Publications

Publications

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192
Zhang, X.; Hao, X.; Liu, L.; Pham, A.-T.; López-Andarias, J.; Frontera, A.; Sakai, N.; Matile, S. “Primary Anion-π Catalysis and Autocatalysis”, J. Am. Chem. Soc. 2018, in press.

Epoxide-opening ether cyclizations are shown to occur on π-acidic aromatic surfaces without the need of additional activating groups and with autocatalytic amplification. Increasing activity with the intrinsic π acidity of benzenes, naphthalenediimides (NDIs) and perylenediimides (PDIs) support that anion−π interactions account for function. Rate enhancements maximize at 270 for anion−π catalysis on fullerenes and at 5100 M–1 for autocatalysis. The occurrence of anion−π autocatalysis is confirmed with increasing initial rates in the presence of additional product. Computational studies on autocatalysis reveal transition state and product forming a hydrogen-bonded noncovalent macrocycle, like holding their hands and dancing on the active π surface, with epoxide opening and nucleophile being activated by anion−π interactions and hydrogen bonds to the product, respectively.

191
Rosspeintner, A.; Koch, M.; Angulo, G.; Vauthey, E. “Salt Effect in Ion-Pair Dynamics after Bimolecular Photoinduced Electron Transfer in a Room-Temperature Ionic Liquid”, J. Phys. Chem. Lett. 2018, 9, 7015-7020.

Bimolecular photoinduced electron transfer between perylene and two quenchers was investigated in an imidazolium room-temperature ionic liquid (RTIL) and in a dipolar solvent mixture of the same viscosity using transient absorption on the subpicosecond to submicrosecond timescales. Whereas charge separation dynamics were similar in both solvents, significant differences were observed in the temporal evolution of the ensuing radical ions: although small, the free ion yield is significantly larger in the RTIL, and recombination of the ion pair to the triplet state of perylene is more efficient in the dipolar solvent. The temporal evolution of reactant, ion and triplet state populations could be well reproduced using Unified Encounter Theory. This analysis reveals that the observed differences can be explained by the strong screening of the Coulomb potential in the ion pair by the ionic solvent. In essence, RTILs favor free ions compared to highly dipolar solvents of the same viscosity.

190
McAlpine, J. B.; Chen, S.-N.; Kutateladze, A.; MacMillan, J. B.; Appendino, G.; Barison, A.; Beniddir, M. A.; Biavatti, M. W.; Bluml, S.; Boufridi, A.; Butler, M. S.; Capon, R. J.; Choi, Y. H.; Coppage, D.; Crews, P.; Crimmins, M. T.; Csete, M.; Dewapriya, P.; Egan, J. M.; Garson, M. J.; Genta-Jouve, G.; Gerwick, W. H.; Gross, H.; Harper, M. K.; Hermanto, P.; Hook, J. M.; Hunter, L.; Jeannerat, D.; Ji, N.-Y.; Johnson, T. A.; Kingston, D. G. I.; Koshino, H.; Lee, H.-W.; Lewin, G.; Li, J.; Linington, R. G.; Liu, M.; McPhail, K. L.; Molinski, T. F.; Moore, B. S.; Nam, J.-W.; Neupane, R. P.; Niemitz, M.; Nuzillard, J.-M.; Oberlies, N. H.; Ocampos, F. M. M.; Pan, G.; Quinn, R. J.; Reddy, D. S.; Renault, J.-H.; Rivera-Chávez, J.; Robien, W.; Saunders, C. M.; Schmidt, T. J.; Seger, C.; Shen, B.; Steinbeck, C.; Stuppner, H.; Sturm, S.; Taglialatela-Scafati, O.; Tantillo, D. J.; Verpoorte, R.; Wang, B.-G.; Williams, C. M.; Williams, P. G.; Wist, J.; Yue, J.-M.; Zhang, C.; Xu, Z.; Simmler, C.; Lankin, D. C.; Bisson, J.; Pauli, G. F. “Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research”, Nat. Prod. Rep. 2019, in press.

Correction for ‘The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research’ by James B. McAlpine et al., Nat. Prod. Rep., 2018, DOI: 10.1039/c7np00064b.

189
Letrun, R.; Lang, B.; Yushchenko, O.; Wilcken, R.; Svechkarev, D.; Kolodieznyi, D.; Riedle, E.; Vauthey, E. “Excited-state dynamics of a molecular dyad with two orthogonally-oriented fluorophores”, Phys. Chem. Chem. Phys. 2018, in press.

The excited-state dynamics of a T-shaped bichromophoric molecule, consisting of two strong fluorophores, diphenyloxazole and diphenylpyrazoline, directly linked in an orthogonal geometry, was investigated. Despite the weak coupling ensured by this geometry and confirmed by the electronic absorption spectra, this dyad exhibits only weak fluorescence in both apolar and polar solvents, with fluorescence lifetimes ranging from 200 ps in CHX to 10 ps in ACN. Ultrafast spectroscopic measurements reveal that the fluorescence quenching in polar solvents is due to the population of a charge-separated state. In non-polar solvents, this process is energetically not feasible, and a quenching due to an efficient intersystem crossing (ISC) to the triplet manifold is proposed, based on quantum-chemical calculations. This process occurs via the spin–orbit charge-transfer (SOCT) ISC mechanism, which is enabled by the charge-transfer character acquired by the S1 state of the dyad upon structural relaxation and by the orthogonal arrangement of the molecular orbitals involved in the transition. The same mechanism is proposed to explain why the recombination of the charge-separated state is faster in medium than in highly polar solvents, as well as to account for the fast decay of the lowest triplet state to the ground state.

188
Tromayer, M.; Gruber, P.; Rosspeintner, A.; Ajami, A.; Husinsky, W.; Plasser, F.; González, L.; Vauthey, E.; Ovsianikov, A.; Liska, R. “Wavelength-optimized Two-Photon Polymerization Using Initiators Based on Multipolar Aminostyryl-1,3,5-triazines”, Sci. Rep. 2018, 115, 450.

Two-photon induced polymerization (2PP) based 3D printing is a powerful microfabrication tool. Specialized two-photon initiators (2PIs) are critical components of the employed photosensitive polymerizable formulations. This work investigates the cooperative enhancement of two-photon absorption cross sections (σ2PA) in a series of 1,3,5-triazine-derivatives bearing 1-3 aminostyryl-donor arms, creating dipolar, quadrupolar and octupolar push-pull systems. The multipolar 2PIs were successfully prepared and characterized, σ2PA were determined using z-scan at 800 nm as well as spectrally resolved two-photon excited fluorescence measurements, and the results were compared to high-level ab initio computations. Modern tunable femtosecond lasers allow 2PP-processing at optimum wavelengths tailored to the absorption behavior of the 2PI. 2PP structuring tests revealed that while performance at 800 nm is similar, at their respective σ2PA-maxima the octupolar triazine-derivative outperforms a well-established ketone-based quadrupolar reference 2PI, with significantly lower fabrication threshold at exceedingly high writing speeds up to 200 mm/s and a broader window for ideal processing parameters.

187
Anzola, M.; Winssinger, N. “Turn On of a Ruthenium(II) Photocatalyst by DNA-Templated Ligation”, Chem. Eur. J. 2018, in press.

Here, the synthesis of a RuII photocatalyst by light‐directed oligonucleotide‐templated ligation reaction is described. The photocatalyst was found to have tremendous potential for signal amplification with >15000 turnovers measured in 9 hours. A templated reaction was used to turn on the activity of this ruthenium(II) photocatalyst in response to a specific DNA sequence. The photocatalysis of the ruthenium(II) complex was harnessed to uncage a new precipitating dye that is highly fluorescent and photostable in the solid state. This reaction was used to discriminate between different DNA analytes based on localization of the precipitate as well as for in cellulo miRNA detection. Finally, a bipyridine ligand functionalized with two different peptide nucleic acid (PNA) sequences was shown to enable template‐mediated ligation (turn on of the ruthenium(II) photocatalysis) and recruitment of substrate for templated photocatalysis.

186
Ulm, F.; Poblador-Bahamonde, A. I.; Choppin, S.; Bellemin-Laponnaz, S.; Chetcuti, M. J.; Achards, T.; Ritleng, V. “Synthesis, characterization, and catalytic application in aldehyde hydrosilylation of half-sandwich nickel complexes bearing (κ1-C)- and hemilabile (κ2-C,S)-thioether-functionalised NHC ligands”, Dalton Trans. 2018, 47, 17134-17145.open archive unige:111955 pdf full text [restricted access]

Neutral nickel−N-Heterocyclic carbene complexes, (κ1-C)-[NiCpBr{R-NHC-(CH2)2SR’}] [Cp = η5-C5H5; R-NHC-(CH2)2SR’ = 1-mesityl-3-[2-(tert-butylthio)ethyl]- (1a), 1-mesityl-3-[2-(phenylthio)ethyl]- (1b), 1-benzyl-3-[2-(tert-butylthio)ethyl]- (1c), 1-benzyl-3-[2-(phenylthio)ethyl]-imidazol-2-ylidene (1d)], which bear a N-bound thioether side arm, were prepared by the reaction of nickelocene with the corresponding imidazolium bromides [R-NHC-(CH2)2SR’·HBr] (a-d), via conventional or microwave heating. The 1H NMR spectra of the benzyl-substituted species 1c and 1d showed signals for diastereotopic NCH2CH2S protons at room temperature. However, structural studies established the absence of coordination of the sulphur atom in the solid state, and solvent DFT calculations showed that bromide displacement by sulphur is an unfavourable process (ΔG = + 13.5 kcal/mol for 1d), thereby suggesting that the observed disatereotopicity is more likely due to significant steric congestion rather than to a possible C,S-chelation in solution. Treatment of these complexes with KPF6 in tetrahydrofuran (THF) led to bromide abstraction to afford the cationic complexes [NiCp{R-NHC-(CH2)2SR’}](PF6) (2a-c). Alternatively, 2a-c could also be prepared by the direct reaction of nickelocene with the corresponding imidazolium hexafluorophosphate salts [R-NHC-(CH2)2SR’·HPF6]. Inversely to the neutral species, whereas X-ray crystallography established C,S-chelation in the solid state, the 1H NMR spectra (CDCl3, CD2Cl2, or thf-d8) at room temperature showed no diastereotopic NCH2CH2S protons, thus suggesting the possible displacement of the sulphur atom by the respective solvents and/or very fast sulphur inversion. DFT calculations established a low energy inversion process in all cases (+9 ≤ ΔG‡ ≤ +13 kcal/mol) as well as a favourable solvent coordination process (ΔG‡ ≈ +11 kcal/mol; ΔG ≈ -7 kcal/mol) with a solvent such as THF, thus suggesting that sulphur inversion and/or solvent coordination can both account for the absence of diastereotopy at room temperature, depending on the solvent. While all complexes catalysed the hydrosilylation of benzaldehyde in the absence of any additive, the cationic C,S-chelated complexes 2 proved more active than the sterically constrained neutral species 1. In particular, 2c proved to be the most active pre-catalyst and its catalytic charge could be lowered down to 2 mol% with PhSiH3 as the hydrogen source.

185
Dordević, N.; Beckwith, J. S.; Yarema, M.; Yarema, O.; Rosspeintner, A.; Yazdani, N.; Leuthold, J.; Vauthey, E.; Wood, V. “Machine Learning for Analysis of Time-resolved Luminescence Data”, ACS Photonics 2018, in press.

Time-resolved photoluminescence is one of the most standard techniques to understand and systematically optimize the performance of optical materials and optoelectronic devices. Here, we present a machine learning code to analyze time-resolved photoluminescence data and determine the decay rate distribution of an arbitrary emitter without any a priori assumptions. To demonstrate and validate our approach, we analyze computer-generated time-resolved photoluminescence datasets and show its benefits for studying the photoluminescence of novel semiconductor nanocrystals (quantum dots), where it quickly provides insight into the possible physical mechanisms of luminescence without the need for educated guessing and fitting.

184
Wasnik, V. H.; Lipp, P.; Kruse, K. “Positional information readout in Ca2+ signaling”, arXiv.org, e-Print Arch., Quant. Biol. 2018, in press.

Living cells respond to spatial signals. Signal transmission to the cell interior often involves the release of second messengers like Ca2+ . They will eventually trigger a physiological response by activating kinases that in turn activate target proteins through phosphorylation. Here, we investigate theoretically how positional information can be accurately read out by protein phosphorylation in spite of rapid second messenger diffusion. We find that accuracy is increased by binding of the kinases to the cell membrane prior to phosphorylation and by increasing the rate of Ca2+ loss from the cell interior. These findings could explain some salient features of conventional protein kinases C.

183
Delgado, T.; Enachescu, C.; Tissot, A.; Hauser, A.; Guénée, L.; Besnard, C. “Evidencing size-dependent cooperative effects on spin crossover nanoparticles following their HS→LS relaxation”, J. Mater. Chem. C 2018, 6, 12698-12706.

The HS→LS relaxation at cryogenic temperatures after photo-excitation through the light-induced excited spin-state trapping (LIESST) effect of the [Fe(pz)Pt(CN)4] micro- and nanoparticles is probed by optical-absorption spectroscopy and X-Ray Powder Diffraction (XRPD) using synchrotron radiation. A size dependence of the relaxation mechanism is evidenced, due to the inhibition of cluster formation for smaller size particles. This result is explained by simulations performed in the frame of the mechanoelastic model.

182
Nieto-Ortega, B.; Bürgi, T. “Vibrational Properties of Thiolate-Protected Gold Nanoclusters”, Acc. Chem. Res. 2018, 51, 2811-2819.

Over recent years, the field of thiolate-protected gold nanoclusters has made remarkable progress. The successful determination of the structure of some of these clusters by X-ray crystallography was a milestone in this field. X-ray crystallography is arguably the most important technique in the field up to now, and it enabled the study of structure evolution as a function of cluster size. It also shed light on the structure of the Au–S interface. Recently, it has been realized that thiolate-protected gold clusters are very dynamic systems. Metal atoms and ligands can exchange easily between clusters. Furthermore, the adsorbed ligands bear conformational dynamics. Such dynamic effects call for experimental methods that can cope with it.

Future efforts in this field will be directed toward applications of thiolate-protected clusters, and many of them will rely on dissolved clusters. Therefore, structure determination in solution is an important issue, though it is very challenging. The structure of the metal core and the Au–S interface is not expected to change in solution with respect to the crystal. However, the structure of the adsorbed ligand itself is sensitive to the environment and may be different in the solid state and in solution, as has been shown in fact in the past. It is this (dynamic) structure of the ligand that determines the interaction between the cluster and its environment, which is crucial, for example, for sensing applications.

Vibrational spectroscopy is a promising technique to characterize thiolate-protected clusters in different environments. A vibrational spectrum is sensitive to structure (conformation) although this information is often “hidden” in the spectrum, requiring detailed analysis and support from theory to be deciphered. Compared to other techniques like UV–vis spectroscopy and mass spectrometry, vibrational spectroscopy was not extensively used in the field of thiolate-protected clusters, but we believe that the technique will be very valuable for the future developments in the field.

We have used vibrational spectroscopy to investigate thiolate-protected gold clusters for mainly two lines of research. In the first, we studied in detail the low energy region of the vibrational spectrum, in particular the Au–S vibrational modes, in order to understand the structure sensitivity. It emerges that the Au–S vibrational spectrum is indeed sensitive to the structure of the interface but also to other factors, especially the organic part of the thiol, in a complex way. The ability to directly correlate structure, from X-ray crystallography, and vibrational spectra for thiolate-protected clusters, should lead to a database that will help in the future the structure determination of the Au–S interface by vibrational spectroscopy for systems where direct structure determination is not possible, for example, for flat surfaces.

A second line of research focused on the determination of the structure of the adsorbed ligands for dissolved clusters. Such information is mostly extracted by the comparison of theoretical and calculated spectra for different conformers. In this respect, vibrational circular dichroism (VCD) is particularly powerful as it strongly depends on the conformation, more than conventional infrared spectroscopy. VCD can be applied to chiral nonracemic compounds, and it is a sensitive probe for chirality. Using this method, it was possible to demonstrate that a cluster can transfer its chirality to achiral thiolate ligands.

In this Account, we summarize the possibilities and challenges of vibrational spectroscopy in the field of thiolate-protected clusters.

181
Yang, Y.; Cuartero, M.; Gonçales, V. R.; Gooding, J. J.; Bakker, E. “Light‐Addressable Ion Sensing for Real‐Time Monitoring of Extracellular Potassium”, Angew. Chem. Int. Ed. 2018, in press.

We report here on a light addressable potassium (K+) sensor where light illumination of a semiconducting silicon electrode substrate results in a localized activation of the faradaic electrochemistry at the illuminated spot. This allows one, by electrochemical control, to oxidize surface bound ferrocene moieties that in turn trigger K+ transfer from the overlaid K+‐selective film to the solution phase. The resulting voltammetric response is shown to be K+‐selective, where peak position is a direct function of K+ activity at the surface of electrode. This concept was used to measure extracellular K+ concentration changes by stimulating living breast cancer cells. The associated decrease of intracellular K+ level was confirmed with a fluorescent K+ indicator. In contrast to light addressable potentiometry, the approach introduced here relies on dynamic electrochemistry and may be performed in tandem with other electrochemical analysis when studying biological events on the electrode.

180
Jiménez, J.-R.; Doistau, B.; Besnard, C.; Piguet, C. “Versatile heteroleptic bis-terdentate Cr(III) chromophores displaying room temperature millisecond excited state lifetimes ”, Chem. Commun. 2018, 54, 13228-13231.

Substitution of Ru(II)-based chromophores with cheaper Cr(III)-based complexes in optically active metallo-supramolecular architectures is limited by the lack of synthetic strategies leading to heteroleptic Cr(III)-polypyridyl complexes with long excited-state lifetimes. Herein, we report on a versatile method yielding heteroleptic bis(terdentate) Cr(III) complexes with room temperature millisecond range excited-state lifetimes, tuneable electronic and photophysical properties and easy anchoring possibilities.

179
Dereka, B.; Helbing, J.; Vauthey, E. “Transient Glass Formation around a Quadrupolar Photoexcited Dye in a Strongly H-Bonding Liquid Observed by Transient 2D-IR Spectroscopy”, Angew. Chem. Int. Ed. 2018, in press.

Intermolecular H‐bonding dynamics around a photoexcited quadrupolar dye is directly observed using transient 2D‐IR spectroscopy. Upon solvent‐induced symmetry breaking, the H‐bond accepting abilities of the two nitrile end‐groups change drastically, and in extreme protic ('superprotic') solvents, a tight H‐bond complex forms at one end. The time evolution of the 2D C≡N lineshape in methanol points to rapid, 2‐3 ps, spectral diffusion due to fluctuations of the H‐bonding network. Similar behaviour is observed in a superprotic solvent shortly after photoexcitation of the dye. However, at later time, the completely inhomogeneous band does not exhibit spectral diffusion for at least 5 ps, pointing to a glass‐like environment around one side of the dye. About half of the excited dyes show this behaviour attributed to the tight H‐bond complex, whereas the others are loosely bound. A weak cross peak indicates partial exchange between these excited state sub‐populations.

178
Cao, T.; Trefalt, G.; Borkovec, M. “Aggregation of Colloidal Particles in the Presence of Hydrophobic Anions: Importance of Attractive Non-DLVO Forces”, Langmuir 2018, 34, 14368-14377.

Aqueous suspensions of amidine latex (AL) and sulfate latex (SL) particles containing sodium tetraphenylborate and NaCl are studied with electrokinetic and time-resolved light scattering techniques. In monovalent salt solutions, AL is positively charged, while SL negatively. Electrophoretic mobility measurements demonstrate that adsorption of tetraphenylborate anions leads to a charge reversal of the AL particles. At higher concentrations, both types of particles accumulate negative charge. For the AL particles, the charge reversal leads to a narrow fast aggregation region and an intermediate regime of slow aggregation. For the SL particles, the intermediate slow regime is also observed. These aspects can be explained with classical theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO). Another regime of fast aggregation is observed at intermediate concentrations, and the existence of this regime can be rationalized by an additional attractive non-DLVO force. We suspect that this additional force is caused by surface charge heterogeneities.

177
Sateanchok, S.; Pankratova, N.; Cuartero, M.; Cherubini, T.; Grudpan, K.; Bakker, E. “In-Line Seawater Phosphate Detection with Ion-Exchange Membrane Reagent Delivery”, ACS Sens. 2018, 3, 2455-2462.

There is an urgent need for reliable seawater phosphate measuring tools to better assess eutrophication. Today, most accepted sensing approaches are based on the established colorimetric molybdenum blue assay. It requires one to modify the sample to strongly acidic conditions and to add various reagents, principally molybdate and reducing agent (e.g. ascorbic acid), to form a blue colored phosphate complex that is subsequently detected spectrophotometrically. The associated need for large sample and mobile phase reservoirs and mixing coils are, unfortunately, not ideally adapted for the development of operationally simple in situ sensing instruments. It is here demonstrated for the first time that the key reagents needed to achieve phos-phate detection by the molybdate method may be delivered by passive counter transport across ion-exchange membranes. A cation-exchange Donnan exclusion membrane placed in contact with a sample flow (450 µm thick) is shown to provide the strongly acidic conditions (pH~1) necessary for phosphate determination. Proton transport is driven, via cation-exchange, by the high sodium content of the seawater sample. Molybdate was similarly released through an anion-exchange membrane by chloride counter transport. Consequently, an in-line flow system containing the two membrane modules in series was used for delivering both hydrogen and molybdate ions into the sample to form the desired phosphomolybdate complex for subse-quent spectrophotometric detection. A linear calibration graph in the range of 0.1–10 µM phosphate (3–300 ppb inorganic P) was achieved, which is sufficiently attractive for environmental work. A range of seawater samples was tested and the results from this membrane delivery device showed no significant differences compared to the classical molybdate assay chosen as the reference method.

176
Doistau, B.; Collet, G.; Bolomey, E. A.; Sadat-Noorbakhsh, V.; Besnard, C.; Piguet, C. “Heteroleptic Ter–Bidentate Cr(III) Complexes as Tunable Optical Sensitizers”, Inorg. Chem. 2018, 57, 14362-14373.

To exploit Cr(III) coordination complexes as sensitizers in supramolecular energy-converting devices, the latter optical relays should display long-lived excited states, broad emission bands, and tunable spatial and electronic connections to activator units. An ad-hoc versatile strategy has been therefore developed for the preparation of a family of luminescent pseudo-octahedral [CrN6] chromophores made up of ter–bidentate heteroleptic [Cr(phen)2(N–N’′)]3+ complexes, where phen is 1,10-phenanthroline, and N–N′ stands for α,α′-diimine ligands possessing peripheral substituents compatible with both electronic tuning and structure extensions. As long as the ligand field in these [CrN6] chromophores remains sufficiently strong to avoid back-intersystem crossing, photophysical studies indicate that the lifetime of the near-infrared emissive Cr(2E) excited state is poorly sensitive to ligand-based electronic effects. On the contrary, a drop in symmetry, the coupling with high frequency oscillators, and the implementation of sterical constraints in heteroleptic [Cr(phen)2(N–N′)]3+ complexes affect both Cr(2E → 4A2) energies and Cr(2E) lifetimes. Altogether, [Cr(phen)2(phenAlkyn)]3+ (phenAlkyn = 5-ethynyl-1,10-phenanthroline) and [Cr(phen)2(dpma)]3+ (dpma = di(pyrid-2-yl)(methyl)amine) complexes mirror the favorable photophysical properties of homoleptic [Cr(phen)3]3+ and thus emerge as the best heteroleptic candidates for acting as sensitizers at room temperature, and below 100 K, respectively, in more complicated architectures.

175
Burankova, T.; Roedern, E.; Maniadaki, A. E.; Hagemann, H.; Rentsch, D.; Łodziana, Z.; Battaglia, C.; Remhof, A.; Embs, J. P. “Dynamics of the Coordination Complexes in a Solid-State Mg Electrolyte”, J. Phys. Chem. Lett. 2018, 9, 6450-6455.

Coordination complexes of magnesium borohydride show promising properties as solid electrolytes for magnesium ion batteries and warrant a thorough microscopic description of factors governing their mobility properties. Here, the dynamics of Mg(BH4)2- diglyme0.5 on the atomic level are investigated by means of quasielastic neutron scattering (QENS) supported by DFT calculations, IR and NMR spectroscopy. Employing deuterium labelling we can unambiguously separate all the hydrogen containing electrolyte components, which facilitate Mg2+ transport, and provide a detailed analytical description of their motions on the picosecond time scale. The planar diglyme chain coordinating the central Mg atom appears to be flexible, while two dynamically different groups of [BH4] anions undergo reorientations. The latter has important implications for the thermal stability and conductivity of Mg(BH4)2-diglyme0.5 and demonstrates that the presence of excess Mg(BH4)2 units in partially chelated Mg complexes may improve the overall performance of related solid-state electrolytes.

174
Bonner, R.; Hopfgartner, G. “SWATH data independent acquisition mass spectrometry for metabolomics”, TrAC, Trends Anal. Chem. 2019, in press.

Systems Biology and ‘Omics’ require reproducible identification and quantitation of many compounds, preferably in large sample cohorts. Liquid chromatography-mass spectrometry is important since data generated can be used for structure elucidation and highly specific targeted quantitation. Despite great success, the technique has limitations such as: compound coverage in one analysis, method development time and single sample analysis time which determines throughput. New instrument capabilities have led to improved methods, including ‘Data Independent Acquisition’ so-called because acquisition is not changed by acquired data. SWATH-MS is a specific example that has quickly become prominent in proteomics because of increased peptide coverage, high quantitation accuracy, excellent reproducibility and the generation of a ‘digital map’. These capabilities are important in small molecules analyses although uptake in these applications has been slower. We describe the SWATH-MS technique, review its use in applications such as metabolomics and forensics, and summarize on-going improvements and future prospects.

