Publications

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154
Achard, T.; Egger, L.; Tortoreto, C.; Guénée, L.; Lacour, J. “Preparation and structural characterization of [CpRu(1,10-phenanthroline)(CH3CN)][X] and precursor complexes (X= PF6, BArF, TRISPHAT-N)”, Helv. Chim. Acta 2020, in press.

Cationic [Ru(η5-C5H5 )(CH3CN)3] + complex, tris(acetonitrile)(cyclopentadienyl)ruthenium(II), gives rise to a very rich organometallic chemistry. Combined with diimine ligands, and 1,10-phenanthroline in particular, this system efficiently catalyzes diazo decomposition processes to generate metal-carbenes which undergo series of original transformations in presence of Lewis basic substrates. Herein, syntheses and characterizations of [CpRu(Phen)(L)] complexes with (large) lipophilic non-coordinating (PF6 and BArF ) and coordinating N-TRISPHAT anions are reported. Complex [CpRu(η6-naphthalene)][BArF] [1][BArF] is readily accessible, in high yield, by direct counterion exchange between [1][PF6] and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF) salts. Ligand exchange of [1][BArF] in acetonitrile generated stable [Ru(η5-C5H5)(CH3CN)3][BArF] [2][BArF] complex in high yield. Then, the desired [CpRu(Phen)(CH3 CN)] [3] complexes were obtained from either the [1] or [2] complex in the presence of the 1,10-phenanthroline as ligand. For characterization and comparison purposes, the anionic hemilabile ligand TRISPHAT-N (TTN) was introduced on the ruthenium center, from the complex [3][PF6] , to quantitatively generate the desired complex [CpRu(Phen)(TTN)] [4] by displacement of the remaining acetonitrile ligand and of the PF6 anion. Solid state structures of complexes [1][BArF] , [2][BArF] , [3][BArF] , [3][PF6] and [4] were determined by X-ray diffraction studies and are discussed herein.

153
Soda, Y.; Gao, W.; Bosset, J.; Bakker, E. “Emulsion Doping of Ionophores and Ion-Exchangers into Ion-Selective Electrode Membranes”, Anal. Chem. 2020, in press.

Ion-selective electrodes (ISEs) are widely used analytical devices to selectively measure ionic species. Despite significant advances in recent years, ion-selective membranes are still mostly prepared in the same manner, by preloading the selective components into a solvent that is subsequently cast into a membrane or film. This paper describes an alternative method to prepare ISE membranes by mass transfer of the sensing components from an emulsion phase. Specifically, blank (undoped) plasticized poly(vinyl chloride) (PVC) membranes mounted into an electrode body are immersed into an aqueous solution containing analyte ions and an appropriate emulsion of the desired sensing components to allow their transfer into the membrane. The concept is demonstrated with conventional membrane electrodes containing an inner solution as well as all-solid-state electrodes. It is shown to be universally useful for the realization of ISEs for K+, Na+, Ca2+, and NO3.

152
Kato, T.; Strakova, K.; García-Calvo, J.; Sakai, N.; Matile, S. “Mechanosensitive Fluorescent Probes, Changing Color Like Lobsters During Cooking:  Cascade Switching Variations”, Bull. Chem. Soc. Jpn. 2020, 93, 1401-1411.open archive unige:143116 pdf full text [restricted access]

Fluorescent flipper probes have been introduced recently to image physical forces in biology. Their design is inspired by the combination of planarization and polarization that makes the color of astaxanthin, a carotenoid, turn blue in living lobsters or shrimps. Flipper probes are constructed around twisted dithienothiophene dimers. Upon planarization, donors and acceptors placed on both sides are coupled to generate push-pull systems that shift excitation maxima to the red, while the emission wavelength is mechanoinsensitive. To assure chemical stability, these donors and acceptors have to turn on only upon planarization. In living lobster, this is achieved most beautifully with non-covalent hydrogen bonds to and from the surrounding, planarizing protein. With flipper probes, the unorthodox chalcogen bonds prove best to produce turn-on donors and acceptors. The specific objective of this study was to explore different turn-on donors for the resulting chalcogen-bonding cascade switches. The focus is on substitution of the original triazoles with ethylenedioxythiophene (EDOT) and ortho-hydroxyphenyl (HOP) donors. Design, synthesis and evaluation of the respective flipper probes are described.

