Order”, J. Chem. Theory Comput. 2017, 13, 4711-4725.open archive unige:98053 pdf full text [restricted access]

Implementation, benchmarking, and representative applications of the new FDE-ADC(3) method for describing environmental effects on excited states as a combination of frozen density embedding (FDE) and the algebraic-diagrammatic construction scheme for the polarization propagator of third order (ADC(3)) are presented. Results of FDE-ADC(3) calculations are validated with respect to supersystem calculations on test systems with varying molecule–environment interaction strengths from dispersion up to multiple hydrogen bonds. The overall deviation compared to the supersystem calculations is as small as 0.029 eV for excitation energies, which is even smaller than the intrinsic error of ADC(3). The dependence of the accuracy on the choice of method and functional for the calculation of the environment and the nonelectrostatic part of the system–environment interaction is evaluated. In three representative examples, the FDE-ADC method is applied to investigate larger systems and to analyze excited state properties using visualization of embedded densities and orbitals.

146
Shinde, A. B.; Baboota, R. K.; Denis, S.; Loizides-Mangold, U.; Peeters, A.; Espeel, M.; Malheiro, A. R.; Riezman, H.; Vinckier, S.; Vaz, F. M.; Brites, P.; Ferdinandusse, S.; Van Veldhoven, P. P.; Baes, M. “Mitochondrial disruption in peroxisome deficient cells is hepatocyte selective but is not mediated by common hepatic peroxisomal metabolites”, Mitochondrion 2018, in press.

The structural disruption of the mitochondrial inner membrane in hepatocytes lacking functional peroxisomes along with selective impairment of respiratory complexes and depletion of mitochondrial DNA was previously reported. In search for the molecular origin of these mitochondrial alterations, we here show that these are tissue selective as they do neither occur in peroxisome deficient brain nor in peroxisome deficient striated muscle. Given the hepatocyte selectivity, we investigated the potential involvement of metabolites that are primarily handled by hepatic peroxisomes. Levels of these metabolites were manipulated in L-Pex5 knockout mice and/or compared with levels in different mouse models with a peroxisomal β-oxidation deficiency. We show that neither the deficiency of docosahexaenoic acid nor the accumulation of branched chain fatty acids, dicarboxylic acids or C27 bile acid intermediates are solely responsible for the mitochondrial anomalies. In conclusion, we demonstrate that peroxisomal inactivity differentially impacts mitochondria depending on the cell type but the cause of the mitochondrial destruction needs to be further explored.

145
Yoon, S.; Son, K.; Hagemann, H.; Widenmeyer, M.; Weidenkaff, A. “Cr-substitution in Ba2In2O5·(H2O)x (x = 0.16, 0.74)”, Solid State Sci. 2017, 73, 1-6.open archive unige:98054 pdf full text [restricted access]

Cr-substituted and pristine Ba2In2O5·(H2O)x powders were synthesized by solid state reaction. The influence of Cr-substitution on the crystal structure, chemical composition, magnetic and optical properties were investigated. Powder X-ray diffraction (XRD), elemental analysis and TGA-MS reveal that with substitution of In for Cr, the unit cell volume and the unit cell parameter b increase together with the oxygen and hydrogen content. Magnetic property measurements indicate that Ba2In2O5·(H2O)x is diamagnetic in the temperature range of 2 K < T < 300 K becoming ferromagnetic upon Cr-substitution. In the UV–vis spectra of the Cr-substituted sample a distinctive shift of the absorption-edge energy from 430 to 690 nm was observed corresponding to a bandgap narrowing from 2.88 to 1.80 eV. The replacement of tetrahedral InO4 units by octahedral CrO6 units was found to be the main factor for the drastic change of the magnetic and optical properties.

144
Jansod, S.; Wang, L.; Cuartero, M.; Bakker, E. “Electrochemical ion transfer mediated by a lipophilic Os(II)/Os(III) dinonyl bipyridyl probe incorporated in thin film membranes”, Chem. Commun. 2017, 53, 10757-10760.open archive unige:97881 pdf full text [restricted access]

A new lipophilic dinonyl bipyridyl Os(II)/Os(III) complex successfully mediates ion transfer processes across voltammetric thin membranes. An added lipophilic cation-exchanger may impose voltammetric anion or cation transfer waves of Gaussian shape that are reversible and repeatable. The peak potential is found to shift with the ion concentration in agreement with the Nernst equation. The addition of tridodecylmethylammonium nitrate to the polymeric film dramatically reduces the peak separation from 240 mV to 65 mV, and the peak width to a near-theoretical value of 85 mV, which agrees with a surface confined process. It is suggested that the cationic additive serves as a phase transfer catalyst.

143
Mueller, J.; Szep, G.; Nemethova, M.; de Vries, I.; Lieber, A. D.; Winkler, C.; Kruse, K.; Small, J. V.; Schmeiser, C.; Keren, K.; Hauschild, R.; Sixt, M. “Load Adaptation of Lamellipodial Actin Networks”, Cell 2017, 171, 188-200.e16.

Actin filaments polymerizing against membranes power endocytosis, vesicular traffic, and cell motility. In vitro reconstitution studies suggest that the structure and the dynamics of actin networks respond to mechanical forces. We demonstrate that lamellipodial actin of migrating cells responds to mechanical load when membrane tension is modulated. In a steady state, migrating cell filaments assume the canonical dendritic geometry, defined by Arp2/3-generated 70° branch points. Increased tension triggers a dense network with a broadened range of angles, whereas decreased tension causes a shift to a sparse configuration dominated by filaments growing perpendicularly to the plasma membrane. We show that these responses emerge from the geometry of branched actin: when load per filament decreases, elongation speed increases and perpendicular filaments gradually outcompete others because they polymerize the shortest distance to the membrane, where they are protected from capping. This network-intrinsic geometrical adaptation mechanism tunes protrusive force in response to mechanical load.

142
Muriel, O.; Scott, C. C.; Larios, J.; Mercier, V.; Gruenberg, J. “In Vitro Polymerization of F-actin on Early Endosomes”, J. Visualized Exp. 2017, (126), e55829.

Many early endosome functions, particularly cargo protein sorting and membrane deformation, depend on patches of short F-actin filaments nucleated onto the endosomal membrane. We have established a microscopy-based in vitro assay that reconstitutes the nucleation and polymerization of F-actin on early endosomal membranes in test tubes, thus rendering this complex series of reactions amenable to genetic and biochemical manipulations. Endosomal fractions are prepared by floatation in sucrose gradients from cells expressing the early endosomal protein GFP-RAB5. Cytosolic fractions are prepared from separate batches of cells. Both endosomal and cytosolic fractions can be stored frozen in liquid nitrogen, if needed. In the assay, the endosomal and cytosolic fractions are mixed, and the mixture is incubated at 37 °C under appropriate conditions (e.g., ionic strength, reducing environment). At the desired time, the reaction mixture is fixed, and the F-actin is revealed with phalloidin. Actin nucleation and polymerization are then analyzed by fluorescence microscopy. Here, we report that this assay can be used to investigate the role of factors that are involved either in actin nucleation on the membrane, or in the subsequent elongation, branching, or crosslinking of F-actin filaments.

141
Gooding, J. J.; Bakker, E.; Kelley, S.; Long, Y.; Merkx, M.; Sailor, M.; Tao, N.; Mazur, A. “Editorial: August 2017 – Two years of submissions”, ACS Sens. 2017, 2, 1068-1069.open archive unige:97918 pdf full text [restricted access]

140
Stoleriu, L.; Nishino, M.; Miyashita, S.; Stancu, A.; Hauser, A.; Enachescu, C. “Cluster evolution in molecular three-dimensional spin-crossover systems”, Phys. Rev. B 2017, 96, 064115.open archive unige:98051 pdf full text [restricted access]

The nucleation and growth properties of domains of molecules of the same state in open boundary three-dimensional (3D) spin-crossover systems of various shapes are discussed within the framework of the mechanoelastic model. The molecules are situated on face-centered-cubic lattices and are linked by springs through which they interact. Monte Carlo simulations imply that clusters nucleate from corners in the case of systems having well-developed faces and from kinks in the case of spherical samples, in accordance with available experimental data. In addition, a method to characterize the cooperativity in these systems is proposed, which by scanning the fluctuations in the 3D samples can be related directly to powder x-ray-diffraction experiments.

139
Rouster, P.; Pavlovic, M.; Horváth, E.; Forró, L.; Dey, S. K.; Szilágyi, I. “Influence of Protamine Functionalization on the Colloidal Stability of 1D and 2D Titanium Oxide Nanostructures”, Langmuir 2017, 33, 9750-9758.

The colloidal stability of titanium oxide nanosheets (TNS) and nanowires (TiONW) was studied in the presence of protamine (natural polyelectrolyte) in aqueous dispersions, where the nanostructures possessed negative net charge and the protamine was positively charged. Regardless of their shape, similar charging and aggregation behaviors were observed for both TNS and TiONW. Electrophoretic experiments performed at different protamine loadings revealed that the adsorption of protamine led to charge neutralization and charge inversion depending on the polyelectrolyte dose applied. Light scattering measurements indicated unstable dispersions once the surface charge was close to zero or slow aggregation below and above the charge neutralization point with negatively or positively charged nanostructures, respectively. These stability regimes were confirmed by the electron microscopy images taken at different polyelectrolyte loadings. The protamine dose and salt-dependent colloidal stability confirmed the presence of DLVO-type interparticle forces and no experimental evidences were found for additional interactions (e.g., patch-charge, hydrophobic or steric forces), which are usually present in similar polyelectrolyte-particle systems. These findings indicate that the polyelectrolyte adsorbs on the TNS and TiONW surfaces in a flat and extended conformation giving rise to the absence of surface heterogeneities. Therefore, protamine is an excellent biocompatible candidate to form smooth surfaces, for instance in multilayers composed of polyelectrolytes and particles to be used in biomedical applications.

138
Akbal, L.; Hopfgartner, G. “Effects of liquid post-column addition in electrospray ionization performance in supercritical fluid chromatography–mass spectrometry”, J. Chromatogr. A 2017, 1517, 176-184.

In supercritical fluid chromatography coupled to atmospheric pressure ionization mass spectrometry (SFC-MS), the use of a make-up post-column is almost mandatory to avoid analyte precipitation, especially when using low percentage of modifier (<5%) in the mobile phase. Due to the specific nature of gaseous CO2, the tuning of the make-up conditions in electrospray becomes an important factor and can be used to tune analyte sensitivity. Neither a dilution effect (loss of signal) nor a relevant degradation of chromatographic performances is observed with the addition of a make-up at various flow-rates, up to 0.7 mL/min. From supercritical conditions (1 mL/min 40 °C, 150 bar) to gaseous state (room temperature, atmospheric pressure), the CO2 expands around 430 times, contributing to almost 5% of the nebulizing process. In positive mode, the presence of ammonium ions either in the mobile phase or in the make-up did significantly increase the MS signal, even at basic apparent pH. The ionization performance of electrospray is influenced by the acidic buffer power of the carbon dioxide, and was found to be restricted in the apparent pH range of 3.8–7.2 in the various conditions investigated. This may challenge sensitive detection in negative mode, as illustrated for bosentan. The use of DMSO as make-up additive (up to 30%) showed a simplification of the full scan spectrum regarding the adducts. Finally, the optimization of make-up composition leads to an enhancement up to a factor of 69 on the electrospray MS response signal, for the SFC-SRM/MS analysis of HIV protease inhibitors in plasma extracted from Dried Plasma Spots.

137
Coll Crespi, M.; Crespo, G. A.; Xie, X.; Touilloux, R.; Tercier-Waeber, M.; Bakker, E. “Agarose hydrogel containing immobilized pH buffer microemulsion without increasing permselectivity”, Talanta 2018, 177, 191-196.

A heterogeneous pH buffer based on a colloidal emulsion containing ion-exchanger and lipophilic base is described that can be integrated into hydrogels without affecting their ion-exchange properties. Each sphere works on the basis of reversible ion-exchange of hydrogen ions with solution cations, acting as a pH buffer while staying removed from solution in the nonpolar core of the spheres. The ion-exchange mechanism is supported by titration experiments in aqueous emulsion, showing that the nature and concentration of the exchanging solution cations influences the buffer action, with increasing lipophilicity moving the equilibrium to lower pH values. Agarose gels with entrapped pH buffer emulsions and mounted in a transport cell are shown by zero current potentiometry to exhibit negligible permselective properties above an ionic strength of 1 mM, a behavior no different from unmodified agarose, with an observed ion-exchanger concentration of 7 mM in dry agarose. This suggests that such pH buffers do not give rise to substantial ion-exchange properties of the gel material. In a first attempt to control the pH in the vicinity of an electrode surface by this approach, the emulsion was entrapped in an agarose gel in direct contact with a pH electrode, demonstrating the ability to buffer such gel films.

136
Wang, C.; Matile, S. “Anion-π Catalysts with Axial Chirality”, Chem. Eur. J. 2017, 23, 11955-11960.open archive unige:96473 pdf full text [restricted access]

The idea of anion-π catalysis is to stabilize anionic transition states by anion-π interactions on aromatic surfaces. For asymmetric anion-π catalysis, π-acidic surfaces have been surrounded with stereogenic centers. This manuscript introduces the first anion-π catalysts that operate with axial chirality. Bifunctional catalysts with tertiary amine bases next to π-acidic naphthalenediimide planes are equipped with a bulky aromatic substituent in the imide position to produce separable atropisomers. The addition of malonic acid half thioesters to enolate acceptors is used for evaluation. In the presence of a chiral axis, the selective acceleration of the disfavored but relevant enolate addition was much better than with point chirality, and enantioselectivity could be observed for the first time for this reaction with small-molecule anion-π catalysts. Enantioselectivity increased with the π acidity of the π surface, whereas the addition of stereogenic centers around the aromatic plane did not cause further improvements. These results identify axial chirality of the active aromatic plane generated by atropisomerism as an attractive strategy for asymmetric anion-π catalysis.

135
Baudet, K.; Guerra, S.; Piguet, C. “Chemical Potential of the Solvent: a Crucial Player for Rationalizing Host−Guest Affinities”, Chem. Eur. J. 2017, 23, 16787-16798.open archive unige:99910 pdf full text [restricted access]

An access to reliable values of the thermodynamic constants which controls simple host-guest association, is crucial in medicine, biology, pharmacy and chemistry since the optimum concentration of an effector (i.e. a drug) acting on a receptor is set to the inverse of these constants. Intermolecular association between charged species in polar solvents largely obeys this principle. Any deviation from ideality is mastered by the Debye-Hückel theory of ionic atmosphere. Much less is known for related association reactions involving neutral species in non-polar (lipophilic) media such as membranes, bilayers or organic polymers. Taking the intermolecular association between [La(hfa)3dig] guest and tridentate polyaromatic host receptors L1-L3 in dichloromethane as a proof-of-concept, we show that the progress of the association reactions disrupt the chemical potential of the solvent to such an extent that may seemingly be shifted by two orders of magnitude, thus leading to erroneous dose-response prescriptions. A simple chemical model, which considers a subset of solvent molecules in surface contact with the partners of the association reaction, restores a reliable access to true and interpretable thermodynamic constants. This 'complement' to the law of mass action offers a simple method for safely taking care of the non-predictable variations of the activity coefficients of the various partners when host-guest reactions are conducted in non-polar media.

134
Dereka, B.; Vauthey, E. “Solute–Solvent Interactions and Excited-State Symmetry Breaking: Beyond the Dipole–Dipole and the Hydrogen-Bond Interactions”, J. Phys. Chem. Lett. 2017, 8, 3927-3932.open archive unige:96310 pdf full text [restricted access]

Symmetry breaking of the excited state of a linear quadrupolar acceptor–donor–acceptor molecule was investigated using time-resolved infrared spectroscopy in 55 solvents allowing the influence of several solute–solvent interactions to be examined separately. No symmetry breaking was found in nonpolar solvents irrespective of their refractive index, indicating that differences in dispersion interactions between the two arms of the molecule do not suffice to induce an asymmetric distribution of the excitation. However, symmetry breaking was observed in nondipolar but quadrupolar solvents like benzene to an extent that can be as large as that found in medium dipolar solvents like THF. Whereas larger symmetry breaking occurs in the most dipolar solvents, the strongest are observed in protic solvents due to hydrogen bonding. Strong evidence of the formation of halogen bonds in the excited state is also presented, confirming the idea of symmetry-breaking-induced asymmetrical photochemistry.

133
Dewhurst-Maridor, G.; Abegg, D.; David, F. P.; Rougemont, J.; Scott, C. C.; Adibekian, A.; Riezman, H.; Drubin, D. G. “The SAGA complex, together with transcription factors and the endocytic protein Rvs167p, coordinate the reprofiling of gene expression in response to changes in sterol composition in Saccharomyces cerevisiae”, Mol. Biol. Cell 2017, 28, 2637-2649.open archive unige:97265 pdf full text [restricted access]

Changes in cellular sterol species and concentrations can have profound effects on the transcriptional profile. In yeast, mutants defective in sterol biosynthesis show a wide range of changes in transcription, including a co-induction of anaerobic genes and ergosterol biosynthesis genes, biosynthesis of basic amino acids, and several stress genes. However the mechanisms underlying these changes are unknown. We identified mutations in the SAGA complex, a co-activator of transcription, which abrogate the ability to carry out most of these sterol-dependent transcriptional changes. In the erg3 mutant, the SAGA complex increases its occupancy time on many of the induced ergosterol and anaerobic gene promotors, increases its association with several relevant transcription factors, the SWI/SNF chromatin remodeling complex and surprisingly, associates with an endocytic protein, Rvs167p, suggesting a moonlighting function for this protein in the sterol-regulated induction of the heat shock protein, HSP42 and HSP102, mRNAs.

132
Duwald, R.; Pascal, S.; Bosson, J.; Grass, S.; Besnard, C.; Bürgi, T.; Lacour, J. “Enantiospecific Elongation of Cationic Helicenes by Electrophilic Functionalization at Terminal Ends”, Chem. Eur. J. 2017, 23, 13596-13601.open archive unige:97330 pdf full text [restricted access]

A strategy for late-stage electrophilic functionalizations of cationic helicenes is exposed. Thanks to strongly acidic conditions that permit reversible electrophilic substitutions, regioselective acylations, sulfonylations or alkylations occur at the extremity(ies) of the helical cores. Extended [5] or [6]helicenes can then be generated from cationic [4]helicenes in successive one-pot elongation processes. Retention of configuration and excellent enantiospecificity (up to 99%) are observed for the helicene growth in the enantiopure series.

131
Repnik, U.; Borg Distefano, M.; Speth, M. T.; Ng, M. Y. W.; Progida, C.; Hoflack, B.; Gruenberg, J.; Griffiths, G. “L-leucyl-L-leucine methyl ester does not release cysteine cathepsins to the cytosol but inactivates them in transiently permeabilized lysosomes”, J. Cell Sci. 2017, 79, 3124-3140.

L-leucyl-L-leucine methyl ester (LLOMe) induces apoptosis, which is thought to be mediated by release of lysosomal cysteine cathepsins from permeabilized lysosomes into the cytosol. Here, we demonstrated in HeLa cells that apoptotic as well as sub-apoptotic concentrations of LLOMe caused rapid and complete lysosomal membrane permeabilization (LMP), as evidenced by loss of the proton gradient and release into the cytosol of internalized lysosomal markers below a relative molecular mass of 10,000. However, there was no evidence for the release of cysteine cathepsins B and L into the cytosol; rather they remained within lysosomes, where they were rapidly inactivated and degraded. LLOMe-induced adverse effects, including LMP, loss of cysteine cathepsin activity, caspase activation and cell death could be reduced by inhibition of cathepsin C, but not by inhibiting cathepsins B and L. When incubated with sub-apoptotic LLOMe concentrations, lysosomes transiently lost protons but annealed and re-acidified within hours. Full lysosomal function required new protein synthesis of cysteine cathepsins and other hydrolyses. Our data argue against the release of lysosomal enzymes into the cytosol and their proposed proteolytic signaling during LLOMe-induced apoptosis.

130
Bakker, E. “Editorial: Celebrating Electrochemical Sensors at the 2017 Matrafured Meeting”, ACS Sens. 2017, 2, 854.open archive unige:97917 pdf full text [restricted access]

129
Biet, T.; Cauchy, T.; Sun, Q.; Ding, J.; Hauser, A.; Oulevey, P.; Bürgi, T.; Jacquemin, D.; Vanthuyne, N.; Crassous, J.; Avarvari, N. “Triplet state CPL active helicene–dithiolene platinum bipyridine complexes”, Chem. Commun. 2017, 53, 9210-9213.open archive unige:93612 pdf full text [restricted access]

Chiral metal dithiolene complexes represent a family of chiral precursors, which can give rise to molecular materials with properties resulting from the interplay of chirality with conductivity, magnetism, and photophysics. We describe herein the first examples of chiral metal diimine dithiolene complexes, by the use of a platinum(II) centre coordinated by 2,2′-bipyridine and helicene–dithiolene ligands. The straightforward synthesis of racemic and enantiopure complexes allows the preparation of luminescent Pt(bipy) [4] and [6]helicene compounds for which the solid-state structure was determined as well. TD-DFT calculations support the assignment of the low-energy bands observed in the UV-vis absorption spectra as mixed metal-ligand-to-ligand charge transfer transitions and confirm that the emission band results from the T1excited state. Interestingly, the enantiopure [6]helicene complexes show CPL activity at room temperature in acetonitrile solutions with an anisotropy factor of 3 × 10−4.

128
Uzelac, B.; Valmacco, V.; Trefalt, G. “Interactions between silica particles in the presence of multivalent coions”, Soft Matter 2017, 13, 5741-5748.

Forces between charged silica particles in solutions of multivalent coions are measured with colloidal probe technique based on atomic force microscopy. The concentration of 1:z electrolytes is systematically varied to understand the behavior of electrostatic interactions and double-layer properties in these systems. Although the coions are multivalent the Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory perfectly describes the measured force profiles. The diffuse-layer potentials and regulation properties are extracted from the forces profiles by using the DLVO theory. The dependencies of the diffuse-layer potential and regulation parameter shift to lower concentration with increasing coion valence when plotted as a function of concentration of 1:z salt. Interestingly, these profiles collapse to a master curve if plotted as a function of monovalent counterion concentration.