173
Zdrachek, E.; Bakker, E. “Potentiometric Sensing”, Anal. Chem. 2018, in press.

This review describes, with 186 references, progress in the field of potentiometric sensing in the period between January 2016 and August 2018. January 2016 was when the last fundamental review covering the topic of potentiometric sensors appeared in the special issue of Analytical Chemistry and was set as start date. This review starts with a description of progress in the development and improve-ment of reference electrodes, which represent an indispensable part of any electro-chemical cell and has a particularly important influence on the accuracy of potentiometric measurements. It continues with an overview of recent achievements and discoveries in the domain of solid-contact ion-selective electrodes. This section was structured mainly by the type of ion-to-electron transducing material dis-cussed. Next, insights into modern theory of potentiometry is given, describing the use of numerical simulation to predict time dependent potential changes at ion-selective membranes as well as new protocols for determining selectivity coefficient. Subsequently, new and non-classical readout principles for ion-selective electrodes are presented. It is followed by a section dedicated to new materials ex-ploited for ion-selective electrodes (ISEs), including membrane materials, ion-exchange nanopores, room temperature ionic liquids, molecular imprinted polymers and new ionophores. Recent developments in the area of miniaturized ISEs, including paper-based devices, wearable sensors, miniaturized pH sensors, ion-selective microelectrodes and ion-selective field effect transistors (ISFET), are discussed in the next section. The review ends with a discussion of some analytical applications for potentiometric sensors, including polyion detection and environmental, clinical and surfactant analysis.

172
Goujon, A.; Straková, K.; Sakai, N.; Matile, S. “Streptavidin Interfacing as a General Strategy to Localize Fluorescent Membrane Tension Probes in Cells”, Chem. Sci. 2018, in press.

To image the mechanical properties of biological membranes, twisted push–pull mechanophores that respond to membrane tension by planarization in the ground state have been introduced recently. For their application in biological systems, these so-called fluorescent flippers will have to be localized to specific environments of cellular membranes. In this report, we explore streptavidin as a versatile connector between biotinylated flipper probes and biotinylated targets. Fluorescence spectroscopy and microscopy with LUVs and GUVs reveal the specific conditions needed for desthiobiotin-loaded streptavidin to deliver biotinylated flippers selectively to biotinylated membranes. Selectivity for biotinylated plasma membranes is also observed in HeLa cells, confirming the compatibility of this strategy with biological systems. Streptavidin interfacing does not affect the mechanosensitivity of the flipper probes, red shift in the excitation maximum and fluorescence lifetime increase with membrane order and tension, as demonstrated, inter alia, using FLIM.

171
Lorenzen, E.; Ceraudo, E.; Berchiche, Y. A.; Rico, C. A.; Fürstenberg, A.; Sakmar, T. P.; Huber, T. “G protein subtype–specific signaling bias in a series of CCR5 chemokine analogs”, Sci. Signal. 2018, 11, eaao6152.

Chemokines and some chemical analogs of chemokines prevent cellular HIV-1 entry when bound to the HIV-1 coreceptors C-C chemokine receptor 5 (CCR5) or C-X-C chemokine receptor 4 (CXCR4), which are G protein–coupled receptors (GPCRs). The ideal HIV-1 entry blocker targeting the coreceptors would display ligand bias and avoid activating G protein–mediated pathways that lead to inflammation. We compared CCR5-dependent activation of second messenger pathways in a single cell line. We studied two endogenous chemokines [RANTES (also known as CCL5) and MIP-1α (also known as CCL3)] and four chemokine analogs of RANTES (5P12-, 5P14-, 6P4-, and PSC-RANTES). We found that CCR5 signaled through both Gi/o and Gq/11. IP1 accumulation and Ca2+ flux arose from Gq/11 activation, rather than from Gβγ subunit release after Gi/o activation as had been previously proposed. The 6P4- and PSC-RANTES analogs were superagonists for Gq/11 activation, whereas the 5P12- and 5P14-RANTES analogs displayed a signaling bias for Gi/o. These results demonstrate that RANTES analogs elicit G protein subtype–specific signaling bias and can cause CCR5 to couple preferentially to Gq/11 rather than to Gi/o signaling pathways. We propose that G protein subtype–specific signaling bias may be a general feature of GPCRs that can couple to more than one G protein family.

170
Ding, J.; Cherubini, T.; Yuan, D.; Bakker, E. “Paper-supported thin-layer ion transfer voltammetry for ion detection”, Sens. Actuators, B 2019, 280, 69-76.

We report here on paper-supported thin sample layer voltammetry for the determination of ions. To achieve this goal, a simple setup for the coupling of a commercially available electrode to a silver rod electrode was designed and evaluated for paper-supported thin-layer voltammetry. Linear scan ion transfer voltammetry was explored here for ion-selective membranes doped with an ionophore. The ion-transfer processes and electrochemical behaviors of the system are here evaluated and confirmed by numerical simulation. In the proof-of-concept experiments described, the ions tetrabutylammonium chloride (TBA+) and potassium (K+) were studied as model analytes at membranes without and with ionophore, respectively. A linear relationship from 0.1 mM to 1.0 mM K+ was obtained between the charge and ion concentration. The coexistence of background sodium ions did not give appreciable interference, but the background wave was not completely isolated from the analyte wave, as also confirmed by the model. The methodology was successfully demonstrated for determination of K+ in mineral water. It is anticipated that this paper-supported thin-layer detection approach may provide an attractive readout protocol for disposable paper-based analytical devices as the methodology does not place strict demands on reference electrode performance.

169
Ricardi, N.; Zech, A.; Gimbal-Zofka, Y.; Wesolowski, T. A. “Explicit vs. implicit electronic polarisation of environment of an embedded chromophore in frozen-density embedding theory”, Phys. Chem. Chem. Phys. 2018, 20, 26053-26062.

Frozen-Density Embedding Theory (FDET) provides a system-independent formal framework for multi-level computational methods. Despite apparent similarity, the interaction energy components commonly used in QM/MM methods do not have their corresponding counterparts in FDET. We show how the effect of the polarisation on the electron distribution in the environment can be (or is) accounted for either explicitly or implicitly within the FDET framework. Numerical examples are provided for vertical excitation energies in four representative cases of embedded chromophores.

168
Adriouach, S.; Vorobiev, V.; Trefalt, G.; Allémann, E.; Lange, N.; Babič, A. “Squalene-PEG: Pyropheophorbide–a nanoconstruct for tumor theranostics”, Nanomedicine 2019, 15, 243-251.

Novel nanoscale drug delivery biomaterials are of great importance for the diagnosis and treatment of different cancers. We have developed a new pegylated squalene (SQ-PEG) derivative with self-assembly properties. Supramolecular assembly with a lipophilic photosensitizer pyropheophorbide-a (Ppa) by nanoprecipitation gave nanoconstructs SQ-PEG:Ppa with an average size of 200 nm in diameter and a drug loading of 18% (w/w). The composite material demonstrates nanoscale optical properties by tight packing of Ppa within Sq-PEG:Ppa resulting in 99.99% fluorescence self-quenching. The biocompatibility of the nanomaterial and cell phototoxicity under light irradiation were investigated on PC3 prostate tumor cells in vitro. SQ-PEG:Ppa showed excellent phototoxic effect at low light dose of 5.0 J/cm2 as a consequence of efficient cell internalization of Ppa by the nanodelivery system. The diagnostic potential of SQ-PEG:Ppa nanoconstructs to deliver Ppa to tumors in vivo was demonstrated in chick embryo model implanted with U87MG glioblastoma micro tumors.

167
Olchowka, J.; Hagemann, H.; Delgado, M.; Wickleder, C. “The influence of ionothermal synthesis using BmimBF4 as solvent on nanophosphors BaFBr:Eu2+ photoluminescence”, Nanoscale 2018, 10, 19706-19710.

Ionothermal synthesis is a strongly growing research area due to the outstanding physical and chemical properties of ionic liquid (IL) to design new materials, however the effect of these ILs on material’s luminescence properties is poorly known. In this work, it is shown that the imidazolium based BmimBF4 ionic liquid, used as a solvent during the synthesis, tethers at the surface of the nanoparticles and influences the photoluminescence of the nanophosphor BaFBr:Eu2+ materials. By time resolved spectroscopy two different emissions are observed for the material synthesized by ionothermal approach, one corresponding to Eu(II) 5d-4f transitions in BaFBr host with a decay time of 843 ns and the other with a much faster decay time to the ionic liquid BmimBF4.

166
Du, S.; Pichoff, S.; Kruse, K.; Lutkenhaus, J. “FtsZ filaments have the opposite kinetic polarity of microtubules”, Proc. Natl. Acad. Sci. USA 2018, 115, 10768-10773.

FtsZ is the ancestral homolog of tubulin and assembles into the Z ring that organizes the division machinery to drive cell division in most bacteria. In contrast to tubulin that assembles into 13 stranded microtubules that undergo dynamic instability, FtsZ assembles into single-stranded filaments that treadmill to distribute the peptidoglycan synthetic machinery at the septum. Here, using longitudinal interface mutants of FtsZ, we demonstrate that the kinetic polarity of FtsZ filaments is opposite to that of microtubules. A conformational switch accompanying the assembly of FtsZ generates the kinetic polarity of FtsZ filaments, which explains the toxicity of interface mutants that function as a capper and reveals the mechanism of cooperative assembly. This approach can also be employed to determine the kinetic polarity of other filament-forming proteins.

165
Lombardot, T.; Morgat, A.; Axelsen, K. B.; Aimo, L.; Hyka-Nouspikel, N.; Niknejad, A.; Ignatchenko, A.; Xenarios, I.; Coudert, E.; Redaschi, N.; Bridge, A. “Updates in Rhea: SPARQLing biochemical reaction data”, Nucleic Acids Res. 2018, in press.

Rhea (http://www.rhea-db.org) is a comprehensive and non-redundant resource of over 11 000 expert-curated biochemical reactions that uses chemical entities from the ChEBI ontology to represent reaction participants. Originally designed as an annotation vocabulary for the UniProt Knowledgebase (UniProtKB), Rhea also provides reaction data for a range of other core knowledgebases and data repositories including ChEBI and MetaboLights. Here we describe recent developments in Rhea, focusing on a new resource description framework representation of Rhea reaction data and an SPARQL endpoint (https://sparql.rhea-db.org/sparql) that provides access to it. We demonstrate how federated queries that combine the Rhea SPARQL endpoint and other SPARQL endpoints such as that of UniProt can provide improved metabolite annotation and support integrative analyses that link the metabolome through the proteome to the transcriptome and genome. These developments will significantly boost the utility of Rhea as a means to link chemistry and biology for a more holistic understanding of biological systems and their function in health and disease.

164
Piguet, C.; Golesorkhi, B.; Nozary, H.; Guénée, L.; Fürstenberg, A. “Room-Temperature Linear Light Upconversion in a Mononuclear Erbium Molecular Complex”, Angew. Chem., Int. Ed. 2018, 57, 15172-15176.

Up to now, the piling up of successive photons of low energies (near‐infrared = NIR) using a single lanthanide center and linear optics in order to ultimately produce upconverted visible emission was restricted to low‐phonon solid materials and nanoparticles. We show here that the tight helical wrapping of three terdentate N‐donor ligands around a single nine‐coordinate trivalent erbium cation provides favorable conditions for a mononuclear molecular complex to exhibit unprecedented related upconverted emission. Low power NIR laser excitations into the metal‐centered transitions Er(4I11/2‐4I15/2) at 801 nm or Er(4I13/2‐4I15/2) at 966 nm result in upconverted blue‐green emissions, where two, respectively three photons are successively absorbed by a molecular lanthanide complex possessing high‐energy vibrations.

163
Tiraferri, A.; Maroni, P. “Rapid Desorption of Polyelectrolytes from Solid Surfaces Induced by Changes of Aqueous Chemistry”, Langmuir 2018, 34, 12302-12309.

The short-term desorption induced by changes of aqueous chemistry of pre-deposited polyelectrolyte layers on solid surfaces was studied with reflectometry. The behavior of a strong polycation, polydiallydimethylammonium chloride (PDADMAC), interacting with flat silica was investigated in detail. Results showed that partial desorption of pre-adsorbed polymer chains can be quickly triggered by changes in ionic strength and pH. When lowering these parameters in the PDADMAC-silica system, the increased lateral repulsive potential of neighboring chains drove the desorption of some of the polymer. Furthermore, layer desorption was favored when electrostatic interactions between a polyelectrolyte and the underlying surface became less attractive or switched to repulsive. At the investigated timescales (< 1 h), adlayer desorption was always partial and often incomplete. When initiating desorption from a condition of large adsorbed mass, desorption effects did not result in the plateau mass obtained by adsorption on a clean surface: an excess mass remained deposited. The results thus suggest that a relatively large energy barrier needs to be overcome to induce re-dissolution of pre-deposited chains and that this barrier may be function of the number of polymer-surface interactions, which are in turn correlated with polymer molecular mass. These mechanisms have important implications for environmental processes and colloidal systems because they imply that, once adsorbed, polymeric chains may be re-dissolved but only to a limited degree at typical engineering timescales.

162
Angulo, G.; Rosspeintner, A.; Lang, B.; Vauthey, E. “Optical Transient Absorption Experiments Reveal the Failure of Formal Kinetics in Diffusion Assisted Electron Transfer Reactions”, Phys. Chem. Chem. Phys. 2018, 20, 25531-25546.

The ultimate goal of chemical kinetics is to understand why a given reaction is fast or not. To this end it is necessary to count on robust and experimentally well tested theories. One of the difficulties, long recognized in the study of bimolecular reactions, is the role of the molecular displacement, i.e. diffusion. Nonetheless the field is still lacking a compelling amount of case studies contrasting physical models to experiments. By performing transient absorption experiments on the photo-induced electron transfer reaction between perylene and N,N-dimethylaniline in liquid solutions over many orders of magnitude in time, we try to understand the factors determining the kinetics and yields of the full photocycle. We present a method to overcome potential pitfalls in the extraction of the relevant quantities, the transient populations, from the experimental data due to the changes in band shapes and positions. The results are compared to simulations of two different theories: a reaction-diffusion approach based on the encounter theories, and a formal kinetic scheme. We conclude that while the former explains the observed trends in the kinetics with quencher concentration and viscosity exceptionally well, the latter fails. Moreover the analysis of the data with the assistance of encounter theory unveils effects that otherwise would pass unnoticed. This approach and its results exemplify the path to follow in other condensed media whenever diffusion is involved.

161
Lang, B. “Photometrics of ultrafast and fast broadband electronic transient absorption spectroscopy: State of the art”, Rev. Sci. Instrum. 2018, 89, 093112.

The physical limits of the photometric resolution in broadband electronic transient absorption spectroscopy are discussed together with solutions for how to reach these limits in practice. In the first part, quantitative expressions for the noise contributions to the transient absorption signal are derived and experimentally tested. Experimental approaches described in the literature are discussed and compared on this basis. Guide-lines for designing a setup are established. In the second part, a method for obtaining nearly shot-noise limited kinetics with photometric resolution of the order of 100 μOD in overall measurement times of a few minutes from femtosecond to microsecond time scale is presented. The results are discussed in view of other experiments of step-scan type which are subject to a background or to correlated noise. Finally, detailed information is provided on how to obtain transient absorption spectra where counting statistics are the sole source of noise. A method for how to suppress outliers without introducing bias is discussed. An application example is given to demonstrate the achievable signal-to-noise level and the fast acquisition time.

160
Granelli, M.; Downward, A. M.; Deville, C.; Rodriguez Franco, A.; Guenée, L.; Besnard, C.; Williams, A. F. “Coordination Chemistry of the Chiral, Facially Coordinating Tridentate Ligand 1,2‐Bis(benzimidazol‐2‐yl)ethanol with 3d Transition Metals”, Eur. J. Inorg. Chem. 2018, 4181-4189.

1,2‐Bis(benzimidazol‐2‐yl)ethanol (1) and its bis‐N‐methylated derivative (2) act as chiral tridentate facially coordinating ligands capable of binding metals right across the d‐series. Octahedral complexes of divalent and trivalent metal ions are synthesised and characterised by X‐ray crystallography. Only two of the three possible diastereomers are observed in complexes of the type [M(1,2)2] and appear to be close in energy. In complexes of MII ions, the alcohol function of the ligand stays protonated, but the proton is lost in complexes of MIII ions. Electronic and CD spectra are reported. Slow oxidation of the vanadium(III) complex leads to a mixed valence compound where one ligand has been oxidised.

159
Zhang, B.; Sels, A.; Salassa, G.; Pollitt, S.; Truttmann, V.; Rameshan, C.; Llorca, J.; Olszewski, W.; Rupprechter, G.; Bürgi, T.; Barrabes, N. “Ligand migration from cluster to support: A crucial factor for catalysis by thiolate-protected gold clusters”, ChemCatChem 2018, in press.

Thiolate protected metal clusters are valuable precursors for the design of tailored nano‐sized catalysts. Their performance can be tuned precisely at atomic level, e.g. by the configuration/type of ligands or by partial/complete removal of the ligand shell through controlled pre‐treatment steps. However, the interaction between the ligand shell and the oxide support, as well as ligand removal by oxidative pre‐treatment, are still poorly understood. Typically, it was assumed that the thiolate ligands are simply converted into SO2, CO2 and H2O. Herein, we report the first detailed observation of sulfur ligand migration from Au to the oxide support upon deposition and oxidative pre‐treatment, employing mainly S K‐edge XANES. Consequently, thiolate ligand migration not only produces clean Au cluster surfaces but also the surrounding oxide support is modified by sulphur‐containing species, with pronounced effects on catalytic properties.

158
Delgado Perez, M. T.; Tissot, A.; Guénée, L.; Hauser, A.; Valverde-Muñoz, F. J.; Seredyuk, M.; Real, J. A.; Pillet, S.; Bendeif, E.-E.; Besnard, C. “Very long-lived photogenerated high-spin phase of a multistable spin-crossover molecular material”, J. Am. Chem. Soc. 2018, 140, 12870-12876.

The spin-crossover compound [Fe(n-Bu-im)3(tren)](PF6)2 shows an unusual long relaxation time of 20 h after light-induced excited spin state trapping (LIESST) when irradiating at 80 K. This is more than 40 times longer than when irradiating at 10 K. Optical absorption spectroscopy and X-ray diffraction using synchrotron radiation were used to characterize and compare the LIESST behavior of this compound after irradiation at around 10 K and 80 K. Rearrangement of the butyl chains of the ligands occurring during the relaxation after irradiation at 80 K are thought to be responsible for the unusually long relaxation time at this temperature.

157
Delgado, T.; Meneses-Sánchez, M.; Piñeiro-López, L.; Bartual-Murgui, C.; Muñoz, M. C.; Real, J. A. “Thermo- and photo-modulation of exciplex fluorescence in a 3D spin crossover Hofmann-type coordination polymer”, Chem. Sci. 2018, 9, 8446-8452.

The search for bifunctional materials showing synergies between spin crossover (SCO) and luminescence has attracted substantial interest since they could be promising platforms for new switching electronic and optical technologies. In this context, we present the first three-dimensional FeII Hofmann-type coordination polymer exhibiting SCO properties and luminescence. The complex {FeII(bpben)[Au(CN)2]}@pyr (bpben = 1,4-bis(4-pyridyl)benzene) functionalized with pyrene (pyr) guests undergoes a cooperative multi-step SCO, which has been investigated by single crystal X-ray diffraction, single crystal UV-Vis absorption spectroscopy, and magnetic and calorimetric measurements. The resulting fluorescence from pyrene and exciplex emissions are controlled by the thermal and light irradiation (LIESST effect) dependence of the high/low-spin state population of FeII. Conversely, the SCO can be tracked by monitoring the fluorescence emission. This ON–OFF interplay between SCO and luminescence combined with the amenability of Hofmann-type materials to be processed at the nano-scale may be relevant for the generation of SCO-based sensors, actuators and spintronic devices.

156
Payne, R. J.; Winssinger, N. “Editorial overview: Synthetic biomolecules”, Curr. Opin. Chem. Biol. 2018, 46, A3-A4.open archive unige:109866 pdf full text [restricted access]

155
Zhao, Y.; Cotelle, Y.; Liu, L.; López-Andarias, J.; Bornhof, A.-B.; Akamatsu, M.; Sakai, N.; Matile, S. “The Emergence of Anion-π Catalysis”, Acc. Chem. Res. 2018, 51, 2255-2263.open archive unige:108070 pdf full text [free access]

The objective of this Account is to summarize the first five years of anion−π catalysis. The general idea of anion−π catalysis is to stabilize anionic transition states on aromatic surfaces. This is complementary to the stabilization of cationic transition states on aromatic surfaces, a mode of action that occurs in nature and is increasingly used in chemistry. Anion−π catalysis, however, rarely occurs in nature and has been unexplored in chemistry. Probably because the attraction of anions to π surfaces as such is counterintuitive, anion−π interactions in general are much younger than cation−π interactions and remain under-recognized until today. Anion−π catalysis has emerged from early findings that anion−π interactions can mediate the transport of anions across lipid bilayer membranes. With this evidence for stabilization in the ground state secured, there was no reason to believe that anion−π interactions could not also stabilize anionic transition states.

154
Palermo, G.; Guglielmelli, A.; Pezzi, L.; Cataldi, U.; De Sio, L.; Caputo, R.; De Luca, A.; Bürgi, T.; Tabiryan, N.; Umeton, C. “A command layer for anisotropic plasmonic photo-thermal effects in liquid crystal”, Liq. Cryst. 2018, in press.

Photo-anisotropic properties of a particular command layer for Liquid Crystals (LCs), based on azo-benzene material, are exploited to control the photo-thermal response of a single layer of homogeneously and uniformly distributed Au nanoparticles, immobilised on a glass substrate. Experiments demonstrate that the intrinsic anisotropy of materials can influence the photo-thermal response of plasmonic systems. Indeed, the resonant absorption of radiation by plasmonic subunits is followed by a noticeable increase of their temperature. However, the thermal response observed in presence of a homogeneous and random array of AuNPs directly exposed to air or embedded in ice is typically isotropic; on the contrary, a homogenous, yet thin, coating made of a particular command layer for LCs, deposited on a large-area carpet of AuNPs, influences their thermal response in an anisotropic way. In particular, the temperature increase, induced by pumping with a laser source of resonant wavelength with the plasmonic AuNPs, strongly depends on the alignment direction of the command layer. This effect makes the command layer of particular interest for its capability to drive intriguing optically induced ‘thermal-reorientational’ effects in a liquid crystal film.

153
Athavale, R.; Pankratova, N.; Dinkel, C.; Bakker, E.; Wehrli, B.; Brand, A. “Fast Potentiometric CO2 Sensor for High-resolution In situ Measurements in Fresh Water Systems”, Environ. Sci. Technol. 2018, 52, 11259-11266.

We present a new potentiometric sensor principle and a calibration protocol for in situ profiling of dissolved CO2 with high temporal and spatial resolution in fresh water lakes. The sensor system is based on the measurement of EMF between two solid contact ion selective electrodes (SC-ISEs), a hydrogen ion selective and a carbonate selective sensor. Since it relies on SC-ISEs, it is insensitive to changes in the pressure, thus suitable for in situ studies. Also, as it offers a response time (t95%) of in situ protocol accounts for the continuous drift and change in offset that remains a challenge during profiling in natural waters. The fast response resolves features that are usually missed by standard methods like the classical Severinghaus CO2 probe. In addition, the insensitivity of the presented setup to dissolved sulfide allows also for measurements in anoxic zones of eutrophic systems. Highly resolved CO2 concentration profiles obtained by presented novel and robust SC-ISE setup along with the developed optimum in situ protocol allow investigating hotspots of biogeochemical processes such as mineralization and primary production in the water column and help improving estimates for CO2 turnover in freshwater systems.

152
Mazet, C. “Editorial: Organometallics and Catalysis”, CHIMIA 2018, 72, 577.open archive unige:108876 pdf full text [free access]

151
Lathion, T.; Guénée, L.; Besnard, C.; Bousseksou, A.; Piguet, C. “Deciphering the Influence of Meridional versus Facial Isomers in Spin Crossover Complexes”, Chem. Eur. J. 2018, 24, 16873-16888.

Chelate coordination of non-symmetrical didentate pyrazine-benzimidazole (L1) or pyridinebenzimidazole (L2) N-donor ligands around divalent iron in acetonitrile produces stable homoleptic triple-helical spin crossover [Fe(Lk)3]2+ complexes existing as mixtures of meridional (C1-symmetry) and facial (C3-symmetry) isomers in slow exchange on the NMR time scale. The speciation deviates from the expected statistical ratio mer/fac = 3:1, a trend assigned to the thermodynamic trans-influence combined with solvation effects. Consequently, the observed spin state FeIIlow-spin ↔ FeIIhighspin equilibria occurring in [Fe(Lk)3]2+ refer to mixtures of complexes in solution, an issue usually not considered in this field, but which limits rational structure-properties correlations. Taking advantage of the selective and quantitative formation of isostructural facial isomers in non-constrained related spin crossover d-f helicates (HHH)-[LnFe(Lk)3]5+ (Ln is a trivalent lanthanide, Lk = L5, L6), we propose a novel strategy for assigning pertinent thermodynamic driving forces to each spin crossover triple-helical isomer. The different enthalpic contributions to the spin state equilibrum found in mer- [Fe(Lk)3]2+ and fac-[Fe(Lk)3]2+ reflect the Fe-N bond strengths dictated by the trans-influence, while a concomitant solvent-based entropic contribution reinforces the latter effect and results in systematic shifts of the spin crossover transitions toward higher temperature in the facial isomers.

150
Bouilloux, J.; Yuschenko, O.; Dereka, B.; Boso, G.; Babic, A.; Zbinden, H.; Vauthey, E.; Lange, N. “CycloPeptidic Photosensitizer Prodrugs as Proteolytically Triggered Drug Delivery Systems of Pheophorbide a With Defined Structures for Selective PhotoDiagnosis and PhotoDynamic Therapy: Part II - Co-loading of Pheophorbide a and Black Hole Quencher”, Photochem. Photobiol. Sci. 2018, 17, 1739-1748.