151
Shybeka, I.; Aster, A.; Cheng, Y.; Sakai, N.; Frontera, A.; Vauthey, E.; Matile, S. “Naphthalenediimides with Cyclic Oligochalcogenides in Their Core”, Chem. Eur. J. 2020, in press.

Naphthalenediimides (NDIs) are privileged scaffolds par excellence, of use in functional systems from catalysts to ion channels, photosystems, sensors, ordered matter in all forms, tubes, knots, stacks, sheets, vesicles, and colored over the full visible range. Despite this extensively explored chemical space, there is still room to discover core-substituted NDIs with fundamentally new properties: NDIs with cyclic trisulfides (i.e., trisulfanes) in their core absorb at 668?nm, emit at 801?nm, and contract into disulfides (i.e., dithietes) upon irradiation at <475?nm. Intramolecular 1,5-chalcogen bonds account for record redshifts with trisulfides, ring-tension mediated chalcogen-bond-mediated cleavage for blueshifts to 492?nm upon ring contraction. Cyclic oligochalcogenides (COCs) in the NDI core open faster than strained dithiolanes as in asparagusic acid and are much better retained on thiol exchange affinity columns. This makes COC-NDIs attractive not only within the existing multifunctionality, particularly artificial photosystems, but also for thiol-mediated cellular uptake.

150
Wesolowski, T. A. “On the correlation potential in Frozen-Density Embedding Theory”, J. Chem. Theory Comput. 2020, in press.

The correlation functional Ec[ρ] known in Levy's constrained search formulation of density functional theory is also one of the components of the energy functional in Frozen-Density Embedding Theory (FDET) [Wesolowski, Phys. Rev. A, 77 (2008) 012504] if the embedded wavefunction has the single determinant form. The relation between the FDET energy and quantities available from an auxiliary system is derived. In the auxiliary system, Ec[ρ] and its functional derivative (correlation potential) are entirely neglected. The relation is exact up to the quadratic terms density changes caused by electron-electron correlation. It is discussed in view of its practical applications in modelling electronic structure of embedded species.

149
Kubiak, K.; Maroni, P.; Trefalt, G.; Borkovec, M. “Oscillatory structural forces between charged interfaces in solutions of oppositely charged polyelectrolytes”, Soft Matter 2020, in press.

Forces between negatively charged micron-sized silica particles were measured in aqueous solutions of cationic polyelectrolytes with an atomic force microscope (AFM). In these oppositely charged systems, damped oscillatory force profiles were systematically observed in systems at higher polyelectrolyte concentrations, typically around few g L−1. The wavelength of these oscillations is decreasing with increasing concentration. When the wavelength and concentration are normalized with the cross-over concentration, universal power-law dependence is found. Thereby, the corresponding scaling exponent changes from 1/3 in the dilute regime to 1/2 in the semi-dilute regime. This dependence is the same as in the like-charged systems, which were described in the literature earlier. This common behavior suggests that these oscillatory forces are related to the structuring of the polyelectrolyte solutions. The reason that the oppositely charged systems behave similarly to like-charged ones is that the former systems undergo a charge reversal due to the adsorption of the polyelectrolytes to the oppositely charged surface, whereby sufficiently homogeneous adsorbed layers are being formed. The main finding of the present study is that at higher polyelectrolyte concentrations such oscillatory forces are the rule, including the oppositely charged ones.

148
Martinent, R.; Du, D.; López-Andarias, J.; Sakai, N.; Matile, S. “Oligomers of Cyclic Oligochalcogenides for Enhanced Cellular Uptake”, ChemBioChem 2020, in press.