127
Derivery, E.; Bartolami, E.; Matile, S.; Gonzalez-Gaitan, M. “Efficient Delivery of Quantum Dots into the Cytosol of Cells Using Cell-Penetrating Poly(disulfide)s”, J. Am. Chem. Soc. 2017, 139, 10172-10175.open archive unige:95795 pdf full text [restricted access]

Quantum dots (QDs) are extremely bright, photostable, nanometer particles broadly used to investigate single molecule dynamics in vitro. However, the use of QDs in vivo to investigate single molecule dynamics is impaired by the absence of an efficient way to chemically deliver them into the cytosol of cells. Indeed, current methods (using cell-penetrating peptides for instance) provide very low yields: QDs stay at the plasma membrane or are trapped in endosomes. Here, we introduce a technology based on cell-penetrating poly(disulfide)s that solves this problem: we deliver about 70 QDs per cell, and 90% appear to freely diffuse in the cytosol. Furthermore, these QDs can be functionalized, carrying GFP or anti-GFP nanobodies for instance. Our technology thus paves the way toward single molecule imaging in cells and living animals, allowing to probe biophysical properties of the cytosol.

126
Burankova, T.; Duchéne, L.; Łodziana, Z.; Frick, B.; Yan, Y.; Kühnel, R.-S.; Hagemann, H.; Remhof, A.; Embs, J. P. “Reorientational Hydrogen Dynamics in Complex Hydrides With Enhanced Li+ Conduction”, J. Phys. Chem. C 2017, 121, 17693-17702.open archive unige:96311 pdf full text [restricted access]

Lithium amide-borohydrides Li[BH4]1-x[NH2]x possess liquid like Li superionic conductivity at nearly ambient temperature. The fast Li+ diffusion facilitated by the localized motions of the anions is proposed to occur through a network of vacant tetrahedral sites, acting as conduction channels. To study the reorientational dynamics of the anions, we have performed quasielastic neutron scattering experiments on samples with different compositions (x = 2/3, 0.722, 0.737, 3/4) over a broad temperature and time range. To unambiguously disentangle the contributions of the two species, [BH4] and [NH2]−, we took advantage of deuterium labelling and could clearly demonstrate that the quasielastic broadening is mainly determined by the [BH4] reorientations. With the help of a newly developed model, supported by ab initio molecular dynamics calculations, we have identified three relaxation components, which account for generally anisotropic C3-rotations of the [BH4] tetrahedra including jumps by a small angle from the equilibrium position.

125
Merzouki, A.; Malaspinas, O.; Trushko, A.; Roux, A.; Chopard, B. “Influence of cell mechanics and proliferation on the buckling of simulated tissues using a vertex model”, Nat. Comput. 2018, in press.

Tissue folding is a frequently observed phenomenon, from the cerebral cortex gyrification, to the gut villi formation and even the crocodile head scales development. Although its causes are not yet well understood, some hypotheses suggest that it is related to the physical properties of the tissue and its growth under mechanical constraints. In order to study the underlying mechanisms affecting tissue folding, experimental models are developed where epithelium monolayers are cultured inside hydrogel microcapsules. In this work, we use a 2D vertex model of circular cross-sections of cell monolayers to investigate how cell mechanical properties and proliferation affect the shape of in-silico growing tissues. We observe that increasing the cells’ contractility and the intercellular adhesion reduces tissue buckling. This is found to coincide with smaller and thicker cross-sections that are characterized by shorter relaxation times following cell division. Finally, we show that the smooth or folded morphology of the simulated monolayers also depends on the combination of the cell proliferation rate and the tissue size.

124
Ouertatani-Sakouhi, H.; Kicka, S.; Chiriano, G.; Harrison, C. F.; Hilbi, H.; Scapozza, L.; Soldati, T.; Cosson, P.; Neyrolles, O. “Inhibitors of Mycobacterium marinum virulence identified in a Dictyostelium discoideum host model”, PLoS ONE 2017, 12, e0181121.open archive unige:96991 pdf full text [free access]

Tuberculosis remains one of the major threats to public health worldwide. Given the prevalence of multi drug resistance (MDR) in Mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. Inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. In this study, we used a Dictyostelium discoideum host model to assess virulence of Mycobacterium marinum and to identify compounds inhibiting mycobacterial virulence. Among 9995 chemical compounds, we selected 12 inhibitors of mycobacterial virulence that do not inhibit mycobacterial growth in synthetic medium. Further analyses revealed that 8 of them perturbed functions requiring an intact mycobacterial cell wall such as sliding motility, bacterial aggregation or cell wall permeability. Chemical analogs of two compounds were analyzed. Chemical modifications altered concomitantly their effect on sliding motility and on mycobacterial virulence, suggesting that the alteration of the mycobacterial cell wall caused the loss of virulence. We characterized further one of the selected compounds and found that it inhibited the ability of mycobacteria to replicate in infected cells. Together these results identify new antimycobacterial compounds that represent new tools to unravel the molecular mechanisms controlling mycobacterial pathogenicity. The isolation of compounds with anti-virulence activity is the first step towards developing new antibacterial treatments.

123
Bruderer, T.; Varesio, E.; Hopfgartner, G. “The use of LC predicted retention times to extend metabolites identification with SWATH data acquisition”, J. Chromatogr. B 2017, in press.

The application of predicted LC retention time to support metabolite identification was evaluated for a metabolomics MS/MS database containing 532 compounds representative for the major human metabolite classes. LC retention times could be measured for two C18 type columns using a mobile phase of pH = 3.0 for positive ESI mode (n = 337, 228) and pH = 8.0 for negative ESI mode (n = 410, 233). A QSRR modelling was applied with a small set of model compound selected based on the Kennard-Stone algorithm. The models were implemented in the R environment and can be applied to any library. The prediction model was built with two molecular descriptors, LogD2 and the molecular volume. A limited set of model compounds (LC CalMix, n = 16) could be validated on two different C18 reversed phase LC columns and with comparable prediction accuracy. The CalMix can be used to compensate for different LC systems. In addition, LC retention prediction was found, in combination with SWATH-MS, to be attractive to eliminate false positive identification as well as for ranking purpose different metabolite isomeric forms.

122
Chiaruttini, N.; Roux, A. “Dynamic and elastic shape transitions in curved ESCRT-III filaments”, Curr. Opin. Cell Biol. 2017, 47, 126-135.

The ESCRT-III complex is an evolutionary ancient and conserved complex that catalyzes fission of lipid membranes from the lumen of the neck in many, if not all processes requiring this specific fission reaction. The ESCRT-III membrane remodeling complex is unique as its molecular and polymeric structures do not intuitively suggests how it could deform and break lipid membranes. Here we review the common structural features of the ESCRT-III subunits, and the shape diversity of the various filamentous forms. We propose a simple geometry and elasticity framework that could help to isolate which features of the ESCRT-III filaments are common to all filamentous forms as well as to explain their diversity. We speculate on how these features could provide mechanistic insights into the many functions of the ESCRT-III complex.

121
Guerreiro, J. F.; Mira, N. P.; Santos, A. X. S.; Riezman, H.; Sá-Correia, I. “Membrane Phosphoproteomics of Yeast Early Response to Acetic Acid: Role of Hrk1 Kinase and Lipid Biosynthetic Pathways, in Particular Sphingolipids”, Front. Microbiol. 2017, 8:1302.

Saccharomyces cerevisiae response and tolerance to acetic acid is critical in industrial biotechnology and in acidic food and beverages preservation. The HRK1 gene, encoding a protein kinase of unknown function belonging to the “Npr1-family” of kinases known to be involved in the regulation of plasma membrane transporters, is an important determinant of acetic acid tolerance. This study was performed to identify the alterations occurring in yeast membrane phosphoproteome profile during the adaptive early response to acetic acid stress (following 1 h of exposure to a sub-lethal inhibitory concentration; 50 mM at pH 4.0) and the effect of HRK1 expression on the phosphoproteome. Results from mass spectrometry analysis following the prefractionation and specific enrichment of phosphorylated peptides using TiO2 beads highlight the contribution of processes related with translation, protein folding and processing, transport, and cellular homeostasis in yeast response to acetic acid stress, with particular relevance for changes in phosphorylation of transport-related proteins, found to be highly dependent on the Hrk1 kinase. Twenty different phosphoproteins known to be involved in lipid and sterol metabolism were found to be differently phosphorylated in response to acetic acid stress, including several phosphopeptides that had not previously been described as being phosphorylated. The suggested occurrence of cellular lipid composition remodeling during the short term yeast response to acetic acid was confirmed: Hrk1 kinase-independent reduction in phytoceramide levels and a reduction in phosphatidylcholine and phosphatidylinositol levels under acetic acid stress in the more susceptible hrk1Δ strain were revealed by a lipidomic analysis.

120
Yuan, D.; Bakker, E. “Overcoming Pitfalls in Boundary Elements Calculations with Computer Simulations of Ion Selective Membrane Electrodes”, Anal. Chem. 2017, 89, 7828-7831.open archive unige:97903 pdf full text [restricted access]

Finite difference analysis of ion-selective membranes is a valuable tool for understanding a range of time dependent phenomena such as response times, long and medium term potential drifts, determination of selectivity, and (re)conditioning kinetics. It is here shown that an established approach based on the diffusion layer model applied to an ion-exchange membrane fails to use mass transport to account for concentration changes at the membrane side of the phase boundary. Instead, such concentrations are imposed by the ion-exchange equilibrium condition, without taking into account the source of these ions. The limitation is illustrated with a super-Nernstian potential jump, where a membrane initially void of analyte ion is exposed to incremental concentrations of analyte in the sample. To overcome this limitation, the two boundary elements, one at either side of the sample–membrane interface, are treated here as a combined entity and its total concentration change is dictated by diffusional fluxes into and out of the interface. For each time step, the concentration distribution between the two boundary elements is then computed by ion-exchange theory. The resulting finite difference simulation is much more robust than the earlier model and gives a good correlation to experiments.

119
Babič, A.; Pascal, S.; Duwald, R.; Moreau, D.; Lacour, J.; Allémann, E. “[4]Helicene-squalene fluorescent nanoassemblies for specific targeting of mitochondria in live-cell imaging”, Adv. Funct. Mater. 2017, 27, 1701839.open archive unige:96561 pdf full text [restricted access]

Ester, amide and directly-linked composites of squalene and cationic diaza [4]helicenes 1 were readily prepared. These lipid-dye constructs 2, 3 and 4 gave in aqueous media monodispersed spherical nanoassemblies around 100-130 nm in diameter with excellent stability for several months. Racemic and enantiopure nanoassemblies of compound 2 were fully characterized, including by TEM and cryo-TEM imaging that did not reveal higher order supramolecular structures. Investigations of their (chir)optical properties showed red absorption maxima ca. 600 nm and red fluorescence spanning up to the near-infrared region, with average Stokes shifts of 1350-1550 cm-1. Live-cell imaging by confocal microscopy revealed rapid internalization on the minute time scale and organelle-specific accumulation. Co-localization with MitoTracker in several cancer cell lines demonstrated a specific staining of mitochondria by the [4]helicene-squalene nanoassemblies. To our knowledge, it is the first report of a sub-cellular targeting by squalene-based nanoassemblies.

118
Pankratova, N.; Cuartero, M.; Jowett, L. A.; Howe, E. N. W.; Gale, P. A.; Bakker, E.; Crespo, G. A. “Fluorinated tripodal receptors for potentiometric chloride detection in biological fluids”, Biosens. Bioelectron. 2018, 99, 70-76.open archive unige:97878 pdf full text [restricted access]

Fluorinated tripodal compounds were recently reported to be efficient transmembrane transporters for a series of inorganic anions. In particular, this class of receptors has been shown to be suitable for the effective complexation of chloride, nitrate, bicarbonate and sulfate anions via hydrogen bonding. The potentiometric properties of urea and thiourea-based fluorinated tripodal receptors are explored here for the first time, in light of the need for reliable sensors for chloride monitoring in undiluted biological fluids. The ion selective electrode (ISE) membranes with tren-based tris-urea bis(CF3) tripodal compound (ionophore I) were found to exhibit the best selectivity for chloride over major lipophilic anions such as salicylate (logKCl−/Sal−pot=+1.0" role="presentation" style="box-sizing: border-box; display: inline-block; font-style: normal; font-weight: normal; line-height: normal; font-size: 14.4px; text-indent: 0px; text-align: left; text-transform: none; letter-spacing: normal; word-spacing: 0px; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; color: rgb(80, 80, 80); font-family: Arial, Helvetica, "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", STIXGeneral, "Cambria Math", "Arial Unicode MS", sans-serif; font-variant-ligatures: normal; font-variant-caps: normal; orphans: 2; widows: 2; -webkit-text-stroke-width: 0px; text-decoration-style: initial; text-decoration-color: initial; position: relative;">logKCl−/Sal−pot=+1.0) and thiocyanate (logKCl−/SCN−pot=+0.1" role="presentation" style="box-sizing: border-box; display: inline-block; font-style: normal; font-weight: normal; line-height: normal; font-size: 14.4px; text-indent: 0px; text-align: left; text-transform: none; letter-spacing: normal; word-spacing: 0px; word-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; color: rgb(80, 80, 80); font-family: Arial, Helvetica, "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", STIXGeneral, "Cambria Math", "Arial Unicode MS", sans-serif; font-variant-ligatures: normal; font-variant-caps: normal; orphans: 2; widows: 2; -webkit-text-stroke-width: 0px; text-decoration-style: initial; text-decoration-color: initial; position: relative;">logKCl−/SCN−pot=+0.1). Ionophore I-based ISEs were successfully applied for chloride determination in undiluted human serum as well as artificial serum sample, the slope of the linear calibration at the relevant background of interfering ions being close to Nernstian (49.8±1.7 mV). The results of potentiometric measurements were confirmed by argentometric titration. Moreover, the ionophore I-based ISE membrane was shown to exhibit a very good long-term stability of potentiometric performance over the period of 10 weeks. Nuclear magnetic resonance (NMR) titrations, potentiometric sandwich membrane experiments and density functional theory (DFT) computational studies were performed to determine the binding constants and suggest 1:1 complexation stoichiometry for the ionophore I with chloride as well as salicylate.

117
Domínguez-Martín, E.; Cardenal-Muñoz, E.; King, J.; Soldati, T.; Coria, R.; Escalante, R. “Methods to Monitor and Quantify Autophagy in the Social Amoeba Dictyostelium discoideum”, Cells 2017, 6, 18.open archive unige:96992 pdf full text [free access]

Autophagy is a eukaryotic catabolic pathway that degrades and recycles cellular components to maintain homeostasis. It can target protein aggregates, superfluous biomolecular complexes, dysfunctional and damaged organelles, as well as pathogenic intracellular microbes. Autophagy is a dynamic process in which the different stages from initiation to final degradation of cargo are finely regulated. Therefore, the study of this process requires the use of a palette of techniques, which are continuously evolving and whose interpretation is not trivial. Here, we present the social amoeba Dictyostelium discoideum as a relevant model to study autophagy. Several methods have been developed based on the tracking and observation of autophagosomes by microscopy, analysis of changes in expression of autophagy genes and proteins, and examination of the autophagic flux with various techniques. In this review, we discuss the pros and cons of the currently available techniques to assess autophagy in this organism.

116
Dorsaz, S.; Snäka, T.; Favre-Godal, Q.; Maudens, P.; Boulens, N.; Furrer, P.; Ebrahimi, S. N.; Hamburger, M.; Allémann, E.; Gindro, K.; Queiroz, E. F.; Riezman, H.; Wolfender, J.-L.; Sanglard, D. “Identification and mode of action of a plant natural product targeting human fungal pathogens”, Antimicrob. Agents Chemother. 2017, 61, e00829-17.

Candida albicans is a major cause of fungal diseases in humans and its resistance to available drugs is of concern. In an attempt to identify novel antifungal agents, we initiated a small scale screening of a 199 natural plant compounds (NPs) library. In vitro susceptibility profiling experiments identified 33 NPs with activity against C. albicans (MIC50 ≤ 32 μg/ml). Among the selected NPs, the sterol alkaloid tomatidine was further investigated. Tomatidine originates from Solanum lycopersicum (tomato) and exhibited high fungistatic activity against Candidaspecies (MIC50 ≤ 1 μg/ml) but no cytotoxicity against mammalian cells. Genome-wide transcriptional analysis of C. albicans tomatidine-treated cells revealed a major alteration (upregulation) of ergosterol genes suggesting that the ergosterol pathway was targeted by this NP. Consistent with this transcriptional response, sterol content analysis of tomatidine-treated cells showed not only inhibition of Erg6 (C-24 sterol methyltransferase) but also of Erg4 (C-24 sterol reductase) activity. A forward genetic approach in Saccharomyces cerevisiae coupled with whole genome sequencing identified 2 non-synonymous mutations in ERG6(amino acids: D249G and G132D) responsible for tomatidine resistance. Our results therefore identified unambiguously Erg6, a sterol C-24 methyltransferase absent in mammals, as the main direct target of tomatidine. We tested the in vivoefficacy of tomatidine in a mouse model of C. albicans systemic infection. Treatment with a nano-crystal pharmacological formulation successfully decreased the fungal burden in infected kidneys as compared to placebo and thus confirmed the potential of tomatidine as a therapeutic agent.

115
Angulo, G.; Jedrak, J.; Ochab-Marcinek, A.; Pasitsuparoad, P.; Radzewicz, C.; Wnuk, P.; Rosspeintner, A. “How good is the generalized Langevin equation to describe the dynamics of photo-induced electron transfer in fluid solution?”, J. Chem. Phys. 2017, 146, 244505.open archive unige:98052 pdf full text [restricted access]

The dynamics of unimolecular photo-triggered reactions can be strongly affected by the surrounding medium for which a large number of theoretical descriptions have been used in the past. An accurate description of these reactions requires knowing the potential energy surface and the friction felt by the reactants. Most of these theories start from the Langevin equation to derive the dynamics, but there are few examples comparing it with experiments. Here we explore the applicability of a Generalized Langevin Equation (GLE) with an arbitrary potential and a non-Markovian friction. To this end, we have performed broadband fluorescence measurements with sub-picosecond time resolution of a covalently linked organic electron donor-acceptor system in solvents of changing viscosity and dielectric permittivity. In order to establish the free energy surface (FES) of the reaction, we resort to stationary electronic spectroscopy. On the other hand, the dynamics of a non-reacting substance, Coumarin 153, provide the calibrating tool for the non-Markovian friction over the FES, which is assumed to be solute independent. A simpler and computationally faster approach uses the Generalized Smoluchowski Equation (GSE), which can be derived from the GLE for pure harmonic potentials. Both approaches reproduce the measurements in most of the solvents reasonably well. At long times, some differences arise from the errors inherited from the analysis of the stationary solvatochromism and at short times from the excess excitation energy. However, whenever the dynamics become slow, the GSE shows larger deviations than the GLE, the results of which always agree qualitatively with the measured dynamics, regardless of the solvent viscosity or dielectric properties. The method applied here can be used to predict the dynamics of any other reacting system, given the FES parameters and solvent dynamics are provided. Thus no fitting parameters enter the GLE simulations, within the applicability limits found for the model in this work.

114
Rouster, P.; Pavlovic, M.; Szilagyi, I. “Destabilization of Titania Nanosheet Suspensions by Inorganic Salts: Hofmeister Series and Schulze-Hardy Rule”, J. Phys. Chem. B 2017, 121, 6749-6758.

Ion specific effects on colloidal stability of titania nanosheets (TNS) were investigated in aqueous suspensions. The charge of the particles was varied by the pH of the solutions, therefore, the influence of mono- and multivalent anions on the charging and aggregation behavior could be studied when they were present either as counter or co-ions in the systems. The aggregation processes in the presence of inorganic salts were mainly driven by interparticle forces of electrostatic origin, however, chemical interactions between more complex ions and the surface led to additional attractive forces. The adsorption of anions significantly changed the surface charge properties and hence, the resistance of the TNS against salt-induced aggregation. On the basis of their ability in destabilization of the dispersions, the monovalent ions could be ordered according to the Hofmeister series in acidic solutions, where they act as counterions. However, the behavior of the biphosphate anion was atypical and its adsorption induced charge reversal of the particles. The multivalent anions destabilized the oppositely charged TNS more effectively and the aggregation processes followed the Schulze-Hardy rule. Only weak or negligible interactions were observed between the anions and the particles in alkaline suspensions, where the TNS possessed negative charge.

113
Riveline, D.; Kruse, K. “Interface between Physics and Biology: Training a New Generation of Creative Bilingual Scientists”, Trends Cell Biol. 2017, 27, 541-543.

Whereas physics seeks for universal laws underlying natural phenomena, biology accounts for complexity and specificity of molecular details. Contemporary biological physics requires people capable of working at this interface. New programs prepare scientists who transform respective disciplinary views into innovative approaches for solving outstanding problems in the life sciences.

112
Zare, D.; Doistau, B.; Nozary, H.; Besnard, C.; Guénée, L.; Suffren, Y.; Pelé, A.-L.; Hauser, A.; Piguet, C. “CrIII as an alternative to RuII in metallo-supramolecular chemistry”, Dalton Trans. 2017, 46, 8992-9009.open archive unige:95682 pdf full text [restricted access]

Compared to divalent ruthenium coordination complexes, which are widely exploited as parts of multi-component photonic devices, optically active trivalent chromium complexes are under-represented in multi-metallic supramolecular architectures performing energy conversion mainly because of the tricky preparation of stable heteroleptic CrIII building blocks. We herein propose some improvements with the synthesis of a novel family of kinetically inert heteroleptic bis-terdentate mononuclear complexes, which can be incorporated into dinuclear rod-like dyads as a proof-of-concept. The mechanism and magnitude of intermetallic Cr⋯Cr communication have been unraveled by a combination of magnetic, photophysical and thermodynamic investigations. Alternated aromatic/alkyne connectors provided by Sonogashira coupling reactions emerge as the most efficient wires for long-distance communication between two chromium centres bridged by Janus-type back-to-back bis-terdentate receptors.

111
Shydlovskyi, S.; Zienert, A. Y.; Ince, S.; Dovengerds, C.; Hohendahl, A.; Dargazanli, J. M.; Blum, A.; Günther, S. D.; Kladt, N.; Stürzl, M.; Schauss, A. C.; Kutsch, M.; Roux, A.; Praefcke, G. J. K.; Herrmann, C. “Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1”, Proc. Natl. Acad. Sci. U.S.A 2017, 114, E5559-E5568.

Dynamin-like proteins (DLPs) mediate various membrane fusion and fission processes within the cell, which often require the polymerization of DLPs. An IFN-inducible family of DLPs, the guanylate-binding proteins (GBPs), is involved in antimicrobial and antiviral responses within the cell. Human guanylate-binding protein 1 (hGBP1), the founding member of GBPs, is also engaged in the regulation of cell adhesion and migration. Here, we show how the GTPase cycle of farnesylated hGBP1 (hGBP1F) regulates its self-assembly and membrane interaction. Using vesicles of various sizes as a lipid bilayer model, we show GTP-dependent membrane binding of hGBP1F. In addition, we demonstrate nucleotide-dependent tethering ability of hGBP1F. Furthermore, we report nucleotide-dependent polymerization of hGBP1F, which competes with membrane binding of the protein. Our results show that hGBP1F acts as a nucleotide-controlled molecular switch by modulating the accessibility of its farnesyl moiety, which does not require any supportive proteins.