Previously, we have shown that the use of a cyclopeptidic carrier could be of great interest for the design of fully characterized prodrugs for further use in photodynamic therapy. In order to further optimize the design, we decided to modify the highly quenched conjugate uPA-cPPP4/5 by co-loading a long-distance fluorescence quencher. For this purpose we tethered two black hole quenchers (BHQ3) together with two pheophorbide A moities onto the same PEGylated backbone and assessed the modified photophysical properties. In addition, to prove the reliability of our concept, we designed two analogues, uPA-cPPQ2+2/5 and CathB-cPPQ2+2/5, by using two different peptidic linkers as substrates for uPA and cathepsin B, respectively. These two conjugates proved to be much more water-soluble than their analogues bearing only Phas. These conjugates are not only highly quenched in their native state with regard to their fluorescence emission (up to 850 ± 287 times less fluorescent for CathB-cPPQ2+2/5 as compared to the unquenched monosubstituted reference uPA-cPPP1/5), but also prevent singlet oxygen production (with a total quenching of the emission when the quenchers are co-loaded with photosensitizers) when the photosentistizers are excited. After proteolytic activation, these conjugates recover their photophysical properties in the same way as occurred for uPA-cPPP4/5, with up to a 120-fold increase in fluorescence emission for uPA-cPPQ2+2/5 after two hours of incubation with uPA.

149
Lindberg, E.; Angerani, S.; Anzola, M.; Winssinger, N. “Luciferase-induced photoreductive uncaging of small-molecule effectors”, Nat. Commun. 2018, 9, art. 3539.open archive unige:108348 pdf full text [free access]

Bioluminescence resonance energy transfer (BRET) is extensively used to study dynamic systems and has been utilized in sensors for studying protein proximity, metabolites, and drug concentrations. Herein, we demonstrate that BRET can activate a ruthenium-based photocatalyst which performs bioorthogonal reactions. BRET from luciferase to the ruthenium photocatalyst is used to uncage effector molecules with up to 64 turnovers of the catalyst, achieving concentrations >0.6 μM effector with 10 nM luciferase construct. Using a BRET sensor, we further demonstrate that the catalysis can be modulated in response to an analyte, analogous to allosterically controlled enzymes. The BRET-induced reaction is used to uncage small-molecule drugs (ibrutinib and duocarmycin) at biologically effective concentrations in cellulo.

148
Wettmann, L.; Bonny, M.; Kruse, K. “Effects of geometry and topography on Min-protein dynamics”, PLoS ONE 2018, 13, e0203050.

In the rod-shaped bacterium Escherichia coli, the center is selected by the Min-proteins as the site of cell division. To this end, the proteins periodically translocate between the two cell poles, where they suppress assembly of the cell division machinery. Ample evidence notably obtained from in vitro reconstitution experiments suggests that the oscillatory pattern results from self-organization of the proteins MinD and MinE in presence of a membrane. A mechanism built on cooperative membrane attachment of MinD and persistent MinD removal from the membrane induced by MinE has been shown to be able to reproduce the observed Min-protein patterns in rod-shaped E. coli and on flat supported lipid bilayers. Here, we report our results of a numerical investigation of patterns generated by this mechanism in various geoemtries. Notably, we consider the dynamics on membrane patches of different forms, on topographically structured lipid bilayers, and in closed geometries of various shapes. We find that all previously described patterns can be reproduced by the mechanism. However, it requires different parameter sets for reproducing the patterns in closed and in open geometries.

147
Bouilloux, J.; Yuschenko, O.; Dereka, B.; Boso, G.; Zbinden, H.; Vauthey, E.; Babic, A.; Lange, N. “CycloPeptidic Photosensitizer Prodrugs as Proteolytically Triggered Drug Delivery Systems of Pheophorbide a With Defined Structures for Selective PhotoDiagnosis and PhotoDynamic Therapy: Part I - Self-quenched Prodrugs”, Photochem. Photobiol. Sci. 2018, 17, 1728-1738.

We report here the synthesis of a new prodrug system consisting in a Regioselectively Addressable Functionalized Templates bearing multiple pheophorbide a moieties for a use in Photodynamic Therapy. These coupling were achieved using copper-free “click” chemistry, namely Strain-Promoted Azide-Alkyne Cycloaddition. This new design was directed to obtain well-defined quenched photosensitizer prodrugs with perfect knowledge of the number and position of loaded photosensitizers, providing here structures bearing up to six photosentitizers and two PEG chains. These conjugates are ideally quenched in their native state regarding their fluorescence emission (up to 155 ± 28 times less fluorescent for an hexasubstituted conjugate as compared to a monosubstituted non-quenched reference compound) or singlet oxygen production (with a decrease by a factor 8.7 in the best case) when excited. After two hours of proteolytic activation, fluorescence emission of a tetrasubstituted conjugate was increased by a factor of 17 as compared to the initial fluorescence emission.

146
Fiorito, D.; Mazet, C. “Ir-Catalyzed Selective Hydroboration of 2-Substituted 1,3-Dienes: A General Method to Access Homoallylic Boronates”, ACS Catal. 2018, 8, 9382-9387.open archive unige:107880 pdf full text [restricted access]

An operationally simple protocol for the 4,3-selective hydroboration of 2-substituted 1,3-dienes using an iridium catalyst is described. Independently of the nature (alkyl, aryl, heteroaryl) and the size of the substituent in 2-position, it provides access to a variety of homoallylic boronates featuring a 1,1-disubstituted olefin in high yield, chemo- and regioselectivity. An array of potentially sensitive functional groups is well-tolerated and the method can be extend to 1,2-disubstituted 1,3-dienes. Derivatization of the homoallylic boronates is also demonstrated using contemporary catalytic and enantioselective processes.

145
Sakai, N.; Matile, S. “Conjugated Polyimine Dynamers as Phase-Sensitive Membrane Probes”, J. Am. Chem. Soc. 2018, 140, 11438-11443.open archive unige:107782 pdf full text [restricted access]

In this report, dynamic polyimines are introduced as multifunctional sensors of lipid bilayer phases. Under mildly acidic conditions, self-condensation of push–pull amino formyl fluorenes into polyimines occurs in solid- or liquid-ordered phases but not in liquid-disordered phases of vesicular membranes. The obtained conjugated polymers are characterized by a progressive red shift of the absorption maxima, the appearance of exciton-coupled circular dichroism (CD) bands, and fluorescence quenching. These characteristics allow multiple modes of detection of membrane phases, which are known to change under membrane tension.

144
Lagoutte, R.; Pastor, M.; Berthet, M.; Winssinger, N. “Rapid and scalable synthesis of chiral bromolactones as precursors to α-exo-methylene-γ-butyrolactone-containing sesquiterpene lactones”, Tetrahedron 2018, 74, 6012-6021.open archive unige:107781 pdf full text [restricted access]

The sesquiterpene lactones cover a diverse and pharmacologically important diversity space. In particular, the electrophilic α-exo-methylene-γ-butyrolactone moiety that is preponderant in this natural product family has been shown to readily engage in covalent inhibition via conjugate addition of cysteine residues in target proteins. However, the synthetic accessibility of sesquiterpenes or related probes to investigate their mode of action remains laborious. Herein, we present a rapid and scalable route to chiral bromolactones as enabling precursors in the synthesis of sesquiterpene lactones.

143
Bravo-Veyrat, S.; Hopfgartner, G. “High-throughput liquid chromatography differential mobility spectrometry mass spectrometry for bioanalysis: determination of reduced and oxidized form of glutathione in human blood”, Anal. Bioanal. Chem. 2018, 410, 7153-7161.

Currently, the measure of the oxidative stress, from oxidized and reduced glutathione (GSSG and GSH respectively), for large cohorts of samples, is generally limited to spectrometric methods. In this study, a high-throughput assay for GSH after derivatization with N-ethylmaleimide and GSSG in blood sample was developed with an analysis time of 1.5 min. The method combines protein precipitation and a short LC (10-mm length) column where compounds were trapped in front-flush mode and eluted in back-flush mode. This setup is combined with modifier-assisted differential ion mobility spectrometry (DMS, SelexIon) and detection is performed in the selected reaction monitoring mode using positive electrospray ionization. In DMS, various modifiers were investigated including N2, methanol, toluene, ethanol, acetonitrile, and isopropanol to improve assay selectivity. Using EtOH as modifier, the limit of quantification (LOQ) was found to be 0.4 μM for GSSG and 3.2 μM for GS-N-ethylmaleimide (NEM) using a blood volume of 60 μL. The method is linear over a wide dynamic concentration range of 0.4 to 400 μM for GSSG and from 3.2 to 3200 μM for GS-NEM. The inter-assay precision of QC samples were ≤ 6.7%, with accuracy values between 98.3 and 103%. The method was further cross-validated with a LC Hypercarb-DMS-MS/MS method by the analysis of human blood samples. The bias between both assays ranged from − 0.3 to 0.2%.

142
Cougnon, F. B. L.; Caprice, K.; Pupier, M.; Bauza, A.; Frontera, A. “A Strategy to Synthesize Molecular Knots and Links Using the Hydrophobic Effect”, J. Am. Chem. Soc. 2018, 140, 12442-12450.open archive unige:109018 pdf full text [restricted access]

Conventional approaches to the synthesis of molecular knots and links mostly rely on metal-templation. We present here an alternative strategy that uses the hydrophobic effect to drive the formation of complex interlocked structures in water. We designed an aqueous dynamic combinatorial system that can generate knots and links. In this system, the self-assembly of a topologically complex macrocycle is thermodynamically favored only if an optimum packing of all its components minimizes the hydrophobic surface area in contact with water. Therefore, the size, geometry and rigidity of the initial building blocks can be exploited to control the formation of a specific topology. We illustrate the validity of this concept with the syntheses of a Hopf link, a Solomon link and a trefoil knot. This latter molecule, whose self-assembly is templated by halides, binds iodide with high affinity in water. Overall, this work brings a fresh perspective on the synthesis of topologically complex molecules: solvophobic effects can be intentionally harnessed to direct the efficient and selective self-assembly of knots and links.

141
Tavallaie, R.; McCarroll, J.; Le Grand, M.; Ariotti, N.; Schuhmann, W.; Bakker, E.; Tilley, R. D.; Hibbert, D. B.; Kavallaris, M.; Gooding, J. J. “Nucleic acid hybridization on an electrically reconfigurable network of gold-coated magnetic nanoparticles enables microRNA detection in blood”, Nature Nanotech. 2018, 13, 1066-1071.

There is intense interest in quantifying the levels of microRNA because of its importance as a blood-borne biomarker. The challenge has been to develop methods that can monitor microRNA expression both over broad concentration ranges and in ultralow amounts directly in a patient’s blood. Here, we show that, through electric-field-induced reconfiguration of a network of gold-coated magnetic nanoparticles modified by probe DNA (DNA–Au@MNPs), it is possible to create a highly sensitive sensor for direct analysis of nucleic acids in samples as complex as whole blood. The sensor is the first to be able to detect concentrations of microRNA from 10 aM to 1 nM in unprocessed blood samples. It can distinguish small variations in microRNA concentrations in blood samples of mice with growing tumours. The ultrasensitive and direct detection of microRNA using an electrically reconfigurable DNA–Au@MNPs network makes the reported device a promising tool for cancer diagnostics.

140
Riggi, M.; Niewola-Staszkowska, K.; Chiaruttini, N.; Colom, A.; Kusmider, B.; Mercier, V.; Soleimanpour, S.; Stahl, M.; Matile, S.; Roux, A.; Loewith, R. “Decrease in Plasma Membrane Tension Triggers PtdIns(4,5)P2 Phase Separation to Inactivate TORC2”, Nat. Cell. Biol. 2018, 20, 1043-1051.open archive unige:107468 pdf full text [restricted access]

The target of rapamycin complex 2 (TORC2) plays a key role in maintaining the homeostasis of plasma membrane (PM) tension. TORC2 activation following increased PM tension involves redistribution of the Slm1 and 2 paralogues from PM invaginations known as eisosomes into membrane compartments containing TORC2. How Slm1/2 relocalization is triggered, and if/how this plays a role in TORC2 inactivation with decreased PM tension, is unknown. Using osmotic shocks and palmitoylcarnitine as orthogonal tools to manipulate PM tension, we demonstrate that decreased PM tension triggers spontaneous, energy-independent reorganization of pre-existing phosphatidylinositol-4,5-bisphosphate into discrete invaginated membrane domains, which cluster and inactivate TORC2. These results demonstrate that increased and decreased membrane tension are sensed through different mechanisms, highlighting a role for membrane lipid phase separation in mechanotransduction.

139
Colom, A.; Derivery, E.; Soleimanpour, S.; Tomba, C.; Dal Molin, M.; Sakai, N.; González-Gaitán, M.; Matile, S.; Roux, A. “A Fluorescent Membrane Tension Probe”, Nat. Chem. 2018, 10, 1118-1125.open archive unige:107802 pdf full text [restricted access]

Cells and organelles are delimited by lipid bilayers in which high deformability is essential to many cell processes, including motility, endocytosis and cell division. Membrane tension is therefore a major regulator of the cell processes that remodel membranes, albeit one that is very hard to measure in vivo. Here we show that a planarizable push–pull fluorescent probe called FliptR (fluorescent lipid tension reporter) can monitor changes in membrane tension by changing its fluorescence lifetime as a function of the twist between its fluorescent groups. The fluorescence lifetime depends linearly on membrane tension within cells, enabling an easy quantification of membrane tension by fluorescence lifetime imaging microscopy. We further show, using model membranes, that this linear dependency between lifetime of the probe and membrane tension relies on a membrane-tension-dependent lipid phase separation. We also provide calibration curves that enable accurate measurement of membrane tension using fluorescence lifetime imaging microscopy.

138
Dordevic, L.; Arcudi, F.; D'Urso, A.; Cacioppo, M.; Micali, N.; Bürgi, T.; Purrello, R.; Prato, M. “Design principles of chiral carbon nanodots help convey chirality from molecular to nanoscale level”, Nat. Commun. 2018, 9, 7710.

The chirality of (nano)structures is paramount in many phenomena, including biological processes, self-assembly, enantioselective reactions, and light or electron spin polarization. In the quest for new chiral materials, metallo-organic hybrids have been attractive candidates for exploiting the aforementioned scientific fields. Here, we show that chiral carbon nanoparticles, called carbon nanodots, can be readily prepared using hydrothermal microwave-assisted synthesis and easily purified. These particles, with a mean particle size around 3 nm, are highly soluble in water and display mirror-image profile both in the UV–Vis and in the infrared regions, as detected by electronic and vibrational circular dichroism, respectively. Finally, the nanoparticles are used as templates for the formation of chiral supramolecular porphyrin assemblies, showing that it is possible to use and transfer the chiral information. This simple (and effective) methodology opens up exciting opportunities for developing a variety of chiral composite materials and applications.

137
Bakker, E. “Editorial - So, you have a great new sensor. How will you validate it?”, ACS Sens. 2018, 3, 1431.

136
Apichai, S.; Wang, L.; Pankratova, N.; Grudpan, K.; Bakker, E. “Ion-Exchange Microemulsions for Eliminating Dilute Interferences in Potentiometric Determinations”, Electroanalysis 2018, 30, 2462-2466.

We report here for the first time on the use of functional microemulsions in potentiometric assays to remove dilute interferences from solution when measuring high concentrations of analyte. The microemulsions are similarly formulated to the ion‐selective membrane used in the measurement and act as sacrificial material. They are here stabilized by the triblock copolymer pluronic F‐127 and contain the chloride salt of the tridodecylmethylammonium cation, which also serves as anion‐exchanger in the membrane electrode. Both membrane and microemulsion are preconditioned with chloride. If an anionic interference is present at moderate concentration, the rapid equilibration with the functionalized microemulsion results in a quantitative removal. The principle is explored with salicylate as common interference in the detection of chloride in physiological samples. The data agree well to an equilibrium ion‐exchange model for the microemulsion. Salicylate levels up to millimolar can be effectively removed. Unfortunately, quaternary ammonium salt from the microemulsion is found to contaminate the ion‐selective membrane phase. Indeed, a cation‐exchanging valinomycin membrane in contact with concentrated anion‐exchanging microemulsions shows a large potential increase. This indicates that the membrane changes from cation to anion permselectivity. This contamination of the membrane by the microemulsion phase must be overcome for a practical application of the approach.

135
Zimmer, P.; Kruse, K.; Nagler, J. “Anomalous percolation features in molecular evolution”, Phys. Rev. E 2018, 98, 022408.

Self-replication underlies every species of living beings and simple physical intuition dictates that some sort of autocatalysis invariably constitutes a necessary ingredient for the emergence of molecular life. This led Worst et al. [E. G. Worst, P. Zimmer, E. Wollrab, K. Kruse, and A. Ott, New J. Phys. 18, 103003 (2016)] to study a model of molecular evolution of self-replicating molecules where spontaneous ligation and simple autocatalysis are in competition for their building blocks. We revisit this model, where irreversible aggregation leads to a transition from a regime of small molecules to macromolecules, and find an array of anomalous percolation features, some of them predicted for very specific percolation processes [R. M. D'Souza and J. Nagler, Nat. Phys. 11, 531 (2015)].

134
He, C.; Hu, X.; Weston, T. A.; Jung, R. S.; Sandhu, J.; Huang, S.; Heizer, P.; Kim, J.; Ellison, R.; Xu, J.; Kilburn, M.; Bensinger, S. J.; Riezman, H.; Tontonoz, P.; Fong, L. G.; Jiang, H.; Young, S. G. “Macrophages release plasma membrane-derived particles rich in accessible cholesterol”, Proc. Natl. Acad. Sci. USA 2018, 115, E8499-E8508.

Macrophages are generally assumed to unload surplus cholesterol through direct interactions between ABC transporters on the plasma membrane and HDLs, but they have also been reported to release cholesterol-containing particles. How macrophage-derived particles are formed and released has not been clear. To understand the genesis of macrophage-derived particles, we imaged mouse macrophages by EM and nanoscale secondary ion mass spectrometry (nanoSIMS). By scanning EM, we found that large numbers of 20- to 120-nm particles are released from the fingerlike projections (filopodia) of macrophages. These particles attach to the substrate, forming a “lawn” of particles surrounding macrophages. By nanoSIMS imaging we showed that these particles are enriched in the mobile and metabolically active accessible pool of cholesterol (detectable by ALO-D4, a modified version of a cholesterol-binding cytolysin). The cholesterol content of macrophage-derived particles was increased by loading the cells with cholesterol or by adding LXR and RXR agonists to the cell-culture medium. Incubating macrophages with HDL reduced the cholesterol content of macrophage-derived particles. We propose that release of accessible cholesterol-rich particles from the macrophage plasma membrane could assist in disposing of surplus cholesterol and increase the efficiency of cholesterol movement to HDL.

133
Collet, G.; Lathion, T.; Besnard, C.; Piguet, C.; Petoud, S. “On-Demand Degradation of Metal–Organic Framework Based on Photocleavable Dianthracene-Based Ligand”, J. Am. Chem. Soc. 2018, 140, 10820-10828.open archive unige:108077 pdf full text [restricted access]

We have designed a rigid photocleavable dianthracene-based ligand that reacts with ytterbium as coordination metal ion for the creation of a class of tridimensional light-degradable metal–organic framework (MOF). We demonstrated that we can obtain a high level of control on the disassembly of the MOF formed with this ligand which can be triggered either through light irradiation or temperature increase. The reversible 4π-4π photodimerization is the intrinsic chemical mechanism ruling the ligand and MOF cleavage. In the fields of biology and medicine, MOFs have sparked a strong interest as highly porous vehicles for drug release but have only been explored so far through the passive leakage of their payloads. The designed light-degradable MOFs can potentially overcome this limitation and serve as prototypes for drug delivery and corresponding therapeutic applications.

132
Lee, K.; Famiglietti, M. L.; McMahon, A.; Wei, C.-H.; MacArthur, J. A. L.; Poux, S.; Breuza, L.; Bridge, A.; Cunningham, F.; Xenarios, I.; Lu, Z.; Xu, R. “Scaling up data curation using deep learning: An application to literature triage in genomic variation resources”, PLoS Comput. Biol. 2018, 14, e1006390.

Manually curating biomedical knowledge from publications is necessary to build a knowledge based service that provides highly precise and organized information to users. The process of retrieving relevant publications for curation, which is also known as document triage, is usually carried out by querying and reading articles in PubMed. However, this query-based method often obtains unsatisfactory precision and recall on the retrieved results, and it is difficult to manually generate optimal queries. To address this, we propose a machine-learning assisted triage method. We collect previously curated publications from two databases UniProtKB/Swiss-Prot and the NHGRI-EBI GWAS Catalog, and used them as a gold-standard dataset for training deep learning models based on convolutional neural networks. We then use the trained models to classify and rank new publications for curation. For evaluation, we apply our method to the real-world manual curation process of UniProtKB/Swiss-Prot and the GWAS Catalog. We demonstrate that our machine-assisted triage method outperforms the current query-based triage methods, improves efficiency, and enriches curated content. Our method achieves a precision 1.81 and 2.99 times higher than that obtained by the current query-based triage methods of UniProtKB/Swiss-Prot and the GWAS Catalog, respectively, without compromising recall. In fact, our method retrieves many additional relevant publications that the query-based method of UniProtKB/Swiss-Prot could not find. As these results show, our machine learning-based method can make the triage process more efficient and is being implemented in production so that human curators can focus on more challenging tasks to improve the quality of knowledge bases.

131
Daeden, A.; Gonzalez-Gaitan, M. “Endosomal Trafficking During Mitosis and Notch-Dependent Asymmetric Division”, In Endocytosis and Signaling”, Lamaze, C.; Prior, I. (Eds.), Collection “Progress in Molecular and Subcellular Biology” vol. 57, Springer, Cham 2018, p. 301-329.

Endocytosis is key in a number of cell events. In particular, its role during cell division has been a challenging question: while early studies examined whether endocytosis occurs during cell division, recent works show that, during division, cells do perform endocytosis actively. More importantly, during asymmetric cell division, endocytic pathways also control Notch signaling: endocytic vesicles regulate the presence, at the plasma membrane, of receptors and ligands at different levels between the two-daughter cells. Both early and late endocytic compartments have been shown to exert key regulatory controls by up-regulating or down-regulating Notch signaling in those cells. This biased Notch signaling enable finally cell fate assignation and specification which play a central role in development and physiology. In this chapter, we cover a number of significant works on endosomal trafficking evincing the importance of endocytosis in Notch-mediated cell fate specification during development.

130
Klinkert, K.; Levernier, N.; Gross, P.; Gentili, C.; von Tobel, L.; Pierron, M.; Busso, C.; Herrman, S.; Grill, S. W.; Kruse, K.; Gonczy, P. “Aurora A depletion reveals centrosome-independent polarization mechanism in C. elegans”, bioRxiv, Cell Biol. 2018, in press.

How living systems break symmetry in an organized manner is an important question in biology. In C. elegans zygotes, symmetry breaking normally occurs in the vicinity of centrosomes, resulting in anterior-directed cortical flows and establishment of a single posterior PAR-2 domain. Here, we report that zygotes depleted of the Aurora A kinase AIR-1 or of centrosomes establish two posterior domains, one at each pole. Using transgenic animals and microfabricated triangular chambers, we establish that such bipolarity occurs in a PAR-2- and curvature-dependent manner. Furthermore, we develop an integrated physical model of symmetry breaking, establishing that local PAR-dependent weakening of the actin cortex, together with mutual inhibition of anterior and posterior PAR proteins, provides a mechanism for self-organized PAR polarization without functional centrosomes in C. elegans.

129
Saad, M. M.; Michalet, S.; Fossou, R. K.; Putnik-Delić, M.; Crèvecoeur, M.; Meyer, J.; De Malézieux, C.; Hopfgartner, G.; Maksimovic, I.; Perret, X. “Loss of NifQ leads to accumulation of porphyrins and altered metal-homeostasis in nitrogen-fixing symbioses”, Mol. Plant-Microbe Interact. 2018, in press.

Symbiotic nitrogen fixation between legumes and rhizobia involves a coordinated expression of many plant and bacterial genes as well as finely tuned metabolic activities of micro- and macro-symbionts. In spite of such complex interactions, symbiotic proficiency remains a resilient process with host plants apparently capable of compensating for some deficiencies in rhizobia. What controls nodule homeostasis is still poorly understood and probably varies between plant species. In this respect, the promiscuous Sinorhizobium (Ensifer) fredii strain NGR234 has become a model to assess the relative contribution of single gene products to many symbioses. Here, we describe how a deletion in nifQ of NGR234 (strain NGRΔnifQ) makes nodules of Vigna unguiculata, Vigna radiata and Macroptilium atropurpureum but not of the mimisoid tree Leucaena leucocephala, purple red. This peculiar dark-nodule phenotype did not necessarily correlate with a decreased proficiency of NGRΔnifQ, but coincided with a twenty-fold or more accumulation of coproporphyrin III and uroporphyrin III in V. unguiculata nodules. Porphyrin accumulation was not restricted to plant cells infected with bacteroids but also extended to nodule cortex. Nodule metal-homeostasis was altered but not sufficiently to prevent assembly and functioning of nitrogenase. Although NifQ role in donating molybdenum during assembly of nitrogenase cofactor FeMo-co makes it essential in free-living diazotrophs, our results highlight NifQ dispensability in many legume species.

128
Palermo, G.; Cataldi, U.; Condello, A.; Caputo, R.; Bürgi, T.; Umeton, C.; De Luca, A. “Flexible thermo-plasmonics: an opto-mechanical control of the heat generated at the nanoscale”, Nanoscale 2018, 10, 16556-16561.

The opto-mechanical control of the heat generated by an amorphous arrangement of homogenously distributed gold nanoparticles (AuNPs), excited by an external laser source, is investigated. Application of a macroscopic mechanical strain to the biocompatible elastomeric tape supporting the particles leads to a nanoscale modification of their mutual inter-distance. The resulting strong variation of the particles near-field coupling gives rise to a macroscopic variation of the photogenerated heat. A fine control of the amount of generated heat is thus possible by stretching the initially isotropic sample of only few percents. Due to the anisotropy of the stretching procedure, the plasmon band shift and thus the heat generation results to be strongly polarization-dependent. A model of the system based on Mie Theory is implemented by using a finite element method. Under optical excitation, two configurations of AuNPs, representing the same cluster of particles at rest ad under stretching, show a relative increase of temperature that is in good quantitativen agreement with experimental data, if normalized to the number of involved particles. This system realizes for the first time an opto-mechanical control of the temperature at the nanoscale which holds promises for the development of optically-active thermal patches, usable for biomedical applications, and flexible platforms for microfluidics and lab-on-a-chip devices.