Monomeric cyclic oligochalcogenides (COCs) are emerging as attractive transporters to deliver substrates of interest into the cytosol through thiol-mediated uptake. The objective of this study was to explore COC oligomers.   We report a systematic evaluation of monomers, dimers, and trimers of asparagusic, lipoic, and diselenolipoic acid as well as their supramolecular monomers, dimers, trimers, and tetramers.   COC dimers were more than twice more active than the monomers on the covalent and the non-covalent level, while COC trimers were not much better than dimers.   These trends might suggest that thiol-mediated uptake of COCs is synergistic over both short and long distances, i.e., involves more than two COCs and more than one membrane protein, although other interpretations cannot be excluded at this level of complexity.   These results thus provide attractive perspectives for structural evolution as well as imminent use in practice.   Moreover, they validate automated HC-CAPA as an invaluable method to collect comprehensive data on cytosolic delivery within a reasonable time at a level of confidence that is otherwise inconceivable.

147
Moneva Lorente, P.; Wallabregue, A.; Zinna, F.; Besnard, C.; Di Bari, L.; Lacour, J. “Synthesis and properties of chiral fluorescent helicene-BODIPY conjugates”, Org. Biomol. Chem. 2020, 18, 7677-7684.open archive unige:142591 pdf full text [free access]

A series of chiral fluorescent helicene-BODIPY conjugates was prepared by the regioselective formylation of aza[4]helicene precursors and then an efficient one-pot two-step BODIPY synthesis (13 examples, 28-82%). Fused conjugates exhibit absorption and fluorescence properties (ΦF 30-45%) in the red visible domain, and a CPL signature could be measured at 605 nm (glum ±5·10-4). Photophysical and electronic properties were investigated and rationalized through first principles.

146
Saleh, N.; Bosmani, A.; Besnard, C.; Bürgi, T.; Jacquemin, D.; Lacour, J. “Access to Chiral Rigid Hemicyanine Fluorophores from Tröger Bases and α-Imino Carbenes”, Org. Lett. 2020, 22, 7599-7603.open archive unige:142473 pdf full text [restricted access]

Chiral hemicyanine fluorophores are afforded in three steps only from Tröger bases via α-imino carbene additions, an original aminal deprotection and Cu(II)-mediated oxidations. The stable benzodiazepinoindolium salts are readily isolated and present (chir)optical properties that can be fine-tuned by late-stage cross-coupling functionalization. The hemicyanine character of dyes was rationalized using first principles.

145
Kraikaew, P.; Sailapu, S. K.; Bakker, E. “Rapid Constant Potential Capacitive Measurements with Solid-Contact Ion-Selective Electrodes Coupled to Electronic Capacitor”, Anal. Chem. 2020, 92, 14174-14180.

A constant potential capacitive readout of solid-contact ion-selective electrodes (SC-ISE) allows one to obtain easily identifiable current transients that can be integrated to obtain a charge vs. logarithmic activity relationship. The resulting readout can therefore be much more sensitive than traditional open circuit potentiometry. Unfortunately, however, comparatively long measurement times and significant baseline current drifts make it currently difficult to fully realize the promise of this technique. We show here that this challenge is overcome by placing the SC-ISE in series with an electronic capacitor, with pH probes as examples. Kirchhoff’s law is shown to be useful to choose an adequate range of added capacitances so that it dominates the overall cell value. Two different ion-to-electron transducing materials, functionalized single wall carbon nanotubes (f-SWCNTs) and poly(3-octyl thiophene) (POT), were explored as solid contact transducing layers. The established SC-ISE based f-SWCNT transducer is found to be compatible with a wide range of external capacitances up to 100 µF, while POT layers require a narrower range of 1 µF to 4.7 µF. Importantly, the time for a charging transient to reach equilibrium was found be less than 10 s, which is dramatically faster than without added electronic component. Owing to the ideal behavior of capacitor, the response current decays rapidly to zero, making the determination of the integrated charge practically applicable.