110
Roux, A.; Loewith, R. “Tensing Up for Lipid Droplet Formation”, Dev. Cell 2017, 41, 571-572.

Lipid droplets are fat storage organelles in cells that physically resemble stable oil-water emulsion droplets. In this issue of Developmental Cell, Ben M’barek et al. (2017) show that the resemblance is more than superficial: physical principles governing emulsion stability also control lipid droplet nucleation and growth.

109
Saarbach, J.; Masi, D.; Zambaldo, C.; Winssinger, N. “Facile access to modified and functionalized PNAs through Ugi-based solid phase oligomerization”, Bioorg. Med. Chem. 2017, 25, 5171-5177.open archive unige:96995 pdf full text [restricted access]

Peptide nucleic acids (PNAs) derivatized with functional molecules are increasingly used in diverse biosupramolecular applications. PNAs have proven to be highly tolerant to modifications and different applications benefit from the use of modified PNAs, in particular modifications at the γ position. Herein we report simple protocols to access modified PNAs from iterative Ugi couplings which allow modular modifications at the α, β or γ position of the PNA backbone from simple starting materials. We demonstrate the utility of the method with the synthesis of several bioactive small molecules (a peptide ligand, a kinase inhibitor and a glycan)-PNA conjugates.

108
Egger, L.; Guénée, L.; Bürgi, T.; Lacour, J. “Regioselective and Enantiospecific Synthesis of Dioxepines by (Cyclopentadienyl)ruthenium-Catalyzed Condensations of Diazocarbonyls and Oxetanes”, Adv. Synth. Catal. 2017, 359, 2918-2923.open archive unige:96477 pdf full text [restricted access]

1,4-Dioxepines result from the decomposition of α-diazo-β-ketoesters in the presence of oxetanes using, as catalyst, a combination of [CpRu(CH3CN)3][BArF] and 1,10-phenanthroline. The regioselective [4+3] insertions follow a SN1-like mechanism and occur yet enantiospecifically (es 74%). The retention of configuration was ascertained by VCD and solid state analyses. Furans, products of [4+1] insertions, are only observed as traces in the above protocol. To promote their formation under CpRu catalysis, it is necessary to use a two-step process with γ-halogenated alcohols as substrates

107
Brändas, E.; Hoffmann, M. R.; Banafsheh, M.; Adam Wesolowski, T. “Nonadditive kinetic potentials from inverted Kohn-Sham problem”, Int. J. Quantum Chem. 2018, 118, e25410.

The nonadditive kinetic potential is a key element in density-dependent embedding methods. The correspondence between the ground-state density and the total effective Kohn–Sham potential provides the basis for various methods to construct the nonadditive kinetic potential for any pair of electron densities. Several research groups used numerical or analytical inversion procedures to explore this strategy which overcomes the failures of known explicit density functional approximations. The numerical inversions, however, apply additional approximations/simplifications. The relations known for the exact quantities cannot be assumed to hold for quantities obtained in numerical inversions. The exact relations are discussed with special emphasis on such issues as: the admissibility of the densities for which the potential is constructed, the choice of densities to be used as independent variables, self-consistency between the potentials and observables calculated using the embedded wavefunction, and so forth. The review focuses on how these issues are treated in practice. The review is supplemented with the analysis of the inverted potentials for weakly overlapping pairs of electron densities—the case not studied previously.

106
Mierzwa, B. E.; Chiaruttini, N.; Redondo-Morata, L.; Moser von Filseck, J.; König, J.; Larios, J.; Poser, I.; Müller-Reichert, T.; Scheuring, S.; Roux, A.; Gerlich, D. W. “Dynamic subunit turnover in ESCRT-III assemblies is regulated by Vps4 to mediate membrane remodelling during cytokinesis”, Nat. Cell Biol. 2017, 19, 787-798.

The endosomal sorting complex required for transport (ESCRT)-III mediates membrane fission in fundamental cellular processes, includingcytokinesis. ESCRT-III is thought to form persistent filaments that over time increase their curvature to constrict membranes. Unexpectedly, we foundthat ESCRT-III at the midbody of human cells rapidly turns over subunits with cytoplasmic pools while gradually forming larger assemblies. ESCRT-IIIturnover depended on the ATPase VPS4, which accumulated at the midbody simultaneously with ESCRT-III subunits, and was required for assemblyof functional ESCRT-III structures. In vitro, the Vps2/Vps24 subunits of ESCRT-III formed side-by-side filaments with Snf7 and inhibited furtherpolymerization, but the growth inhibition was alleviated by the addition of Vps4 and ATP. High-speed atomic force microscopy further revealed highlydynamic arrays of growing and shrinking ESCRT-III spirals in the presence of Vps4. Continuous ESCRT-III remodelling by subunit turnover mightfacilitate shape adaptions to variable membrane geometries, with broad implications for diverse cellular processes.

105
Guarnieri-Ibáñez, A.; Medina, F.; Besnard, C.; Kidd, S. L.; Spring, D. R.; Lacour, J. “Diversity-Oriented Synthesis of Heterocycles and Macrocycles by Controlled Reactions of Oxetanes and α-Iminocarbenes”, Chem. Sci. 2017, 8, 5713-5720.open archive unige:95630 pdf full text [free access]

Using N-sulfonyl triazoles as substrates, compounds as diverse as 2-imino tetrahydrofurans, 13- and 15-membered ring aza-macrocycles can be prepared selectively via formal [1+4], [5+4+4] and [3+4+4+4] condensations of α-imino carbenes and oxetanes under Rh(II)-catalysis or thermal activation. Spirocyclic N-heterocycles are also accessible by means of Buchwald-Hartwig and Pictet-Spengler cyclizations. By reaction control, substrate selection or further derivatization, a large variety of chemical structures is thus achievable. Finally, using triazoles reacting under thermal activation, interesting mechanistic clues were obtained

104
Lagoutte, R.; Patouret, R.; Winssinger, N. “Covalent inhibitors: an opportunity for rational target selectivity”, Curr. Opin. Chem. Biol. 2017, 39, 54-63.open archive unige:95268 pdf full text [restricted access]

There is a resurging interest in compounds that engage their target through covalent interactions. Cysteine’s thiol is endowed with enhanced reactivity, making it the nucleophile of choice for covalent engagement with a ligand aligning an electrophilic trap with a cysteine residue in a target of interest. The paucity of cysteine in the proteome coupled to the fact that closely related proteins do not necessarily share a given cysteine residue enable a level of unprecedented rational target selectivity. The recent demonstration that a lysine’s amine can also be engaged covalently with a mild electrophile extends the potential of covalent inhibitors. The growing database of protein structures facilitates the discovery of covalent inhibitors while the advent of proteomic technologies enables a finer resolution in the selectivity of covalently engaged proteins. Here, we discuss recent examples of discovery and design of covalent inhibitors.

103
Ádok-Sipiczki, M.; Szilagyi, I.; Pálinkó, I.; Pavlovic, M.; Sipos, P.; Nardin, C. “Design of nucleic acid-layered double hydroxide nanohybrids”, Colloid Polym. Sci. 2017, 295, 1463-1473.

We report here on the design of inorganic–organic hybrid materials, which consist of layered double hydroxides (LDHs) as inorganic carrier and short single-stranded nucleic acids (ssDNA) as organic molecules. LDHs were prepared by the co-precipitation method followed by hydrothermal treatment. A model 12-nucleotide-long sequence was immobilized either by ion exchange or covalent grafting. Both the LDH composition and the nucleic acid-to-particle ratio were optimized throughout the synthesis to develop highly stable suspensions of the hybrid materials. Structural characterization revealed that the covalent attachment of the ssDNA was successfully achieved via silanization of the LDHs in aqueous suspension. Covalent linkage of the nucleic acids confers to this model nanoparticulate system promising properties and potential for applications as therapeutic agents. Fragments of nucleic acids could be introduced into living cells without release during the delivery process since LDHs slowly dissolve in the slightly acidic intracellular space.

102
Yan, Y.; Kühnel, R.-S.; Remhof, A.; Duchêne, L.; Reyes, E. C.; Rentsch, D.; Łodziana, Z.; Battaglia, C. “A Lithium Amide-Borohydride Solid-State Electrolyte with Lithium-Ion Conductivities Comparable to Liquid Electrolytes”, Adv. Energy Mater. 2017, 7, 1700294.

High ionic conductivity of up to 6.4 × 10−3 S cm−1 near room temperature (40 °C) in lithium amide-borohydrides is reported, comparable to values of liquid organic electrolytes commonly employed in lithium-ion batteries. Density functional theory is applied coupled with X-ray diffraction, calorimetry, and nuclear magnetic resonance experiments to shed light on the conduction mechanism. A Li4Ti5O12 half-cell battery incorporating the lithium amide-borohydride electrolyte exhibits good rate performance up to 3.5 mA cm−2 (5 C) and stable cycling over 400 cycles at 1 C at 40 °C, indicating high bulk and interfacial stability. The results demonstrate the potential of lithium amide-borohydrides as solid-state electrolytes for high-power lithium-ion batteries.

101
Sheberstov, K.; Sinitsyn, D.; Cheshkov, D.; Jeannerat, D. “Elimination of signals tilting caused by B0 field inhomogeneity using 2D-lineshape reference deconvolution”, J. Magn. Res. 2017, 281, 229-240.open archive unige:95402 pdf full text [restricted access]

An efficient approach for reference deconvolution of two-dimensional spectra aiming at the correction of static field inhomogeneity was established. In comparison to known techniques, a great improvement was achieved using the cross-section along the diagonal of the reference peak instead of its full 2D line shape. The method is termed pseudo-2D diagonal deconvolution. The approach developed allows suppressing the two-dimensional peaks tilting caused by the magnetic field inhomogeneity, while keeping the signal-to-noise ratio constant. Long-known method of 2D reference deconvolution (true-2D reference deconvolution) was also applied for comparison. The neutral and resolution-enhancing pseudo-2D deconvolutions were successfully applied for the resolution of complex overlapping multiplets and for measuring small scalar coupling constants. The new algorithm for the elimination of shape distortion of two-dimensional peaks showed to be promising in the perspective of an automated analysis of 2D correlation NMR spectra.

100
Neuhaus, F.; Zobi, F.; Brezesinski, G.; Dal Molin, M.; Matile, S.; Zumbuehl, A. “Correlation of Surface Pressure and Hue of Planarizable Push-Pull Chromophores at the Air/Water Interface”, Beilstein J. Org. Chem. 2017, 13, 1099-1105.open archive unige:96127 pdf full text [free access]

It is currently not possible to directly measure the lateral pressure of a biomembrane. Mechanoresponsive fluorescent probes are an elegant solution to this problem but it requires first the establishment of a direct correlation between the membrane surface pressure and the induced color change of the probe. Here, we analyze planarizable dithienothiophene push–pull probes in a monolayer at the air/water interface using fluorescence microscopy, grazing-incidence angle X-ray diffraction, and infrared reflection–absorption spectroscopy. An increase of the lateral membrane pressure leads to a well-packed layer of the ‘flipper’ mechanophores and a clear change in hue above 18 mN/m. The fluorescent probes had no influence on the measured isotherm of the natural phospholipid DPPC suggesting that the flippers probe the lateral membrane pressure without physically changing it. This makes the flipper probes a truly useful addition to the membrane probe toolbox.

99
Loubéry, S.; Daeden, A.; Seum, C.; Holtzer, L.; Moraleda, A.; Damond, N.; Derivery, E.; Schmidt, T.; Gonzalez-Gaitan, M. “Sara phosphorylation state controls the dispatch of endosomes from the central spindle during asymmetric division”, Nat. Commun. 2017, 8, 15285.

During asymmetric division, fate assignation in daughter cells is mediated by the partition of determinants from the mother. In the fly sensory organ precursor cell, Notch signalling partitions into the pIIa daughter. Notch and its ligand Delta are endocytosed into Sara endosomes in the mother cell and they are first targeted to the central spindle, where they get distributed asymmetrically to finally be dispatched to pIIa. While the processes of endosomal targeting and asymmetry are starting to be understood, the machineries implicated in the final dispatch to pIIa are unknown. We show that Sara binds the PP1c phosphatase and its regulator Sds22. Sara phosphorylation on three specific sites functions as a switch for the dispatch: if not phosphorylated, endosomes are targeted to the spindle and upon phosphorylation of Sara, endosomes detach from the spindle during pIIa targeting.

98
Harayama, T.; Riezman, H. “Detection of genome-edited mutant clones by a simple competition-based PCR method”, PLoS ONE 2017, 12, e0179165.

Genome editing by the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats / CRISPR-associated protein 9) system is a revolutionary strategy to study gene functions. Since the efficiency of gene disruption in cell culture does not reach 100% typically, cloning of mutant cells is often performed to obtain fully mutated cells. Therefore, a method to discriminate accurately mutated clones easily and quickly is crucial to accelerate the research using CRISPR/Cas9. Here, we show that knockout cells can be discriminated by a competition-based PCR, using a mixture of three primers, among which one primer overlaps with the Cas9 cleavage site. Together, we show how to optimize primer design in order to improve the effectiveness of the discrimination. Finally, we applied this method to show that mutations conferring drug resistance can be detected with high accuracy. The provided method is easy to perform and requires only basic laboratory equipment, making it suitable for almost all laboratories.

97
Barisch, C.; Soldati, T. “Breaking fat! How mycobacteria and other intracellular pathogens manipulate host lipid droplets”, Biochimie 2017, 141, 54-61.open archive unige:96993 pdf full text [restricted access]

Tuberculosis (Tb) is a lung infection caused by Mycobacterium tuberculosis (Mtb). With one third of the world population latently infected, it represents the most prevalent bacterial infectious diseases worldwide. Typically, persistence is linked to so-called “dormant” slow-growing bacteria, which have a low metabolic rate and a reduced response to antibiotic treatments. However, dormant bacteria regain growth and virulence when the immune system is weakened, leading again to the active form of the disease. Fatty acids (FAs) released from host triacylglycerols (TAGs) and sterols are proposed to serve as sole carbon sources during infection. The metabolism of FAs requires beta-oxidation as well as gluconeogenesis and the glyoxylate shunt. Interestingly, the Mtb genome encodes more than hundred proteins involved in the five reactions of beta-oxidation, clearly demonstrating the importance of lipids as energy source. FAs have also been proposed to play a role during resuscitation, the resumption of replicative activities from dormancy. Lipid droplets (LDs) are energy and carbon reservoirs and have been described in all domains. TAGs and sterol esters (SEs) are stored in their hydrophobic core, surrounded by a phospholipid monolayer. Importantly, host LDs have been described as crucial for several intracellular bacterial pathogens and viruses and specifically translocate to the pathogen-containing vacuole (PVC) during mycobacteria infection. FAs released from host LDs are used by the pathogen as energy source and as building blocks for membrane synthesis. Despite their essential role, the mechanisms by which pathogenic mycobacteria induce the cellular redistribution of LDs and gain access to the stored lipids are still poorly understood. This review describes recent evidence about the dual interaction of mycobacteria with host LDs and membrane phospholipids and integrates them in a broader view of the underlying cellular processes manipulated by various intracellular pathogens to gain access to host lipids.

96
Palermo, G.; Cataldi, U.; Pezzi, L.; Bürgi, T.; Umeton, C.; De Luca, A. “Thermo-plasmonic effects on E7 nematic liquid crystal”, Mol. Cryst. Liq. Cryst. 2017, 649, 45-49.

The photo-induced heating from a layer of uniformly distributed gold nanoparticles has been characterized to investigate the impact of a direct interaction of the metallic nanostructures with a drop of E7 nematic liquid crystal. A double effect is obtained: an increase of the photo-induced heating due to a change in the refractive index of the medium surrounding the nanoparticles (from air to E7) and a new way of exploiting this heating to induce a phase transition of the E7 NLC (from anisotropic to isotropic phase), with a significant decrease of the necessary energy density in the case of an impinging green radiation.

95
Saarbach, J.; Lindberg, E.; Folliet, S.; Georgeon, S.; Hantschel, O.; Winssinger, N. “Kinase-templated abiotic reaction”, Chem. Sci. 2017, 8, 5119-5125.open archive unige:95272 pdf full text [free access]

Protein kinases are quintessential regulators of cellular function. Numerous pathologies are intimately linked to the dysregulated activity of a particular protein kinase. Herein we report a technology based on a proximity-induced chemical transformation that enables the detection and imaging of specific kinases. Using two probes that target the nucleotide-binding site and substrate binding site of a target kinase respectively, the reagents appended on the probes are brought within reactive distance thereby enabling the chemical transformation. The reaction used for sensing is a ruthenium-photocatalyzed reduction of a pyridinium immolative linker, which uncages a fluorophore (rhodamine). We demonstrate that this technology can be used to discriminate between closely related kinases with a high signal to noise ratio. We further demonstrate that the technology operates within the complexity of a cellular context with a good correlation between the level of kinase activity and fluorescence output.

94
Athavale, R.; Dinkel, C.; Wehrli, B.; Bakker, E.; Crespo, G. A.; Brand, A. “Robust Solid-Contact Ion Selective Electrodes for High-Resolution”, Environ. Sci. Technol. Lett. 2017, 4, 286-291.open archive unige:97905 pdf full text [free access]

Biogeochemical processes are often confined to very narrow zones in aquatic systems. Therefore, highly resolved in situ measurements are required to study these processes. Potentiometric solid-contact ion selective electrodes (SC-ISEs) are promising tools for such measurements. SC-ISEs show good performance in analyses under controlled experimental conditions. Very few sensor designs, however, can sustain the challenges of natural water matrices and external environmental conditions during in situ applications. We fabricated ammonium and pH selective SC-ISEs with functionalized multiwalled carbon nanotubes (f-MWCNT) as a solid contact. Their functionality was tested in the laboratory and applied in situ for vertical profiling in a eutrophic lake. Sensors were insensitive to strong redox changes, high sulfide concentrations, and bright daylight conditions during the application in the lake. In addition, sensors are easily fabricated and exhibit short response times (in situ profiling of ionic species in fresh water lakes.

93
Cole, L. M.; Flinders, B.; Cuypers, E.; Porta, T.; Varesio, E.; Hopfgartner, G.; Heeren, R. M. A. “Mass Spectrometry Imaging of Drugs of Abuse in Hair”, In Imaging Mass Spectrometry (Methods and Protocols)”, Cole, L. M. (Ed.), Collection “Methods in Molecular Biology” Vol. 1618, Springer: New York 2017, p. 137-147.

Hair testing is a powerful tool routinely used for the detection of drugs of abuse. The analysis of hair is highly advantageous as it can provide prolonged drug detectability versus that in biological fluids and chronological information about drug intake based on the average growth of hair. However, current methodology requires large amounts of hair samples and involves complex time-consuming sample preparation followed by gas or liquid chromatography coupled with mass spectrometry. Mass spectrometry imaging is increasingly being used for the analysis of single hair samples, as it provides more accurate and visual chronological information in single hair samples.

Here, two methods for the preparation of single hair samples for mass spectrometry imaging are presented.

The first uses an in-house built cutting apparatus to prepare longitudinal sections, the second is a method for embedding and cryo-sectioning hair samples in order to prepare cross-sections all along the hair sample.

92
Zala, D.; Schlattner, U.; Desvignes, T.; Bobe, J.; Roux, A.; Chavrier, P.; Boissan, M. “The advantage of channeling nucleotides for very processive functions [version 2]”, F1000Research 2017, 6, 724.

Nucleoside triphosphate (NTP)s, like ATP (adenosine 5’-triphosphate) and GTP (guanosine 5’-triphosphate), have long been considered sufficiently concentrated and diffusible to fuel all cellular ATPases (adenosine triphosphatases) and GTPases (guanosine triphosphatases) in an energetically healthy cell without becoming limiting for function. However, increasing evidence for the importance of local ATP and GTP pools, synthesised in close proximity to ATP- or GTP-consuming reactions, has fundamentally challenged our view of energy metabolism. It has become evident that cellular energy metabolism occurs in many specialised ‘microcompartments’, where energy in the form of NTPs is transferred preferentially from NTP-generating modules directly to NTP-consuming modules. Such energy channeling occurs when diffusion through the cytosol is limited, where these modules are physically close and, in particular, if the NTP-consuming reaction has a very high turnover, i.e. is very processive. Here, we summarise the evidence for these conclusions and describe new insights into the physiological importance and molecular mechanisms of energy channeling gained from recent studies. In particular, we describe the role of glycolytic enzymes for axonal vesicle transport and nucleoside diphosphate kinases for the functions of dynamins and dynamin-related GTPases.