127
Homberg, A.; Brun, E.; Zinna, F.; Pascal, S.; Górecki, M.; Monnier, L.; Besnard, C.; Pescitelli, G.; Di Bari, L.; Lacour, J. “Combined reversible switching of ECD and quenching of CPL with chiral fluorescent macrocycles”, Chem. Sci. 2018, 9, 7043-7052.open archive unige:107800 pdf full text [free access]

Straightforward synthesis and resolution of a series of chiral fluorescent macrocycles are presented, together with their electronic circular dichroism (ECD), strong excimer fluorescence (EF, λ 300 to 650 nm) and allied highly circularly polarized luminescence (CPL, glum up to 1.7×10-2). The ECD, EF and CPL responses are strongly affected by the presence of metal ions (Na+, Ba2+) thanks to deep conformational changes. While ECD signals can be almost completely reversibly inverted upon the complexation/decomplexation of metal ions in a typical binary response, CPL signals are reversibly quenched concomitantly. The designed macrocycles display thus a remarkable combination of both +/− ECD and on/off CPL reversible switching.

126
Sattler, N.; Bosmani, C.; Barisch, C.; Guého, A.; Gopaldass, N.; Dias, M.; Leuba, F.; Bruckert, F.; Cosson, P.; Soldati, T. “Functions of the Dictyostelium LIMP-2/CD36 homologues in bacteria uptake, phagolysosome biogenesis and host cell defence.”, J. Cell Sci. 2018, 131, jcs218040.

Phagocytic cells take up, kill and digest microbes by a process called phagocytosis. To this end these cells bind the particle, rearrange their actin cytoskeleton, and orchestrate transport of digestive factors to the particle-containing phagosome. The mammalian lysosomal membrane protein LIMP-2 and CD36, members of the class B of scavenger receptors, play a crucial role in lysosomal enzyme trafficking and uptake of mycobacteria, respectively, and generally in host cell defences against intracellular pathogens. Here, we show that the Dictyostelium discoideum LIMP-2 homologue LmpA regulates phagocytosis and phagolysosome biogenesis. The lmpA knockdown mutant is highly affected in actin-dependent processes such as particle uptake, cellular spreading and motility. Additionally, the cells are severely impaired in phagosomal acidification and proteolysis, likely explaining the higher susceptibility to infection with the pathogenic bacterium Mycobacterium marinum, a close cousin of the human pathogen Mycobacterium tuberculosis Furthermore, we bring evidence that LmpB is a functional homologue of CD36 and specifically mediates uptake of mycobacteria. Altogether, these data indicate a role for LmpA and LmpB, ancestors of the LIMP-2/CD36 family, in lysosome biogenesis and host cell defence.

125
Gooding, J. J.; Mazur, A.; Merkx, M.; Kelley, S.; Tao, N.; Long, Y.-T.; Bakker, E.; Sailor, M. “Editorial - First Impact Factor for ACS Sensors – 5.711”, ACS Sens. 2018, 3, 1218-1219.

124
Mund, M.; van der Beek, J. A.; Deschamps, J.; Dmitrieff, S.; Hoess, P.; Monster, J. L.; Picco, A.; Nédélec, F.; Kaksonen, M.; Ries, J. “Systematic Nanoscale Analysis of Endocytosis Links Efficient Vesicle Formation to Patterned Actin Nucleation”, Cell 2018, 174, 884-896.e17.

Clathrin-mediated endocytosis is an essential cellular function in all eukaryotes that is driven by a self-assembled macromolecular machine of over 50 different proteins in tens to hundreds of copies. How these proteins are organized to produce endocytic vesicles with high precision and efficiency is not understood. Here, we developed high-throughput superresolution microscopy to reconstruct the nanoscale structural organization of 23 endocytic proteins from over 100,000 endocytic sites in yeast. We found that proteins assemble by radially ordered recruitment according to function. WASP family proteins form a circular nanoscale template on the membrane to spatially control actin nucleation during vesicle formation. Mathematical modeling of actin polymerization showed that this WASP nano-template optimizes force generation for membrane invagination and substantially increases the efficiency of endocytosis. Such nanoscale pre-patterning of actin nucleation may represent a general design principle for directional force generation in membrane remodeling processes such as during cell migration and division.

123
Banafsheh, M.; Wesolowski, T. A. “ERRATUM: Nonadditive kinetic potentials from inverted Kohn-Sham problem”, Int. J. Quantum Chem. 2019, in press.

The following article “Nonadditive kinetic potentials from inverted Kohn–Sham problem” by M Banafsheh and TA Wesolowski has been published in the Int. J. Quantum Chem. 2018;118:e25410, https://doi.org/10.1002/qua.25410. The publisher of the International Journal of Quantum Chemistry, Wiley, has been contacted by the lead author of this article to inform us that his laboratory has found a bug in the code used in the work that affects the reported potential near nuclei in Fig. 3 of this paper. No other data presented in the article is affected by this error. The International Journal of Quantum Chemistry is publishing this note in order to alert readers of the potential errors affecting the data displayed in Fig. 3. The lead author's lab is investigating the bug and reassessing the data presented in Fig 3, and this notice will be updated when a final outcome of the debugging process has been reached.

122
Kreten, F. H.; Hoffmann, C.; Riveline, D.; Kruse, K. “Active bundles of polar and bipolar filaments”, Phys. Rev. E 2018, 110, 012413.

Bundles of actin filaments and molecular motors of the myosin family are a common subcellular organizational motif. Typically, such bundles are under contractile stress resulting from interactions between the filaments and the motors. This holds in particular for contractile rings that appear in the late stages of cell division in animal cells and that cleave the mother into two daughter cells. It was recently shown that myosin organizes into regularly spaced clusters along rings in mammalian cells, whereas myosin clusters in fission yeast travel along the perimeter of actomyosin rings [Wollrab et al., Nat. Commun. 7, 11860 (2016)]. A mechanism based on the association of the structurally polar actin filaments into bipolar structures was shown to provide a common explanation for both observations. Here, we analyze the dynamics of this mechanism in detail. We find a rich phase diagram depending on the actomyosin interaction strength and the stability of the bipolar structures. The system can notably organize into traveling waves. Furthermore, we identify the nature of the bifurcations connecting the various patterns as parameters are changed. Finally, we report experimental patterns observed in cytokinetic rings in fission yeast and link them to solutions of our dynamic equations. Our analysis highlights the possible role played by local polarity sorting of actin filaments for the dynamics and functionality of actomyosin networks.

121
Buckley, C. M.; Heath, V. L.; Gueho, A.; Bosmani, C.; Knobloch, P.; Sikakana, P.; Personnic, N.; Dove, S. K.; Michell, R. H.; Meier, R.; Hilbi, H.; Soldati, T.; Insall, R. H.; King, J. “PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection”, bioRxiv, Cell Biol. 2018, in press.

By engulfing potentially harmful microbes, professional phagocytes are continually at risk from intracellular pathogens. To avoid becoming infected, the host must kill pathogens in the phagosome before they can escape or establish a survival niche. Here, we analyse the role of the phosphoinositide (PI) 5-kinase PIKfyve in phagosome maturation and killing, using the amoeba and model phagocyte Dictyostelium discoideum. PIKfyve plays important but poorly understood roles in vesicular trafficking by catalysing formation of the lipids phosphatidylinositol (3,5)-bisphosphate (PI(3,5)2) and phosphatidylinositol-5-phosphate (PI(5)P). Here we show that its activity is essential during early phagosome maturation in Dictyostelium. Disruption of PIKfyve inhibited delivery of both the vacuolar V-ATPase and proteases, dramatically reducing the ability of cells to acidify newly formed phagosomes and digest their contents. Consequently, PIKfyve- cells were unable to generate an effective antimicrobial environment and efficiently kill captured bacteria. Moreover, we demonstrate that cells lacking PIKfyve are more susceptible to infection by the intracellular pathogen Legionella pneumophila. We conclude that PIKfyve-catalysed phosphoinositide production plays a crucial and general role in ensuring early phagosomal maturation, protecting host cells from diverse pathogenic microbes.

120
Piguet, C.; Golesorkhi, B.; Guénée, L.; Nozary, H.; Fürstenberg, A.; Suffren, Y.; Eliseeva, S.; Petoud, S.; Hauser, A. “Thermodynamic Programming of Erbium(III) Coordination Complexes for Dual Visible/Near-Infrared Luminescence”, Chem. Eur. J. 2018, 24, 13158-13169.open archive unige:108196 pdf full text [restricted access]

Intrigued by the unexpected room‐temperature dual visible‐NIR luminescence observed for fast‐relaxing erbium complexes embedded in triple‐stranded helicates, this contribution explores a series of six tridentate N‐donor receptors L4‐L9 with variable aromaticities and alkyl substituents for extricating the stereo‐electronic requirements responsible for such scarce optical signatures. Detailed solid state (X‐ray diffraction, differential scanning calorimetry, optical spectroscopy) and solution (speciations and thermodynamic stabilities, spectrophotometry, NMR and optical spectroscopy) studies of mononuclear unsaturated [Er(Lk)2]3+ and saturated triple‐helical [Er(Lk)3]3+ model complexes reveal that the stereo‐electronic changes induced by the organic ligands affect inter‐ and intra‐molecular interactions to such an extent that (i) melting temperatures in solids, (ii) the affinity for trivalent erbium in solution, and (iii) optical properties in luminescent complexes can be rationally varied and controlled. With this toolkit in hand, mononuclear erbium complexes with low stabilities displaying only near‐infrared (NIR) emission can be transformed into molecular‐based dual Er‐centered visible/NIR emitters operating at room temperature in solids and in solutions.

119
Picco, A.; Kaksonen, M. “Quantitative imaging of clathrin-​mediated endocytosis”, Curr. Opin. Cell Biol. 2018, 53, 105-110.

Clathrin-​mediated endocytosis is a process by which eukaryotic cells bend a small region of their plasma membrane to form a transport vesicle that carries specific cargo mols. into the cell.  Endocytosis controls the compn. of the plasma membrane, imports nutrients and regulates many signalling pathways.  The roles of most of the proteins involved in endocytosis have been thoroughly characterised.  However, how these proteins cooperate in the cell to drive the endocytic process is not well understood.  Microscopy methods have been instrumental in describing the dynamics and the mol. mechanism of endocytosis.  Here, we will review the challenges and the recent advances in visualising the endocytic machinery and we will reflect on how the integration of current imaging technologies can lead us toward a quant. understanding of the mol. mechanisms of endocytosis.

118
McAlpine, J. B.; Chen, S.-N.; Kutateladze, A.; MacMillan, J. B.; Appendino, G.; Barison, A.; Beniddir, M. A.; Biavatti, M. W.; Bluml, S.; Boufridi, A.; Butler, M. S.; Capon, R. J.; Choi, Y. H.; Coppage, D.; Crews, P.; Crimmins, M. T.; Csete, M.; Dewapriya, P.; Egan, J. M.; Garson, M. J.; Genta-Jouve, G.; Gerwick, W. H.; Gross, H.; Harper, M. K.; Hermanto, P.; Hook, J. M.; Hunter, L.; Jeannerat, D.; Ji, N.-Y.; Johnson, T. A.; Kingston, D. G. I.; Koshino, H.; Lee, H.-W.; Lewin, G.; Li, J.; Linington, R. G.; Liu, M.; McPhail, K. L.; Molinski, T. F.; Moore, B. S.; Nam, J.-W.; Neupane, R. P.; Niemitz, M.; Nuzillard, J.-M.; Oberlies, N. H.; Ocampos, F. M. M.; Pan, G.; Quinn, R. J.; Reddy, D. S.; Renault, J.-H.; Rivera-Chávez, J.; Robien, W.; Saunders, C. M.; Schmidt, T. J.; Seger, C.; Shen, B.; Steinbeck, C.; Stuppner, H.; Sturm, S.; Taglialatela-Scafati, O.; Tantillo, D. J.; Verpoorte, R.; Wang, B.-G.; Williams, C. M.; Williams, P. G.; Wist, J.; Yue, J.-M.; Zhang, C.; Xu, Z.; Simmler, C.; Lankin, D. C.; Bisson, J.; Pauli, G. F. “The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research”, Nat. Prod. Rep. 2018, in press.

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

117
Maechler, F.; Allier, C.; Roux, A.; Tomba, C. “Curvature Dependent constraints drive remodeling of epithelia”, bioRxiv, Bioeng. 2018, in press.

Epithelial tissues are essential to keep a proper barrier for the organism. They usually have highly curved shapes, such as tubules or cysts. However, interplays between the environment and cell mechanical properties to set the shape are not known. In this study, we encapsulated two epithelial cell lineages, MDCK and J3B1A, into hollow alginate tubes and grew them under cylindrical confinement. Once formed, the epithelial MDCK layer detached from the alginate shell, while J3B1A layer remained adherent. Detachment resulted from contractile forces within cell layers that pulled cells away from the shell. We concluded that J3B1A cells have lower contractility than MDCK cells. As the pulling forces depend on the radius of the tube, we induced detachment of J3B1A cells by reducing the size of the hollow tube by two. Moreover, in bent tubes, detachment was more pronounced on the outer side of the turn, while extrusion occurred in the inner side, further highlighting the coupling between curvature and cell contractility.

116
Baghdasaryan, A.; Grillo, R.; Roy Bhattacharya, S.; Sharma, M.; Reginato, E.; Theraulaz, H.; Dolamic, I.; Dadras, M.; Rudaz, S.; Varesio, E.; Burgi, T. “Facile Synthesis, Size-Separation, Characterization, and Antimicrobial Properties of Thiolated Copper Clusters”, ACS Appl. Nano Mater. 2018, 1, 4258-4267.

Metal nanomaterials have attracted extensive attention in biological labelling and imaging due to their controllable physical and chemical properties. Recently, a lot of effort has been devoted to preparing various ultra-small and functional copper nanoclusters (CuNCs) with different emissions from blue to red, soluble both in organic and aqueous phases. Herein, a novel one- step synthetic method is proposed for the preparation of stable water-soluble glutathione (GSH) capped CuNCs. The resulting nanoclusters have a good dispersibility and stability in aqueous media. The stability was examined by several test experiments. The mass detection in ESI-HRMS mode allowed to ionize several doubly charged species with formula Cu5L6, Cu6L6, Cu7L6, Cu8L6 and Cu9L6 (L=C10H16N3O6S). The use of advanced separation techniques including liquid chromatography (HPLC), gel electrophoresis (PAGE) and capillary electrophoresis (CE) allowed the separation of several clusters, some of which are larger than Au25(GS)18, as shown by PAGE. To the best of our knowledge, this is the first report on successful size-separation of CuNCs. Moreover, the synthesized CuNCs show dose dependent antimicrobial effect. At lower cluster concentration the growth of bacteria is partially reduced. However, at higher concentrations, the bacterial growth is completely restricted.

115
Barisch, C.; Kalinina, V.; Lefrancois, L. H.; Appiah, J.; Soldati, T. “Think zinc: Role of zinc poisoning in the intraphagosomal killing of bacteria by the amoeba”, bioRxiv, Cell Biol. 2018, in press.

Professional phagocytes have developed an extensive repertoire of autonomous immunity strategies to ensure killing of bacteria. Besides phagosome acidification and the generation of reactive oxygen species, deprivation of nutrients and the lumenal accumulation of toxic metals are essential to kill ingested bacteria or inhibit growth of intracellular pathogens. We use the soil amoeba Dictyostelium discoideum, a professional phagocyte that digests bacteria for nutritional purposes, to decipher the role of zinc poisoning during phagocytosis of non-pathogenic bacteria and visualize the temporal and spatial dynamics of compartmentalized, free zinc using fluorescent probes. Immediately after particle uptake, zinc is delivered to phagosomes by fusion with 'zincosomes' of endosomal origin, but also by the action of one or more zinc transporters. We localize the four Dictyostelium ZnT transporters to endosomes, the contractile vacuole and the Golgi apparatus, and study the impact of znt knockouts on zinc homeostasis. Finally, we show that zinc is delivered into the lumen of Mycobacterium smegmatis-containing vacuoles, and that Escherichia coli deficient in the zinc efflux P1B-type ATPase ZntA is killed faster than wild type bacteria.

114
Benz, S.; Besnard, C.; Matile, S. “Chalcogen-Bonding Catalysis: From Neutral to Cationic Benzodiselenazole Scaffolds”, Helv. Chim. Acta 2018, 101, e1800075.open archive unige:106518 pdf full text [restricted access]

Benzodiselenazoles (BDS) are emerging as privileged structures for chalcogen‐bonding catalysis in the focal point of conformationally immobilized σ holes on strong selenium donors in a neutral scaffold. Whereas much attention has been devoted to work out the advantages of selenium compared to the less polarizable sulfur donors, high expectations concerning bidentate, rigid, and neutral scaffolds have been generated with little experimental support. Here we report design, synthesis and evaluation of the necessary catalysts to confirm that i) bidentate BDS are more effective than their monodentate analogs, ii) conformationally immobilized scaffolds are more effective than more flexible ones, iii) cationic BDS scaffolds are more effective than neutral ones, and iv) in dicationic‐bidentate BDS, contributions from chalcogen‐bonding dominate possible contributions from ion‐pairing catalysis. These conclusions result from rate enhancements found for a Ritter‐type anion‐binding reaction and an X‐ray crystal structure of dicationic BDS with a triflate anion bound with highest precision in the focal point of the σ holes.

113
Ideses, Y.; Erukhimovitch, V.; Brand, R.; Jourdain, D.; Hernandez, J. S.; Gabinet, U. R.; Safran, S. A.; Kruse, K.; Bernheim-Groswasser, A. “Spontaneous buckling of contractile poroelastic actomyosin sheets”, Nat. Commun. 2018, 9, 2461.

Shape transitions in developing organisms can be driven by active stresses, notably, active contractility generated by myosin motors. The mechanisms generating tissue folding are typically studied in epithelia. There, the interaction between cells is also coupled to an elastic substrate, presenting a major difficulty for studying contraction induced folding. Here we study the contraction and buckling of active, initially homogeneous, thin elastic actomyosin networks isolated from bounding surfaces. The network behaves as a poroelastic material, where a flow of fluid is generated during contraction. Contraction starts at the system boundaries, proceeds into the bulk, and eventually leads to spontaneous buckling of the sheet at the periphery. The buckling instability resulted from system self-organization and from the spontaneous emergence of density gradients driven by the active contractility. The buckling wavelength increases linearly with sheet thickness. Our system offers a well-controlled way to study mechanically induced, spontaneous shape transitions in active matter.

112
Naim, A.; Bouhadja, Y.; Cortijo, M.; Duverger-Nédellec, E.; Flack, H. D.; Freysz, E.; Guionneau, P.; Iazzolino, A.; Ould Hamouda, A.; Rosa, P.; Stefańczyk, O.; Valentín-Pérez, .; Zeggar, M. “Design and Study of Structural Linear and Nonlinear Optical Properties of Chiral [Fe(phen)3]2+ Complexes”, Inorg. Chem. 2018, 57, 14501-14512.

The dependence of nonlinear optical properties upon the spin state in molecular switches is still an unexplored area. Chiral [Fe(phen)3]2+ complexes are excellent candidates for those studies because they are expected to show nonlinear optical properties of interest and at the same time show photoconversion to a short-lived metastable high-Spin state by ultrafast optical pumping. Herein, we present the synthesis, crystallographic, and spectroscopic comparison of chiral [Fe(phen)3]2+ complexes obtained with chiral anions, a new lipophilic derivative of the D2-symmetric (As2(tartrate)2)2–, and D3-symmetric tris(catechol)phosphate(V) (TRISCAT), tris(catechol)arsenate(V) (TRISCAS), and 3,4,5,6-tetrachlorocatechol phosphate(V) (TRISPHAT). Complexes [Fe(phen)3](rac-TRISCAT)2 (2) and [Fe(phen)3](X-TRISCAS)2 (X = rac (3), Δ (4), Λ (5)) were found to be isomorphous in the R32 Sohncke space group with twinning by inversion correlated with the starting chiral anion optical purity. The structures show the [Fe(phen)3]2+ complex interacting strongly along its 3-fold axis with two anions. Only the structure of a [Fe(phen)3](rac-TRISPHAT)2 solvate (6) could be obtained, which showed no particular anion/cation interaction contrary to what was observed previously in solution. The [Fe(phen)3](X-As2(tartrate)2) (X = Δ (7), Λ (8), and racemic mixture (9)) crystallizes in enantiomorphic space groups P3121/P3221 with the same solid-state packing. Dichroic electronic absorption studies evidenced racemization for all chiral complexes in solution due to ion pair dissociation, whereas the asymmetric induction is conserved in the solid state in KBr pellets. We evidenced on chiral complexes 4 and 5 strong nonlinear second harmonic generation, the intensity of which could be correlated with the complex electronic absorption.

111
Humeniuk, H. V.; Rosspeintner, A.; Licari, G.; Kilin, V.; Bonacina, L.; Vauthey, E.; Sakai, N.; Matile, S. “White-Fluorescent Dual-Emission Mechanosensitive Membrane Probes that Function by Bending Rather than Twisting”, Angew. Chem. Int. Ed. 2018, 57, 10559-10563.open archive unige:107017 pdf full text [free access]

Bent N,N′‐diphenyl‐dihydrodibenzo[a,c]phenazine amphiphiles are introduced as mechanosensitive membrane probes that operate by an unprecedented mechanism, namely, unbending in the excited state as opposed to the previously reported untwisting in the ground and twisting in the excited state. Their dual emission from bent or “closed” and planarized or “open” excited states is shown to discriminate between micelles in water and monomers in solid‐ordered (So), liquid‐disordered (Ld) and bulk membranes. The dual‐emission spectra cover enough of the visible range to produce vesicles that emit white light with ratiometrically encoded information. Strategies to improve the bent mechanophores with expanded π systems and auxochromes are reported, and compatibility with imaging of membrane domains in giant unilamellar vesicles by two‐photon excitation fluorescence (TPEF) microscopy is demonstrated.

110
Zech, A.; Ricardi, N.; Prager, S.; Dreuw, A.; Wesolowski, T. A. “Benchmark of excitation energy shifts from Frozen-Density Embedding Theory: introduction of a density-overlap based applicability threshold”, J. Chem. Theory Comput. 2018, 14, 4028-4040.

We present a thorough investigation of the errors in results obtained with the combination of Frozen-Density Embedding Theory and the Algebraic Diagrammatic Construction Scheme for the polarization propagator of second order (FDE-ADC(2)). The study was carried out on a set of 52 intermolecular complexes with varying interaction strength, each consisting of a chromophore of fundamental interest and a few small molecules in its environment. The errors emerging in Frozen-Density Embedding Theory based methods originate from: (a) the solver of the quantum many body problem used to obtain the embedded wavefunction (Ψemb), (b) the approximation for the explicit density functional for the embedding potential, and (c) the choice of the density representing the environment (ρB(r)). The present work provides a comprehensive analysis of the errors in the excitation energies based on the last two factors. Furthermore, a density-overlap based parameter is proposed to be used as an a priori criterion of applicability.

109
Jarolimova, Z.; Han, T.; Mattinen, U.; Bobacka, J.; Bakker, E. “Capacitive Model for Coulometric Readout of Ion-Selective Electrodes”, Anal. Chem. 2018, 90, 8700-8707.

We present here a capacitive model for the coulometric signal transduction readout of solid-contact ion-selective membrane electrodes (SC-ISE) with a conducting polymer (CP) as an intermediate layer for the detection of anions. The capacitive model correlates well with experimental data obtained for chloride-selective SC-ISE utilizing poly(3,4-ethylenedioxythiophene) (PEDOT) doped with chloride as the ion-to-electron transducer. Additionally, Prussian blue is used as a simple sodium capacitor to further demonstrate the role of the transduction layer. The influence of different thicknesses of PEDOT as a conducting polymer transducer, different thicknesses of the overlaying ion-selective membranes deposited by drop casting and spin coating, and differ-ent compositions of the chloride-selective membrane are explored. The responses are evaluated in terms of current–time, charge–time and charge–chloride activity relationships. The utility of the sensor with coulometric readout is illustrated by the monitoring of very small concentration changes in solution.

108
Melero, A.; Chiaruttini, N.; Karashima, T.; Riezman, I.; Funato, K.; Barlowe, C.; Riezman, H.; Roux, A. “Lysophospholipids Facilitate COPII Vesicle Formation”, Curr. Biol. 2018, 28, 1950-1958.e6.

Coat protein complex II (COPII) proteins form vesicles from the endoplasmic reticulum to export cargo molecules to the Golgi apparatus. Among the many proteins involved in this process, Sec12 is a key regulator, functioning as the guanosine diphosphate (GDP) exchange factor for Sar1p, the small guanosine triphosphatase (GTPase) that initiates COPII assembly. Here we show that overexpression of phospholipase B3 in the thermosensitive sec12-4 mutant partially restores growth and protein transport at non-permissive temperatures. Lipidomics analyses of these cells show a higher content of lysophosphatidylinositol (lysoPI), consistent with the lipid specificity of PLB3. Furthermore, we show that lysoPI is specifically enriched in COPII vesicles isolated from in vitro budding assays. As these results suggested that lysophospholipids could facilitate budding under conditions of defective COPII coat dynamics, we reconstituted COPII binding onto giant liposomes with purified proteins and showed that lysoPI decreases membrane rigidity and enhances COPII recruitment to liposomes. Our results support a mechanical facilitation of COPII budding by lysophospholipids.