144
Trushko, A.; Di Meglio, I.; Merzouki, A.; Blanch-Mercader, C.; Abuhattum, S.; Guck, J.; Alessandri, K.; Nassoy, P.; Kruse, K.; Chopard, B.; Roux, A. “Buckling of an Epithelium Growing under Spherical Confinement”, Dev. Cell 2020, 54, 655-668.e6.

Many organs are formed through folding of an epithelium. This change in shape is usually attributed to tissue heterogeneities, for example, local apical contraction. In contrast, compressive stresses have been proposed to fold a homogeneous epithelium by buckling. While buckling is an appealing mechanism, demonstrating that it underlies folding requires measurement of the stress field and the material properties of the tissue, which are currently inaccessible in vivo. Here, we show that monolayers of identical cells proliferating on the inner surface of elastic spherical shells can spontaneously fold. By measuring the elastic deformation of the shell, we infer the forces acting within the monolayer and its elastic modulus. Using analytical and numerical theories linking forces to shape, we find that buckling quantitatively accounts for the shape changes of our monolayers. Our study shows that forces arising from epithelial growth in three-dimensional confinement are sufficient to drive folding by buckling.

143
Wang, Y.; Nieto-Ortega, B.; Bürgi, T. “Amplification of enantiomeric excess by dynamic inversion of enantiomers in deracemization of Au38 clusters”, Nat. Commun. 2020, 11, 4562.

Symmetry breaking and amplification processes have likely played a fundamental role in the development of homochirality on earth. Such processes have not been much studied for inorganic matter at the nanoscale. Here, we show that the balance between left- and right-handed intrinsically chiral metal clusters can be broken by adsorbing a small amount of a chiral molecule in its ligand shell. We studied the amplification of enantiomeric excess of the Au38(2-PET)24 cluster (2-PET = 2-phenylethylthiolate). By exchanging a small fraction of the achiral 2-PET ligand by chiral R-1,1′-binaphthyl-2,2′-dithiol (R-BINAS), a mixture of species is obtained composed of anticlockwise (A) and clockwise (C) versions of Au38(2-PET)24 and Au38(2-PET)22(R-BINAS)1. At 70 °C, the system evolves towards the anticlockwise clusters at the expense of the clockwise antipode. It is shown that the interplay between the diastereospecific ligand exchange, which introduces selectivity but does not change the A/C ratio, and the fast racemization of the Au38(2-PET)24 is at the origin of this observation.

142
Marinova, M.; Pascal, S.; Guénée, L.; Besnard, C.; Shivachev, B.; Kostova, K.; Villani, C.; Franzini, R.; Dimitrov, V.; Lacour, J. “Synthesis, Resolution, Configurational Stability, and Properties of Cationic Functionalized [5]Helicenes”, J. Org. Chem. 2020, 85, 11908-11923.open archive unige:142016 pdf full text [free access]

A straightforward approach to the synthesis of two different series of cationic [5]helicenes has been achieved including, in dioxa series, the possibility to introduce aromatic functional groups at the periphery of the helical structure. While photophysical study highlights that the introduction of aryl substituents at position 23 of the helical moieties has a negligible impact on the optical properties, styryl substituents allow a welcoming extension of the conjugation pathways. Finally, a redshift of the optical properties was evidenced upon introduction of nitrogen atoms in the helicene scaffold, leading to particularly good fluorescence efficiencies in the red domain for a helicenic dye. Detailed information on racemization kinetics was collected for the most stable species upon direct HPLC resolution or, when configurational lability was too high, through VT-HPLC analysis on chiral stationary phase (ΔG values ranging from 85.0 to 137.1 kJ.mol-1 and above).