91
Egea, J.; Fabregat, I.; Frapart, Y. M.; Ghezzi, P.; Görlach, A.; Kietzmann, T.; Kubaichuk, K.; Knaus, U. G.; Lopez, M. G.; Olaso-Gonzalez, G.; Petry, A.; Schulz, R.; Vina, J.; Winyard, P.; Abbas, K.; Ademowo, O. S.; Afonso, C. B.; Andreadou, I.; Antelmann, H.; Antunes, F.; Aslan, M.; Bachschmid, M. M.; Barbosa, R. M.; Belousov, V.; Berndt, C.; Bernlohr, D.; Bertrán, E.; Bindoli, A.; Bottari, S. P.; Brito, P. M.; Carrara, G.; Casas, A. I.; Chatzi, A.; Chondrogianni, N.; Conrad, M.; Cooke, M. S.; Costa, J. G.; Cuadrado, A.; My-Chan Dang, P.; De Smet, B.; Debelec-Butuner, B.; Dias, I. H.; Dunn, J. D.; Edson, A. J.; El Assar, M.; El-Benna, J.; Ferdinandy, P.; Fernandes, A. S.; Fladmark, K. E.; Förstermann, U.; Giniatullin, R.; Giricz, Z.; Görbe, A.; Griffiths, H.; Hampl, V.; Hanf, A.; Herget, J.; Hernansanz-Agustín, P.; Hillion, M.; Huang, J.; Ilikay, S.; Jansen-Dürr, P.; Jaquet, V.; Joles, J. A.; Kalyanaraman, B.; Kaminskyy, D.; Karbaschi, M.; Kleanthous, M.; Klotz, L.-O.; Korac, B.; Korkmaz, K. S.; Koziel, R.; Kračun, D.; Krause, K.-H.; Křen, V.; Krieg, T.; Laranjinha, J.; Lazou, A.; Li, H.; Martínez-Ruiz, A.; Matsui, R.; McBean, G. J.; Meredith, S. P.; Messens, J.; Miguel, V.; Mikhed, Y.; Milisav, I.; Milković, L.; Miranda-Vizuete, A.; Mojović, M.; Monsalve, M.; Mouthuy, P.-A.; Mulvey, J.; Münzel, T.; Muzykantov, V.; Nguyen, I. T.; Oelze, M.; Oliveira, N. G.; Palmeira, C. M.; Papaevgeniou, N.; Pavićević, A.; Pedre, B.; Peyrot, F.; Phylactides, M.; Pircalabioru, G. G.; Pitt, A. R.; Poulsen, H. E.; Prieto, I.; Rigobello, M. P.; Robledinos-Antón, N.; Rodríguez-Mañas, L.; Rolo, A. P.; Rousset, F.; Ruskovska, T.; Saraiva, N.; Sasson, S.; Schröder, K.; Semen, K.; Seredenina, T.; Shakirzyanova, A.; Smith, G. L.; Soldati, T.; Sousa, B. C.; Spickett, C. M.; Stancic, A.; Stasia, M. J.; Steinbrenner, H.; Stepanić, V.; Steven, S.; Tokatlidis, K.; Tuncay, E.; Turan, B.; Ursini, F.; Vacek, J.; Vajnerova, O.; Valentová, K.; Van Breusegem, F.; Varisli, L.; Veal, E. A.; Yalçin, A. S.; Yelisyeyeva, O.; Žarković, N.; Zatloukalová, M.; Zielonka, J.; Touyz, R. M.; Papapetropoulos, A.; Grune, T.; Lamas, S.; Schmidt, H. H.; Di Lisa, F.; Daiber, A. “European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)”, Redox Biol. 2017, 13, 94-162.open archive unige:97011 pdf full text [free access]

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

90
Zala, D.; Schlattner, U.; Desvignes, T.; Bobe, J.; Roux, A.; Chavrier, P.; Boissan, M. “The advantage of channeling nucleotides for very processive functions”, F1000Res. 2017, 6, 724.

Nucleoside triphosphate (NTP)s, like ATP (adenosine 5’-triphosphate) and GTP (guanosine 5’-triphosphate), have long been considered sufficiently concentrated and diffusible to fuel all cellular ATPases (adenosine triphosphatases) and GTPases (guanosine triphosphatases) in an energetically healthy cell without becoming limiting for function. However, increasing evidence for the importance of local ATP and GTP pools, synthesised in close proximity to ATP- or GTP-consuming reactions, has fundamentally challenged our view of energy metabolism. It has become evident that cellular energy metabolism occurs in many specialised ‘microcompartments’, where energy in the form of NTPs is transferred preferentially from NTP-generating modules directly to NTP-consuming modules. Such energy channeling occurs when diffusion through the cytosol is limited, where these modules are physically close and, in particular, if the NTP-consuming reaction has a very high turnover, i.e. is veryprocessive. Here, we summarise the evidence for these conclusions and describe new insights into the physiological importance and molecular mechanisms of energy channeling gained from recent studies. In particular, we describe the role of glycolytic enzymes for axonal vesicle transport and nucleoside diphosphate kinases for the functions of dynamins and dynamin-related GTPases.

89
Abouelwafa, A. S.; Hauser, A.; Mereacre, V.; Lan, Y.; Long, G. J.; Grandjean, F.; Buth, G.; Anson, C. E.; Powell, A. K. “Search for Electron Delocalization from [Fe(CN)6]3– to the Dication of Viologen in (DNP)3[Fe(CN)6]2·10H2O”, Inorg. Chem. 2017, 56, 6477-6488.open archive unige:94916 pdf full text [restricted access]

K3Fe(CN)6 reacts with the viologen 1,1′-bis(2,4-dinitrophenyl)-4,4′-bipyridinium dication, (DNP)2+, to form a supramolecular complex, (DNP)3[Fe(CN)6]2·10H2O (1). The crystal structure of 1 reveals that there are two [Fe(CN)6]3– anions within an organic framework of three (DNP)2+cations with the shortest Fe(III)···Fe(III) distances of ca. 9.8 Å, distances that minimize extensive long-range magnetic exchange coupling interactions between the [Fe(CN)6]3– anions, and, thus, 1 is paramagnetic above ca. 17 K and exhibits weak ferromagnetic coupling between 17 and 3 K and antiferromagnetic coupling between 3 and 1.8 K. The long Fe(III)···Fe(III) distances permit slow spin–spin and slow spin–lattice paramagnetic relaxation, relative to the iron-57 Larmor precession frequency, as is evidenced by the Mössbauer spectra measured between 3 and 60 K; between 85 and 295 K, rapid paramagnetic relaxation is observed. Both the slow spin–spin and slow spin–lattice relaxation are mediated by the organic, π-conjugated viologen cations. The Fe–C distances, the Mössbauer isomer shifts, the temperature dependence of the magnetic susceptibility, and the 3 K magnetization results all indicate the presence of low-spin Fe(III) ions in the [Fe(CN)6]3– anions in 1. There is no unequivocal indication of the presence of any formal electron delocalization or transfer from the [Fe(CN)6]3– anion to the (DNP)2+ cations in the results obtained from X-ray crystallography, magnetic measurements, and Mössbauer spectra. Because of enhancement of the spin–orbit coupling by the heavy-atom or -ion effect, the Fe(III) ions in the [Fe(CN)6]3– anions interact with the (DNP)2+ cations, causing them to fluoresce with increasing intensity upon cooling from 90 to 25 K when excited at 300 nm. The resulting luminescence of the viologen (DNP)2+ cation induced by the [Fe(CN)6]3– anions indicates the presence of significant mixing of the molecular orbitals derived from the [Fe(CN)6]3– anions and the molecular orbitals associated with the (DNP)2+ cations to yield bonding supramolecular orbitals in 1, a mixing that is also observed between 50 and 3 K in the temperature dependence of the isomer shift of 1.

88
Dereka, B.; Vauthey, E. “Direct local solvent probing by transient infrared spectroscopy reveals the mechanism of hydrogen-bond induced nonradiative deactivation”, Chem. Sci. 2017, 8, 5057-5066.open archive unige:96313 pdf full text [free access]

The fluorescence quenching of organic dyes via H-bonding interactions is a well-known phenomenon. However, the mechanism of this Hydrogen-Bond Induced Nonradiative Deactivation (HBIND) is not understood. Insight into this process is obtained by probing in the infrared the O–H stretching vibration of the solvent after electronic excitation of a dye with H-bond accepting cyano groups. The fluorescence lifetime of this dye was previously found to decrease from 1.5 ns to 110 ps when going from an aprotic solvent to the strongly protic hexafluoroisopropanol (HFP). Prompt strengthening of the H-bond with the dye was identified by the presence of a broad positive O–H band of HFP, located at lower frequency than the O–H band of the pure solvent. Further strengthening occurs within a few picoseconds before the excited H-bonded complex decays to the ground state in 110 ps. The latter process is accompanied by the dissipation of energy from the dye to the solvent and the rise of a characteristic hot solvent band in the transient spectrum. Polarization-resolved measurements evidence a collinear alignment of the nitrile and hydroxyl groups in the H-bonded complex, which persists during the whole excited-state lifetime. Measurements in other fluorinated alcohols and in chloroform/HFP mixtures reveal that the HBIND efficiency depends not only on the strength of the H-bond interactions between the dye and the solvent but also on the ability of the solvent to form an extended H-bond network. The HBIND process can be viewed as an enhanced internal conversion of an excited complex consisting of the dye molecule connected to a large H-bond network.

87
Machida, T.; Novoa, A.; Gillon, .; Zheng, S.; Claudinon, J.; Eierhoff, T.; Imberty, A.; Römer, W.; Winssinger, N. “Dynamic Cooperative Glycan Assembly Blocks the Binding of Bacterial Lectins to Epithelial Cells”, Angew. Chem. Int. Ed. 2017, 56, 6762-6766.open archive unige:95405 pdf full text [restricted access]

Pathogens frequently rely on lectins for adhesion and cellular entry into the host. Since these interactions typically result from multimeric binding of lectins to cell-surface glycans, novel therapeutic strategies are being developed with the use of glycomimetics as competitors of such interactions. Herein we study the benefit of nucleic acid based oligomeric assemblies with PNA–fucose conjugates. We demonstrate that the interactions of a lectin with epithelial cells can be inhibited with conjugates that do not form stable assemblies in solution but benefit from cooperativity between ligand–protein interactions and PNA hybridization to achieve high affinity. A dynamic dimeric assembly fully blocked the binding of the fucose-binding lectin BambL of Burkholderia ambifaria, a pathogenic bacterium, to epithelial cells with an efficiency of more than 700-fold compared to l-fucose.

86
Cao, T.; Sugimoto, T.; Szilagyi, I.; Trefalt, G.; Borkovec, M. “Heteroaggregation of oppositely charged particles in the presence of multivalent ions”, Phys. Chem. Chem. Phys. 2017, 19, 15160-15171.

Time-resolved dynamic light scattering is used to measure absolute heteroaggregation rate coefficients and the corresponding stability ratios for heteroaggregation between amidine and sulfate latex particles. These measurements are complemented by the respective quantities for the homoaggregation of the two systems and electrophoresis. Based on the latter measurements, the stability ratios are calculated using Derjaguin–Landau–Verwey–Overbeek (DLVO) theory. In monovalent salt solutions, the two types of particles investigated are oppositely charged. In the presence of multivalent ions, however, one particle type reverses its charge, while the charge of the other particle type is hardly affected. In this region, the heteroaggregation stability ratio goes through a pronounced maximum when plotted versus concentration. This region of slow aggregation is wider than the one observed in the corresponding homoaggregation process. One also finds that the onset of this region sensitively depends on the boundary conditions used to calculate the double layer force. The present results are more in line with constant potential boundary conditions.

85
Capasso, S.; Sticco, L.; Rizzo, R.; Pirozzi, M.; Russo, D.; Dathan, N. A.; Campelo, F.; van Galen, J.; Hölttä-Vuori, M.; Turacchio, G.; Hausser, A.; Malhotra, V.; Riezman, I.; Riezman, H.; Ikonen, E.; Luberto, C.; Parashuraman, S.; Luini, A.; D'Angelo, G. “Sphingolipid metabolic flow controls phosphoinositide turnover at the trans‐Golgi network”, EMBO J. 2017, 36, 1736-1754.

Sphingolipids are membrane lipids globally required for eukaryotic life. The sphingolipid content varies among endomembranes with pre‐ and post‐Golgi compartments being poor and rich in sphingolipids, respectively. Due to this different sphingolipid content, pre‐ and post‐Golgi membranes serve different cellular functions. The basis for maintaining distinct subcellular sphingolipid levels in the presence of membrane trafficking and metabolic fluxes is only partially understood. Here, we describe a homeostatic regulatory circuit that controls sphingolipid levels at the trans‐Golgi network (TGN). Specifically, we show that sphingomyelin production at the TGN triggers a signalling pathway leading to PtdIns(4)P dephosphorylation. Since PtdIns(4)P is required for cholesterol and sphingolipid transport to the trans‐Golgi network, PtdIns(4)P consumption interrupts this transport in response to excessive sphingomyelin production. Based on this evidence, we envisage a model where this homeostatic circuit maintains a constant lipid composition in the trans‐Golgi network and post‐Golgi compartments, thus counteracting fluctuations in the sphingolipid biosynthetic flow.

84
Kazan, R.; Zhang, B.; Bürgi, T. “Au38Cu1(2-PET)24 Nanocluster : Synthesis, Enantioseparation and Luminescence”, Dalton Trans. 2017, 46, 7708-7713.open archive unige:96314 pdf full text [restricted access]

A CuAu38 bimetallic nanocluster was synthesized by adding a single copper atom to the Au38(2-PET)24 nanocluster. The absence of CuxAu38(2-PET)24 doped species was demonstrated by MALDI-TOF mass spectrometry. A separation of bimetallic clusters was attained for the first time where isomers of the E2 enantiomer of the Au38Cu1(2-PET)24 adduct were successfully isolated from their parent cluster using chiral HPLC. The CD of the isolated isomers revealed a change in their electronic structure upon copper addition. The luminescence of the Au38Cu1 adduct is significantly enhanced in comparison with the parent Au38 nanocluster. The stability of the newly formed adduct is strongly dependent on the coexistence of the Au38 nanoclusters.

83
Daumke, O.; Roux, A. “Mitochondrial Homeostasis: How Do Dimers of Mitofusins Mediate Mitochondrial Fusion?”, Curr. Biol. 2017, 27, R353-R356.

Mitochondria have high fusion and fission rates to maintain their size and number throughout the cell cycle. How is fusion mediated? New structural studies propose mechanisms by which the dynamin-like mitofusin proteins promote fusion of mitochondria.

82
Colom, A.; Redondo-Morata, L.; Chiaruttini, N.; Roux, A.; Scheuring, S. “Dynamic remodeling of the dynamin helix during membrane constriction”, Proc. Natl. Acad. Sci. USA 2017, 114, 5449-5454.

Dynamin is a dimeric GTPase that assembles into a helix around the neck of endocytic buds. Upon GTP hydrolysis, dynamin breaks these necks, a reaction called membrane fission. Fission requires dynamin to first constrict the membrane. It is unclear, however, how dynamin helix constriction works. Here we undertake a direct high-speed atomic force microscopy imaging analysis to visualize the constriction of single dynamin-coated membrane tubules. We show GTP-induced dynamic rearrangements of the dynamin helix turns: the average distances between turns reduce with GTP hydrolysis. These distances vary, however, over time because helical turns were observed to transiently pair and dissociate. At fission sites, these cycles of association and dissociation were correlated with relative lateral displacement of the turns and constriction. Our findings show relative longitudinal and lateral displacements of helical turns related to constriction. Our work highlights the potential of high-speed atomic force microscopy for the observation of mechanochemical proteins onto membranes during action at almost molecular resolution.

81
Akamatsu, M.; Sakai, N.; Matile, S. “Electric-Field-Assisted Anion-π Catalysis”, J. Am. Chem. Soc. 2017, 139, 6558-6561.open archive unige:94491 pdf full text [restricted access]

This report focuses on the remote control of anion−π catalysis by electric fields. We have synthesized and immobilized anion−π catalysts to explore the addition reaction of malonic acid half thioesters to enolate acceptors on conductive indium tin oxide surfaces. Exposed to increasing electric fields, anion−π catalysts show an increase in activity and an inversion of selectivity. These changes originate from a more than 100-fold rate enhancement of the disfavored enolate addition reaction that coincides with an increase in selectivity of transition-state recognition by up to −14.8 kJ mol–1. The addition of nitrate with strong π affinity nullified (IC50 = 2.2 mM) the responsiveness of anion−π catalysts to electric fields. These results support that the polarization of the π-acidic naphthalenediimide surface in anion−π catalysts with electric fields increases the recognition of anionic intermediates and transition states on this polarized π surface, that is, the existence and relevance of electric-field-assisted anion−π catalysis.

80
Ivanov, A. I.; Dereka, B.; Vauthey, E. “A simple model of solvent-induced symmetry-breaking charge transfer in excited quadrupolar molecules”, J. Chem. Phys. 2017, 146, 164306.open archive unige:94061 pdf full text [restricted access]

A simple model has been developed to describe the symmetry-breaking of the electronic distribution of AL–D–AR type molecules in the excited state, where D is an electron donor and AL and AR are identical acceptors. The origin of this process is usually associated with the interaction between the molecule and the solvent polarization that stabilizes an asymmetric and dipolar state, with a larger charge transfer on one side than on the other. An additional symmetry-breaking mechanism involving the direct Coulomb interaction of the charges on the acceptors is proposed. At the same time, the electronic coupling between the two degenerate states, which correspond to the transferred charge being localised either on AL or AR, favours a quadrupolar excited state with equal amount of charge-transfer on both sides. Because of these counteracting effects, symmetry breaking is only feasible when the electronic coupling remains below a threshold value, which depends on the solvation energy and the Coulomb repulsion energy between the charges located on AL and AR. This model allows reproducing the solvent polarity dependence of the symmetry-breaking reported recently using time-resolved infrared spectroscopy.

79
Gooding, J. J.; Long, Y.-T.; Tao, N.; Kelley, S.; Merkx, M.; Sailor, M.; Bakker, E.; Mazur, A. “Editorial: Reflecting on How ACS Sensors Can Help Advance the Field of Sensing”, ACS Sens. 2017, 2, 455-456.open archive unige:97916 pdf full text [restricted access]

78
Moazzami Gudarzi, M. “Comment on “Colloidal stability of reduced graphene oxide materials prepared using different reducing agents” by Y. Qi, T. Xia, Y. Li, L. Duan and W. Chen, Environ. Sci.: Nano, 2016, 3, 1062”, Environ. Sci.: Nano 2017, 4, 2418-2420.

The colloidal stability of graphene oxide (GO) and its reduced forms can be described using classical DLVO theory. This contradicts the claims by Qi et al. (Environ. Sci.: Nano, 2016, 3, 1062–1071). Lower colloidal stability of reduced GO is caused by changes in surface charging and optical properties of GO upon reduction which leads to the suppression of double layer forces but enhancement of van der Waals forces, respectively.

77
Radiom, M.; Kozhuharov, S.; Kong, P.; di Giannantonio, M.; Ayer, M.; Maroni, P.; Kilbinger, A. M.; Fromm, K.; Weder, C.; Borkovec, M. “Quantitative Nano-characterization of Polymers Using Atomic Force Microscopy”, Chimia 2017, 71, 195-198.

The present article offers an overview on the use of atomic force microscopy (AFM) to characterize the nanomechanical properties of polymers. AFM imaging reveals the conformations of polymer molecules at solid– liquid interfaces. In particular, for polyelectrolytes, the effect of ionic strength on the conformations of molecules can be studied. Examination of force versus extension profiles obtained using AFM-based single molecule force spectroscopy gives information on the entropic and enthalpic elasticities in pN to nN force range. In addition, single molecule force spectroscopy can be used to trigger chemical reactions and transitions at the molecular level when force-sensitive chemical units are embedded in a polymer backbone.

76
Murray, J. I.; Flodén, N. J.; Bauer, A.; Fessner, N. D.; Dunklemann, D. L.; Bob-Egbe, O.; Rzepa, H. S.; Bürgi, T.; Richardson, J.; Spivey, A. C. “Kinetic Resolution of 2-Substituted Indolines by N-Sulfonylation using an Atropisomeric 4-DMAP-N-oxide Organocatalyst”, Angew. Chem. Int. Ed. 2017, 56, 5760-5764.open archive unige:94104 pdf full text [restricted access]

The first catalytic kinetic resolution by N-sulfonylation is described. 2-Substituted indolines are resolved (s=2.6–19) using an atropisomeric 4-dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst. Use of 2-isopropyl-4-nitrophenylsulfonyl chloride is critical to the stereodiscrimination and enables facile deprotection of the sulfonamide products with thioglycolic acid. A qualitative model that accounts for the stereodiscrimination is proposed.

75
Aroussi, B. E.; Hamacek, J. “Understanding the speciation of Ln(III) complexes with octadentate tripodal ligands”, New J. Chem. 2017, 41, 4390-4399.

Two new dissymmetrical tripodal ligands bearing three multidentate pyridine moieties (L5 and L6) have been synthesised and the speciation of their Ln(III) complexes in solution has been studied. The complexation behaviour with selected Ln(III) has been investigated by combining ESMS, spectrophotometric and NMR titrations. For both ligands LX (X = 5, 6), the Ln2(LX)3 species are abundantly present at stoichiometry in the form of unconventional low-symmetrical complexes. However, the complexes with L5 at [Ln]/[L5] ∼1 are much better defined and allow the corresponding 1H-NMR spectrum to be completely assigned. Indeed, the latter points out that the structure of complexes [Ln2(L5)2]6+ in solution is best described as an unsaturated dinuclear helicate, where the tridentate sites are wrapped about the metallic cations, and the bidentate strand does not coordinate. Compared to L4 and L6, the prolongation of the spacer in L5 (glycine moiety) has in fact allowed thermodynamic and kinetic stabilities to increase, especially for the Lu(III) complexes. Finally, the structure of dinuclear species [Ln2(LX)2]6+ (X = 4–6) is apparently independent of the structure of the bidentate moieties, which are involved in complexation in metal excess only.

74
Cardenal-Muñoz, E.; Arafah, S.; López-Jiménez, A. T.; Kicka, S.; Falaise, A.; Bach, F.; Schaad, O.; King, J. S.; Hagedorn, M.; Soldati, T.; Lewinsohn, D. M. “Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner”, PLoS Pathog. 2017, 13, e1006344.open archive unige:96994 pdf full text [free access]

Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV.

73
Phan, H.; Hrudka, J. J.; Igimbayeva, D.; Lawson Daku, L. M.; Shatruk, M. “A Simple Approach for Predicting the Spin State of Homoleptic Fe(II) Tris-diimine Complexes”, J. Am. Chem. Soc. 2017, 139, 6437-6447.open archive unige:94103 pdf full text [restricted access]

We propose a simple method for predicting the spin state of homoleptic complexes of the Fe(II) d6 ion with chelating diimine ligands. The approach is based on the analysis of a single metric parameter within a free (noncoordinated) ligand: the interatomic separation between the N-donor metal-binding sites. An extensive analysis of existing complexes allows the determination of critical N···N distances that dictate the regions of stability for the high-spin and low-spin complexes, as well as the intermediate range in which the magnetic bistability (spin crossover) can be observed. The prediction has been tested on several complexes that demonstrate the validity of our method.

72
Zhai, J.; Xie, X.; Cherubini, T.; Bakker, E. “Ionophore-Based Titrimetric Detection of Alkali Metal Ions in Serum”, ACS Sens. 2017, 2, 606-612.open archive unige:95396 pdf full text [free access]

While the titrimetric assay is one of the most precise analytical techniques available, only a limited list of complexometric chelators is available, as many otherwise promising reagents are not water-soluble. Recent work demonstrated successful titrimetry with ion-exchanging polymeric nanospheres containing hydrophobic complexing agents, so-called ionophores, opening an exciting avenue in this field. However, this method was limited to ionophores of very high affinity to the analyte and exhibited a relatively limited titration capacity. To overcome these two limitations, we report here on solvent based titration reagents. This heterogeneous titration principle is based on the dissolution of all hydrophobic recognition components in a solvent such as dichloromethane (CH2Cl2) where the ionophores are shown to maintain a high affinity to the target ions. HSV (hue, saturation, value) analysis of the images captured with a digital camera provides a convenient and inexpensive way to determine the end point. This approach is combined with an automated titration setup. The titrations of the alkali metals K+, Na+, and Li+ in aqueous solution are successfully demonstrated. The potassium concentration in human serum without pretreatment was precisely and accurately determined as 4.38 mM ± 0.10 mM (automated titration), which compares favorably with atomic emission spectroscopy (4.47 mM ± 0.20 mM).