107
Veciana, J.; Ardizzone, A.; Blasi, D.; Grimaldi, N.; Sala, S.; Ratera, I.; Vona, D.; Rosspeintner, A.; Punzi, A.; Altamura, E.; Vauthey, E.; Farinola, G. M.; Ventosa, N. “Highly Stable and Red-Emitting Nanovesicles Incorporating Lipophilic Diketopyrrolopyrroles for Cell Imaging”, Chem. Eur. J. 2018, 24, 11386-11392.

Diketopyrrolopyrroles (DPPs) have recently attracted large interest as highly bright and photostable red‐emitting molecules. However, their tendency to form non‐fluorescent aggregates in water via the so‐called Aggregation Caused Quenching (ACQ) effect is a major issue that limits their application under the microscope. In this work, two DPP molecules have been incorporated in the membrane of highly stable and water‐soluble Quatsomes (QS, nanovesicles made by surfactants and sterols), allowing their nanostructuration in water limiting at the same time the ACQ effect. The obtained fluorescent organic nanoparticles (FONs) showed superior structural homogeneity along with long‐time colloidal and optical stability. A thorough one‐ (1P) and two‐photon (2P) fluorescence characterization revealed the promising photophysical features of these fluorescent nanovesicles, which showed a high 1P and 2P brightness. Finally, the fluorescent QSs were used for the in vitro bioimaging of Saos‐2 osteosarcoma cell lines, demonstrating their potential as nanomaterials for bioimaging applications.

106
Sels, A.; Salassa, G.; Cousin, F.; Lee, L.-T.; Bürgi, T. “Covalently bonded multimers of Au25(SBut)18 as a conjugated system”, Nanoscale 2018, 10, 12754-12762.

Aromatic dithiol linkers were used to prepare aggregates of Au25(SR)18 clusters (SR: thiolate) via ligand exchange reactions. Fractions of different aggregate sizes were separated by size exclusion chromatography (SEC). The aggregates were characterized by UV-vis absorption spectroscopy, matrix assisted laser desorption ionization (MALDI) mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy (including diffusion-ordered spectroscopy, DOSY) and small angle X-ray scattering (SAXS). At 2:1 cluster: dithiol ratio small aggregates were formed (dimers, trimers) but also larger aggregates consisting of 10-20 Au25 clusters, according to DOSY, besides unreacted (monomeric) Au25(SR)18. MALDI mass spectrometry shows signals consistent with dimers and trimers (doubly charged). The SAXS curves for the small aggregates can be well fitted by a pearl-necklace model. For the bigger aggregates the SAXS curves evidence a characteristic separation distance between the clusters within the aggregates, which is imposed by the length of the linker. The SAXS curves of these larger aggregates can be well fitted with a core-shell sphere model with a sticky hard-sphere structure factor, in agreement with closely packed aggregates. The absorption spectra of smaller aggregates resemble the one of individual Au25(SR)18 clusters, however, and most importantly, the larger aggregates show completely different, less structured spectra with a new band emerging at 840 nm. We assign this drastic change of the absorption spectra and the new band to the electronic coupling between the clusters through the all aromatic linker. In accordance with this view, aggregates formed with a linker containing methylene groups, thus breaking conjugation do not show the band at 840 nm. By addition of monothiols to the larger aggregates their size can be reduced through an “unlinking” reaction. This reaction also affects the band at 840 nm, which moves to higher energy when reducing the aggregate size, as would be expected within a particle in a box model. The electronic coupling between the clusters through the linker is the basis for future applications in nanoelectronics.

105
Picco, A.; Kukulski, W.; Manenschijn, H. E.; Specht, T.; Briggs, J. A. G.; Kaksonen, M.; Lemmon, S. “The contributions of the actin machinery to endocytic membrane bending and vesicle formation”, Mol. Biol. Cell 2018, 29, 1346-1358.

Branched and cross-linked actin networks mediate cellular processes that move and shape membranes. To understand how actin contributes during the different stages of endocytic membrane reshaping, we analyzed deletion mutants of yeast actin network components using a hybrid imaging approach that combines live imaging with correlative microscopy. We could thus temporally dissect the effects of different actin network perturbations, revealing distinct stages of actin-based membrane reshaping. Our data show that initiation of membrane bending requires the actin network to be physically linked to the plasma membrane and to be optimally cross-linked. Once initiated, the membrane invagination process is driven by nucleation and polymerization of new actin filaments, independent of the degree of cross-linking and unaffected by a surplus of actin network components. A key transition occurs 2 s before scission, when the filament nucleation rate drops. From that time point on, invagination growth and vesicle scission are driven by an expansion of the actin network without a proportional increase of net actin amounts. The expansion is sensitive to the amount of filamentous actin and its cross-linking. Our results suggest that the mechanism by which actin reshapes the membrane changes during the progress of endocytosis, possibly adapting to varying force requirements.

104
Lopez-Jimenez, A. T.; Cardenal Munoz, E.; Leuba, F.; Gerstenmaier, L.; Hagedorn, M.; King, J. S.; Soldati, T. “ESCRT and autophagy cooperate to repair ESX-1-dependent damage to the Mycobacterium-containing vacuole”, bioRxiv, Microbiol. 2018, in press.

Phagocytes capture invader microbes within the bactericidal phagosome. Some pathogens subvert killing by damaging and escaping from this compartment. To prevent and fight bacterial escape, cells contain and repair the membrane damage, or finally eliminate the cytosolic escapees. All eukaryotic cells engage highly conserved mechanisms to ensure integrity of membranes in a multitude of physiological and pathological situations, including the Endosomal Sorting Complex Required for Transport (ESCRT) and autophagy machineries. In Dictyostelium discoideum, recruitment of the ESCRT-III protein Snf7/Chmp4/Vps32 and the ATPase Vps4 to sites of membrane repair relies on the ESCRT-I component Tsg101 and occurs in absence of Ca2+. The ESX-1 dependent membrane perforations produced by the pathogen Mycobacterium marinum separately engage both ESCRT and autophagy. In absence of Tsg101, M. marinum escapes earlier to the cytosol, where it is restricted by xenophagy. We propose that ESCRT has an evolutionary conserved function in containing intracellular pathogens in intact compartments.

103
Zdrachek, E.; Bakker, E. “Electrochemically Switchable Polymeric Membrane Ion-Selective Electrodes”, Anal. Chem. 2018, 90, 7591-7599.

We present here for the first time a solid contact ion-selective electrode suitable for the simultaneous sensing of cations (tetrabutylammonium) and anions (hexafluorophosphate), achieved by electrochemical switching. The membrane is based on a thin plasticized polyurethane membrane deposited on poly(3-octylthiophene) (POT) and contains a cation-exchanger and lipophilic electrolyte (ETH 500). The cation-exchanger is initially in excess, the ion-selective electrode exhibits an initial potentiometric response to cations. During an oxidative current pulse, POT is converted into POT+, which results in the expulsion of cations from the membrane followed by the extraction of anions from the sample solution to fulfil the electroneutrality condition. This creates a defined excess of lipophilic cation in the membrane, resulting in a potentiometric anion response. A reductive current pulse restores the original cation response by triggering the conversion of POT+ back into POT, which is accompanied by the expulsion of anions from the membrane and the extraction of cations from the sample solution. Various current pulse magnitudes and durations are explored, and the best results in terms of response slope values and signal stability were observed with oxidation current pulse of 140 A cm-2 applied for 8 s and reduction current pulse of –71 A cm-2 applied for 8 s.

102
Liu, Y.; Fiorito, D.; Mazet, C. “Copper-Catalyzed Enantioselective 1,2-Borylation of 1,3-Dienes”, Chem. Sci. 2018, 9, 5284-5288.open archive unige:105717 pdf full text [free access]

A highly enantioselective Cu-catalyzed borylation of 2-substituted 1,3-dienes is reported. The use of a chiral phosphanamine ligand is essential in achieving high chemo-, regio-, diastereo- and enantioselectivity. It provides access to a variety of homoallylic boronates in consistently high yield and enantiomeric excess with 2-aryl and 2-heteroaryl 1,3-dienes as well as sterically demanding 2-alkyl 1,3-dienes. Preliminary investigations based on a non-linear effect study point to a mechanism involving more than one metal center.

101
López-Andarias, J.; Bauzá, A.; Sakai, N.; Frontera, A.; Matile, S. “Remote Control of Anion-π Catalysis on Fullerene-Centered Catalytic Triads”, Angew. Chem. Int. Ed. 2018, 57, 10883-10887.open archive unige:107049 pdf full text [free access]

The design, synthesis and evaluation of catalytic triads composed of a central C60 fullerene with an amine base on one side and polarizability enhancers on the other side are reported. According to an enolate addition benchmark reaction, fullerene–fullerene–amine triads display the highest selectivity in anion–π catalysis observed so far, whereas NDI–fullerene–amine triads are not much better than fullerene–amine controls (NDI=naphthalenediimide). These large differences in activity are in conflict with the small differences in intrinsic π acidity, that is, LUMO energy levels and π holes on the central fullerene. However, they are in agreement with the high polarizability of fullerene–fullerene–amine triads. Activation and deactivation of the fullerene‐centered triads by intercalators and computational data on anion binding further indicate that for functional relevance, intrinsic π acidity is less important than induced π acidity, that is, the size of the oriented macrodipole of polarizable π systems that emerges only in response to the interaction with anions and anionic transition states. The resulting transformation is thus self‐induced, the anionic intermediates and transition states create their own anion–π catalyst.

100
Jansod, S.; Cuartero, M.; Cherubini, T.; Bakker, E. “Colorimetric Readout for Potentiometric Sensors with Closed Bipolar Electrodes”, Anal. Chem. 2018, 90, 6376-6379.

We present here a general strategy to translate potential change at a potentiometric probe into a tunable color readout. It is achieved with a closed bipolar electrode where the ion-selective component is confined to one end of the electrode while color is generated at the opposite pole, allowing one to physically separate the detection compartment from the sample. An electrical potential is imposed across the bipolar electrode by solution contact such that the potentiometric signal change at the sample side modulates the potential at the detection side. This triggers the turnover of a redox indi-cator in the thin detection layer until a new equilibrium state is established. The approach is demonstrated in separate experiments with a chloride responsive Ag/AgCl element and a liquid membrane based calcium-selective membrane electrode, using the redox indicator ferroin in the detection compartment. The principle can be readily extended to other ion detection materials and optical readout principles.

99
Okamoto, Y.; Kojima, R.; Schwizer, F.; Bartolami, E.; Heinisch, T.; Matile, S.; Fussenegger, M.; Ward, T. R. “A Cell-Penetrating Artificial Metalloenzyme Regulates a Gene Switch in a Designer Mammalian Cell”, Nat. Commun. 2018, 9, 1943.open archive unige:105117 pdf full text [free access]

Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone. This bioorthogonal reaction causes the upregulation of a gene circuit, which in turn leads to the expression of a nanoluc-luciferase. Relying on the biotin–streptavidin technology, variation of the biotinylated ruthenium complex: the biotinylated cell-penetrating poly(disulfide) ratio can be combined with point mutations on streptavidin to optimize the catalytic uncaging of an allyl-carbamate-protected thyroid hormone triiodothyronine. These results demonstrate that artificial metalloenzymes offer highly modular tools to perform bioorthogonal catalysis in live HEK cells.

98
Pearson, S.; Pavlovic, M.; Augé, T.; Torregrossa, V.; Szilagyi, I.; D'Agosto, F.; Lansalot, M.; Bourgeat-Lami, E.; Prévot, V. “Controlling the Morphology of Film-Forming, Nanocomposite Latexes Containing Layered Double Hydroxide by RAFT-Mediated Emulsion Polymerization”, Macromolecules 2018, 51, 3953-3966.

Stable nanocomposite latexes with sandwich, encapsulated, or armored morphology were produced by starved-feed emulsion polymerization in the presence of layered double hydroxide (LDH) nanoparticles. Four statistical copolymers of acrylic acid (AA) and n-butyl acrylate (BA) were adsorbed on the LDH surface, and a film-forming methyl acrylate (MA)/BA (8:2 mass/mass) monomer feed was chosen to facilitate subsequent film formation under ambient conditions. P(AA17.5-co-BA17.5)-R (R = RAFT function) produced the sandwich morphology, while P(AA7.5-co-BA7.5)-R gave the encapsulated morphology, which is remarkable given that nonencapsulated morphologies are normally considered to be the preferred equilibrium structures for nanocomposite particles. Adsorption behavior and monomer conversion profiles were very similar for the two systems, and we tentatively ascribe the morphological difference to the higher density of RAFT functions in the P(AA7.5-co-BA7.5)-R system. A RAFT-free analogue produced armored latexes, highlighting the importance of the RAFT function for promoting growth of the polymer shell from the nanoparticle surface.

97
Rouster, P.; Pavlovic, M.; Sáringer, S.; Szilagyi, I. “Functionalized Titania Nanosheet Dispersions of Peroxidase Activity”, J. Phys. Chem. C 2018, 122, 11455-11463.

Nanocomposites of titania nanosheets (TNS), horseradish peroxidase (HRP) and poly(diallyldimethylammonium chloride) (PDADMAC) were prepared and their colloidal and functional stabilities were assessed. HRP quantitatively adsorbed on bare TNS and the adsorption process did not affect the charging and aggregation behavior of the colloidal system. The obtained TNS-HRP composite was functionalized by PDADMAC to stabilize the enzyme on the surface and to maintain good colloidal stability. Depending on the PDADMAC dose applied, its adsorption on TNS-HRP led to charge reversal of the particles from negative to positive. The formation of a saturated polyelectrolyte layer on the TNS-HRP (TNS-HRP-PDADMAC) gave rise to highly stable colloids, especially the resistance against salt-induced aggregation was excellent. The enzymatic activity of different systems was investigated as a function of the pH of the medium and over time. The results indicated that HRP remained enzymatically active upon immobilization, in addition, the pH range of application broadened compared to its native form. The developed TNS-HRP-PDADMAC system can thus be used in a wider pH range and possesses the advantages of a heterogeneous catalysts compared to the bare enzyme.

96
Thajee, K.; Wang, L.; Grudpan, K.; Bakker, E. “Colorimetric ionophore-based coextraction titrimetry of potassium ions”, Anal. Chim. Acta 2018, 1029, 37-43.

Potassium ion concentration can be successfully determined volumetrically by moving the titration from a homogeneous phase to a two phase solvent system. This is because potassium can be readily complexed in a selective and thermodynamically stable manner by ionophores such as valinomycin. Previous work demonstrated the successful titration of potassium by ion-exchange into an organic phase containing valinomycin, but the sample itself served as titrant, which is not sufficiently practical for routine applications. This problem is overcome here by a co-extraction based approach, with the sodium salt of the water soluble lipophilic anion tetraphenylborate as titrant. The extraction of potassium tetraphenylborate must be preferred over that of the hydrogen ion-tetraphenylborate pair, which is used to indicate the endpoint by the presence of a lipophilic indicator in the organic phase. This is controlled by the sample pH, which for the conditions chosen here is around 7 for optimal sharpness and accuracy of the endpoint. The approach is demonstrated in a colorimetric detection approach, by use of a tethered digital camera and subsequent automated analysis of the resulting image files. The potassium analysis in a variety of samples is successfully demonstrated, including blood serum.

95
Ortuso, R. D.; Sugihara, K. “Detailed Study on the Failure of the Wedge Calibration Method at Nanonewton Setpoints for Friction Force Microscopy”, J. Phys. Chem. C 2018, 122, 11464-11474.

The wedge calibration method is the most popular calibration technique in friction force microcopy for converting raw lateral laser deflection signals (in volt) into forces (in newton). Recent trends in nanotribology demand the use of the method at nanonewton (nN) force ranges, however, this method fails at these small forces. The objective of the present work is to identify the reason why the conventional wedge calibration method fails at nN force ranges. We found that the equation used in the model in this method amplifies experimental errors by orders of magnitude only at small setpoints purely due to its mathematical expression. This low tolerance against experimental errors in nanonewton force ranges is the reason for the failure. We identified that the condition, under which the method operates accurately, is adhesion << setpoint. Discovery of this operation range (adhesion << setpoint) is important, because performing the calibration under other conditions can wrongly calibrate the system by orders of magnitude.

94
Strakova, K.; Soleimanpour, S.; Diez-Castellnou, M.; Sakai, N.; Matile, S. “Ganglioside-Selective Mechanosensitive Fluorescent Membrane Probes”, Helv. Chim. Acta 2018, 101, e1800019.open archive unige:104622 pdf full text [restricted access]

The development of fluorescent probes to image forces in cells is an important challenge in chemistry and biology. Planarizable push‐pull probes have been introduced recently for this purpose. To provide most valuable information on forces in complex systems, these mechanosensitive ‘flipper’ probes will have to be localized by molecular recognition of targets of interest. Here we report fluorescent flippers that selectively recognize gangliosides on the surface of lipid bilayer membranes by formation of dynamic covalent boronate esters. The original flipper probes were equipped with 2‐fluorophenyl boronic acids and benzoboroxoles using consecutive triazole and oxime ligation. Evaluation was done in large unilamellar vesicles composed of EYPC/SM/CL/GM 40:40‐x:20:x to obtain mixed membranes with separate liquid‐disordered (Ld) and ganglioside (GM) containing liquid‐ordered (Lo) domains. With increasing GM concentration, fluorescence intensities increased and excitation maximum shifted to the red. Deconvolution of the spectra confirmed that these changes originate from a migration of the flipper probes from Ld to Lo domains upon binding to the gangliosides and thus the planarization in the more ordered environment. Control mechanophores without boronic acids failed to show the same response, and fructose partially inhibited the ganglioside sensitivity. These results demonstrate that it is possible to selectively accumulate mechanosensitive flipper probes in Lo domains and, more generally, that probe localization in complex membranes is possible and matters.

93
Sherin, P. S.; Tsentalovich, Y. P.; Vauthey, E.; Benassi, E. “Ultrafast excited state decay of natural UV filters: from intermolecular hydrogen bonds to conical intersection”, Phys. Chem. Chem. Phys. 2018, 20, 15074-15085.

Kynurenines (KNs) are natural UV filters of the human eye lens, protecting the eye tissues from the solar UV radiation. Key points of their effective protection are the intramolecular charge transfer (ICT) in the excited state and the fast dissipation of absorbed light energy into heat via the intermolecular H-bonds. Herein we report that the introduction of unsaturated double bond in the amino acid side chain, operating as ICT-enhancing electron donor group, drastically accelerates the internal conversion (IC) due to a conical intersection (CI) between the potential energy surfaces of excited and ground states. Our photophysical study of a deaminated KN (carboxyketoalkene, CKA), an intrinsic product of KN thermal decomposition, demonstrates an unusually fast excited state decay in a broad range of solvents of different polarity and proticity. The detailed analysis of interactions in the excited state by different computational techniques revealed that the changes in molecular structure – the twist of carbonyl group from the plane of aromatic ring followed by the formation of two mutually orthogonal conjugated substructures – are responsible for the CI of the excited and ground state potential energy surfaces. Intermolecular H-bonds facilitate the transition to CI, but do not play a crucial role in the fast decay of the excited state. An extremely fast and efficient IC in CKA opens the way for the design of new types of organic UV filters and their applications in material sciences, cosmetics and medicine.

92
Kozhuharov, S.; Radiom, M.; Maroni, P.; Borkovec, M. “Persistence Length of Poly(vinyl amine): Quantitative Image Analysis versus Single Molecule Force Response”, Macromolecules 2018, 51, 3632-3639.

Single molecules of poly(vinyl amine) are analyzed in the adsorbed state by atomic force microscopy (AFM) in two different ways. First, high-resolution images of individual adsorbed polymers were recorded in monovalent electrolyte solutions. The backbone of the imaged polymers was digitized, and the directional correlation function and internal mean-square end-to-end distance were evaluated. These quantities were analyzed with the wormlike chain (WLC) model, and the persistence length was extracted. Second, individual polymer chains were picked up from the surface, and their force–extension behavior was recorded in the same electrolyte solutions. These force profiles were also interpreted in terms of the WLC model, whereby the elastic contribution was also considered. Both techniques yield the persistence length of the polymer. From imaging one obtains a persistence length of about 1.6 nm, while the force experiments yield a value around 0.51 nm. We suspect that the force experiments reflect the intrinsic part of the persistence length, while the imaging experiments yield the persistence length including the electrostatic part.

91
Kündig, E. P. “Editorial”, CHIMIA 2018, 72, 273.

90
Hernández Delgado, I.; Pascal, S.; Besnard, C.; Voci, S.; Bouffier, L.; Sojic, N.; Lacour, J. “C-Functionalized Cationic Diazaoxatriangulenes: Late-Stage Synthesis and Tuning of Physicochemical Properties”, Chem. Eur. J. 2018, 24, 10186-10195.open archive unige:106840 pdf full text [free access]

A series of nine C‐functionalized cationic diazaoxa triangulene dyes (DAOTA) has been successfully synthesized and fully characterized, including X‐ray structural analysis of four derivatives. The introduction of electron‐withdrawing or donating functions enables a tuning of both electrochemical and photochemical properties with, for instance, two consecutive (reversible) reductions or oxidations observed for nitro or amino derivatives, respectively. The substituents impacted also the optical properties, with absorption maxima varying from 529 to 640 nm and fluorescence being shifted from the yellow to the red range, up to 656 nm.

89
Saarbach, J.; Lindberg, E.; Winssinger, N. “Ruthenium-based Photocatalysis in Templated Reactions”, CHIMIA 2018, 72, 207-211.open archive unige:105650 pdf full text [free access]

Templated reactions proceed by bringing reagents in close proximity through their interaction with a template thus raising their effective concentrations. Templated reactions empower chemists to perform reactions at low concentrations in complex environments. Herein, we discuss our work on templated reactions leveraged on ruthenium photocatalysis. Over the past five years, we have used this reaction to uncage reporter molecules and sense or image nucleic acids or proteins of interest. The ruthenium photocatalysis chemistry has proven to be extremely robust and compatible with complex biological environments.

88
Aguilar Hidalgo, D.; Werner, S.; Wartlick, O.; González-Gaitán, M.; Friedrich, B.; Jülicher, F. “Critical Point in Self-Organized Tissue Growth”, Phys. Rev. Lett. 2018, 120, 198102.

We present a theory of pattern formation in growing domains inspired by biological examples of tissue development. Gradients of signaling molecules regulate growth, while growth changes these graded chemical patterns by dilution and advection. We identify a critical point of this feedback dynamics, which is characterized by spatially homogeneous growth and proportional scaling of patterns with tissue length. We apply this theory to the biological model system of the developing wing of the fruit fly \textit{Drosophila melanogaster} and quantitatively identify signatures of the critical point.

87
Salassa, G.; Bürgi, T. “NMR spectroscopy: a potent tool for studying monolayer-protected metal nanoclusters”, Nanoscale Horiz. 2018, 3, 457-463.

Monolayer protected metal clusters are currently in the focus of interest both for fundamental reasons and for their use in possible applications. In the past two decades the interest was mainly focused on the evolution of the structrue and properties as the clusters grow in size. The field profited tremednously from mass spectrometry and X-ray structure analysis. For future applications of monolayer protected clusters other properties like the interaction of the clusters with molecules will become important. Also, it has been realized more recently that these monolayer protected clusters are rather dynamic, which calls for techniques able to address this property. By discussing selected examples we demonstrate the power of nuclear magnetic resonance (NMR) spectroscopy to study the structure and the dynamics of clusters and their interacion with molecules (sensing). NMR spectroscopy is an abundant technique and has become very sophisticated. Future work in the field of monolayer protected clusters may greatly profit from this. We believe that NMR spectroscopy, although not yet used much in the field of monolayer protected clusters, has the potential to become a key technique complementary to mass spectrometry and X-ray structure determination.

86
Bauer, G.; Fakhri, N.; Kicheva, A.; Kondev, J.; Kruse, K.; Noji, H.; Riveline, D.; Saunders, T. E.; Thattai, M.; Wieschaus, E. “The Science of Living Matter for Tomorrow”, Cell Syst. 2018, 6, 400-402.

85
Bosmani, A.; Guarnieri-Ibáñez, A.; Goudedranche, S.; Besnard, C.; Lacour, J. “Polycyclic Indoline-Benzodiazepines by Electrophilic Additions of α-Imino Carbenes to Tröger Bases”, Angew. Chem. Int. Ed. 2018, 57, 7151-7155.open archive unige:105328 pdf full text [restricted access]

Polycyclic indoline-benzodiazepines are afforded by the intermolecular reaction of Tröger bases with N-sulfonyl-1,2,3-triazoles. Under Rh(II)-catalysis, α-imino carbenes are generated and a subsequent cascade of [1,2]-Stevens, Friedel-Crafts, Grob and aminal formation reactions yield the polycyclic heterocycles as single isomers (d.r.>49:1, four stereocenters incl. two bridgehead N-atoms). Further ring-expansion by insertion of a second α-imino carbene leads to elaborated polycyclic 9-membered ring triazonanes.

84
Delgado, T.; Enachescu, C.; Tissot, A.; Guénée, L.; Hauser, A.; Besnard, C. “The influence of the sample dispersion on a solid surface in the thermal spin transition of [Fe(pz)Pt(CN)4] nanoparticles”, Phys. Chem. Chem. Phys. 2018, 20, 12493-12502.

The thermal spin transition of [Fe(pz)Pt(CN)4], pz = pyrazine, nanoparticles is compared with the one of the microcrystalline powder by magnetic susceptibility measurements, absorption spectroscopy and X-ray powder diffraction (XRPD) using synchrotron radiation. The thermal transition shows less cooperativity when decreasing the size due to the reduction of cluster formation. Surprisingly, the dispersion of the nanoparticles on a surface entails important effects on the spin crossover properties of the system. These effects are simulated and explained within the framework of the mechanoelastic model.

83
Perrin, L.; Loizides-Mangold, U.; Chanon, S.; Gobet, C.; Hulo, N.; Isenegger, L.; Weger, B. D.; Migliavacca, E.; Charpagne, A.; Betts, J. A.; Walhin, J.-P.; Templeman, I.; Stokes, K.; Thompson, D.; Tsintzas, K.; Robert, M.; Howald, C.; Riezman, H.; Feige, J. N.; Karagounis, L. G.; Johnston, J. D.; Dermitzakis, E. T.; Gachon, F.; Lefai, E.; Dibner, C. “Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle”, eLife 2018, 7, e34114.