141
Farrera-Soler, L.; Daguer, J.-P.; Barluenga, S.; Vadas, O.; Cohen, P.; Pagano, S.; Yerly, S.; Kaiser, L.; Vuilleumier, N.; Winssinger, N. “Identification of immunodominant linear epitopes from SARS-CoV-2 patient plasma”, PLoS One 2020, 15, e0238089.open archive unige:141686 pdf full text [free access]

A novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) is the source of a current pandemic (COVID-19) with devastating consequences in public health and economic stability. Using a peptide array to map the antibody response of plasma from healing patients (12) and heathy patients (6), we identified three immunodominant linear epitopes, two of which correspond to key proteolytic sites on the spike protein (S1/S2 and S2’) known to be critical for cellular entry. We show biochemical evidence that plasma positive for the epitope adjacent to the S1/S2 cleavage site inhibits furin-mediated proteolysis of spike.

Preprint in medRxiv 2020, 2020.06.15.20131391

140
Jiménez, J.-R.; Poncet, M.; Doistau, B.; Besnard, C.; Piguet, C. “Luminescent polypyridyl heteroleptic CrIII complexes with high quantum yields and long excited state lifetimes”, Dalton Trans. 2020, 49, 13528-13532.open archive unige:142590 pdf full text [free access]

Implementing high quantum yields and long-lived excited state lifetimes within heteroleptic luminescent CrIII complexes is a keystone for the design of supramolecular energy-converting devices exploiting this cheap metal. In this contribution, we discuss the stepwise and rational optimization of these two limiting factors within a series of heteroleptic CrIII complexes.

139
Pfitzner, A.-K.; Mercier, V.; Jiang, X.; Moser von Filseck, J.; Baum, B.; Zaric, A.; Roux, A. “An ESCRT-III Polymerization Sequence Drives Membrane Deformation and Fission”, Cell 2020, 182, 1140-1155.e18.

The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.

138
Sailapu, S. K.; Kraikaew, P.; Sabaté, N.; Bakker, E. “Self-Powered Potentiometric Sensor Transduction to a Capacitive Electronic Component for Later Readout”, ACS Sens. 2020, 5, 2909-2914.

Potentiometric sensors operate as galvanic cells where the voltage is spontaneously generated as a function of the sample composition. We show here that energy can be harvested, stored during the sensing process without external power, and physically isolated from the sensor circuit for later readout. This is accomplished by placing an electronic capacitor as a portable transduction component between the indicator and the reference electrode at the point where one would ordinarily connect the high-input-impedance voltmeter. The voltage across this isolated capacitor indicates the originally measured ion activity and can be read out conveniently, for example, using a simple handheld multimeter. The capacitor is shown to maintain the transferred charge for hours after its complete disconnection from the sensor. The concept is demonstrated to detect the physiological concentrations of K+ in artificial sweat samples. The methodology provides a readout principle that could become very useful in portable form factors and opens possibilities for potentiometric detection in point-of-care applications and inexpensive sensing devices where an external power source is not desired.

137
Cheng, Y.; Pham, A.-T.; Kato, T.; Lim, B.; Moreau, D.; López-Andarias, J.; Zong, L.; Sakai, N.; Matile, S. “Inhibitors of Thiol-Mediated Uptake”, ChemRxiv 2020, in press.

Viral entry into cells can involve thiol-disulfide exchange with exofacial thiols on cell surfaces. The importance of thiol-mediated uptake for viral entry and beyond is poorly understood because efficient inhibitors do not exist. Here we use fluorescent cyclic oligochalcogenides that enter cells by thiol-mediated uptake to systematically screen for inhibitors, including epidithiodiketopiperazines, benzopolysulfanes, disulfide-bridged g-turned peptides, heteroaromatic sulfones and cyclic thiosulfonates, thiosulfinates and disulfides. Different activities found with different reporters reveal thiol-mediated uptake as a complex multitarget process. Initial tests with pseudo-lentivectors expressing SARS-CoV-2 spike protein do not exclude potential for the development of new antivirals.