71
Bosmani, A.; Pujari, S.; Guenée, L.; Besnard, C.; Poblador Bahamonde, A. I.; Lacour, J. “Stereoselective and Enantiospecific Mono- and Bis-C−H azidation of Tröger Bases. Insight on Bridgehead Iminium Intermediates and Application to Anion-Binding Catalysis”, Chem. Eur. J. 2017, 23, 8678-8684.open archive unige:95273 pdf full text [restricted access]

In the context to Tröger base chemistry, regio and stereoselective Csp3-H azidation reactions are reported. Azide functional groups are introduced at either one or the two benzylic positions selectively. Mild conditions and good yields are afforded by the combination of TMSN3 and iodosobenzene PhIO. The process occurs with high enantiospecificity (es 96-99%) and, interestingly and importantly, via bridgehead iminium intermediates as shown by mechanistic and in-silico studies. Finally, mono and bis triazole derivatives were prepared in high yields and enantiospecificity using CuAAC reactions; some of the products being used as anion-binding organocatalysts for the tritylation of amines and alcohols.

70
Kozintsev, A.; Sugihara, K. “Artificial tubular connections between cells based on synthetic lipid nanotubes”, RSC Adv. 2017, 7, 20700-20708.open archive unige:94060 pdf full text [free access]

Tunneling nanotubes (TNTs) have become a major topic of interest as a form of intercellular communication due to their recent discovery. However, research on this subject has often suffered from a lack of controllability in the generation of the nanotubular connections. In this work, we demonstrate a simplified approach to selectively create a direct nanotubular connection between eukaryotic cells by manually manipulating self-assembling lipid nanotubes (LNTs) from inverted hexagonal-phase lipid blocks. The technique requires minimal instrumentation for creating the LNT connection between cells compared to conventional approaches. Based on the diffusion of fluorescent lipids from LNTs into cell membranes (D = 0.032 ± 0.003 μm2s−1), the probability of observing membrane fusion between LNTs and cell membranes was estimated as 30%. Among these cell–LNT junctions the resulting structure is open-ended roughly 75% of the time, as evidenced from observations of the diffusion of a water-soluble dye between two cells connected with this nanotubular structure.

69
Cuartero, M.; Acres, R. G.; Bradley, J.; Jarolimova, Z.; Wang, L.; Bakker, E.; Crespo, G. A.; De Marco, R. “Electrochemical Mechanism of Ferrocene-Based Redox Molecules in Thin Film Membrane Electrodes”, Electrochim. Acta 2017, 238, 357-367.open archive unige:95395 pdf full text [restricted access]

Cyclic voltammetry (CV) in chloride-based aqueous electrolytes of ferrocene molecule doped thin membranes (∼200 nm in thickness) on glassy carbon (GC) substrate electrodes, both plasticized poly(vinyl chloride) (PVC) and unplasticized poly(methyl methacrylate)/poly(decyl methacrylate) (PMMA-PDMA) membranes, has shown that the electrochemical oxidation behavior is irreversible due most likely to degradation of ferrocene at the buried interface (GC|membrane). Furthermore, CV of the ferrocene molecules at GC electrodes in organic solvents employing chloride-based and chloride-free organic electrolytes has demonstrated that the chloride anion is inextricably linked to this irreversible ferrocene oxidation electrochemistry. Accordingly, we have explored the electrochemical oxidation mechanism of ferrocene-based redox molecules in thin film plasticized and unplasticized polymeric membrane electrodes by coupling synchrotron radiation-X-ray photoelectron spectroscopy (SR-XPS) and near edge X-ray absorption fine structure (NEXAFS) with argon ion sputtering to depth profile the electrochemically oxidized thin membrane systems. With the PVC depth profiling studies, it was not possible to precisely study the influence of chloride on the ferrocene reactivity due to the high atomic ratio of chloride in the PVC membrane; however, the depth profiling results obtained with a chlorine-free polymer (PMMA-PDMA) provided irrefutable evidence for the formation of a chloride-based iron product at the GC|PMMA-PDMA interface. Finally, we have identified conditions that prevent the irreversible conversion of ferrocene by utilizing a high loading of redox active reagent and/or an ionic liquid (IL) membrane plasticizer with high ionicity that suppresses the mass transfer of chloride.

68
Zong#, L.; Bartolami#, E.; Abegg, D.; Adibekian, A.; Sakai, N.; Matile, S. “Epidithiodiketopiperazines: Strain-Promoted Thiol-Mediated Cellular Uptake at the Highest Tension”, ACS Cent. Sci. 2017, 3, 449-453.open archive unige:95404 pdf full text [free access]

The disulfide dihedral angle in epidithiodiketopiperazines (ETPs) is near 0°. Application of this highest possible ring tension to strain-promoted thiol-mediated uptake results in efficient delivery to the cytosol and nucleus. Compared to the previous best asparagusic acid (AspA), ring-opening disulfide exchange with ETPs occurs more efficiently even with nonactivated thiols, and the resulting thiols exchange rapidly with nonactivated disulfides. ETP-mediated cellular uptake is more than 20 times more efficient compared to AspA, occurs without endosomal capture, depends on temperature, and is “unstoppable” by inhibitors of endocytosis and conventional thiol-mediated uptake, including siRNA against the transferrin receptor. These results suggest that ETP-mediated uptake not only maximizes delivery to the cytosol and nucleus but also opens the door to a new multitarget hopping mode of action.

67
Moazzami-Gudarzi, M.; Maroni, P.; Borkovec, M.; Trefalt, G. “Depletion and double layer forces acting between charged particles in solutions of like-charged polyelectrolytes and monovalent salts”, Soft Matter 2017, 13, 3284-3295.

Interaction forces between silica particles were measured in aqueous solutions of the sodium salt of poly(styrene sulphonate) (PSS) and NaCl using the colloidal probe technique based on an atomic force microscope (AFM). The observed forces can be rationalized through a superposition of damped oscillatory forces and double layer forces quantitatively. The double layer forces are modeled using Poisson–Boltzmann (PB) theory for a mixture of a monovalent symmetric electrolyte and a highly asymmetric electrolyte, whereby the multivalent coions represent the polyelectrolyte chains. The effective charge of the polyelectrolyte is found to be smaller than the bare number of charged groups residing on one polyelectrolyte molecule. This effect can be explained by counterion condensation. The interplay between depletion and double layer forces can be further used to predict the phase of the depletion force oscillations. However, this picture holds only at not too elevated concentrations of the polyelectrolyte and salt. At higher salt concentrations, attractive van der Waals forces become important, while at higher polyelectrolyte concentrations, the macromolecules adsorb onto the like-charged silica interface.

66
Sethio, D.; Lawson Daku, L. M.; Hagemann, H. “Computational study of the vibrational spectroscopy properties of boron-hydrogen compounds: Mg(B3H8)2, CB9H10- and CB11H12-”, Int. J. Hydrogen Energy 2017, 42, 22496-22501.open archive unige:96315 pdf full text [restricted access]

We report the DFT study of the vibrational spectroscopy properties of Mg(B3H8)2, a potential intermediate in the decomposition of Mg(BH4)2, as well as those of CB11H12and CB9H10, whose salts can exhibit high ionic conductivities. Because the inclusion of anharmonicity is key to the accurate description of the vibrational properties of BH species [D. Sethio, L. M. Lawson Daku, H. Hagemann. Int. J. Hydrogen Energy, 41 (2016) 6814], the calculations were performed both in the harmonic and in the anharmonic approximation. The IR and Raman spectra of Cs(CB11H12) and Na2(B10H10) have also been measured. The calculated and experimental spectra are in good agreement. A comparative analysis of the vibrational spectroscopy properties is made for B3H8 and Mg(B3H8)2, B12H122− and CB11H12, and for B10H102− and CB9H10

65
Cougnon, F. B. L. “Tight Embrace in a Molecular Knot with Eight Crossings”, Angew. Chem. Int. Ed. 2017, 56, 4918-4919.open archive unige:93930 pdf full text [restricted access]

When it takes eight to tango: Since the synthesis of the simplest of all knots, the trefoil knot, in 1989, the formation of more complex knots has remained extremely challenging. The synthesis of the most complex molecular knot made to date, the 819, by Leigh and co-workers thus represents a major step towards building topologically complex architectures.

64
Hui, X.; Sauer, B.; Kaestner, L.; Kruse, K.; Lipp, P. “PKCα diffusion and translocation are independent of an intact cytoskeleton”, Sci. Rep. 2017, 7, art. num. 475.

Translocation of cytosolic cPKC to the plasma membrane is a key event in their activation process but its exact nature is still unclear with particular dispute whether sole diffusion or additional active transport along the cell’s cytoskeleton contributes to cPKC’s dynamics. This was addressed by analyzing the recruitment behavior of PKCα while manipulating the cytoskeleton. Photolytic Ca2+ uncaging allowed us to quantify the kinetics of PKCα redistribution to the plasma membrane when fused to monomeric, dimeric and tetrameric fluorescence proteins. Results indicated that translocation kinetics were modulated by the state of oligomerization as expected for varying Stokes’ radii of the participating proteins. Following depolymerization of the microtubules and the actin filaments we found that Ca2+ induced membrane accumulation of PKCα was independent of the filamentous state of the cytoskeleton. Fusion of PKCα to the photo-convertible fluorescent protein Dendra2 enabled the investigation of PKCα-cytoskeleton interactions under resting conditions. Redistribution following spatially restricted photoconversion showed that the mobility of the fusion protein was independent of the state of the cytoskeleton. Our data demonstrated that in living cells neither actin filaments nor microtubules contribute to PKCα’s cytosolic mobility or Ca2+-induced translocation to the plasma membrane. Instead translocation is a solely diffusion-driven process.

63
Kanduč, M.; Moazzami-Gudarzi, M.; Valmacco, V.; Podgornik, R.; Trefalt, G. “Interactions between charged particles with bathing multivalent counterions: experiments vs. dressed ion theory”, Phys. Chem. Chem. Phys. 2017, 19, 10069-10080.

We compare the recent experimentally measured forces between charged colloidal particles, as well as their effective surface potentials (surface charge) in the presence of multivalent counterions in a bathing monovalent salt solution, with the predictions of the dressed ion theory of strongly charged colloidal systems. The benchmark for comparison is provided by the DLVO theory and the deviations from its predictions at small separations are taken as an indication of the additional non-DLVO attractions that can be fitted by an additional phenomenological exponential term. The parameters characterizing this non-DLVO exponential term as well as the dependencies of the effective potential on the counterion concentration and valency predicted by the dressed ion theory are well within the experimental values. This suggests that the deviations from the DLVO theory are probably caused by ion correlations as formalized within the dressed ion theory.

62
Duchêne, L.; Kühnel, R.-S.; Rentsch, D.; Remhof, A.; Hagemann, H.; Battaglia, C. “A highly stable sodium solid-state electrolyte based on a dodeca/deca-borate equimolar mixture”, Chem. Commun. 2017, 6, 4195-4198.open archive unige:93532 pdf full text [restricted access]

Na2(B12H12)0.5(B10H10)0.5, a new solid-state sodium electrolyte is shown to offer high Na+conductivity of 0.9 mS cm−1 at 20 °C, excellent thermal stability up to 300 °C, and a large electrochemical stability window of 3 V including stability towards sodium metal anodes, all essential prerequisites for a stable room-temperature 3 V all-solid-state sodium-ion battery.

61
Williams, A. F.; Granelli, M.; Downward, A. M.; Huber, R.; Guenée, L.; Besnard, C.; Krämer, K. W.; Decurtins, S.; Liu, S.-X.; Thompson, L. K. “Dinuclear complexes formed by hydrogen bonds: synthesis, structure and magnetic and electrochemical properties”, Chem. Eur. J. 2017, 23, 7104-7112.

The synthesis is reported of a series of homo- and hetero-dinuclear octahedral complexes of the ligand 1, 1,2-bis(1-methyl-benzimidazol-2-yl) ethanol, where the two metal centres are linked by hydrogen bonds between coordinated alcohols and coordinated alkoxides. Homonuclear divalent M(II)M(II), mixed valent M(II)M(III) and heteronuclear M(II)M'(III) species are prepared. The complexes have been characterised by X-ray crystallography and show unusually short O…O distances for the hydrogen bonds. Magnetic measurements show the hydrogen bond bridges can lead to ferromagnetic or antiferromagnetic coupling. The electrochemistry of the dinuclear species is significantly different from the mononuclear systems: the latter show irreversible waves in cyclic voltammograms as a result of the need to couple proton and electron transfer. The dinuclear species, in contrast, show reversible waves which are attributed to rapid intramolecular proton transfer facilitated by the hydrogen bonded structure.

60
Yen, A.; Choo, K.-L.; Yazdi, S. K.; Franke, P. T.; Webster, R.; Franzoni, I.; Loh, C. C. J.; Poblador-Bahamonde, A. I.; Lautens, M. “Rhodium-Catalyzed Enantioselective Isomerization of meso-Oxabenzonorbornadienes to 1,2-Naphthalene Oxides”, Angew. Chem. Int. Ed. 2017, 56, 6307-6311.open archive unige:94490 pdf full text [restricted access]

Herein we describe a rhodium-catalyzed enantioselective isomerization of meso-oxabicyclic alkenes to 1,2-naphthalene oxides. These potentially useful building blocks can be accessed in moderate to excellent yields with impressive enantioselectivities. Additionally, experimental findings supported by preliminary computations suggest that ring-opening reactions of bridgehead disubstituted oxabicyclic alkenes proceed through the intermediacy of these epoxides and may point to a kinetically and thermodynamically favored reductive elimination as the origin for the observed enantioselectivities.

59
Jeannerat, D. “Analysis of the phases of signals in two-dimensional NMR”, In eMagRes” Volume 6, Issue 1, John Wiley and Sons, Inc 2017, p. 161-172.open archive unige:93864 pdf full text [restricted access]

Some two-dimensional experiments suffer from “phase problems”, meaning that instead of resulting with spectra with absorptive signals they have a dispersive component causing extensive line broadening and baseline distortions. We shall illustrate how a spectral decomposition determining the phases of the peaks together with the other lineshape parameters makes it possible to reconstruct synthetic spectra containing signals with corrected phases. When applied to the two-pulses COSY spectra, this type of analysis allows one to discriminate the diagonal and the cross peaks according to their phases and reconstruct separate synthetic spectra with pure-absorption lineshapes. Similarly, J-resolved spectra producing phase-twisted signals can be analysed and have their phases corrected. This method can also exploit spectra generated by NMR pulse sequences encoding an NMR parameter as a controlled phase distortion in F1 dimension. In the case of chemical shift encoding, the extracted information were used to resolve the ambiguities caused by spectral aliasing. Finally it can be used to identify and eliminate signal artefacts when their phase properties differ from those of normal signals.

58
Licari, G.; Cwiklik, L.; Jungwirth, P.; Vauthey, E. “Exploring Fluorescent Dyes at Biomimetic Interfaces with Second Harmonic Generation and Molecular Dynamics”, Langmuir 2017, 33, 3373-3383.open archive unige:93531 pdf full text [restricted access]

The adsorption of a DNA fluorescent probe belonging to the thiazole orange family at the dodecane/water and dodecane/phospholipid/water interfaces has been investigated using a combination of surface second harmonic generation (SSHG) and all-atomistic molecular dynamics (MD) simulations. Both approaches point to a high affinity of the cationic dye for the dodecane/water interface with a Gibbs free energy of adsorption on the order of −45 kJ/mol. Similar affinity was observed with a monolayer of negatively charged DPPG (1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol)) lipids. On the other hand, no significant adsorption could be found with the zwitterionic DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) lipids. This was rationalized in terms of Coulombic interactions between the monolayer surface and the cationic dye. The similar affinity for the interface with and without DPPG, despite the favorable Coulombic attraction in the latter case, could be explained after investigating the interfacial orientation of the dye. In the absence of a monolayer, the dye adsorbs with its molecular plane almost flat at the interface, whereas in the presence of DPPG it has to intercalate into the monolayer and adopt a significantly different orientation to benefit from the electrostatic stabilization.

57
Liu, L.; Cotelle, Y.; Klehr, J.; Sakai, N.; Ward, T. R.; Matile, S. “Anion-π Catalysis: Bicyclic Products with Four Contiguous Stereogenic Centers from Otherwise Elusive Diastereospecific Domino Reactions on π-Acidic Surfaces”, Chem. Sci. 2017, 8, 3770-3774.open archive unige:94018 pdf full text [free access]

Anion–π interactions have been introduced recently to catalysis. The idea of stabilizing anionic intermediates and transition states on π-acidic surfaces is a new fundamental concept. By now, examples exist for asymmetric enolate, enamine, iminium and transamination chemistry, and the first anion–π enzyme has been created. Delocalized over large aromatic planes, anion–π interactions appear particularly attractive to stabilize extensive long-distance charge displacements during domino processes. Moving on from the formation of cyclohexane rings with five stereogenic centers in one step on a π-acidic surface, we here focus on asymmetric anion–π catalysis of domino reactions that afford bicyclic products with quaternary stereogenic centers. Catalyst screening includes a newly synthesized, better performing anion–π version of classical organocatalysts from cinchona alkaloids, and anion–π enzymes. We find stereoselectivities that are clearly better than the best ones reported with conventional catalysts, culminating in unprecedented diastereospecificity. Moreover, we describe achiral salts as supramolecular chirality enhancers and report the first artificial enzyme that operates in neutral water with anion–π interactions, i.e., interactions that are essentially new to enzymes. Evidence in support of contributions of anion–π interactions to asymmetric catalysis include increasing diastereo- and enantioselectivity with increasing rates, i.e., asymmetric transition-state stabilization in the presence of π-acidic surfaces and inhibition with the anion selectivity sequence NO3 > Br > BF4 > PF6.

56
Kumpulainen, T.; Rosspeintner, A.; Vauthey, E. “Probe dependence on polar solvation dynamics from fs broadband fluorescence”, Phys. Chem. Chem. Phys. 2017, 19, 8815-8825.open archive unige:93533 pdf full text [restricted access]

Polar solvation dynamics of six 7-aminocoumarins and 4-aminophthalimide (4AP) are investigated using broadband FLuorescence UP-conversion Spectroscopy (FLUPS) combined with a global analysis based on time-dependent band-shape functions. The solvation dynamics of the coumarins in ethanol exhibit only minor differences but are, however, significantly different from that of 4AP. The band-shape parameters, width and asymmetry, exhibit much larger variation even among the coumarins and are correlated with the amount of excess excitation energy. Differences in the solvation dynamics of 4AP and a selected coumarin, C151, are also observed in dimethyl sulfoxide demonstrating the molecularity of solvation i.e. solvation depends on the solute and does not solely reflect the dynamic properties of the solvent. These differences are attributed to specific solute–solvent interactions due to hydrogen bonding. In a weakly interacting solvent, benzonitrile, the solvation dynamics of 4AP and C151 are nearly identical.

55
Hannich, J. T.; Mellal, D.; Feng, S.; Zumbuehl, A.; Riezman, H. “Structure and conserved function of iso-branched sphingoid bases from the nematode Caenorhabditis elegans”, Chem. Sci. 2017, 8, 3676-3686.

Sphingolipids are bio-active metabolites that show structural diversity among eukaryotes. They are essential for growth of all eukaryotic cells but when produced in an uncontrolled manner can lead to cell death and pathologies including auto-immune reactions, cancer, diabetes and neurodegeneration.Caenorhabditis elegans is an important genetic model organism both to find new drug-targets against parasitic nematodes and to study the conserved roles of sphingolipids in animals like their essential functions in very basic cellular processes ranging from maintenance of cell polarity and mitochondrial repair to growth and survival. C. elegans produces sphingoid bases which are structurally distinct from those of other animals as both iso- and anteiso-branched species have been reported. Using metabolic labeling we show that most worm sphingoid bases are iso-branched. We have synthesized the nematode-specific C17 iso-branched sphinganine and its 1-deoxy analogue and could show that both the iso-branch and the 1-hydroxyl group are essential to form functional nematode sphingolipids which are needed to maintain intestinal function. The organism specificity was examined by complementation experiments in Saccharomyces cerevisiae yeast cells lacking sphingoid base synthesis. We found that iso-branched sphingoid base did not support growth of mutant cells and was toxic to wild type yeast. 1-deoxy sphingolipids have been linked to the hereditary disease HSAN1A and other metabolic disorders including diabetes. We found that in C. elegans the 1-deoxy analogue cannot rescue the intestinal phenotype caused by sphingoid base depletion. In fact, in wild-type animals with normal sphingoid base biosynthesis, exogenous 1-deoxy analogue had a disruptive effect on apical cytoskeletal organization of intestinal cells indicating that atypical bases can interfere with normal sphingolipid function.

54
Flack, H. D. “Symmetry, Spectroscopy, and Crystallography: The Structural Nexus.”, Acta Crystallogr., Sect. A: Found. Crystallogr. 2017, 73, 207.

The content of this book comes from a graduate-level course entitled `Special topics in structural chemistry and symmetry'. It is written in easy-to-follow modern-day English. Most of the illustrations are in black-and-white with a few colour pictures thrown in for good measure. The hardcover version of the book is well bound.

A nexus is a link or connection, a connected group, a network, or a central or focal point. However, the content of this book seems to flit from subject to subject in a uncoordinated manner and one is sometimes at a loss to know what particular point of interest the author wishes to stress. For example, history is mixed with a discussion of nomenclature. The text reads exactly like the content of a lecture, for which one is permitted a wider style of presentation than in a written document.

The presentation of symmetry and crystallography lack precision and clarity. If you wish to learn about either, this is not the book that you need.

53
Moury, R.; Gigante, A.; Hagemann, H. “An alternative approach to the synthesis of NaB3H8 and Na2B12H12 for solid electrolyte applications”, Int. J. Hydrogen Energy 2017, 42, 22417-22421.open archive unige:96316 pdf full text [restricted access]

Alkaline or alkaline earth octahydrotriborate M(B3H8)x and dodecahydro-closo-dodecaborate MxB12H12 (M = Li, Na, Mg or Ca with x = 1 or 2) have recently attracted a lot of interest for hydrogen storage and solid electrolyte applications. Nevertheless, their syntheses are still a roadblock for large scale applications. In this paper we propose a novel approach for their syntheses starting from the cheapest borohydride NaBH4. The process involves first the solvothermal synthesis of tetrabutylammonium octahydrotriborate (C4H9)4NB3H8 (TBAB3H8) being the basis for the syntheses of the others boranes. Starting from TBAB3H8, we have synthesized pure and unsolvated NaB3H8 by salt metathesis reaction with sodium tetraphenylborate. Then, we have successfully obtained Na2B12H12 by solvothermal decomposition of NaB3H8. This approach has shown to be quantitative and reproducible, which could lead to the development of these boranes in real life applications.