Circadian regulation of transcriptional processes has a broad impact on cell metabolism. Here, we compared the diurnal transcriptome of human skeletal muscle conducted on serial muscle biopsies in vivo with profiles of human skeletal myotubes synchronized in vitro. More extensive rhythmic transcription was observed in human skeletal muscle compared to in vitro cell culture as a large part of the in vivo mRNA rhythmicity was lost in vitro. siRNA-mediated clock disruption in primary myotubes significantly affected the expression of ~8% of all genes, with impact on glucose homeostasis and lipid metabolism. Genes involved in GLUT4 expression, translocation and recycling were negatively affected, whereas lipid metabolic genes were altered to promote activation of lipid utilization. Moreover, basal and insulin-stimulated glucose uptake were significantly reduced upon CLOCK depletion. Our findings suggest an essential role for the circadian coordination of skeletal muscle glucose homeostasis and lipid metabolism in humans.

82
Macchione, M.; Tsemperouli, M.; Goujon, A.; Mallia, A. R.; Sakai, N.; Sugihara, K.; Matile, S. “Mechanosensitive Oligodithienothiophenes:  Transmembrane Anion Transport Along Chalcogen-Bonding Cascades”, Helv. Chim. Acta 2018, 101, e1800014.open archive unige:103818 pdf full text [free access]

The design, synthesis, and evaluation of multifunctional dithieno[3,2‐b;2′,3′‐d]thiophene (DTT) trimers is described. Twisted push‐push‐pull or donor‐donor‐acceptor (DDA) trimers composed of one DTT acceptor and two DTT donors show strong mechanochromism in lipid bilayer membranes. Red shifts in excitation rather than emission and fluorescence recovery with increasing membrane order are consistent with planarization of the twisted, extra‐long mechanophores in the ground state. The complementary pull‐pull‐pull or AAA trimers with deep σ holes all along the scaffold are not mechanochromic in membranes but excel with submicromolar anion transport activity. Anion transport along membrane‐spanning strings of chalcogen‐bond donors is unprecedented and completes previous results on transmembrane cascades that operate with equally unorthodox interactions such as halogen bonds and anion‐π interactions.

81
Pupier, M.; Nuzillard, J.-M.; Wist, J.; Schlörer, N. E.; Kuhn, S.; Erdelyi, M.; Steinbeck, C.; Williams, A. J.; Butts, C.; Claridge, T. D. W.; Mikhova, B.; Robien, W.; Dashti, H.; Eghbalnia, H. R.; Farès, C.; Adam, C.; Kessler, P.; Moriaud, F.; Elyashberg, M.; Argyropoulos, D.; Pérez, M.; Giraudeau, P.; Gil, R. R.; Trevorrow, P.; Jeannerat, D. “NMReDATA, a standard to report the NMR assignment and parameters of organic compounds”, Magn. Reson. Chem. 2018, 56, 703-715.open archive unige:106258 pdf full text [free access]

Even though NMR has found countless applications in the field of small molecule characterization, there is no standard file format available for the NMR data relevant to structure characterization of small molecules. A new format is therefore introduced to associate the NMR parameters extracted from 1D and 2D spectra of organic compounds to the proposed chemical structure. These NMR parameters, which we shall call NMReDATA (for nuclear magnetic resonance extracted data), include chemical shift values, signal integrals, intensities, multiplicities, scalar coupling constants, lists of 2D correlations, relaxation times and diffusion rates. The file format is an extension of the existing SDF (Structure Data Format), which is compatible with the commonly used MOL format. The association of an NMReDATA file with the raw and spectral data from which it originates constitutes an NMR record. This format is easily readable by humans and computers and provides a simple and efficient way for disseminating results of structural chemistry investigations, allowing automatic verification of published results, and for assisting the constitution of highly needed open-source structural databases.

80
Hoch, D. G.; Abegg, D.; Adibekian, A. “Cysteine-reactive probes and their use in chemical proteomics”, Chem. Commun. 2018, 54, 4501-4512.open archive unige:104188 pdf full text [restricted access]

Proteomic profiling using bioorthogonal chemical probes that selectively react with certain amino acids is now a widely used method in life sciences to investigate enzymatic activities, study posttranslational modifications and discover novel covalent inhibitors. Over the past two decades, researchers have developed selective probes for several different amino acids, including lysine, serine, cysteine, threonine, tyrosine, aspartate and glutamate. Among these amino acids, cysteines are particularly interesting due to their highly diverse and complex biochemical role in our cells. In this feature article, we focus on the chemical probes and methods used to study cysteines in complex proteomes.

79
Sugimoto, T.; Cao, T.; Szilagyi, I.; Borkovec, M.; Trefalt, G. “Aggregation and Charging of Sulfate and Amidine Latex Particles in the Presence of Oxyanions”, J. Colloid Interface Sci. 2018, 254, 456-464.

Electrophoretic mobility and time resolved light scattering are used to measure the effect on charging and aggregation of amidine and sulfate latex particles of different oxyanions namely, phosphate, arsenate, sulfate, and selenate. In the case of negatively charged sulfate latex particles oxyanions represent the coions, while they represent counterions in the case of the positively charged amidine latex. Repulsive interaction between the sulfate latex surface and the coions results in weak ion specific effects on the charging and aggregation. On the other hand the interaction of oxyanions with the amidine latex surface is highly specific. The monovalent dihydrogen phosphate ion strongly adsorbs to the positively charged surface and reverses the charge of the particle. This charge reversal leads also to the restabilization of the amidine latex suspension at the intermediate phosphate concentrations. In the case of dihydrogen arsenate the adsorption to amidine latex surface is weaker and no charge reversal and restabilization occurs. Similar differences are seen between the sulfate and selenate analogues, where selenate adsorbs more strongly to the surface as compared to the sulfate ion and invokes charge reversal. The present results indicate that ion specificity is much more pronounced in the case of counterions.

78
Rohwer, E. J.; Akbarimoosavi, M.; Meckel, S. E.; Liu, X.; Geng, Y.; Lawson Daku, L. M.; Hauser, A.; Cannizzo, A.; Decurtins, S.; Stanley, R. J.; Liu, S.-X.; Feurer, T. “Dipole Moment and Polarizability of Tunable Intramolecular Charge Transfer States in Heterocyclic π-Conjugated Molecular Dyads Determined by Computational and Stark Spectroscopic Study”, J. Phys. Chem. C 2018, 122, 9346-9355.

The annulation of two redox-active molecules into a compact and planar structure paves the way towards a new class of electronically versatile materials whose physical properties can be tuned via a substitution of one of the constituting moieties. Specifically, we present tetrathiafulvalene-benzothiadiazole donor-acceptor molecules. The critical role played by the dielectric properties of these molecules is evident by the large spectral shifts of the ground-state absorption spectra in a range of solvents. Stark spectroscopy is performed to determine experimentally dipole- and polarizability change over transitions in the visible range with particular attention to the transition from HOMO to LUMO. The experimental results are compared to the results of TD-DFT calculations and we reciprocally validate results from calculation and experiment. This allows us to filter out effective models and reveal important insights. The calculations are initially performed in the gas phase and subsequently a polarizable continuum model is adopted to probe the influence of the solvent on the molecular dielectric properties. The results show a large charge displacement from HOMO to LUMO and confirm the intramolecular charge transfer nature of the lowest-energy transition. Substitution of the acceptor moiety with electron-withdrawing groups results in changes to the experimentally determined molecular properties consistent with the effects predicted by computational results. The dominant contribution to the electro-absorption signal is due to the change in dipole moment, which is measured to be roughly 20 Debye for all samples and forms a small angle with the transition dipole moment in a toluene solvent environment.

77
Wettmann, L.; Kruse, K. “The Min-protein oscillations in Escherichia coli: an example of self-organized cellular protein waves”, Philos. Trans. R. Soc., B 2018, 373, 20170111.

In the rod-shaped bacterium Escherichia coli, selection of the cell centre as the division site involves pole-to-pole oscillations of the proteins MinC, MinD and MinE. This spatio-temporal pattern emerges from interactions among the Min proteins and with the cytoplasmic membrane. Combining experimental studies in vivo and in vitro together with theoretical analysis has led to a fairly good understanding of Min-protein self-organization. In different geometries, the system can, in addition to standing waves, also produce travelling planar and spiral waves as well as coexisting stable stationary distributions. Today it stands as one of the best-studied examples of cellular self-organization of proteins.

76
Pavlovic, M.; Rouster, P.; Somosi, Z.; Szilagyi, I. “Horseradish peroxidase-nanoclay hybrid particles of high functional and colloidal stability”, J. Colloid Interface Sci. 2018, 524, 114-121.

Highly stable dispersions of enzyme-clay nanohybrids of excellent horseradish peroxidase activity were developed. Layered double hydroxide nanoclay was synthesized and functionalized with heparin polyelectrolyte to immobilize the horseradish peroxidase enzyme. The formation of a saturated heparin layer on the platelets led to charge inversion of the positively charged bare nanoclay and to highly stable aqueous dispersions. Great affinity of the enzyme to the surface modified platelets resulted in strong horseradish peroxidase adsorption through electrostatic and hydrophobic interactions as well as hydrogen bonding network and prevented enzyme leakage from the obtained material. The enzyme kept its functional integrity upon immobilization and showed excellent activity in decomposition of hydrogen peroxide and oxidation of an aromatic compound in the test reactions. In addition, remarkable long term functional stability of the enzyme-nanoclay hybrid was observed making the developed colloidal system a promising antioxidant candidate in biomedical treatments and industrial processes.

75
Bornhof, A.-B.; Bauzá, A.; Aster, A.; Pupier, M.; Frontera, A.; Vauthey, E.; Sakai, N.; Matile, S. “Synergistic Anion-(π)n-π Catalysis on π-Stacked Foldamers”, J. Am. Chem. Soc. 2018, 140, 4884-4892.open archive unige:103467 pdf full text [restricted access]

In this report, we demonstrate that synergistic effects between π–π stacking and anion−π interactions in π-stacked foldamers provide access to unprecedented catalytic activity. To elaborate on anion–(π)n–π catalysis, we have designed, synthesized and evaluated a series of novel covalent oligomers with up to four face-to-face stacked naphthalenediimides (NDIs). NMR analysis including DOSY confirms folding into π stacks, cyclic voltammetry, steady-state and transient absorption spectroscopy the electronic communication within the π stacks. Catalytic activity, assessed by chemoselective catalysis of the intrinsically disfavored but biologically relevant addition reaction of malonate half thioesters to enolate acceptors, increases linearly with the length of the stacks to reach values that are otherwise beyond reach. This linear increase violates the sublinear power laws of oligomer chemistry. The comparison of catalytic activity with ratiometric changes in absorption and decreasing energy of the LUMO thus results in superlinearity, that is synergistic amplification of anion−π catalysis by remote control over the entire stack. In computational models, increasing length of the π-stacked foldamers correlates sublinearly with changes in surface potentials, chloride binding energies, and the distances between chloride and π surface and within the π stack. Computational evidence is presented that the selective acceleration of disfavored but relevant enolate chemistry by anion−π catalysis indeed originates from the discrimination of planar and bent tautomers with delocalized and localized charges, respectively, on π-acidic surfaces. Computed binding energies of keto and enol intermediates of the addition reaction as well as their difference increase with increasing length of the π stack and thus reflect experimental trends correctly. These results demonstrate that anion–(π)n–π interactions exist and matter, ready for use as a unique new tool in catalysis and beyond.

74
Kruse, K.; Sugihara, K. “2018 International Symposium on Chemical Biology of the NCCR Chemical Biology Campus Biotech, Geneva 10.–12.01.2018”, CHIMIA 2018, 72, 160-164.

73
Jeannerat, D. “Editorial of a special issue on "Software tools and tutorials in liquid state NMR"”, Magn. Reson. in Chem. 2018, 56, 373.open archive unige:104623 pdf full text [restricted access]

This special issue entitled “Software tools and tutorials in liquid-state NMR” expresses the cutting edge of computational applications in Nuclear Magnetic Resonance and related fields. 

This issue contains a range of contributions presenting: NMR simulations (SpinDynamica, Spinach, Simpson, Anatolia), improved assignment tools (LSD, Plasmodesma, CMC-se), scalar coupling prediction (MSpin) and new processing software (Craft, Gnat). These papers are complemented by a discussion on data handling in chemistry laboratories, the presentation of the C6H6.org database to share small molecule spectral assignments and a platform to create browser-based NMR exercises for teaching. 

 

I would like to thank all of the authors for their contributions to this issue. Special acknowledgement is extended to Jean-Marc Nuzillard for his help and advice during its preparation.

 

Damien Jeannerat

Department of organic chemistry, University of Geneva, 30 Quai E. Ansermet, CH-1211-Geneva 4, Switzerland

72
Wang, L.; Xie, X.; Cao, T.; Bosset, J.; Bakker, E. “Surface‐Doped Polystyrene Microsensors Containing Lipophilic Solvatochromic Dye Transducers”, Chem. Eur. J. 2018, 24, 7921-7925.

Ion‐selective optical microsensors based on surface modified polystyrene (PS) beads with positively charged lipophilic solvatochromic dye (SD) on the surface, with K+ as model ion, are studied here for the first time. Water soluble SDs are expelled to the aqueous phase by ion‐exchange with the cationic analyte of interest, resulting in a detectable color change. In contrast, lipophilic SDs are more attractive as they appear to remain anchored onto the surface after expulsion from the sensing phase. This transfers just the ionic chromophore functionality into the aqueous phase and allows the system to act as a reversible, truly self‐contained sensor. This work evaluates this mechanism with ζ‐potential measurements on microsensor suspensions. It indeed provides experimental evidence for the mechanism of SD transfer, as a reversal of the ζ‐potential of the PS microsensors is observed for higher potassium concentration with valinomycin doped microspheres. For a discriminated ion such as sodium, the ζ ‐potential change occurs at much higher electrolyte concentrations, in agreement with sensor selectivity. Undoped microspheres give no apparent dependence of ζ‐potential on electrolyte concentration. The study also shows that the effective microsensor surface charge range is tunable and depends on the concentration of the SD on the coating phase.

71
Romano, C.; Mazet, C. “Multicatalytic Stereoselective Synthesis of Highly Substituted Alkenes by Sequential Isomerization/Cross-Coupling Reactions”, J. Am. Chem. Soc. 2018, 140, 4743-4750.open archive unige:103401 pdf full text [restricted access]

Starting from readily available alkenyl methyl ethers, the stereoselective preparation of highly substituted alkenes by two complementary multicatalytic sequential isomerization/cross-coupling sequences is described. Both elementary steps of these sequences are challenging processes when considered independently. A cationic iridium catalyst was identified for the stereoselective isomerization of allyl methyl ethers and was found to be compatible with a nickel catalyst for the subsequent cross-coupling of the in situ generated methyl vinyl ethers with various Grignard reagents. The method is compatible with sensitive functional groups and a multitude of olefinic substitution patterns to deliver products with high control of the newly generated C=C bond. A highly enantioselective variant of this [Ir/Ni] sequence has been established using a chiral iridium precatalyst. A complementary [Pd/Ni] catalytic sequence has been optimized for alkenyl methyl ethers with a remote C=C bond. The final alkenes were isolated with a lower level of stereocontrol. Upon proper choice of the Grignard reagent, we demonstrated that C(sp2)-C(sp2) and C(sp2)-C(sp3) bonds can be constructed with both systems delivering products that would be difficult to access by conventional methods.

70
Benz, S.; Poblador-Bahamonde, A. I.; Low-Ders, N.; Matile, S. “Catalysis with Pnictogen, Chalcogen and Halogen Bonds”, Angew. Chem. Int. Ed. 2018, 57, 5408-5412.open archive unige:103996 pdf full text [free access]

Halogen‐ and chalcogen‐based σ‐hole interactions have recently received increased interest in non‐covalent organocatalysis. However, the closely related pnictogen bonds have been neglected. In this study, we introduce conceptually simple, neutral, and monodentate pnictogen‐bonding catalysts. Solution and in silico binding studies, together with high catalytic activity in chloride abstraction reactions, yield compelling evidence for operational pnictogen bonds. The depth of the σ holes is easily varied with different substituents. Comparison with homologous halogen‐ and chalcogen‐bonding catalysts shows an increase in activity from main group VII to V and from row 3 to 5 in the periodic table. Pnictogen bonds from antimony thus emerged as by far the best among the elements covered, a finding that provides most intriguing perspectives for future applications in catalysis and beyond.

69
Gerold, C. T.; Bakker, E.; Henry, C. S. “Selective Distance-Based K+ Quantification on Paper-Based Microfluidics”, Anal. Chem. 2018, 90, 4894-4900.

In this study, paper-based microfluidic devices (µPADs) capable of K+ quantification in aqueous and human serum samples using both colorimetric and distance-based methods is described. A lipophilic phase containing potassium ionophore I (valinomycin) was utilized to achieve highly selective quantification of K+ in the presence of Na+, Li+ and Mg2+ ions. Successful addition of a suspended lipophilic phase to a wax printed paper-based device is described and offers a solution to current approaches that rely on organic solvents which damage wax barriers. The approach provides an avenue for future alkali/alkaline quantification utilizing µPADs. Colorimetric spot tests allowed for K+ quantification from 0.1–5.0 mM using only 3.00 µL of sample solution. Selective distance-based quantification required small sample volumes (6.00 µL) and gave responses sensitive enough to distinguish between 1.0 and 2.5 mM of sample K+. µPADs using distance-based methods were also capable of differentiating between 4.3 and 6.9 mM K+ (normal versus abnormal levels) in human serum samples. Distance-based methods required no digital analysis, electronic hardware or pumps; any steps required for quantification could be carried out using a naked eye.

68
Dhakshinamoorthy, R.; Bitzhenner, M.; Cosson, P.; Soldati, T.; Leippe, M. “The Saposin-Like Protein AplD Displays Pore-Forming Activity and Participates in Defense Against Bacterial Infection During a Multicellular Stage of Dictyostelium discoideum”, Front. Cell. Infect. Microbiol. 2018, 8, art. 73.

Due to their archaic life style and microbivor behavior, amoebae may represent a source of antimicrobial peptides and proteins. The amoebic protozoon Dictyostelium discoideum has been a model organism in cell biology for decades and has recently also been used for research on host-pathogen interactions and the evolution of innate immunity. In the genome of D. discoideum, genes can be identified that potentially allow the synthesis of a variety of antimicrobial proteins. However, at the protein level only very few antimicrobial proteins have been characterized that may interact directly with bacteria and help in fighting infection of D. discoideum with potential pathogens. Here, we focus on a large group of gene products that structurally belong to the saposin-like protein (SAPLIP) family and which members we named provisionally Apls (amoebapore-like peptides) according to their similarity to a comprehensively studied antimicrobial and cytotoxic pore-forming protein of the protozoan parasite Entamoeba histolytica. We focused on AplD because it is the only Apl gene that is reported to be primarily transcribed further during the multicellular stages such as the mobile slug stage. Upon knock-out (KO) of the gene, aplD slugs became highly vulnerable to virulent Klebsiella pneumoniae. AplD slugs harbored bacterial clumps in their interior and were unable to slough off the pathogen in their slime sheath. Re-expression of AplD in aplD slugs rescued the susceptibility toward K. pneumoniae. The purified recombinant protein rAplD formed pores in liposomes and was also capable of permeabilizing the membrane of live Bacillus megaterium. We propose that the multifarious Apl family of D. discoideum comprises antimicrobial effector polypeptides that are instrumental to interact with bacteria and their phospholipid membranes. The variety of its members would allow a complementary and synergistic action against a variety of microbes, which the amoeba encounters in its environment.

67
Hamacek, J.; Vuillamy, A.; Peterhans, L.; Homberg, A.; Poggiali, D.; Schneider, M. W.; Mastalerz, M. “Ln(III) complexes with triptycene based tripodal ligands: speciation and equilibria ”, New J. Chem. 2018, 42, 7803-7809.

Triaminotriptycene was used as a rigid anchoring platform for preparing several organic ligands for Ln(III) complexation. In this work we present detailed speciation studies with a tripodal ligand L6 possessing terminal carboxamide coordinating moieties. The solution speciation for different [Ln]/[L] ratios is investigated using NMR and mass spectrometry and compared with those of closely related ligands L7 and L8. A special interest is devoted to chemical equilibria in metal excess, whereby different complex species are generated through slow transformations. The effect of the ionic radius along the lanthanide series is discussed for tetranuclear and trinuclear complexes.

66
Moazzami-Gudarzi, M.; Adam, P.; Smith, A. M.; Trefalt, G.; Szilágyi, I.; Maroni, P.; Borkovec, M. “Interactions between similar and dissimilar charged interfaces in the presence of multivalent anions”, Phys. Chem. Chem. Phys. 2018, 20, 9436-9448.

Direct force measurements involving amidine latex (AL) and sulfate latex (SL) particles in aqueous solutions containing multivalent ferrocyanide anions are presented. These measurements feature three different pairs of particles, namely SL–SL, AL–SL, and AL–AL. The force profiles are quantitatively interpreted in terms of the theory by Derjaguin, Landau, Verwey, and Overbeek (DLVO) that is combined with a short-ranged exponential attraction. In monovalent salt solutions, the AL particles are positively charged, while the SL particles are negatively charged. In solutions containing ferrocyanide, the charge of the AL particles is reversed as the concentration is increased. The longer-ranged component of all force profiles is fully compatible with DLVO theory, provided effects of charge regulation are included. At shorter distances, an additional exponential attraction must be introduced, whereby the respective decay length is about 2 nm for the AL–AL pair, and below 1 nm for the SL–SL pair. This non-DLVO force is intermediate for the asymmetric AL–SL pair. These additional forces are probably related to charge fluctuations, patch-charged interactions, or hydrophobic forces.

65
Cuartero, M.; Crespo, G. A.; Cherubini, T.; Pankratova, N.; Confalonieri, F.; Massa, F.; Tercier-Waeber, M.-L.; Abdou, M.; Schaefer, J.; Bakker, E. “In Situ Detection of Macronutrients and Chloride in Seawater by Submersible Electrochemical Sensors”, Anal. Chem. 2018, 90, 4702-4710.

A new submersible probe for the in situ detection of nitrate, nitrite and chloride in seawater is presented. Inline coupling of a desalination unit, an acidification unit and a sensing flow cell containing all-solid-state membrane electrodes allows for the potentiometric detection of nitrate and nitrite after removal of the key interfering ions in seawater, chloride and hydroxide. Thus, the electrodes exhibited attractive analytical performances for the potentiometric detection of nitrate and nitrite in desalinated and acidified seawater: fast response time (t95

64
Jarolímová, Z.; Bosson, J.; Labrador, G. M.; Lacour, J.; Bakker, E. “Ion Transfer Voltammetry in Polyurethane Thin Films Based on Functionalised Cationic [6]Helicenes for Carbonate Detection”, Electroanalysis 2018, 30, 1378-1385.open archive unige:106433 pdf full text [restricted access]

We explore here molecular ion-to-electron redox probes based on cationic diaza, azaoxa, and dioxa[6] helicenes and their derivatives as ion to electron transducers for the electrochemical detection of anions. These cationic [6] helicenes exhibit reversible and reproducible oxidation/reduction behavior and facilitate the anion transfer of Gaussian shape into polymeric thin layer sensing films.

63
Trofimov, V.; Kicka, S.; Mucaria, S.; Hanna, N.; Ramon-Olayo, F.; Del Peral, L. V.-G.; Lelièvre, J.; Ballell, L.; Scapozza, L.; Besra, G. S.; Cox, J. A. G.; Soldati, T. “Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets”, Sci. Rep. 2018, 983, art. 3939.open archive unige:103009 pdf full text [free access]

Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13–14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential “universal” targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK.

62
Trofimov, V.; Kicka, S.; Mucaria, S.; Hanna, N.; Ramon-Olayo, F.; Del Peral, L. V.-G.; Lelièvre, J.; Ballell, L.; Scapozza, L.; Besra, G. S.; Cox, J. A. G.; Soldati, T. “Antimycobacterial drug discovery using Mycobacteria-infected amoebae identifies anti-infectives and new molecular targets”, Sci. Rep. 2018, 983, 403.

Tuberculosis remains a serious threat to human health world-wide, and improved efficiency of medical treatment requires a better understanding of the pathogenesis and the discovery of new drugs. In the present study, we performed a whole-cell based screen in order to complete the characterization of 168 compounds from the GlaxoSmithKline TB-set. We have established and utilized novel previously unexplored host-model systems to characterize the GSK compounds, i.e. the amoeboid organisms D. discoideum and A. castellanii, as well as a microglial phagocytic cell line, BV2. We infected these host cells with Mycobacterium marinum to monitor and characterize the anti-infective activity of the compounds with quantitative fluorescence measurements and high-content microscopy. In summary, 88.1% of the compounds were confirmed as antibiotics against M. marinum, 11.3% and 4.8% displayed strong anti-infective activity in, respectively, the mammalian and protozoan infection models. Additionally, in the two systems, 13–14% of the compounds displayed pro-infective activity. Our studies underline the relevance of using evolutionarily distant pathogen and host models in order to reveal conserved mechanisms of virulence and defence, respectively, which are potential “universal” targets for intervention. Subsequent mechanism of action studies based on generation of over-expresser M. bovis BCG strains, generation of spontaneous resistant mutants and whole genome sequencing revealed four new molecular targets, including FbpA, MurC, MmpL3 and GlpK.