52
Zimmermann, C.; Santos, A.; Gable, K.; Epstein, S.; Gururaj, C.; Chymkowitch, P.; Pultz, D.; Rødkær, S. V.; Clay, L.; Bjørås, M.; Barral, Y.; Chang, A.; Færgeman, N. J.; Dunn, T. M.; Riezman, H.; Enserink, J. M. “Correction: TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy”, Cell Rep. 2017, 18, 2073-2074.

In the originally published version of this article, part of a panel shown in Figure 3D was inadvertently duplicated from Figure 3C during preparation of the figure. The correct version of this figure is shown above.

51
Vuillamy, A.; Zebret, S.; Besnard, C.; Placide, V.; Petoud, S.; Hamacek, J. “Functionalized Triptycene-Derived Tripodal Ligands: Privileged Formation of Tetranuclear Cage Assemblies with Larger Ln(III)”, Inorg. Chem. 2017, 56, 2742-2749.

In this Article, we report the self-assembly of lanthanide complexes formed with two new tripodal ligands, L2 and L3, where binding strands are connected to a rigid triptycene anchor. The pyridine moieties are functionalized with methoxy and PEG groups to enhance ligand solubility and to evaluate the effect of these substituents on lanthanide coordination. These ligands were successfully synthesized and characterized, and their coordination properties were examined along the lanthanide series through speciation studies with NMR and ESI-MS. Well-defined tetranuclear complexes are formed with both ligands, but their stabilities with heavier lanthanides are considerably reduced, especially for complexes with L3. This is attributed to a destabilizing effect of pending PEG arms in combination with increased steric hindrance between binding strands upon complexation with smaller cations. The sensitization of lanthanide luminescence in tetranuclear complexes occurs despite one water molecule being coordinated to a metal ion.

50
Macchione, M.; Chuard, N.; Sakai, N.; Matile, S. “Planarizable Push-Pull Probes: Overtwisted Flipper Mechanophores”, ChemPlusChem 2017, 82, 1062-1066.open archive unige:95494 pdf full text [free access]

Planarizable push–pull fluorescent probes, also referred to as flipper probes, have been introduced as conceptually innovative mechanophores that report on forces in their local environment in lipid bilayer membranes. The best flipper probes respond to a change from liquid disordered to solid ordered membranes with a red shift in excitation of 50–90 nm. A simultaneous increase in fluorescence lifetime and negligible background fluorescence from the aqueous phase qualifies these fluorescent probes for meaningful imaging in live cells. Here, we report that the replacement of methyl with isobutyl substituents along the scaffold of a dithienothiophene dimer strongly reduces fluorescence intensity but increases solvatochromism slightly. These trends imply that the large substituents in “leucine flippers” hinder the planarization in the first excited state to result in twisted intramolecular charge transfer (TICT). As a result of this overtwisting, the leucine flippers form interesting fluorescent micelles in water but fail to respond to changes in membrane order. These dramatic changes in function provide one of the most impressive illustrations for the hypersensitivity of fluorescent membrane probes toward small changes in their structure.

49
Alghanem, B.; Nikitin, F.; Stricker, T.; Duchoslav, E.; Luban, J.; Strambio-De-Castillia, C.; Muller, M.; Lisacek, F.; Varesio, E.; Hopfgartner, G. “Optimization by infusion of multiple reaction monitoring transitions for sensitive quantification of peptides by liquid chromatography/mass spectrometry”, Rapid Commun. Mass Spectrom. 2017, 31, 753-761.

Rationale

In LC-MS peptide quantification, the optimization of multiple reaction monitoring (MRM) parameters is essential for sensitive detection. We have compared different approaches to build MRM assays, based either on flow injection analysis (FIA) of isotopically labelled peptides, or on the knowledge and the prediction of the best settings for MRM transitions and collision energies (CE). In this context, we introduce MRMOptimizer, an open source software tool that processes spectra and assists the user in selecting transitions in the FIA workflow.

Methods

MS/MS spectral libraries with CE voltages from 10 to 70 V are automatically acquired in FIA mode for isotopically labelled peptides. Then MRMOptimizer determines the optimal MRM settings for each peptide. To assess the quantitative performance of our approach, 155 peptides representing 84 proteins, were analysed by LC-MRM/MS and the peak areas were compared between: A) the MRMOptimizer-based workflow, B1) the SRMAtlas transitions set used “as-is”; B2) the same SRMAtlas set with CE parameters optimized by Skyline.

Results

51% of the 3 most intense transitions per peptide were shown to be common to both A and B1/B2 methods, and displayed similar sensitivity and peak area distributions. The peak areas obtained with MRMOptimizer for transitions sharing either the precursor ion charge state or the fragment ions with the SRMAtlas set at unique transitions were increased 1.8 to 2.3-fold. The gain of sensitivity using MRMOptimizer for transitions with different precursor ion charge state and fragment ions (8% of the total), reaches a ~11-fold increase.

Conclusions

Isotopically labelled peptides can be used to optimize MRM transitions more efficiently in FIA than by searching databases. The MRMOptimizer software is MS independent and enables the post-acquisition selection of MRM parameters. Coefficients of variation for optimal CE values are lower than those obtained with the SRMAtlas approach (B2) and one additional peptide was detected.

48
Spannl, S.; Kumichel, A.; Hebbar, S.; Kapp, K.; Gonzalez-Gaitan, M.; Winkler, S.; Blawid, R.; Jessberger, G.; Knust, E. “The Crumbs_C isoform of Drosophila shows tissue- and stage-specific expression and prevents light-dependent retinal degeneration”, Biol. Open 2017, 6, 165-175.

Drosophila Crumbs (Crb) is a key regulator of epithelial polarity and fulfils a plethora of other functions, such as growth regulation, morphogenesis of photoreceptor cells and prevention of retinal degeneration. This raises the question how a single gene regulates such diverse functions, which in mammals are controlled by three different paralogs. Here, we show that in Drosophila different Crb protein isoforms are differentially expressed as a result of alternative splicing. All isoforms are transmembrane proteins that differ by just one EGF-like repeat in their extracellular portion. Unlike Crb_A, which is expressed in most embryonic epithelia from early stages onward, Crb_C is expressed later and only in a subset of embryonic epithelia. Flies specifically lacking Crb_C are homozygous viable and fertile. Strikingly, these flies undergo light-dependent photoreceptor degeneration despite the fact that the other isoforms are expressed and properly localised at the stalk membrane. This allele now provides an ideal possibility to further unravel the molecular mechanisms by which Drosophila crb protects photoreceptor cells from the detrimental consequences of light-induced cell stress.

47
Guzinski, M.; Jarvis, J. M.; Perez, F.; Pendley, B. D.; Lindner, E.; de Marco, R.; Crespo, G. A.; Acres, R. G.; Walker, R.; Bishop, J. L. “PEDOT(PSS) as solid contact for ion-selective electrodes: the influence of the PEDOT(PSS) film thickness on the equilibration times”, Anal. Chem. 2017, 89, 3508-3516.

To understand the rate determining processes during the equilibration of poly(3,4-ethylenedioxythiophene):polystyrene sulfonate-based (PEDOT(PSS)-based) solid contact (SC) ion-selective electrodes (ISEs), the surfaces of Pt, Au, and GC electrodes were coated with 0.1, 1.0, 2.0 and 4.0μm thick galvanostatically deposited PEDOT(PSS) films. Next, potential vs. time transients were recorded with these electrodes, with and without an additional potassium ion-selective membrane (ISM) coating, following their first contact with 0.1M KCl solutions. The transients were significantly different when the multi-layered sensor structures were assembled on Au or GC compared to Pt. The differences in the rate of equilibration were interpreted as a consequence of differences in the hydrophilicity of PEDOT(PSS) in contact with the substrate electrode surfaces based on X-ray photoelectron spectroscopy (XPS) and synchrotron radiation-XPS (SR-XPS) analysis of 10 to 100nm thick PEDOT(PSS) films. The influence of the layer thickness of the electrochemically deposited PEDOT(PSS)-films on the hydrophilicity of these films has been documented by contact angle measurements over PEDOT(PSS)-coated Au, GC, and Pt electrode surfaces. This study demonstrates that it is possible to minimize the equilibration (conditioning) time of SC ISEs with aqueous solutions before usage by optimizing the thickness of the SC layer with a controlled ISM thickness. PEDOT(PSS)-coated Au, and GC electrodes exhibit a significant negative potential drift during their equilibration in an aqueous solution. By coating the PEDOT(PSS) surface with an ISM, the negative potential drift is compensated by a positive potential drift related to the hydration of the ISM and activity changes at the PEDOT(PSS)|ISM interface. The potential drifts related to activity changes in the ISM have been determined by a novel adaptation of the “sandwich membrane” method.

46
Petrone, D. A.; Franzoni, I.; Ye, J.; Rodriguez, J. F.; Poblador-Bahamonde, A. I.; Lautens, M. “Palladium-Catalyzed Hydrohalogenation of 1,6-Enynes: Hydrogen Halide Salts and Alkyl Halides as Convenient HX Surrogates”, J. Am. Chem. Soc. 2017, 139, 3546-3557.open archive unige:92434 pdf full text [restricted access]

Difficulties associated with the handling H2 and CO in metal-catalyzed processes has led to the development of chemical surrogates to these species. Despite many successful examples using this strategy, the application of convenient hydrogen halide (HX) surrogates in catalysis has lagged behind considerably. We now report the use of ammonium halides as HX surrogates to accomplish a novel Pd-catalyzed hydrohalogenation of enynes. These safe and practical salts avoid many drawbacks associated with traditional HX sources including toxicity and corrosiveness. Experimental and computational studies support a reaction mechanism involving a crucial E-to-Z vinyl–Pd isomerization and a carbon–halogen bond-forming reductive elimination. Furthermore, rare examples of C(sp3)–Br and –Cl reductive elimination from Pd(II) as well as transfer hydroiodination using 1-iodobutane as an alternate HI surrogate are also presented.

45
Lovric, S.; Goncalves, S.; Gee, H. Y.; Oskouian, B.; Srinivas, H.; Choi, W.-I.; Shril, S.; Ashraf, S.; Tan, W.; Rao, J.; Airik, M.; Schapiro, D.; Braun, D. A.; Sadowski, C. E.; Widmeier, E.; Jobst-Schwan, T.; Schmidt, J. M.; Girik, V.; Capitani, G.; Suh, J. H.; Lachaussée, N.; Arrondel, C.; Patat, J.; Gribouval, O.; Furlano, M.; Boyer, O.; Schmitt, A.; Vuiblet, V.; Hashmi, S.; Wilcken, R.; Bernier, F. P.; Innes, A. M.; Parboosingh, J. S.; Lamont, R. E.; Midgley, J. P.; Wright, N.; Majewski, J.; Zenker, M.; Schaefer, F.; Kuss, N.; Greil, J.; Giese, T.; Schwarz, K.; Catheline, V.; Schanze, D.; Franke, I.; Sznajer, Y.; Truant, A. S.; Adams, B.; Désir, J.; Biemann, R.; Pei, Y.; Ars, E.; Lloberas, N.; Madrid, A.; Dharnidharka, V. R.; Connolly, A. M.; Willing, M. C.; Cooper, M. A.; Lifton, R. P.; Simons, M.; Riezman, H.; Antignac, C.; Saba, J. D.; Hildebrandt, F. “Mutations in sphingosine-1-phosphase lyase cause nephrosis with ichthyosis and adrenal insufficiency”, J. Clin. Invest. 2017, 127, 912-928.

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1Δ yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS.

44
Li, H.; Voci, S.; Wallabregue, A.; Adam, C.; Labrador, G. M.; Duwald, R.; Hernández Delgado, I.; Pascal, S.; Bosson, J.; Lacour, J.; Bouffier, L.; Sojic, N. “Efficient Annihilation Electrochemiluminescence of Cationic Helicene Luminophores”, ChemElectroChem 2017, 4, 1750-1756.open archive unige:95480 pdf full text [free access]

The electrochemistry and annihilation electrochemiluminescence (ECL) of a series of chiral cationic helicene luminophores containing various substituents were investigated in acetonitrile as solvent. The electrochemical characterization evidenced a systematic reversible reduction of the cation whereas the oxidation could be reversible or not depending on the nature of the core heteroatoms within the structure as well as the functional group appendages. One of the key-parameters governing the ECL intensity is indeed the formal redox potentials for the electrogeneration of the neutral radical and dication radical species which will undergo the annihilation reaction. On that basis, a thermodynamic wall of efficiency was proposed in the case of ECL annihilation pathway to predict the formation efficiency of the emitting excited state and eventually light emission strength. This very simple wall is constructed by plotting the difference of formal potentials in function of the fluorescence wavelength delimiting thus two domains where ECL is thermodynamically possible or unfavorable.

43
Jukic, N.; Redondo-Morata, L.; Roux, A.; Scheuring, S. “Recovery of ESCRT-III Filaments Subjected to Force: An 'Invasive Mode' HS-AFM Study”, Biophys. J. 2017, 112, 92a.

Endosomal sorting complex required for transport III (ESCRT-III) proteins are crucial to membrane sculpting processes, including cytokinesis and biogenesis of multivesicular bodies. How ESCRT-III polymerization generates membrane curvature remains debated. Using High-Speed Atomic Force Microscopy (HS-AFM), a versatile technique with unprecedented spatial and temporal resolution, we acquired insights into how Snf7 assemblies, the major component of the ESCRT-III system, changed architecture in the presence of divalent cations and how they recover after being dissected by applying increased forces to well-defined delimited areas of the sample surface.

42
Moreno-Juan, V.; Filipchuk, A.; Antón-Bolaños, N.; Mezzera, C.; Gezelius, H.; Andrés, B.; Rodríguez-Malmierca, L.; Susín, R.; Schaad, O.; Iwasato, T.; Schüle, R.; Rutlin, M.; Nelson, S.; Ducret, S.; Valdeolmillos, M.; Rijli, F. M.; López-Bendito, G. “Prenatal thalamic waves regulate cortical area size prior to sensory processing”, Nat. Commun. 2017, 14172.

The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing.

41
Chuard, N.; Gasparini, G.; Moreau, D.; Lörcher, S.; Palivan, C.; Meier, W.; Sakai, N.; Matile, S. “Strain-Promoted Thiol-Mediated Cellular Uptake of Giant Substrates: Liposomes and Polymersomes”, Angew. Chem. Int. Ed. 2017, 56, 2947-2950.open archive unige:92406 pdf full text [restricted access]

Simple cyclic disulfides under high tension mediate the uptake of giant substrates, that is, liposomes and polymersomes with diameters of up to 400 nm, into HeLa Kyoto cells. To place them at the surface of the vesicles, the strained disulfides were attached to the head-group of cationic amphiphiles. Bell-shaped dose response curves revealed self-activation of the strained amphiphiles by self-assembly into microdomains at low concentrations and self-inhibition by micelle formation at high concentrations. Poor colocalization of internalized vesicles with endosomes, lysosomes, and mitochondria indicate substantial release into the cytosol. The increasing activity with disulfide ring tension, inhibition with Ellman's reagent, and inactivity of maleimide and guanidinium controls outline a distinct mode of action that deserves further investigation and is promising for practical applications.

40
Lindahl, L.; Santos, A. X. S.; Olsson, H.; Olsson, L.; Bettiga, M. “Membrane engineering of S. cerevisiae targeting sphingolipid metabolism”, Sci. Rep. 2017, 7, 41868.

The sustainable production of fuels and chemicals using microbial cell factories is now well established. However, many microbial production processes are still limited in scale due to inhibition from compounds that are present in the feedstock or are produced during fermentation. Some of these inhibitors interfere with cellular membranes and change the physicochemical properties of the membranes. Another group of molecules is dependent on their permeation rate through the membrane for their inhibition. We have investigated the use of membrane engineering to counteract the negative effects of inhibitors on the microorganism with focus on modulating the abundance of complex sphingolipids in the cell membrane of Saccharomyces cerevisiae. Overexpression of ELO3, involved in fatty acid elongation, and AUR1, which catalyses the formation of complex sphingolipids, had no effect on the membrane lipid profile or on cellular physiology. Deletion of the genes ORM1 and ORM2, encoding negative regulators of sphingolipid biosynthesis, decreased cell viability and considerably reduced phosphatidylinositol and complex sphingolipids. Additionally, combining ELO3 and AUR1 overexpression with orm1/ improved cell viability and increased fatty acyl chain length compared with only orm1/. These findings can be used to further study the sphingolipid metabolism, as well as giving guidance in membrane engineering.

39
Ortuso, R. D.; Cataldi, U.; Sugihara, K. “Mechanosensitivity of polydiacetylene with a phosphocholine headgroup”, Soft Mater 2017, 13, 1728-1736.open archive unige:92341 pdf full text [restricted access]

We demonstrated colorimetric and fluorescence detection of peptide, melittin, with polydiacetylene (PDA) made of 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC(8,9)PC). The PDA used in this work has a phosphocholine headgroup, which mimics peptide-cell membrane interactions better than the conventional PDA assays with carboxyl headgroup. The dose curve (colorimetric response vs melittin concentration) showed a half maximum response at the melittin concentration of 0.1 mg/ml, which is similar to the traditional PDA assays. It suggests that the replacement of the headgroup was achieved without sacrificing the sensitivity. From the dose curve, Hill coefficient was extracted as alpha_Hill = 2.1. The value is in agreement with previous melittin studies with standard phospholipids, which reflects the benefit of having a biologically relevant headgroup. In addition, we found an unexpectedly slow spectral change when DC(8,9)PC-PDA was incubated with melittin. The origin of the time-dependent signal was studied by combining UV/VIS spectroscopy, fluorescence spectroscopy and dynamic light scattering.

38
Gooding, J. J.; Bakker, E.; Long, Y.; Tao, N.; Kelley, S.; Merkx, M.; Sailor, M.; Mazur, A. “Editorial: Welcome to the First Anniversary Issue of ACS Sensors”, ACS Sens. 2017, 2, 1-2.

37
Trefalt, G.; Szilágyi, I.; Tellez, G.; Borkovec, M. “Colloidal Stability in Asymmetric Electrolytes: Modifications of the Schulze-Hardy Rule”, Langmuir 2017, 33, 1695-1704.

The Schulze-Hardy rule suggests a strong dependence of the critical coagulation concentration (CCC) on the ionic valence. This rule is addressed theoretically and confronted with recent experimental results. The commonly presented derivation of this rule assumes symmetric electrolytes and highly charged particles. Both assumptions are incorrect. Symmetric electrolytes containing multivalent ions are hardly soluble, and experiments are normally carried out with the well soluble salts of asymmetric electrolytes containing monovalent and multivalent ions. In this situation, however, the behavior is completely different whether the multivalent ions represent the counterions or coions. When these ions represent the counterions, meaning that the multivalent ions have the opposite sign than the charge of the particle, these ions adsorb strongly to the particles. Thereby, they progressively reduce the magnitude of the surface charge with increasing valence. In fact, this dependence of the charge density on the counterion valence is mainly responsible for the decrease of the CCC with the valence. In the coion case, where the multivalent ions have the same sign as the charge of the particle, the multivalent ions are repelled from the particles, and the surfaces remain highly charged. In this case, the inverse Schulze-Hardy rule normally applies, whereby the CCC varies inversely proportional to the coion valence.

36
Picco, A.; Irastorza-Azcarate, I.; Specht, T.; Böke, D.; Pazos, I.; Rivier-Cordey, A.-S.; Devos, D. P.; Kaksonen, M.; Gallego, O. “The In Vivo Architecture of the Exocyst Provides Structural Basis for Exocytosis”, Cell 2017, 168, 400-412.e18.

The structural characterization of protein complexes in their native environment is challenging but crucial for understanding the mechanisms that mediate cellular processes. We developed an integrative approach to reconstruct the 3D architecture of protein complexes in vivo. We applied this approach to the exocyst, a hetero-octameric complex of unknown structure that is thought to tether secretory vesicles during exocytosis with a poorly understood mechanism. We engineered yeast cells to anchor the exocyst on defined landmarks and determined the position of its subunit termini at nanometer precision using fluorescence microscopy. We then integrated these positions with the structural properties of the subunits to reconstruct the exocyst together with a vesicle bound to it. The exocyst has an open hand conformation made of rod-shaped subunits that are interlaced in the core. The exocyst architecture explains how the complex can tether secretory vesicles, placing them in direct contact with the plasma membrane.

35
Sels, A.; Salassa, G.; Pollitt, S.; Guglieri, C.; Rupprechter, G.; Barrabes, N.; Burgi, T. “Structural Investigation of Ligand Exchange Reaction with Rigid Dithiol on Doped (Pt, Pd) Au25 Clusters”, J. Phys. Chem. C 2017, 121, 10919-10926.open archive unige:94915 pdf full text [restricted access]

The ligand exchange reaction between heteroatom doped (Pd, Pt) Au25(2-PET)18 (2-PET = 2-phenylethylthiolate) clusters and enantiopure 1,1′-binaphthyl-2,2′-dithiol (BINAS) was monitored in situ using chiral high-performance liquid chromatography (HPLC). During the ligand exchange reactions, replacement of two protecting thiols (2-PET) with one new entering BINAS ligand on the cluster surface occurs. The rigid dithiol BINAS adsorbs in a specific mode that bridges the apex and one core site of two adjacent S(R)-Au-S(R)-Au-S(R) units. This is the most favorable binding mode and theoretically preserves the original structure. A kinetic investigation on these in-situ ligand exchange reactions revealed a decrease in reactivity after multiple exchange. A comparison of relative rate constants demonstrates a similar exchange affinity towards BINAS for both (Pd, Pt) systems. The possible structural deformation after incorporation of BINAS was investigated by X-ray absorption spectroscopy (XAS) in the S K edge and Au L3 edge. First, a thorough assignment of all sulfur contributions to the XANES spectrum was performed, distinguishing for the first time long and short staple motifs. Following, a structural comparison of doped systems using XANES and EXAFS confirmed the unaltered Au25 structure, except for some slight influence on the Au-S bonds. Additionally, intact staple motif was confirmed after incorporation of rigid dithiol BINAS by both XANES and EXAFS. This finding agrees with calculations prediction an interstaple binding mode by BINAS, which does not perturb the cluster structure.

34
Barisch, C.; Soldati, T.; Sassetti, C. M. “Mycobacterium marinum Degrades Both Triacylglycerols and Phospholipids from Its Dictyostelium Host to Synthesise Its Own Triacylglycerols and Generate Lipid Inclusions”, PLoS Pathog. 2017, 13, e1006095.open archive unige:92040 pdf full text [free access]

During a tuberculosis infection and inside lipid-laden foamy macrophages, fatty acids (FAs) and sterols are the major energy and carbon source for Mycobacterium tuberculosis. Mycobacteria can be found both inside a vacuole and the cytosol, but how this impacts their access to lipids is not well appreciated. Lipid droplets (LDs) store FAs in form of triacylglycerols (TAGs) and are energy reservoirs of prokaryotes and eukaryotes. Using the Dictyostelium discoideum/Mycobacterium marinum infection model we showed that M. marinum accesses host LDs to build up its own intracytosolic lipid inclusions (ILIs). Here, we show that host LDs aggregate at regions of the bacteria that become exposed to the cytosol, and appear to coalesce on their hydrophobic surface leading to a transfer of diacylglycerol O-acyltransferase 2 (Dgat2)-GFP onto the bacteria. Dictyostelium knockout mutants for both Dgat enzymes are unable to generate LDs. Instead, the excess of exogenous FAs is esterified predominantly into phospholipids, inducing uncontrolled proliferation of the endoplasmic reticulum (ER). Strikingly, in absence of host LDs, M. marinum alternatively exploits these phospholipids, resulting in rapid reversal of ER-proliferation. In addition, the bacteria are unable to restrict their acquisition of lipids from the dgat1&2 double knockout leading to vast accumulation of ILIs. Recent data indicate that the presence of ILIs is one of the characteristics of dormant mycobacteria. During Dictyostelium infection, ILI formation in M. marinum is not accompanied by a significant change in intracellular growth and a reduction in metabolic activity, thus providing evidence that storage of neutral lipids does not necessarily induce dormancy.

33
Chang, D.; Lindberg, E.; Winssinger, N. “Critical Analysis of Rate Constants and Turnover Frequency in Nucleic Acid-Templated Reactions: Reaching Terminal Velocity”, J. Am. Chem. Soc. 2017, 139, 1444-1447.open archive unige:91539 pdf full text [restricted access]

Nucleic acid-templated reactions have attracted significant attention for nucleic acid sensing and imaging. The level of signal amplification obtained from templated reactions is a function of the template turnover, wherein the template acts as the catalyst. Herein, we report the application of a pyridinium linker that immolates upon photocatalytic reduction with a ruthenium complex to yield the fastest nucleic acid templated reaction reported to date. We show that the templated reaction turnover is limited by the duplex dissociation kinetics beyond probes longer than a 6-mer and proceeded fastest for a 5-mer PNA probe. Using a beacon architecture that masks the catalytic template, we show that this methodology can be used for nucleic acid sensing extending the analyte recognition beyond a 5-mer. The system proceeds with a catalytic efficiency of 105 M–1 s–1 and achieves turnover frequency of >100 h–1.

32
Li, H.; Fiorito, D.; Mazet, C. “Exploring Site Selectivity of Iridium Hydride Insertion into Allylic Alcohols: Serendipitous Discovery and Comparative Study of an Organic and an Organometallic Catalysts for the Vinylogous Peterson Elimination”, ACS Catal. 2017, 7, 1554-1562.open archive unige:95401 pdf full text [free access]

The vinylogous Peterson elimination of a broad range of primary, secondary and tertiary silylated allylic alcohols by two distinct and complementary catalytic systems - a cationic iridium complex and a Brønsted acid - is reported. These results are unexpected. Non-silylated substrates are typically isomerized into aldehydes and silylated allylic alcohols into homoallylic alcohols with structurally related iridium complexes. Although several organic acids and bases are known to promote the vinylogous Peterson elimination, the practicality, mildness, functional group tolerance and generality of both catalysts are simply unprecedented. Highly substituted C=C bonds, stereochemically complex scaffolds, vicinal tertiary and quaternary (stereo)centers are also compatible with the two methods. Both systems are stereospecific and enantiospecific. After optimization, a vast number of dienes with substitution patterns that would be difficult to generate by established strategies are readily accessible. Importantly, control experiments secured that traces of acid that may be generated upon decomposition of the in situ generated iridium hydride are not responsible for the activity observed with the organometallic species. Upon inspection of the reaction scope and on the basis of preliminary investigations, a mechanism involving iridium-hydride and iridium-allyl intermediates is proposed to account for the elimination reaction. Overall, this study confirms that site selectivity for [Ir−H] insertion across the C=C bond of allylic alcohols is a key parameter for the reaction outcome.

31
Ghosh, H.; Burgi, T. “Mapping Infrared Enhancement Around Gold Nanoparticles Using Polyelectrolytes”, J. Phys. Chem. C 2017, 121, 2355-2363.open archive unige:94059 pdf full text [restricted access]

Enhancement of infrared signals from polyelectrolyte (PE) adsorbed on gold nanoparticles (GNPs) was studied in situ by attenuated total reflection infrared (ATR-IR) spectroscopy. Nanoparticles and polyelectrolytes were deposited using layer by layer (LBL) techniques and the IR signal of PE was studied as a function of particles size, particles density and distance from particle surface. It was observed that enhancement is more pronounced for larger nanoparticles and it decreases with increasing distance from the particles surface. Furthermore at high GNPs coverage the signal from the first polyelectrolyte layer is particularly enhanced and the signal increases slowly with time in contrast to subsequent layers. We assign this to polyelectrolyte adsorption within narrow gaps between nanoparticles, where the electric field is enhanced. Furthermore enhanced absorption was observed in the gap between the GNPs and the germanium (Ge) internal element, which was confirmed by polarized measurements. This enhancement is more pronounced for silver particles and it represents a promising route for analysis of surfaces by infrared spectroscopy.

30
Leiba, J.; Sabra, A.; Bodinier, R.; Marchetti, A.; Lima, W. C.; Melotti, A.; Perrin, J.; Burdet, F.; Pagni, M.; Soldati, T.; Lelong, E.; Cosson, P. “Vps13F links bacterial recognition and intracellular killing in Dictyostelium”, Cell. Microbiol. 2017, 19, e12722.open archive unige:92039 pdf full text [free access]

Bacterial sensing, ingestion and killing by phagocytic cells are essential processes to protect the human body from infectious microorganisms. The cellular mechanisms involved in intracellular killing, their relative importance, and their specificity towards different bacteria are however poorly defined. In this study, we used Dictyostelium discoideum, a phagocytic cell model amenable to genetic analysis, to identify new gene products involved in intracellular killing. A random genetic screen led us to identify the role of Vps13F in intracellular killing of Klebsiella pneumoniae. Vps13F KO cells exhibited a delayed intracellular killing of K. pneumoniae, although the general organization of the phagocytic and endocytic pathway appeared largely unaffected. Transcriptomic analysis revealed that vps13F KO cells may be functionally similar to previously characterized fspA KO cells, shown to be defective in folate sensing. Indeed, vps13F KO cells showed a decreased chemokinetic response to various stimulants, suggesting a direct or indirect role of Vps13F in intracellular signaling. Overstimulation with excess folate restored efficient killing in vps13F KO cells. Finally, genetic inactivation of Far1, the folate receptor, resulted in inefficient intracellular killing of K. pneumoniae. Together, these observations show that stimulation of Dictyostelium by bacterial folate is necessary for rapid intracellular killing of K. pneumoniae.

29
Morelli, P.; Matile, S. “Sidechain Engineering in Cell-Penetrating Poly(disulfide)s”, Helv. Chim. Acta 2017, 100, e1600370.open archive unige:93861 pdf full text [restricted access]

Cell-penetrating poly(disulfide)s (CPDs) have been introduced recently to explore new ways to enter into cells. In this report, we disclose a general method to covalently modify the sidechains of CPDs. Compatibility of copper-catalyzed alkyne-azide cycloaddition (CuAAC) with the addition of either strained cyclic disulfides of varied ring tension or increasing numbers of guanidinium and phosphonium cations is demonstrated. Reloading CPDs with disulfide ring tension results in an at least 20-fold increase in activity with preserved sensitivity toward inhibition with the Ellman's reagent. The cumulation of permanent positive charges by sidechain engineering affords Ellman-insensitive CPDs with similarly increased activity. Co-localization experiments indicate the CPDs reach endosomes, cytosol and nucleus, depending on their nature and their concentration. Supported by pertinent controls, these trends confirm that CPDs operate with combination of counterion- and thiol-mediated uptake, and that the balance between the two can be rationally controlled. For the most active CPDs, uptake can be observed at substrate (fluorophore) concentrations as low as 5 nM.

28
Dereka, B.; Koch, M.; Vauthey, E. “Looking at Photoinduced Charge Transfer Processes in the IR: Answers to Several Long-Standing Questions”, Acc. Chem. Res. 2017, 50, 426-434.open archive unige:92342 pdf full text [restricted access]

Because of its crucial role in many areas of science and technology, photoinduced electron transfer is the most investigated photochemical reaction. Despite this, several important questions remain open. We present recent efforts to answer some of them, which concern both inter- and intramolecular processes. The decisive factor that allowed these issues to be successfully addressed was the use of time-resolved infrared (TRIR) spectroscopy.

Many different transient species, such as tight and loose ion pairs (TIPs and LIPs) and exciplexes, have been invoked to explain the dynamics of intermolecular photoinduced charge separation reactions (i.e., electron transfer between two neutral species) and the production of free ions. However, their structures are essentially unknown, and their exact roles in the reaction mechanism are unclear. Indeed, the commonly used transient electronic absorption spectroscopy does not give much structural insight and cannot clearly distinguish ion pairs from free ions, at least in the visible region. Unambiguous spectral signatures of TIPs, LIPs, and exciplexes could be observed in the IR using electron donor/acceptor (D/A) pairs with adequate vibrational marker modes. The ability to spectrally distinguish these intermediates allowed their dynamics to be disentangled and their roles to be determined. Structural information could be obtained using polarization-resolved TRIR spectroscopy. Our investigations reveal that moderately to highly exergonic reactions result in the formation of both TIPs and LIPs. TIPs are not only generated upon direct charge-transfer excitation of DA complexes, as usually assumed, but are also formed upon static quenching with reactant pairs at distances and orientations enabling charge separation without diffusion. On the other hand, dynamic quenching produces primarily LIPs. In the case of highly exergonic reactions, strong indirect evidence for the generation of ion pairs in an electronic excited state was found, accounting for the absence of an inverted region. Finally, weakly exergonic reactions produce predominantly exciplexes, which can evolve further into ion pairs or recombine to the neutral ground state.

The high sensitivity of specific vibrational modes to the local electronic density was exploited to visualize the photoinduced charge flow in symmetric A–(π–D)2- and D–(π–A)2-type molecules developed for their two-photon absorption properties. The electronic ground state and Franck–Condon S1 state of these molecules are purely quadrupolar, but the strong solvatochromism of their fluorescence points to a highly dipolar relaxed S1 state. This has been explained in terms of excited-state symmetry breaking induced by solvent and/or structural fluctuations. However, real-time observation of this process was missing. Direct visualization of symmetry-breaking charge transfer was achieved using TRIR spectroscopy by monitoring vibrations localized in the two arms of these molecules. A transition from a purely quadrupolar state to a symmetry-broken state on the timescale of solvent relaxation could be clearly observed in polar solvents, indicating that symmetry breaking occurs primarily via solvent fluctuations. In the case of the D–(π–A)2 molecule, this breaking results in different basicities at the two A ends and consequently in different affinities for H-bonds, which in turn leads to the formation of an asymmetric tight H-bonded complex in highly protic solvents.

27
Pavlovic, M.; Rouster, P.; Bourgeat-Lami, E.; Prevot, V.; Szilagyi, I. “Design of latex-layered double hydroxide composites by tuning the aggregation in suspensions”, Soft Matter 2017, 13, 842-851.

Colloidal stability of polymeric latex particles was studied in the presence of oppositely charged layered double hydroxide (LDH) platelets of different interlayer anions. Adsorption of the LDH particles led to charge neutralization and to overcharging of the latex at appropriate concentrations. Mixing stable colloidal suspensions of individual particles results in rapid aggregation once the LDH adsorption neutralizes the negative charges of the polymer spheres, while stable suspensions were observed at high and low LDH doses. The governing interparticle interactions included repulsive electrical double layer forces as well as van der Waals and patch-charge attractions, whose strength depended on the amount of LDH particles adsorbed on the latex surface. The type of the LDH interlayer anions did not affect the colloidal stability of the samples. Structural investigation of the obtained latex–LDH composites revealed that the polymer spheres were completely coated with the inorganic platelets once their concentration was sufficiently high. These results are especially important for designing synthetic routes for hybrid systems in suspensions, where stable colloids are required for uniform film-formation and for the homogeneous distribution of the inorganic filler within the composite materials.

26
Piou, T.; Romanov-Michailidis, F.; Romanova-Michaelides, M.; Jackson, K. E.; Semakul, N.; Taggart, T. D.; Newell, B. S.; Rithner, C. D.; Paton, R. S.; Rovis, T. “Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study”, J. Am. Chem. Soc. 2017, 139, 1296-1310.

CpXRh(III)-catalyzed C–H functionalization reactions are a proven method for the efficient assembly of small molecules. However, rationalization of the effects of cyclopentadienyl (CpX) ligand structure on reaction rate and selectivity has been viewed as a black box, and a truly systematic study is lacking. Consequently, predicting the outcomes of these reactions is challenging because subtle variations in ligand structure can cause notable changes in reaction behavior. A predictive tool is, nonetheless, of considerable value to the community as it would greatly accelerate reaction development. Designing a data set in which the steric and electronic properties of the CpXRh(III) catalysts were systematically varied allowed us to apply multivariate linear regression algorithms to establish correlations between these catalyst-based descriptors and the regio-, diastereoselectivity, and rate of model reactions. This, in turn, led to the development of quantitative predictive models that describe catalyst performance. Our newly described cone angles and Sterimol parameters for CpX ligands served as highly correlative steric descriptors in the regression models. Through rational design of training and validation sets, key diastereoselectivity outliers were identified. Computations reveal the origins of the outstanding stereoinduction displayed by these outliers. The results are consistent with partial η5–η3 ligand slippage that occurs in the transition state of the selectivity-determining step. In addition to the instructive value of our study, we believe that the insights gained are transposable to other group 9 transition metals and pave the way toward rational design of C–H functionalization catalysts.

25
Picco, A.; Kaksonen, M. “Precise tracking of the dynamics of multiple proteins in endocytic events”, In Cell Polarity and Morphogenesis” Chapter 3, Thomas, L. (Ed.), Collection “Methods in Cell Biology” Volume 139, Academic Press 2017, p. 51-68.

Endocytosis is a complex and dynamic process that involves dozens of different proteins to define the site of endocytosis, form a membrane invagination, and pinch off a membrane vesicle into the cytoplasm. Fluorescent light microscopy is a powerful tool to visualize the dynamic behaviors of the proteins taking part in the endocytic process. The resolution of light microscopy is, however, a serious limitation. Here, we detail a fluorescence microscope method that we have developed to visualize the dynamics of the clathrin-mediated endocytic protein machinery in yeast cells. This method is based on subpixel centroid tracking of endocytic proteins. For each endocytic protein, the centroid trajectories obtained from multiple endocytic events are used to compute an average trajectory that describes, at nanometer scale, the assembly and movement of the protein during endocytosis. The average trajectories of the different endocytic proteins are then aligned together in space and time to reconstruct how the different proteins behave relative to each other during the endocytic process.

24
Fedunov, R. G.; Plotnikova, A. V.; Ivanov, A. I.; Vauthey, E. “Simulations of the Ultrafast Transient Absorption Dynamics of a Donor-Acceptor Biaryl in Solution”, J. Phys. Chem. A 2017, 121, 471-481.open archive unige:91448 pdf full text [restricted access]

A model for simulating the transient electronic absorption spectra of donor-acceptor dyads undergoing ultrafast intramolecular charge transfer in solution has been developed. It is based on the stochastic multichannel point-transition approach and includes the reorganization of high-frequency intramolecular modes (treated quantum mechanically) and of low frequency intramolecular and solvent modes (described classically). The relaxation of the slow modes is assumed to be exponential with time constants taken from experiments. The excited-state dynamics is obtained by simulating the population distribution of each quantum state after optical excitation and upon electronic and vibrational transitions. This model was used to simulate the transient electronic absorption spectra measured previously with a pyrylium phenolate in acetonitrile. A very good agreement between the simulated and measured spectra was obtained assuming a three-level model including the ground state, the optically excited state and a dark state with large charge-transfer character and a substantially different geometry relative to that of the optically excited state. The merit of this approach to disentangle the contributions of both population changes and relaxation processes to the ultrafast spectral dynamics will be discussed.

23
Olchowka, J.; Colmont, M.; Aliev, A.; Thao Tran, T.; Shiv Halasyamani, P.; Hagemann, H.; Mentré, O. “Original oxo-centered bismuth oxo-arsenates; critical effect of PO4 for AsO4 substitution”, CrystEngComm 2017, 19, 936-945.open archive unige:92340 pdf full text [restricted access]

This work deals with the synthesis and crystal structure study of new bismuth oxo-arsenates and their homologous oxo-phosphates: Bi6ZnO7(AsO4)2 vs. Bi6ZnO7(PO4)2 and Bi3.667Cd3O4(AsO4)3vs. Bi3Cd4O4(PO4)3. Their crystal structures were solved using single crystal X-ray diffraction. These are two other examples of crystal structures built on ribbon-like polycations formed of the linkage of oxo-centered O(Bi,M)4 tetrahedra sharing edges and surrounded by isolated XO4groups (X = As or P), where the O(Bi,M)4 units are derived from the fluorite topology structure. Dealing with Bi6ZnO7(PO4), its acentric space group was confirmed by preliminary second harmonic generation (SHG). The P/As substitution led to a centrosymmetric space group due to local reorientation of oxo-anions. This is strongly related to steric effects between AsO4 (d As–O = 1.6–1.7 Å) and PO4 (d P–O = 1.4–1.5 Å). Concerning Bi3.667Cd3O4(AsO4)3 and Bi3Cd4O4(PO4)3, they show a second example of the reorientation of the XO4 groups depending of the X chemical nature. Finally, we present an original topology of oxo-centered units obtained with Bi5KO5(AsO4). The photoluminescence properties of Bi5KO5(AsO4) and Bi6ZnO7(AsO4)2were also investigated. The first one emits at room temperature in the reddish-orange range (single band peak at 615 nm assigned to the Bi3+: 3P11S0 transition) whereas the second exhibits a weak emission in the green range (peak at 530 nm). Its intriguing temperature dependence is discussed in the paper.

22
Huang, H.; Humbert, N.; Bizet, V.; Patra, M.; Chao, H.; Mazet, C.; Gasser, G. “Influence of the dissolution solvent on the cytotoxicity of octahedral cationic Ir(III) hydride complexes”, J. Organomet. Chem. 2017, 839, 15-18.open archive unige:94020 pdf full text [restricted access]

The stability of a compound in the solvent in which it is dissolved is a fundamental parameter in medicinal chemistry. In this article, we report on the results of our investigations on the stability of five Ir(III) complexes in DMF and DMSO. Importantly, we demonstrate that the rate of ligand exchange/decomposition of these compounds has an influence on their in vitro anticancer properties. The compounds were generally found to be less toxic to cancer cells after having been dissolved for longer time (24 h) in DMSO compared to short incubation time (1 h) in the same solvent. On the contrary, only minor differences in cytotoxicity were observed when the compounds were dissolved in DMF, emphasizing that this solvent should be employed instead of DMSO when unstable compounds are investigated, provided that the concentration of DMF is kept at a low concentration level.

21
Benz, S.; López-Andarias, J.; Mareda, J.; Sakai, N.; Matile, S. “Catalysis with Chalcogen Bonds”, Angew. Chem. Int. Ed. 2017, 56, 812-815.open archive unige:90954 pdf full text [restricted access]

Herein, we introduce catalysts that operate with chalcogen bonds. Compared to conventional hydrogen bonds, chalcogen bonds are similar in strength but more directional and hydrophobic, thus ideal for precision catalysis in apolar solvents. For the transfer hydrogenation of quinolines and imines, rate enhancements well beyond a factor of 1000 are obtained with chalcogen bonds. Better activities with deeper σ holes and wider bite angles, chloride inhibition and correlation with computed anion binding energies are consistent with operational chalcogen bonds. Comparable to classics, such as 2,2′-bipyrroles or 2,2′-bipyridines, dithieno[3,2-b;2′,3′-d]thiophenes (DTTs), particularly their diimides, but also wide-angle cyclopentadithiazole-4-ones are identified as privileged motifs to stabilize transition states in the focal point of the σ holes on their two co-facial endocyclic sulfur atoms.

20
Verolet, Q.; Dal Molin, M.; Colom, A.; Roux, A.; Guénée, L.; Sakai, N.; Matile, S. “Twisted Push-Pull Probes with Turn-On Sulfide Donors”, Helv. Chim. Acta 2017, 100, e1600328.open archive unige:91890 pdf full text [restricted access]

Planarizable and polarizable dithieno[3,2-b;2’,3′-d]thiophene (DTT) dimers have been introduced recently as fluorescent probes that report on membrane fluidity with red shifts in excitation, i.e. planarization in the ground state. In this study, we elaborate on the hypothesis that twisted push-pull probes could perform best in the presence of one unorthodox substituent that acts as a weak acceptor with electron-rich and as a strong donor with electron-poor aromatics. According to Hammett constants, we thought that sulfides could provide access to such a conceptually innovative donor-acceptor switch. To elaborate on this hypothesis, we here describe the design, synthesis and evaluation of a comprehensive series of twisted push-pull probes with turn-on sulfide donors. Their planarization is explored in lipid bilayer membranes of different thickness and fluidity from liquid-disordered to liquid-ordered and solid-ordered phases. Results from membranes are compared to the planarization of turn-on mechanophores in crystals, proteins and cyclodextrin macrocycles of varied diameter.