61
Licari, G.; Beckwith, J. S.; Soleimanpour, S.; Matile, S.; Vauthey, E. “Detecting Order and Lateral Pressure at Biomimetic Interfaces Using a Mechanosensitive Second-Harmonic-Generation Probe”, Phys. Chem. Chem. Phys. 2018, 20, 9328-9336.open archive unige:103402 pdf full text [restricted access]

A planarizable push-pull molecular probe with mechanosensitive properties has been investigated at several biomimetic interfaces, consisting of different phospholipid monolayers located between dodecane and an aqueous buffer solution, using the interface-specific surface-second-harmonic-generation (SSHG) technique. Whereas the SSHG spectra recorded at liquid-disordered interfaces were similar to the absorption spectra in bulk solutions, those measured liquid-ordered phases exhibited a remarkable shift towards lower energies to an extent depending on the surface pressure of the phospholipid monolayer. On the basis of quantum-chemical calculations, this effect was accounted for by the planarization of the mechanosensitive probe. Polarization-resolved SSHG measurements revealed that the average orientation of the probe at the interface is an even more a sensitive reporter of lateral pressure and order than the spectral shape. Additionally, time-resolved SSHG measurements pointed to slower dynamics upon intercalation inside the phospholipid monolayer, most likely due to the more constrained environment. This study demonstrates that the concept of mechanosensitive optical probes can be further exploited when combined with a surface-selective nonlinear optical technique.

60
Castillon, G. A.; Burriat-Couleru, P.; Abegg, D.; Criado Santos, N.; Watanabe, R. “Clathrin and AP1 are required for apical sorting of glycosyl phosphatidyl inositol-anchored proteins in biosynthetic and recycling routes in Madin-Darby canine kidney cells”, Traffic 2018, 19, 215-228.

Recently, studies in animal models demonstrate potential roles for clathrin and AP1 in apical protein sorting in epithelial tissue. However, the precise functions of these proteins in apical protein transport remain unclear. Here, we reveal mistargeting of endogenous glycosyl phosphatidyl inositol-anchored proteins (GPI-APs) and soluble secretory proteins in Madin-Darby canine kidney (MDCK) cells upon clathrin heavy chain or AP1 subunit knockdown (KD). Using a novel directional endocytosis and recycling assay, we found that these KD cells are not only affected for apical sorting of GPI-APs in biosynthetic pathway but also for their apical recycling and basal-to-apical transcytosis routes. The apical distribution of the t-SNARE syntaxin 3, which is known to be responsible for selective targeting of various apical-destined cargo proteins in both biosynthetic and endocytic routes, is compromised suggesting a molecular explanation for the phenotype in KD cells. Our results demonstrate the importance of biosynthetic and endocytic routes for establishment and maintenance of apical localization of GPI-APs in polarized MDCK cells.

59
Kruse, K.; Chiaruttini, N.; Roux, A. “Optical control of cytoplasmic flows”, Nat. Cell Biol. 2018, 20, 227-228.

Cytoplasmic flows are essential for various cellular processes. However, tools to manipulate these flows within cells are still lacking. Now research shows that an optical tool allows for control of cytoplasmic flows and can be used as a subcellular rheometer.

58
Nançoz, C.; Licari, G.; Beckwith, J. S.; Soederberg, M.; Dereka, B.; Rosspeintner, A.; Yushchenko, O.; Letrun, R.; Richert, S.; Lang, B.; Vauthey, E. “Influence of the hydrogen-bond interactions on the excited-state dynamics of a push–pull azobenzene dye: the case of Methyl Orange”, Phys. Chem. Chem. Phys. 2018, 20, 7254-7264.

The excited-state dynamics of the push–pull azobenzene Methyl Orange (MO) were investigated in several solvents and water/glycerol mixtures using a combination of ultrafast time-resolved fluorescence and transient absorption in both the UV-visible and the IR regions, as well as quantum chemical calculations. Optical excitation of MO in its trans form results in the population of the S2 ππ* state and is followed by internal conversion to the S1 nπ* state in ∼50 fs. The population of this state decays on the sub-picosecond timescale by both internal conversion to the trans ground state and isomerisation to the cis ground state. Finally, the cis form converts thermally to the transform on a timescale ranging from less than 50 ms to several minutes. Significant differences depending on the hydrogen-bond donor strength of the solvents, quantified by the Kamlet Taft parameter α, were observed: compared to the other solvents, in highly protic solvents (α > 1), (i) the viscosity dependence of the S1 state lifetime is less pronounced, (ii) the S1 state lifetime is shorter by a factor of ≈1.5 for the same viscosity, (iii) the trans-to-cis photoisomerisation efficiency is smaller, and (iv) the thermal cis-to-trans isomerisation is faster by a factor of ≥103. These differences are explained in terms of hydrogen-bond interactions between the solvent and the azo nitrogen atoms of MO, which not only change the nature of the S1 state but also have an impact on the shape of ground- and excited-state potentials, and, thus, affect the deactivation pathways from the excited state.

57
Aster, A.; Vauthey, E. “More Than a Solvent: Donor-Acceptor Complexes of Ionic Liquids and Electron Acceptors”, J. Phys. Chem. B 2018, 122, 2646-2654.

The applicability of room temperature ionic liquids (RTILs) as inert solvents is generally based on their electrochemical window. We herein show that this concept has its limitations if RTILs are exposed to an oxidizing environment in the presence of light. Acetonitrile solutions of RTILs with 1-methyl-3-ethyl-imidazolium as cation and five different anions, including thiocyanate (SCN-) and dicyanamide (DCA-), were investigated. Upon addition of organic electron acceptors to solutions of RTILs with SCN- or DCA-, charge transfer (CT) absorption bands due to the formation of donor-acceptor complexes between the anion and the electron acceptor were observed. Time-resolved measurements from the femtosecond to the microsecond regimes were used to investigate the nature and the excited-state dynamics of these complexes upon excitation in the CT band. We show that even though the RTILs are seemingly inert according to their electrochemical properties, the dicyanamide and thiocyanate based RTILs can actively participate in photochemical reactions in oxidizing environments and therefore differ from the behaviour expected for an inert solvent. This has not only important implications for the long term stability of RTIL-based systems but can also lead to misinterpretation of photochemical studies in these solvents.

56
Yoon, S.; Gaul, M.; Sharma, S.; Son, K.; Hagemann, H.; Ziegenbalg, D.; Schwingenschlogl, U.; Widenmeyer, M.; Weidenkaff, A. “Photocatalytic CO2 reduction by Cr-substituted Ba2(In2-xCrx)O5·(H2O)δ (0.04 ≤ x ≤ 0.60)”, Solid State Sci. 2018, 78, 22-29.

Cr-substituted polycrystalline Ba2(In2-xCrx)O5·(H2O)δ powders (0.04 ≤ x ≤ 0.60) were synthesized by solid state reaction to investigate the relation of crystal structure, thermochemical, magnetic, and optical properties. The Cr-substitution results in an unit cell expansion and formation of the higher-symmetric tetragonal phase together with increased oxygen and hydrogen contents. Magnetic property measurements reveal that the diamagnetic pristine Ba2In2O5·(H2O)δ becomes magnetically ordered upon Cr-substitution. By UV–vis spectroscopy a gradual shift of the absorption-edge energy to lower values was observed. Numerical calculations showed that the observed bandgap narrowing was ascribed to the Cr induced states near the Fermi level. The correlation between the changes of crystal chemistry, magnetic, and optical properties of Cr-substituted Ba2(In2-xCrx)O5·(H2O)δ can be explained by the replacement of In by Cr. Consequently, an enhanced photocatalytic CO2 reduction activity was observed with increasing Cr substitution, compatible with the state-of-the-art high surface area TiO2photocatalyst (P-25).

55
Magarkar, A.; Parkkila, P.; Viitala, T.; Lajunen, T.; Mobarak, E.; Licari, G.; Cramariuc, O.; Vauthey, E.; Róg, T.; Bunker, A. “Membrane bound COMT isoform is an interfacial enzyme: general mechanism and new drug design paradigm”, Chem. Commun. 2018, 54, 3440-3443.

The enzyme catechol-O-methyltransferase (COMT) has water soluble (S-COMT) and membrane associated (MB-COMT), bitopic, isoforms. Of these MB-COMT is a drug target in relation to the treatment of Parkinson's disease. Using a combination of computational and experimental protocols, we have determined the substrate selection mechanism specific to MB-COMT. We show: (1) substrates with preferred affinity for MB-COMT over S-COMT orient in the membrane in a fashion conducive to catalysis from the membrane surface and (2) binding of COMT to its cofactor ADOMET induces conformational change that drives the catalytic surface of the protein to the membrane surface, where the substrates and Mg2+ ions, required for catalysis, are found. Bioinformatics analysis reveals evidence of this mechanism in other proteins, including several existing drug targets. The development of new COMT inhibitors with preferential affinity for MB-COMT over S-COMT is now possible and insight of broader relevance, into the function of bitopic enzymes, is provided.

54
Zhang, X.; Liu, L.; López-Andarias, J.; Wang, C.; Sakai, N.; Matile, S. “Anion-π Catalysis: Focus on Nonadjacent Stereocenters”, Helv. Chim. Acta 2018, 101, e1700288.open archive unige:102566 pdf full text [restricted access]

Anion-π interactions have been recently introduced to catalysis with the idea to stabilize anionic intermediates on π-acidic surfaces. Realized examples include enolate, enamine and iminium chemistry, domino processes and Diels–Alder reactions. Moving on from the formation of contiguous stereogenic centers on π-acidic surfaces, herein we report the first asymmetric anion-π catalysis of cascade reactions that afford nonadjacent stereocenters. Conjugate addition-protonation of achiral disubstituted enolate donors to 2-chloroacrylonitrile generates 1,3-nonadjacent stereocenters with moderate enantioselectivity and diastereoselectivity. The explored catalysts operate with complementary naphthalenediimide and fullerene surfaces with highly positive quadrupole moments and high polarizability, respectively, and proximal amine bases. We find that anion-π catalysts can increase the diastereoselectivity of the reaction beyond the maximal 1:4.0 dr with conventional catalysts to maximal 5.3:1 dr on the large fullerene surfaces. The enantioselectivity of anion-π catalysts, best on the confined naphthalenediimide surfaces with strong quadrupole moment, exceed the performance of conventional catalysts except for comparable results with a new, most compact, surprisingly powerful bifunctional control catalyst. Simultaneously increased rates and stereoselectivities compared to control catalysts without π-acidic surface support that contributions of anion-π interactions to the catalytic cascade process are significant.

53
Kaksonen, M.; Roux, A. “Mechanisms of clathrin-mediated endocytosis”, Nat. Rev. Mol. Cell Biol. 2018, 19, 313-326.

Clathrin-mediated endocytosis is a key process in vesicular trafficking that transports a wide range of cargo molecules from the cell surface to the interior. Clathrin-mediated endocytosis was first described over 5 decades ago. Since its discovery, over 50 proteins have been shown to be part of the molecular machinery that generates the clathrin-coated endocytic vesicles. These proteins and the different steps of the endocytic process that they mediate have been studied in detail. However, we still lack a good understanding of how all these different components work together in a highly coordinated manner to drive vesicle formation. Nevertheless, studies in recent years have provided several important insights into how endocytic vesicles are built, starting from initiation, cargo loading and the mechanisms governing membrane bending to membrane scission and the release of the vesicle into the cytoplasm.

52
Harayama, T.; Riezman, H. “Understanding the diversity of membrane lipid composition”, Nat. Rev. Mol. Cell Biol. 2018, 19, 281-296.

Cellular membranes are formed from a chemically diverse set of lipids present in various amounts and proportions. A high lipid diversity is universal in eukaryotes and is seen from the scale of a membrane leaflet to that of a whole organism, highlighting its importance and suggesting that membrane lipids fulfil many functions. Indeed, alterations of membrane lipid homeostasis are linked to various diseases. While many of their functions remain unknown, interdisciplinary approaches have begun to reveal novel functions of lipids and their interactions. We are beginning to understand why even small changes in lipid structures and in composition can have profound effects on crucial biological functions.

51
Bruderer, T.; Varesio, E.; Hidasi, A. O.; Duchoslav, E.; Burton, L.; Bonner, R.; Hopfgartner, G. “Metabolomic spectral libraries for data-independent SWATH liquid chromatography mass spectrometry acquisition”, Anal. Bioanal. Chem. 2018, 410, 1873-1884.open archive unige:108079 pdf full text [free access]

High-quality mass spectral libraries have become crucial in mass spectrometry-based metabolomics. Here, we investigate a workflow to generate accurate mass discrete and composite spectral libraries for metabolite identification and for SWATH mass spectrometry data processing. Discrete collision energy (5–100 eV) accurate mass spectra were collected for 532 metabolites from the human metabolome database (HMDB) by flow injection analysis and compiled into composite spectra over a large collision energy range (e.g., 10–70 eV). Full scan response factors were also calculated. Software tools based on accurate mass and predictive fragmentation were specially developed and found to be essential for construction and quality control of the spectral library. First, elemental compositions constrained by the elemental composition of the precursor ion were calculated for all fragments. Secondly, all possible fragments were generated from the compound structure and were filtered based on their elemental compositions. From the discrete spectra, it was possible to analyze the specific fragment form at each collision energy and it was found that a relatively large collision energy range (10–70 eV) gives informative MS/MS spectra for library searches. From the composite spectra, it was possible to characterize specific neutral losses as radical losses using in silico fragmentation. Radical losses (generating radical cations) were found to be more prominent than expected. From 532 metabolites, 489 provided a signal in positive mode [M+H]+ and 483 in negative mode [M-H]. MS/MS spectra were obtained for 399 compounds in positive mode and for 462 in negative mode; 329 metabolites generated suitable spectra in both modes. Using the spectral library, LC retention time, response factors to analyze data-independent LC-SWATH-MS data allowed the identification of 39 (positive mode) and 72 (negative mode) metabolites in a plasma pool sample (total 92 metabolites) where 81 previously were reported in HMDB to be found in plasma.

50
Lawson Daku, L. M. “Spin-state dependence of the structural and vibrational properties of solvated iron(II) polypyridyl complexes from AIMD simulations: aqueous [Fe(bpy)3]Cl2, a case study”, Phys. Chem. Chem. Phys. 2018, 20, 6236-6253.

The accurate description of transition metal complexes in liquid solutions is a challenging fundamental research problem, which must be tackled when it comes to understanding the role of the solvent in the photoinduced low-spin (LS) → high-spin (HS) transition in solvated Fe(II) complexes. We report an in-depth ab initio molecular dynamics (AIMD) study of the spin-state dependence of the structural and vibrational properties of the prototypical [Fe(bpy)3]2+ (bpy = 2,2′-bipyridine) LS complex in water. The description achieved for the LS and HS solution structures of aqueous [Fe(bpy)3]2+ significantly improves on and actually supersedes the one from our previous AIMD study [Lawson Daku and Hauser, J. Phys. Chem. Lett., 2010, 1, 1830], thanks to substantially longer simulation times and the use of the dispersion-corrected BLYP-D3 functional in place of the standard BLYP functional. The present results confirm the ≈0.19 Å lengthening of the Fe–N bonds and the increased thermal fluctuation of the molecular edifice stemming from the weakening of the Fe–N bonds upon the LS → HS change of states. Revisiting our previous finding on the solvation of [Fe(bpy)3]2+, they indicate that the number of water molecules in its first hydration shell actually increases from ∼15 in the LS state to ∼17 in the HS state. The vibration modes and associated vibrational density of states (VDOS) of [Fe(bpy)3]2+ have been determined from a generalized normal coordinate analysis. The VDOS of the Fe–N stretching and bending modes are located in the far-IR region. For LS [Fe(bpy)3]2+, the peak positions of the VDOS of the Fe–N stretching modes agree very well with the experimental Fe–N stretching frequencies. For HS [Fe(bpy)3]2+, the spanned frequency range encompasses the Fe–N stretching frequency range reported for HS polypyridine Fe(II) complexes. The LS and HS IR spectra of the complex have also been calculated in the 0 ≤ ≤ 2500 cm−1 range from the dynamics of the Wannier function centers. The calculated LS IR spectrum matches available experimental data. The predicted HS–LS IR difference spectrum of aqueous [Fe(bpy)3]2+ shows mostly an increase in intensity upon the LS → HS change of states.

49
Carlini, L.; Mahecic, D.; Kleele, T.; Roux, A.; Manley, S. “Membrane bending energy and tension govern mitochondrial division”, bioRxiv, Biophys. 2018, in press.

Mitochondria rely on cellular machinery for their division, which is an essential component of metabolic response of the cell. Many division factors have been identified; however, a framework accounting for the energetic requirements of the mitochondrial fission process is lacking. We report that the presence of an active constriction does not ensure fission. Instead, by measuring constrictions down to ~100 nm with time-lapse super-resolution microscopy, we found that 34% of constrictions failed to divide and 'reversed' to an unconstricted state. Higher local curvatures - reflecting an increased bending energy - made constriction sites more likely to divide, but often with a significant residual energy barrier to fission. Our data suggest that membrane tension, largely arising from pulling forces, could account for this missing energy. These results lead us to propose that mitochondrial fission is probabilistic, and can be modeled as arising from bending energy complemented by a fluctuating membrane tension.

48
Feng, S.; Harayama, T.; Montessuit, S.; David, F. P. A.; Winssinger, N.; Martinou, J.-C.; Riezman, H. “Mitochondria-specific photoactivation to monitor local sphingosine metabolism and function”, eLife 2018, 7, e34555.open archive unige:103400 pdf full text [free access]

Photoactivation ('uncaging’) is a powerful approach for releasing bioactive small-molecules in living cells. Current uncaging methods are limited by the random distribution of caged molecules within cells. We have developed a mitochondria-specific photoactivation method, which permitted us to release free sphingosine inside mitochondria and thereafter monitor local sphingosine metabolism by lipidomics. Our results indicate that sphingosine was quickly phosphorylated into sphingosine 1-phosphate (S1P) driven by sphingosine kinases. In time-course studies, the mitochondria-specific uncaged sphingosine demonstrated distinct metabolic patterns compared to globally-released sphingosine, and did not induce calcium spikes. Our data provide direct evidence that sphingolipid metabolism and signaling are highly dependent on the subcellular location and opens up new possibilities to study the effects of lipid localization on signaling and metabolic fate.

47
Zhang, B.; Safonova, O. V.; Pollitt, S.; Salassa, G.; Sels, A.; Kazan, R.; Wang, Y.; Rupprechter, G.; Barrabés, N.; Bürgi, T. “On the mechanism of rapid metal exchange between thiolate-protected gold and gold/silver clusters: a time-resolved in situ XAFS study”, Phys. Chem. Chem. Phys. 2018, 20, 5312-5318.

The fast metal exchange reaction between Au38 and AgxAu38−x nanoclusters in solution at −20 °C has been studied by in situ X-ray absorption spectroscopy (time resolved quick XAFS) in transmission mode. A cell was designed for this purpose consisting of a cooling system, remote injection and mixing devices. The capability of the set-up is demonstrated for second and minute time scale measurements of the metal exchange reaction upon mixing Au38/toluene and AgxAu38−x/toluene solutions at both Ag K-edge and Au L3-edge. It has been proposed that the exchange of gold and silver atoms between the clusters occurs via the SR(-M-SR)n (n = 1, 2; M = Au, Ag) staple units in the surface of the reacting clusters during their collision. However, at no point during the reaction (before, during, after) evidence is found for cationic silver atoms within the staples. This means that either the exchange occurs directly between the cores of the involved clusters or the residence time of the silver atoms in the staples is very short in a mechanism involving the metal exchange within the staples.

46
Winssinger, N. “Editorial - Biography of Professor Nicolaou: a journey to the extremes of molecular complexity”, J. Antibiot. 2018, 71, 149-150.open archive unige:101833

45
Gooding, J. J.; Mazur, A.; Sailor, M.; Merkx, M.; Kelley, S.; Tao, N.; Long, Y.; Bakker, E. “Editorial - An Exciting Year Ahead for ACS Sensors”, ACS Sens. 2018, 3, 1-2.

44
Zhou, X.; Friedmann, K. S.; Lyrmann, H.; Zhou, Y.; Schoppmeyer, R.; Knörck, A.; Mang, S.; Hoxha, C.; Angenendt, A.; Backes, C. S.; Mangerich, C.; Zhao, R.; Cappello, S.; Schwär, G.; Hässig, C.; Neef, M.; Bufe, B.; Zufall, F.; Kruse, K.; Niemeyer, B. A.; Lis, A.; Qu, B.; Kummerow, C.; Schwarz, E. C.; Hoth, M. “A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity”, J. Physiol. 2018, 596, 2681-2698.

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are required to protect the human body against cancer. Ca2+ is a key metabolic factor for lymphocyte function and cancer homeostasis. We analysed the Ca2+ dependence of CTL and NK cell cytotoxicity against cancer cells and found that CTLs have a bell‐shaped Ca2+ dependence with an optimum for cancer cell elimination at rather low [Ca2+]o (23–625 μm) and [Ca2+]i (122–334 nm). This finding predicts that a partial inhibition of Orai1 should increase (rather than decrease) cytotoxicity of CTLs at [Ca2+]o higher than 625 μm. We tested this hypothesis in CTLs and indeed found that partial down‐regulation of Orai1 by siRNA increases the efficiency of cancer cell killing. We found two mechanisms that may account for the Ca2+ optimum of cancer cell killing: (1) migration velocity and persistence have a moderate optimum between 500 and 1000 μm [Ca2+]o in CTLs, and (2) lytic granule release at the immune synapse between CTLs and cancer cells is increased at 146 μm compared to 3 or 800 μm, compatible with the Ca2+ optimum for cancer cell killing. It has been demonstrated in many cancer cell types that Orai1‐dependent Ca2+ signals enhance proliferation. We propose that a decrease of [Ca2+]o or partial inhibition of Orai1 activity by selective blockers in the tumour microenvironment could efficiently reduce cancer growth by simultaneously increasing CTL and NK cell cytotoxicity and decreasing cancer cell proliferation.

43
Kim, K. T.; Chang, D.; Winssinger, N. “Double-Stranded RNA-specific Templated Reaction with Triplex Forming PNA”, Helv. Chim. Acta 2018, 101, e170095.open archive unige:103235 pdf full text [restricted access]

RNA, originally perceived as a simple information transfer biopolymer, is emerging as an important regulator in cellular processes. A number of non-coding RNAs are double-stranded and there is a need for technologies to reliably detect and image such RNAs for biological and biomedical research. Herein we report double-stranded RNA-specific templated reaction resulting from PNA-reagent conjugates that are brought within reactive distance through the formation of sequence-specific triplexes onto double-stranded RNA. The reaction makes use of a ruthenium-based photocatalyst that reduces a pyridinium-based immolative linker, unmasking a profluorophore. The reaction was shown to proceed with signal amplification and to be selective for double-stranded RNA over DNA as well as single-stranded RNA. The generality of the triplex formation was enabled by non-canonical nucleobases that extend the Hoogsteen base-pairing repertoire. The technology was applied to a templated reaction using pre-microRNA 31.

42
Garcia-Alai, M. M.; Heidemann, J.; Skruzny, M.; Gieras, A.; Mertens, H. D. T.; Svergun, D. I.; Kaksonen, M.; Uetrecht, C.; Meijers, R. “Epsin and Sla2 form assemblies through phospholipid interfaces”, Nat. Commun. 2018, 9, 328.

In clathrin-mediated endocytosis, adapter proteins assemble together with clathrin through interactions with specific lipids on the plasma membrane. However, the precise mechanism of adapter protein assembly at the cell membrane is still unknown. Here, we show that the membrane–proximal domains ENTH of epsin and ANTH of Sla2 form complexes through phosphatidylinositol 4,5-bisphosphate (PIP2) lipid interfaces. Native mass spectrometry reveals how ENTH and ANTH domains form assemblies by sharing PIP2 molecules. Furthermore, crystal structures of epsin Ent2 ENTH domain from S. cerevisiae in complex with PIP2 and Sla2 ANTH domain from C. thermophilum illustrate how allosteric phospholipid binding occurs. A comparison with human ENTH and ANTH domains reveal only the human ENTH domain can form a stable hexameric core in presence of PIP2, which could explain functional differences between fungal and human epsins. We propose a general phospholipid-driven multifaceted assembly mechanism tolerating different adapter protein compositions to induce endocytosis.

41
Morelli, P.; Bartolami, E.; Sakai, N.; Matile, S. “Glycosylated Cell-Penetrating Poly(disulfide)s: Multifunctional Cellular Uptake at High Solubility”, Helv. Chim. Acta 2018, 101, e1700266.open archive unige:101653 pdf full text [free access]

The glycosylation of cell-penetrating poly(disulfide)s (CPDs) is introduced to increase the solubility of classical CPDs and to achieve multifunctional cellular uptake. With the recently developed sidechain engineering, CPDs decorated with α-d-glucose (Glu), β-d-galactose (Gal), d-trehalose (Tre), and triethyleneglycol (TEG) were readily accessible. Confocal laser scanning microscopy images of HeLa Kyoto cells incubated with the new CPDs at 2.5 μm revealed efficient uptake into cytosol and nucleoli of all glycosylated CPDs, whereas the original CPDs and TEGylated CPDs showed much precipitation into fluorescent aggregates at these high concentrations. Flow cytometry analysis identified Glu-CPDs as most active, closely followed by Gal-CPDs and Tre-CPDs, and all clearly more active than non-glycosylated CPDs. In the MTT assay, all glyco-CPDs were non-toxic at concentrations as high as 2.5 μm. Consistent with thiol-mediated uptake, glycosylated CPDs remained dependent on thiols on the cell surface for dynamic covalent exchange, their removal with Ellman's reagent DTNB efficiently inhibited uptake. Multifunctionality was demonstrated by inhibition of Glu-CPDs with d-glucose (IC50 ca. 20 mm). Insensitivity toward l-glucose and d-galactose and insensitivity of conventional CPDs toward d-glucose supported that glucose-mediated uptake of the multifunctional Glu-CPDs involves selective recognition by glucose receptors at the cell surface. Weaker but significant sensitivity of Gal-CPDs toward d-galactose but not d-glucose was noted (IC50 ca. 110 mm). Biotinylation of Glu-CPDs resulted in the efficient delivery of streptavidin together with a fluorescent model substrate. Protein delivery with Glu-CPDs was more efficient than with conventional CPDs and remained sensitive to DTNB and d-glucose, i.e., multifunctional.