19
Li, H.; Wallabregue, A.; Adam, C.; Labrador Beltran, G. M.; Bosson, J.; Bouffier, L.; Lacour, J.; Sojic, N. “Bright Electrochemiluminescence Tunable in the Near-Infrared of Chiral Cationic Helicene Chromophores”, J. Phys. Chem. C 2017, 121, 785-792.open archive unige:91095 pdf full text [restricted access]

A selection of cationic [4] and [6]helicenes are studied for their electrochemical, fluorescence and electrochemiluminescence (ECL) properties in acetonitrile solutions. Their photophysical and redox responses are drastically tuned by the introduction of auxochrome substituents at their periphery or the interconversion of oxygen and nitrogen atoms within the helical core. All diaza helicenes exhibit a reversible reduction process whereas, in the presence of oxygen instead of nitrogen atoms in the helical core, irreversible oxidations and a decrease of ECL intensity are observed. ECL emission was successfully produced with two sacrificial co-reactants (benzoyl peroxide and tri-n-propylamine, TPrA). [4]Helicene DMQA+, [6]helicene DIAZA(Pr/Br)+ and DIAZA(Hex/Br)+ exhibit similar ECL emission wavelength in the near-infrared region and generates very intense ECL signals. Their ECL efficiencies are up to 2.6 times higher than that of the reference compound [Ru(bpy)3]2+ when using TPrA as co-reactant. A thermodynamic map gathering both oxidation and reduction potentials and fluorescence data is proposed for the prediction of energy sufficiency needed in both co-reactant ECL systems. Such a systematic overview based on the photophysical and electrochemical properties may guide the conception and the synthesis of new chromophores with a strong ECL proficiency.

18
Kumpulainen, T.; Lang, B.; Rosspeintner, A.; Vauthey, E. “Ultrafast Elementary Photochemical Processes of Organic Molecules in Liquid Solution”, Chem. Rev. 2017, 117, 10826-10939.open archive unige:96318 pdf full text [free access]

Ultrafast photochemical reactions in liquids occur on similar or shorter time scales compared to the equilibration of the optically populated excited state. This equilibration involves the relaxation of intramolecular and/or solvent modes. As a consequence, the reaction dynamics are no longer exponential, cannot be quantified by rate constants, and may depend on the excitation wavelength contrary to slower photochemical processes occurring from equilibrated excited states. Such ultrafast photoinduced reactions do no longer obey the Kasha–Vavilov rule. Nonequilibrium effects are also observed in diffusion-controlled intermolecular processes directly after photoexcitation, and their proper description gives access to the intrinsic reaction dynamics that are normally hidden by diffusion. Here we discuss these topics in relation to ultrafast organic photochemical reactions in homogeneous liquids. Discussed reactions include intra- and intermolecular electron- and proton-transfer processes, as well as photochromic reactions occurring with and without bond breaking or bond formation, namely ring-opening reactions and cis–trans isomerizations, respectively.

17
Pankratova, N.; Cuartero, M.; Cherubini, T.; Crespo, G. A.; Bakker, E. “In-line Acidification for Potentiometric Sensing of Nitrite in Natural Waters”, Anal. Chem. 2017, 89, 571-575.open archive unige:95394 pdf full text [restricted access]

We report on a novel approach for in-line sample acidification that results in a significant improvement of the limit of detection of potentiometric anion-selective electrodes aiming at determining nutrients in natural waters. The working principle of the developed acidification module relies on the cation-exchange process between the sample and an ion-exchange Donnan exclusion membrane in its protonated form. The resulting in-line acidification of natural waters with millimolar sodium chloride level (freshwater, drinking water, aquarium water as well as dechloridized seawater) decreases the pH down to ~5. By using the acidification module the limit of detection of nitrite-selective electrodes significantly improves by more than 2 orders of magnitude with respect to that observed at environmental pH. The originality of the proposed flow cell lies in the possibility to adjust the pH of the sample by modifying its exposure time with the membrane by varying the volumetric flow rate. Facile coupling with a detection technique of choice, miniaturized configuration and simple implementation for long-term monitoring with submersible probes for environmental analysis are possible analytical configurations. This approach was here successfully applied for the potentiometric detection of nitrite in aquarium and dechloridized seawater samples.

16
Abegg, D.; Gasparini, G.; Hoch, D.; Shuster, A.; Bartolami, E.; Matile, S.; Adibekian, A. “Strained Cyclic Disulfides Enable Cellular Uptake by Reacting with the Transferrin Receptor”, J. Am. Chem. Soc. 2017, 139, 231-238.open archive unige:90971 pdf full text [restricted access]

In this study, we demonstrate that appendage of a single asparagusic acid residue (AspA tag) is sufficient to ensure effi-cient celullar uptake and intracellular distribution of fully unprotected peptides. We apply this new delivery method to induce apoptotic response in cancer cells using long (up to 20mer) BH3 domain peptides. Moreover, in order to under-stand the molecular mechanism of the cellular uptake, we perform chemical proteomics experiments and identify the direct molecular targets of the asparagusic acid tag. Our findings document covalent bond formation between the aspar-agusic acid moiety and the cysteines 556 and C558 on the surface of the transferrin receptor resulting in subsequent en-docytic uptake of the payload. We believe that the small size, low cellular toxicity and the efficient transferrin receptor-mediated uptake render the AspA tag highly attractive for various life science applications.

15
Pavlovic, M.; Rouster, P.; Szilagyi, I. “Synthesis and formulation of functional bionanomaterials with superoxide dismutase activity”, Nanoscale 2017, 9, 369-379.

Layered double hydroxide (LDH) nanoparticles were prepared and used as solid support for superoxide dismutase (SOD) enzymes. Structural features were studied by XRD, spectroscopic methods (IR, UV-Vis and fluorescence) and TEM, while colloidal stability of the obtained materials was investigated by electrophoresis and light scattering in aqueous dispersions. The SOD quantitatively adsorbed on the LDH by electrostatic and hydrophobic interactions and kept its structural integrity upon immobilization. The composite material showed moderate resistance against salt-induced aggregation in dispersions, therefore, heparin polyelectrolyte was used to improve the colloidal stability of the system. Heparin of highly negative line charge density strongly adsorbed on the oppositely charged hybrid particles leading to charge neutralization and overcharging at appropriate polyelectrolyte loading. Full coverage of the composite platelets with heparin resulted in highly stable dispersions, which contained only primary particles even at elevated ionic strengths. Our results indicate that the developed bionanocomposite of considerable enzymatic function is a suitable candidate for applications, wherever stable dispersions of antioxidant activity are required for instance in biomedical treatments or in chemical manufacturing processes.

14
Yuan, D.; Cuartero, M.; Crespo, G. A.; Bakker, E. “Voltammetric Thin-Layer Ionophore-Based Films: Part 1. Experimental Evidence and Numerical Simulations”, Anal. Chem. 2017, 89, 586-594.open archive unige:95393 pdf full text [restricted access]

Voltammetric thin layer (~200 nm) ionophore-based polymeric films have recently emerged as a promising approach to acquire multi-ion information about the sample, in analogy to performing multiple potentiometric measurements with individual membranes. They behave under two different regimes that depend on the ion concentration. A thin layer control (no mass transport limitation of the polymer film or solution) is identified for ion concentrations higher than 10 µM in which case the peak potential serves as the readout signal in analogy to a potentiometric sensor. On the other hand, ion transfer at lower concentrations is chiefly controlled by diffusional mass transport from the solution to the sensing film, resulting in an increase of peak current with ion concentration. This concentration range is suitable for electrochemical ion transfer stripping analysis. The transition between the two mentioned scenarios is here explored experimentally using a silver selective membrane as a highly selective proof-of-concept under different conditions (variation of ion concentration in the sample from 0.1 µM to 1 mM, scan rate from 25 to 200 mV s-1, and angular frequency from 100 to 6400 rpm). Apart from experimental evidence, a numerical simulation is developed that considers an idealized conducting polymer behavior and permits one to predict experimental behavior under diffusion or thin layer control.

13
Yuan, D.; Cuartero, M.; Crespo, G. A.; Bakker, E. “Voltammetric Thin-Layer Ionophore-Based Films: Part 2. Semi-Empirical Treatment”, Anal. Chem. 2017, 89, 595-602.open archive unige:95392 pdf full text [restricted access]

This work reports on a semi-empirical treatment that allows one to rationalize and predict experimental conditions for thin layer ionophore-based film read out with cyclic voltammetry. The transition between diffusional mass transport and thin layer regime is described with a parameter (), which depends on membrane composition, diffusion coefficient, the scan rate and electrode rotating speed. Once the thin layer regime is fulfilled (alpha=1), the membrane behaves in some analogy to a potentiometric sensor with a second discrimination variable (the applied potential) that allows one to operate such electrodes in a multi-analyte detection mode owing to the variable applied ion transfer potentials. The limit of detection of this regime is defined with a second parameter (beta=2) and is chosen in analogy to the definition of the detection limit for potentiometric sensors provided by the IUPAC. The analytical equations were validated through the simulation of the respective cyclic voltammograms under the same experimental conditions. While simulations of high complexity and better accuracy satisfactorily reproduced the experimental voltammograms during the forward and backward potential sweeps (companion paper 1), the semi-empirical treatment here, while less accurate, is of low complexity and allows one to quite easily predict relevant experimental conditions for this emergent methodology.

12
Tromayer, M.; Gruber, P.; Markovic, M.; Rosspeintner, A.; Vauthey, E.; Redl, H.; Ovsianikov, A.; Liska, R. “A biocompatible macromolecular two-photon initiator based on hyaluronan”, Polym. Chem. 2017, 8, 451-460.open archive unige:91449 pdf full text [free access]

The possibility of the direct encapsulation of living cells via two-photon induced photopolymerization enables the microfabrication of hydrogel scaffolds with high initial cell loadings and intimate matrix–cell contact. While highly efficient water-soluble two-photon initiators based on benzylidene ketone dyes have been developed, they exhibit considerable cyto- and phototoxicity. To address the problem of photoinitiator migration from the extracellular matrix into the cytosol, a two-photon initiator bound to a polymeric hyaluronan backbone (HAPI) was synthesized in this work. HAPI exhibited a distinct improvement of cytocompatibility compared to a reference two-photon initiator. Basic photophysical investigations were performed to characterize the absorption and fluorescence behavior of HAPI. Laser scanning microscopy was used to visualize and confirm the hindered transmembrane migration behavior of HAPI. The performance of HAPI was tested in two-photon polymerization at exceedingly high printing speeds of 100 mm s−1 producing gelatin-based complex 3D hydrogel scaffolds with a water content of 85%. The photodamage of the structuring process was low and viable MC3T3 cells embedded in the gel were monitored for several days after structuring.

11
Guerra, S.; Dutronc, T.; Terazzi, E.; Buchwalder, K.-L.; Guénée, L.; Deschenaux, R.; Eliseeva, S. V.; Petoud, S.; Piguet, C. “Taking a last look at lanthanidomesogens? The use of basic thermodynamics for programming the temperature domains of existence of luminescent liquid crystals”, Coord. Chem. Rev. 2017, 340, 79-97.open archive unige:93495 pdf full text [restricted access]

As for any thermotropic liquid crystals (often referred to as mesogens), those containing transition metals (metallomesogens), and more specifically lanthanides (lanthanidomesogens) would benefit from rational correlations between the microscopic variations introduced by chemists in their molecular structures and some planned macroscopic properties such as temperature domain of existence, viscosity and supramolecular organization. The novel concept of cohesive free energy density (CFED) allows the building of pseudo-phase boundaries, which connect chemical perturbations, usually measured with the help of arbitrary structural parameters, into quantitative pressure increments relevant to those found in pressure-temperature phase diagrams. With the help of this novel toolkit, cyanobiphenyl-based dendrimeric tridentate ligands have been used as a proof-of-concept for exploring the consequences of (i) the successive methylation of polyaromatic termini, (ii) the complexation to luminescent europium carriers and (iii) the statistical doping with structural defects on the thermodynamic parameters which control the phase transitions.

10
Liu, L.; Matile, S. “Anion-π Transaminase Mimics”, Supramol. Chem. 2017, 29, 702-706.open archive unige:95403 pdf full text [restricted access]

The possibility to stabilise anionic transition states on π-acidic aromatic surfaces has been explicitly demonstrated first in 2013. Since then, anion-π catalysis has been introduced to asymmetric enamine and iminium chemistry and to cascade processes, and the first anion-π enzyme has been created. Moving beyond systems that operate with nitronate-π interactions, this report adds transamination to the repertoire of anion-π catalysis. Whereas bioinspired approaches to transamination with pyridoxalphosphate appeared less obvious in this context, the base-catalyzed isomerisation of trifluoromethylimines contains suitable anionic transition states. Run on increasingly π-acidic aromatic surfaces in covalent and supramolecular trifunctional systems, we find that both rate and enantioselectivity of this reaction increase. These results support that anion-π interactions with 2-azaallyl anion intermediates catalyse the isomerisation of trifluoromethylimines by cumulative asymmetric umpolung on π-acidic surfaces.

9
Morgat, A.; Lombardot, T.; Axelsen, K. B.; Aimo, L.; Niknejad, A.; Hyka-Nouspikel, N.; Coudert, E.; Pozzato, M.; Pagni, M.; Moretti, S.; Rosanoff, S.; Onwubiko, J.; Bougueleret, L.; Xenarios, I.; Redaschi, N.; Bridge, A. “Updates in rhea—an expert curated resource of biochemical reactions”, Nucleic Acids Res. 2017, 45, D415-D418.

Rhea (http://www.rhea-db.org) is a comprehensive and non-redundant resource of expert-curated biochemical reactions designed for the functional annotation of enzymes and the description of metabolic networks. Rhea describes enzyme-catalyzed reactions covering the IUBMB Enzyme Nomenclature list as well as additional reactions, including spontaneously occurring reactions, using entities from the ChEBI (Chemical Entities of Biological Interest) ontology of small molecules. Here we describe developments in Rhea since our last report in the database issue of Nucleic Acids Research. These include the first implementation of a simple hierarchical classification of reactions, improved coverage of the IUBMB Enzyme Nomenclature list and additional reactions through continuing expert curation, and the development of a new website to serve this improved dataset.

8
Avarvari, N.; Biet, T.; Martin, K.; Hankache, J.; Hellou, N.; Hauser, A.; Bürgi, T.; Vanthuyne, N.; Aharon, T.; Caricato, M.; Crassous, J. “Triggering the emission by the helical turn in thiadiazole-helicenes”, Chem. Eur. J. 2017, 23, 437-446.open archive unige:91450 pdf full text [restricted access]

Introduction of heterocycles in the helical skeleton of helicenes allows modulation of their redox, chiroptical and photophysical properties. Herein, we describe the straightforward preparation and structural characterization by single crystal X-ray diffraction of thiadiazole-[7]helicene, which has been resolved into (M) and (P) enantiomers by chiral HPLC, together with its S-shaped double [4]helicene isomer, as well as the smaller congeners thiadiazole-[5]helicene and benzothiadiazole-anthracene. A copper(II) complex with two thiadiazole-[5]helicene ligands has been structurally characterized and it shows the presence of both (M) and (P) isomers coordinated to the metal centre. The emission properties of the unprecedented heterohelicenes are highly dependent on the helical turn, as the [7]- and [5]helicene are poorly emissive, whereas their isomers, that is, the S-shaped double [4]helicene and thiadiazole-benzanthracene, are luminescent, with quantum efficiencies of 5.4% and 6.5%, respectively. DFT calculations suggest a quenching of the luminescence of enantiopure [7]helicenes through an intersystem crossing mechanism arising from the relaxed excited S1 state.

7
Mesquita, A.; Cardenal-Muñoz, E.; Dominguez, E.; Muñoz-Braceras, S.; Nuñez-Corcuera, B.; Phillips, B. A.; Tábara, L. C.; Xiong, Q.; Coria, R.; Eichinger, L.; Golstein, P.; King, J. S.; Soldati, T.; Vincent, O.; Escalante, R. “Autophagy in Dictyostelium: Mechanisms, regulation and disease in a simple biomedical model”, Autophagy 2017, 13, 24-40.open archive unige:88892 pdf full text [free access]

Autophagy is a fast-moving field with an enormous impact on human health and disease. Understanding the complexity of the mechanism and regulation of this process often benefits from the use of simple experimental models such as the social amoeba Dictyostelium discoideum. Since the publication of the first review describing the potential of D. discoideum in autophagy, significant advances have been made that demonstrate both the experimental advantages and interest in using this model. Since our previous review, research in D. discoideum has shed light on the mechanisms that regulate autophagosome formation and contributed significantly to the study of autophagy-related pathologies. Here, we review these advances, as well as the current techniques to monitor autophagy in D. discoideum. The comprehensive bioinformatics search of autophagic proteins that was a substantial part of the previous review has not been revisited here except for those aspects that challenged previous predictions such as the composition of the Atg1 complex. In recent years our understanding of, and ability to investigate, autophagy in D. discoideum has evolved significantly and will surely enable and accelerate future research using this model.

6
Trefalt, G.; Palberg, T.; Borkovec, M. “Forces between Colloidal Particles in Aqueous Solutions Containing Monovalent and Multivalent Ions”, Curr. Opin. Colloid Interface Sci. 2017, 27, 9-17.

The present article provides an overview of the recent progress in the direct force measurements between individual pairs of colloidal particles in aqueous salt solutions. Results obtained by two different techniques are being highlighted, namely with the atomic force microscope (AFM) and optical tweezers. One finds that the classical theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO) represents an accurate description of the force profiles even in the presence of multivalent ions, typically down to distances of few nanometers. However, the corresponding Hamaker constants and diffuse layer potentials must be extracted from the force profiles. At low salt concentrations, double layer forces remain repulsive and can be long ranged. At short distances, additional short range non-DLVO interactions may become important. Such an interaction is particularly relevant in the presence of multivalent counterions.

5
Jeannerat, D. “Human- and computer-accessible 2D correlation data for a more reliable structure determination of organic compounds. Future roles of researchers, software developers, spectrometer managers, journal editors, reviewers, publisher and database managers towards artificial-intelligence analysis of NMR spectra”, Magn. Reson. Chem. 2017, 55, 7-14.open archive unige:90778 pdf full text [restricted access]

The introduction of a universal data format to report the correlation data of 2D NMR spectra such as COSY, HSQC and HMBC spectra will have a large impact on the reliability of structure determination of small organic molecules. These lists of assigned cross peaks will bridge signals found in NMR 1D and 2D spectra and the assigned chemical structure. The record could be very compact, human and computer readable so that it can be included in the supplementary material of publications and easily transferred into databases of scientific literature and chemical compounds. The records will allow authors, reviewers and future users to test the consistency and, in favorable situations, the uniqueness of the assignment of the correlation data to the associated chemical structures. Ideally, the data format of the correlation data should include direct links to the NMR spectra to make it possible to validate their reliability and allow direct comparison of spectra. In order to take the full benefits of their potential, the correlation data and the NMR spectra should therefore follow any manuscript in the review process and be stored in open-access database after publication. Keeping all NMR spectra, correlation data and assigned structures together at all time will allow the future development of validation tools increasing the reliability of past and future NMR data. This will facilitate the development of artificial intelligence analysis of NMR spectra by providing a source of data than can be used efficiently because they have been validated or can be validated by future users.

4
Sun, Q.; Dereka, B.; Vauthey, E.; Lawson Daku, L. M.; Hauser, A. “Ultrafast transient IR spectroscopy and DFT calculations of ruthenium(II) polypyridyl complexes”, Chem. Sci. 2017, 8, 223-230.open archive unige:90819 pdf full text [free access]

Ultrafast time-resolved infrared spectroscopy of [Ru(bpy)3]2+ (bpy = 2,2’-bipyridine), [Ru(mbpy)3]2+(mbpy = 6-methyl-2,2’-bipyridine), and [Ru(mphen)3]2+ (mphen = 2-methyl-1,10’-phenanthroline) in deuterated acetonitrile serves to elucidate the evolution of the system following pulsed excitation into the 1MLCT band at 400 nm. Whereas for [Ru(bpy)3]2+ no intermediate state can be evidenced for the relaxation of the corresponding 3MLCT state back to the ground state, for [Ru(mbpy)3]2+ and [Ru(mphen)3]2+ an intermediate state with a lifetime of about 400 ps is observed. The species associated IR difference spectra of this state are in good agreement with the calculated difference spectra of the lowest energy 3dd state using DFT. The calculated potential energy curves for all the complexes in the triplet manifold along the metal-ligand distance show that for [Ru(bpy)3]2+ the 3dd state is at higher energy than the 3MLCT state and that there is a substantial barrier between the two minima. For [Ru(mbpy)3]2+ and [Ru(mphen)3]2+, the3dd state is at lower energy than the 3MLCT state.

3
Pavlovic, M.; Rouster, P.; Oncsik, T.; Szilagyi, I. “Tuning Colloidal Stability of Layered Double Hydroxides: From Monovalent Ions to Polyelectrolytes”, ChemPlusChem 2017, 82, 121-131.

The growing number of applications of layered double hydroxide (LDH) colloids demands for detailed understanding of particle aggregation processes in such samples. Tuning the colloidal stability in aqueous suspensions is essential in order to design stable systems or to induce controlled aggregation of these elongated particles. In this review, we summarize the recent progress in this field, i.e., charging and aggregation of LDHs of various compositions and sizes are discussed in the presence of different aggregating agents. The review focuses on the effect of monovalent salts, multivalent ions and polyelectrolytes on the suspension stability of LDHs. The provided information will help to better understand the origin of interparticle forces responsible for the colloidal stability and to design highly stable or aggregating LDH colloids according to the desired goal in certain applications. Moreover, the potential future research directions to obtain a broader picture about LDH aggregation are also suggested.

2
Degueldre, C. “Uranium as a renewable for nuclear energy”, Prog. Nucl. Energy 2017, 94, 174-186.

Uranium extraction is the first step of the nuclear fuel cycle. Currently, uranium is only extracted from solid ores such as uranium rich minerals (% level) or minerals such as phosphates (ppm level). For some years extraction of uranium from sea water (ppb level) has been the topic of investigations particularly in Japan due to its national interest. In the huge oceanic volume the amount of uranium is constant, regulated by its river input (soluble) and balanced by its scavenging (particulate) on the sea floor. This work shows that the uranium extraction with parsimony from sea water could be carried in a renewable way if its concentration remains quasi constant. Recommendations for the extraction with use of gel panels or with braid of fabric grafted by sorbing groups in high tide or oceanic pelagic current environments are suggested along with a reduction of the uranium consumption.

1
Montes Ruiz-Cabello, F. J.; Moazzami-Gudarzi, M.; Elzbieciak-Wodka, M.; Maroni, P. “Forces between different latex particles in aqueous electrolyte solutions measured with the colloidal probe technique”, Microsc. Res. Tech. 2017, 80, 144-152.

In this article, a compilation of results on direct force measurements between colloidal particles in monovalent salts carried out with the colloidal probe technique based on Atomic Force Microscopy was presented. The interaction forces between similar and dissimilar particles was studied and it was concluded that, in general, these force profiles may be satisfactorily quantified by the DLVO theory down to distances of few nanometers. However, in the specific case where the charge of one of the involved particle is close to neutral, it was found that the surface potential of this particle may change its sign depending on the sign of charge of the opposite particle. In this respect, the assumption that the surface potential of a particle is a property only related to the particle surface features and the bulk properties is called into question.