40
Chuard, N.; Poblador-Bahamonde, A. I.; Zong, L.; Bartolami, E.; Hildebrandt, J.; Weigand, W.; Sakai, N.; Matile, S. “Diselenolane-Mediated Cellular Uptake”, Chem. Sci. 2018, 9, 1860-1866.open archive unige:102319 pdf full text [free access]

The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.

39
Tanasescu, R.; Mettal, U.; Colom, A.; Roux, A.; Zumbuehl, A. “Facile and Rapid Formation of Giant Vesicles from Glass Beads”, Polymers 2018, 10, 54/1-54/11.

Giant vesicles (GVs) are widely-used model systems for biological membranes. The formulation of these vesicles, however, can be problematic and artifacts, such as degraded molecules or left-over oil, may be present in the final liposomes. The rapid formulation of a high number of artifact-free vesicles of uniform size using standard laboratory equipment is, therefore, highly desirable. Here, the gentle hydration method of glass bead-supported thin lipid films has been enhanced by adding a vortexing step. This led to the formulation of a uniform population of giant vesicles. Batches of glass beads coated with different lipids can be combined to produce vesicles of hybrid lipid compositions. This method represents a stable approach to rapidly generate giant vesicles.

38
Cardenal-Muñoz, E.; Barisch, C.; Lefrançois, L. H.; López-Jiménez, A. T.; Soldati, T. “When Dicty Met Myco, a (Not So) Romantic Story about One Amoeba and Its Intracellular Pathogen”, Front. Cell. Infect. Microbiol. 2018, 2, art. 529.open archive unige:102451 pdf full text [free access]

In recent years, Dictyostelium discoideum has become an important model organism to study the cell biology of professional phagocytes. This amoeba not only shares many molecular features with mammalian macrophages, but most of its fundamental signal transduction pathways are conserved in humans. The broad range of existing genetic and biochemical tools, together with its suitability for cell culture and live microscopy, make D. discoideum an ideal and versatile laboratory organism. In this review, we focus on the use of D. discoideum as a phagocyte model for the study of mycobacterial infections, in particular Mycobacterium marinum. We look in detail at the intracellular cycle of M. marinum, from its uptake by D. discoideum to its active or passive egress into the extracellular medium. In addition, we describe the molecular mechanisms that both the mycobacterial invader and the amoeboid host have developed to fight against each other, and compare and contrast with those developed by mammalian phagocytes. Finally, we introduce the methods and specific tools that have been used so far to monitor the D. discoideumM. marinum interaction.

37
Bauer, C. . R.; Duwald, R.; Labrador, G.; Pascal, S.; Moneva Lorente, P.; Bosson, J.; Lacour, J.; Rochaix, J.-D. “Specific labeling of mitochondria of Chlamydomonas with cationic helicene fluorophores”, Org. Biomol. Chem. 2018, 16, 919-923.open archive unige:106910 pdf full text [restricted access]

Thirteen cationic helicenes and triangulene were tested for the specific labeling of mitochondria from algal cells. Octyl ester derivative 5 readily penetrates algal cells and gives rise to clear fluorescence patterns when it is used at concentrations in the mM range. Under these conditions, cell structures are well preserved and cell survival is not compromised. Cationic helicene compounds such as 5 provide new useful tools for examining the mitochondrial network and its dynamics including fission and fusion events

36
Radiom, M.; Maroni, P.; Wesolowski, T. A. “Size extensivity of elastic properties of alkane fragments”, J. Mol. Model. 2018, 24, article 36.open archive unige:102843 pdf full text [free access]

Using MP2, CCSD, and B3LYP methods of computational chemistry, we show length dependence in the intrinsic elastic properties of short alkane fragments. For isolated alkane fragments of finite length in the gas phase and zero temperature, the intrinsic elasticity constants are found to vary with the number of carbon atoms and its parity. From extrapolation of the elasticity constants calculations to infinite chain length, and by comparing with in-situ elasticity constant of single poly(ethylene) molecule obtained with atomic force microscopy, we estimate the softening effect of environment on the extension response of the polymer.

35
Fiorito, D.; Folliet, S.; Liu, Y.; Mazet, C. “A General Nickel-Catalyzed Kumada Vinylation for the Preparation of 2-Substituted 1,3-Dienes”, ACS Catal. 2018, 8, 1392-1398.open archive unige:101654 pdf full text [restricted access]

The identification of two nickel(II) precatalysts for the preparation of 2-substituted 1,3-dienes by a Kumada cross-coupling between vinyl magnesium bromide and vinyl phosphates is described. This is noteworthy as engaging already only one vinyl derivative in a transition metal-catalyzed cross-coupling reaction is reputedly challenging. Salient features of this method are its operational simplicity, the mild reaction conditions, the low catalyst loadings, the short reaction times, its scalability, and the use of stoichiometric quantities of each coupling partner. The tolerance of the two nickel catalysts to an important number of reactive functional groups and their compatibility with structurally complex molecular architectures has been extensively delineated. A Negishi variant of the reaction has been developed for even more sensitive organic functions such as ester or nitrile. Several other conjugated 1,3-dienes with various substitution patterns have been prepared by combining commercial alkenyl Grignard reagents and/or readily available alkenyl enol phosphates. Proper choice of the nickel catalyst and of the reaction temperature gave access to a variety of different olefin isomers with high levels of stereocontrol. In fine, this approach affords conjugated dienes that would not be accessible otherwise and therefore provides a valuable complement to existing methods.

34
Pellizzoni, M. M.; Schwizer, F.; Wood, C. W.; Sabatino, V.; Cotelle, Y.; Matile, S.; Woolfson, D. N.; Ward, T. R. “Chimeric Streptavidins as Host Proteins for Artificial Metalloenzymes”, ACS Catal. 2018, 8, 1476-1484.open archive unige:101713 pdf full text [restricted access]

The streptavidin scaffold was expanded with well-structured naturally occurring motifs. These chimeric scaffolds were tested as host for biotinylated catalysts as artificial metalloenzymes (ArM) for asymmetric transfer hydrogenation, ring closing metathesis and anion-π catalysis. The additional second coordination sphere elements significantly influence both the activity and the selectivity of the resulting hybrid catalysts. These findings lead to identify propitious chimeric streptavidins for future directed evolution efforts of artificial metalloenzymes.

33
Dunn, J. D.; Bosmani, C.; Barisch, C.; Raykov, L.; Lefrançois, L. H.; Cardenal-Muñoz, E.; López-Jiménez, A. T.; Soldati, T. “Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses”, Front. Immunol. 2018, 8, art. 1906.open archive unige:103007 pdf full text [free access]

The soil-dwelling social amoeba Dictyostelium discoideum feeds on bacteria. Each meal is a potential infection because some bacteria have evolved mechanisms to resist predation. To survive such a hostile environment, D. discoideum has in turn evolved efficient antimicrobial responses that are intertwined with phagocytosis and autophagy, its nutrient acquisition pathways. The core machinery and antimicrobial functions of these pathways are conserved in the mononuclear phagocytes of mammals, which mediate the initial, innate-immune response to infection. In this review, we discuss the advantages and relevance of D. discoideum as a model phagocyte to study cell-autonomous defenses. We cover the antimicrobial functions of phagocytosis and autophagy and describe the processes that create a microbicidal phagosome: acidification and delivery of lytic enzymes, generation of reactive oxygen species, and the regulation of Zn2+, Cu2+, and Fe2+ availability. High concentrations of metals poison microbes while metal sequestration inhibits their metabolic activity. We also describe microbial interference with these defenses and highlight observations made first in D. discoideum. Finally, we discuss galectins, TNF receptor-associated factors, tripartite motif-containing proteins, and signal transducers and activators of transcription, microbial restriction factors initially characterized in mammalian phagocytes that have either homologs or functional analogs in D. discoideum.

32
Ray, S. K.; Homberg, A.; Vishe, M.; Besnard, C.; Lacour, J. “Efficient Synthesis of Ditopic Polyamide Receptors for Cooperative Ion Pair Recognition in Solution and Solid States”, Chem. Eur. J. 2018, 24, 2944-2018.open archive unige:102565 pdf full text [restricted access]

Following a late-stage functionalization strategy, a series of heteroditopic cryptand receptors were prepared – in three steps only from 1,4-dioxane. As evidenced by 1H-NMR spectroscopic and solid state analyses, these polyamide-crown ether conjugates present general ion pair binding capacity towards salts of monovalent cations and linear triatomic anions.

31
Diop, E. A.; Queiroz, E. F.; Kicka, S.; Rudaz, S.; Diop, T.; Soldati, T.; Wolfender, J.-L. “Survey on medicinal plants traditionally used in Senegal for the treatment of tuberculosis (TB) and assessment of their antimycobacterial activity”, J. Ethnopharmacol. 2018, 216, 71-78.open archive unige:103010 pdf full text [restricted access]

ETHNOPHARMACOLOGICAL RELEVANCE:

In West Africa, populations are used to taking traditional medicine as a first aid against common health problems. In this aspect, many plants are claimed to be effective in the treatment of Tuberculosis (TB), which according to the World Health Organization (WHO) remains one of the world's deadliest communicable diseases.

AIM OF THE STUDY:

The main aim of this study was to identify plants used to treat TB-symptoms by the population of Senegal and to evaluate their possible concomitant use with clinically approved TB-drugs. This approach allowed the selection of plants effectively used in traditional medicine. In order to verify if the usage of some of these plants can be rationalized, the activity of their traditional preparations was assessed with both an intracellular and extracellular antimycobacterial host-pathogen assays.

MATERIALS AND METHODS:

An ethnopharmacological survey conducted on 117 TB-patients and 30 healers in Senegal from March to May 2014. The questionnaires were focused on the use of medicinal plants to treat common TB -symptoms (cough longer than 2 weeks, fever, night sweats, weight loss and bloody sputum). Local plant names, utilized organs (herbal drugs) and traditional formulations of the plants were recorded. Extracts were prepared by mimicking the traditional decoction in boiling water and screened for their antimycobacterial activity using Mycobacterium marinum, as a validated TB surrogate, and an Acanthamoeba castellanii - M. marinum whole-cell based host-pathogen assay, to detect anti-infective activities.

RESULTS:

By the end of the survey, nearly 30 plants were cited and the 12 most cited herbal drugs were collected and their usage documented by extensive literature search. Extracts of the chosen herbs were screened with the described assays; with a main focus on traditional formulas (mainly herbal decoctions). Two of the water extracts from Combretum aculeatum and Guiera senegalensis showed significant antimycobacterial activities when compared to the positive control drug (rifampin). These extracts showed no observable toxicity against amoeba host cells (Acanthamoeba castellanii).

CONCLUSIONS:

This study demonstrates that most of the patients do not concomitantly use plants and TB drugs (~90% of informants) but, instead, most are treated with medicinal plants before they are admitted to a hospital (41%). Interestingly, among the aqueous extracts assayed, two extracts (Combretum aculeatum (Combretaceae) and Guiera senegalensis (Combretaceae)) collected within this survey demonstrate antimycobacterial activities on the validated whole-cell based host-pathogen assay. Both extracts showed significant activities against intracellular and extracellular - M. marinum growth presenting IC50 lower than 0.5mg/ml compared to the reference drug Rifampin (IC50 of 0.4 and 7µg/ml). No toxicity was observed for amoebae cells at concentration until 0.8mg/ml.

30
Kawano, S.; Tamura, Y.; Kojima, R.; Bala, S.; Asai, E.; Michel, A. H.; Kornmann, B.; Riezman, I.; Riezman, H.; Sakae, Y.; Okamoto, Y.; Endo, T. “Structure–function insights into direct lipid transfer between membranes by Mmm1–Mdm12 of ERMES”, J. Cell Biol. 2018, 217, 959-974.

The endoplasmic reticulum (ER)–mitochondrial encounter structure (ERMES) physically links the membranes of the ER and mitochondria in yeast. Although the ER and mitochondria cooperate to synthesize glycerophospholipids, whether ERMES directly facilitates the lipid exchange between the two organelles remains controversial. Here, we compared the x-ray structures of an ERMES subunit Mdm12 from Kluyveromyces lactis with that of Mdm12 from Saccharomyces cerevisiae and found that both Mdm12 proteins possess a hydrophobic pocket for phospholipid binding. However in vitro lipid transfer assays showed that Mdm12 alone or an Mmm1 (another ERMES subunit) fusion protein exhibited only a weak lipid transfer activity between liposomes. In contrast, Mdm12 in a complex with Mmm1 mediated efficient lipid transfer between liposomes. Mutations in Mmm1 or Mdm12 impaired the lipid transfer activities of the Mdm12–Mmm1 complex and furthermore caused defective phosphatidylserine transport from the ER to mitochondrial membranes via ERMES in vitro. Therefore, the Mmm1–Mdm12 complex functions as a minimal unit that mediates lipid transfer between membranes.

29
Caprice, K.; Pupier, M.; Kruve, A.; Schalley, C.; Cougnon, F. B. L. “Imine-based [2]catenanes in water”, Chem. Sci. 2018, 9, 1317-1322.open archive unige:101920 pdf full text [free access]

We report the efficient condensation of imine-based macrocycles from dialdehyde A and aliphatic diamines Bn in pure water. Within the libraries, we identified a family of homologous amphiphilic [2]catenanes, whose self-assembly is primarily driven by the hydrophobic effect. The length and odd-even character of the diamine alkyl linker dictate both the yield and the conformation of the [2]catenanes, whose particular thermodynamic stability further shifts the overall equilibrium in favour of imine condensation. These findings highlight the role played by solvophobic effects in the self-assembly of complex architectures.

28
Hagemann, H.; Sharma, M.; Sethio, D.; Lawson Daku, L. M. “Correlating boron-hydrogen stretching frequencies with boron-hydrogen bond lengths in closoboranes: an approach using DFT calculations”, Helv. Chim. Acta 2018, 101, e1700239.

Using harmonic and anharmonic DFT calculations, we have established a general correlation between B-H stretching frequencies and B-H bond lengths valid for the closoboranes BxHx2- (x=6-12), substituted closoboranes B12H12-nXn2- (with X=F, Cl, Br and n = 1-3 and 9-12) and the carboranes CB9H10- and CB11H12-, suggesting that this correlation is also applicable to other similar species. It appears that the average B-H stretching frequency observed around 2500 cm−1 shift by about -100 cm−1 if the average B-H bond length increases by 1 pm. In contrast to BH4-, the B-H bond in closoboranes is practically covalent and the correlation evidenced between its stretching frequency and its length proves to be similar to the one observed for the C-H bond.

27
Nicolussi, A.; Dunn, J. D.; Mlynek, G.; Bellei, M.; Zamocky, M.; Battistuzzi, G.; Djinović-Carugo, K.; Furtmüller, P. G.; Soldati, T.; Obinger, C. “Secreted heme peroxidase from Dictyostelium discoideum: Insights into catalysis, structure, and biological role”, J. Biol. Chem. 2018, 293, 1330-1345.open archive unige:103008 pdf full text [restricted access]

Oxidation of halides and thiocyanate by heme peroxidases to antimicrobial oxidants is an important cornerstone in the innate immune system of mammals. Interestingly, phylogenetic and physiological studies suggest that homologous peroxidases are already present in mycetozoan eukaryotes such as Dictyostelium discoideum. This social amoeba kills bacteria via phagocytosis for nutrient acquisition at its single-cell stage and for antibacterial defense at its multicellular stages. Here, we demonstrate that peroxidase A from D. discoideum (DdPoxA) is a stable, monomeric, glycosylated, and secreted heme peroxidase with homology to mammalian peroxidases. The first crystal structure (2.5 Å resolution) of a mycetozoan peroxidase of this superfamily shows the presence of a post-translationally-modified heme with one single covalent ester bond between the 1-methyl heme substituent and Glu-236. The metalloprotein follows the halogenation cycle, whereby compound I oxidizes iodide and thiocyanate at high rates (>108 M−1 s−1) and bromide at very low rates. It is demonstrated that DdPoxA is up-regulated and likely secreted at late multicellular development stages of D. discoideumwhen migrating slugs differentiate into fruiting bodies that contain persistent spores on top of a cellular stalk. Expression of DdPoxA is shown to restrict bacterial contamination of fruiting bodies. Structure and function of DdPoxA are compared with evolutionary-related mammalian peroxidases in the context of non-specific immune defense.

26
Cuartero, M.; Pérez, S.; García, M. S.; García-Cánovas, F.; Ortuño, J. A. “Comparative enzymatic studies using ion-selective electrodes. The case of cholinesterases”, Talanta 2018, 180, 316-322.

The application of traditional ion-selective electrodes for comparative enzymatic analysis was demonstrated for the first time in this study. A kinetic-potentiometric method based on the monitoring of the concentration of the ionic substrate involved in the enzymatic reaction catalyzed by different cholinesterases is used for this purpose. A comparative study was performed comprising both enzymatic assays using different ionic substrates and the corresponding inhibited reactions in presence of neostigmine (a synthetic anticholinesterase). The developed approach is used to obtain valuable comparative results through calculation of kinetic parameters, such as Michaelis and inhibition constants. Interesting results were obtained for acetylcholinesterase and butyrylcholinesterase enzymes, which were selected as proof-of-concept: (i) the binding affinity that these enzymes have for their natural substrates showed to be higher (acetylcholine and butyrylcholine respectively) than for their corresponding thiol derivatives (acetylthiocholine and butyrylthiocholine), which are traditionally used in spectrophotometric enzymatic assays; (ii) as expected, the maximum hydrolysis rate found in the assays of each enzyme was independent of the substrate used; (iii) acetylcholinesterase enzyme inhibition due to neostigmine was found to be higher (higher inhibition constant). Advantageously, the use of ion-selective electrodes permits to perform cholinesterases’ enzymatic assays using their natural substrates and under physiological conditions, unlike the traditional spectrophotometric methods used in routine enzymatic assays. Importantly, while well-known enzymes are use throughout this work, this approach can be extended to other types of enzymatic assays as a tangible alternative to traditional spectrophotometric methods.

25
Brucka, M.; Sheberstov, K.; Jeannerat, D. “Homonuclear decoupling in the 13C indirect dimension of HSQC experiments for 13C-enriched compounds”, Magn. Reson. Chem. 2018, 56, 1021-1028.open archive unige:107879 pdf full text [restricted access]

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.

24
Franzoni, I.; Yoon, H.; García-López, J.-A.; Poblador-Bahamonde, A. I.; Lautens, M. “Exploring the mechanism of the Pd-catalyzed spirocyclization reaction: a combined DFT and experimental study”, Chem. Sci. 2018, 9, 1496-1509.open archive unige:102306 pdf full text [free access]

The mechanism of the palladium-catalyzed spirocyclization of acrylamides has been investigated by density functional theory and experimental studies. The results support a mechanistic pathway that proceeds via oxidative addition, intramolecular carbopalladation, C–H bond activation, and migratory insertion sequence. The M06L/def2-TZVPP//BP86/6-31G(d,p)/LANL2DZ level of theory used and the inclusion of solvent effects provide results in good agreement with the experimental data. The C–H bond activation step proceeds via a concerted outer-sphere metallation deprotonation mechanism that explains the absence of a measurable kinetic isotopic effect. The subsequent intermolecular migratory insertion of arynes is significantly faster than the insertion of internal alkynes. Furthermore, the regioselectivities calculated in the case of unsymmetrical reactants are remarkably close to the experimental values. Evaluation of the potential energy surfaces for specific substrates provides an explanation for the lack of product formation observed experimentally. Finally, the computational and experimental analyses of potential side reactions are also presented and support the initially proposed mechanism.

23
Tsemperouli, M.; Sugihara, K. “Characterization of di-4-ANEPPS with nano-black lipid membranes”, Nanoscale 2018, 10, 1090-1098.

We report a platform based on lateral nano-black lipid membranes (nano-BLMs), where electrical measurements and fluorescence microscopy setup are combined, for the calibration of di-4-ANEPPS, a common voltage sensitive dye (VSD). The advantage of this setup is (1) its flexibility in the choice of lipids and applied voltages, (2) its high stability that enables a high voltage (500 mV) application and long-time measurements and (3) its fluorescence microscopy readout, which can be directly correlated with other fluorescence microscopy experiments using VSDs (e.g. membrane potential measurements in living cells). Using this setup, we observed that the calibration curve of di-4-ANEPPS is strongly dependent on the net electric charge of the lipids. The developed setup can be used to calibrate VSDs in different lipid environments in order to better understand their fundamental voltage-sensing mechanism in the future.

22
Babel, L.; Baudet, K.; Hoang, T. N. Y.; Nozary, H.; Piguet, C. “A Rational Approach to Metal Loading of Organic Multi-Site Polymers: Illusion or Reality?”, Chem. Eur. J. 2018, 24, 5423-5433.open archive unige:104264 pdf full text [restricted access]

Since its identification as an independent topic after the first world war, the chemistry of (bio)polymers and macromolecules rapidly benefited from intense synthetic activities driven by contributors focussing on formulation and structural aspects. Satisfying rationalization and predictions concerning polymer organization, stability and reactivity were however delayed until the late fifties, when physical chemists set the basis of an adapted thermodynamic modelling. The recent emergence of metal-containing (bio)organic polymers (i.e. metallopolymers) thus corresponds to a logical extension of this field with the ultimate goal of combining the rich magnetic and optical properties of open-shell transition metals with the processability and structural variety of polymeric organic scaffolds. Since applications as energy storage materials, drug delivery vectors, shape-memory materials and photonic devices can be easily envisioned for these materials, the development of metallopolymers is faced to some urgency in producing novel exploitable structures, while the rational control of their formation, organization and transformation remains elusive. Caught between the sometimes antagonistic requirements of economic efficiency on one side and of scientific pertinence on the other side, the ongoing achievements in the control of the metal loadings of multi-site polymers are highlighted here with some tutorial discussions of luminescent lanthanidopolymers as proof-of-concept.

21
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, 30, 650-657.open archive unige:103468 pdf full text [restricted access]

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.

20
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, 20, 837-849.

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.

19
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, 47, 596-607.open archive unige:103103 pdf full text [restricted access]

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.

18
Zdrachek, E.; Bakker, E. “Describing Ion Exchange at Membrane Electrodes for Ions of Different Charge”, Electroanalysis 2018, 30, 633-640.

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.

17
Smith, A. M.; Maroni, P.; Borkovec, M. “Attractive Non-DLVO Forces Induced by Adsorption of Monovalent Organic Ions”, Phys. Chem. Chem. Phys. 2018, 20, 158-164.open archive unige:102861 pdf full text [restricted access]

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.

16
Chang, D.; Kim, K. T.; Lindberg, E.; Winssinger, N. “Accelerating Turnover Frequency in Nucleic Acid Templated Reactions”, Bioconjugate Chem. 2018, 29, 158-163.open archive unige:101529 pdf full text [restricted access]

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.

15
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 2018, 101, e1700265.open archive unige:101609 pdf full text [restricted access]

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.

14
Cui, H.; Garrigues, P.; Gauglitz, G.; Hilder, E.; Hopfgartner, G.; Muddiman, D. C.; Roda, A.; Sanz-Medel, A.; Wise, S. A.; Woolley, A. T.; Zhang, L. “Editorial: The scope of Analytical and Bioanalytical Chemistry (ABC)”, Anal. Bioanal. Chem. 2018, 413, 649-650.

13
Sayers, J.; Payne, R. J.; Winssinger, N. “Peptide nucleic acid-templated selenocystine–selenoester ligation enables rapid miRNA detection”, Chem. Sci. 2018, 9, 896-903.open archive unige:101712 pdf full text [free access]

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.

12
Rouster, P.; Pavlovic, M.; Szilagyi, I. “Immobilization of Superoxide Dismutase on Polyelectrolyte-Functionalized Titania Nanosheets”, ChemBioChem 2018, 19, 404-410.

The superoxide dismutase (SOD) enzyme was successfully immobilized on titania nanosheets (TNS) functionalized with the poly(diallyldimethylammonium chloride) (PDADMAC) polyelectrolyte. The TNS–PDADMAC solid support was prepared by hydrothermal synthesis followed by self-assembled polyelectrolyte layer formation. It was found that SOD strongly adsorbed onto oppositely charged TNS–PDADMAC through electrostatic and hydrophobic interactions. The TNS–PDADMAC–SOD material was characterized by light scattering and microscopy techniques. Colloidal stability studies revealed that the obtained nanocomposites possessed good resistance against salt-induced aggregation in aqueous suspensions. The enzyme kept its functional integrity upon immobilization; therefore, TNS–PDADMAC–SOD showed excellent superoxide radical anion scavenging activity. The developed system is a promising candidate for applications in which suspensions of antioxidant activity are required in the manufacturing processes.

11
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, 9, 325-335.open archive unige:101289 pdf full text [free access]

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.

10
Lagoutte, R.; Serba, C.; Winssinger, N. “Synthesis of deoxyelephantopin analogues”, J. Antibiot. 2018, 71, 248-256.open archive unige:101832 pdf full text [restricted access]

Deoxyelephantopin is a sesquiterpene lactone that was reported to be as effective in the treatment of mammary tumours and lung metastasis as taxol based on a murine orthotopic cancer model. Its germacrene skeleton harbours three Michael acceptors that can potentially engage a target covalently. Its strained 10-membered ring is densely functionalised and represents an important synthetic challenge. We herein describe our studies towards deoxyelephantopins using a ring-closing metathesis approach and report some unexpected observations.

9
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, 269, 128-135.

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.

8
Bassolino, G.; Nançoz, C.; Thiel, Z.; Bois, E.; Vauthey, E.; Rivera-Fuentes, P. “Photolabile coumarins with improved efficiency through azetidinyl substitution”, Chem. Sci. 2018, 9, 387-391.

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.

7
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. 2018, 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.

6
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, 30, 596-601.

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.

5
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, 39, 51-59.

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.

4
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.open archive unige:101844 pdf full text [restricted access]

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.

3
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, 17, 511-519.

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.

2
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 (log K pot Cl-/Sal- =+1.0) and thiocyanate (log K pot Cl-/SCN- =+0.1). Ionophore I-based ISEs were successfully applied for chloride determination in undiluted human serumas 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.

1
Banafsheh, M.; Wesolowski, T. A. “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.