136
Kündig, E. P. “Editorial”, CHIMIA 2020, 74, 649.open archive unige:143372 pdf full text [free access]

135
Hoogendoorn, S. “Small Molecules Targeting the Hedgehog Pathway: From Phenotype to Mechanistic Understanding”, CHIMIA 2020, 74, 652-658.open archive unige:143155 pdf full text [free access]

Since the beginning of 2019, the Hoogendoorn lab is active at the University of Geneva. We are a Chemical Biology lab and our research focuses on the Hedgehog (Hh) signalling pathway and the primary cilium, a small cellular organelle which corrects structure and function, is required to conduct the Hh signal. Ciliary Hh signalling plays an important role in embryonic development, and its dysregulation consequently results in developmental disorders as well as a variety of cancers. We use an interdisciplinary approach, ranging from organic chemistry to cell biology and genetics, to develop chemical tools to study and perturb ciliary signalling. In this account, I will highlight existing small molecules that target the Hh pathway, our efforts to discover new compounds, and the methodologies that we employ for target deconvolution and mechanism of action studies.

134
Shao, W.; Besnard, C.; Guénée, L.; Mazet, C. “Ni-Catalyzed Regiodivergent and Stereoselective Hydroalkylation of Acyclic Branched Dienes with Unstabilized C(sp3) Nucleophiles”, J. Am. Chem. Soc. 2020, 142, 16486-16492.open archive unige:141221 pdf full text [restricted access]

Two complementary regiodivergent [(P,N)Ni]-catalyzed hydroalkylations of branched dienes are reported. When amides are employed as unstabilized C(sp3) nucleophiles, a highly regioselective 1,4-addition process is favored. The addition products are obtained in high yield and with excellent stereocontrol of the internal olefin. Using a chiral ligand and imides as carbon nucleophiles, a 3,4-addition protocol was developed enabling to construct two contiguous tertiary stereocenters in a single step with moderate to high levels of diastereocontrol and excellent enantiocontrol. Both methods operate under mild reaction conditions, display broad scope and excellent functional group tolerance. The synthetic potential of the 3,4-hydroalkylation reaction was established via a series of post-catalytic modifications.

133
Bakker, E. “Editorial - Triumph and Misery of Measurement Science”, ACS Sens. 2020, 5, 2264-2265.open archive unige:140950 pdf full text [restricted access]

132
Jiménez-Rojo, N.; Leonetti, M. D.; Zoni, V.; Colom, A.; Feng, S.; Iyengar, N. R.; Matile, S.; Roux, A.; Vanni, S.; Weissman, J. S.; Riezman, H. “Conserved Functions of Ether Lipids and Sphingolipids in the Early Secretory Pathway”, Curr. Biol. 2020, 30, 3775-3787.e7.open archive unige:141206 pdf full text [restricted access]

Sphingolipids play important roles in physiology and cell biology, but a systematic examination of their functions is lacking. We performed a genome-wide CRISPRi screen in sphingolipid-depleted human cells and identified hypersensitive mutants in genes of membrane trafficking and lipid biosynthesis, including ether lipid synthesis. Systematic lipidomic analysis showed a coordinate regulation of ether lipids with sphingolipids, suggesting an adaptation and functional compensation. Biophysical experiments on model membranes show common properties of these structurally diverse lipids that also share a known function as glycosylphosphatidylinositol (GPI) anchors in different kingdoms of life. Molecular dynamics simulations show a selective enrichment of ether phosphatidylcholine around p24 proteins, which are receptors for the export of GPI-anchored proteins and have been shown to bind a specific sphingomyelin species. Our results support a model of convergent evolution of proteins and lipids, based on their physico-chemical properties, to regulate GPI-anchored protein transport and maintain homeostasis in the early secretory pathway.

131
Martinent, R.; López-Andarias, J.; Moreau, D.; Cheng, Y.; Sakai, N.; Matile, S. “Automated High-Content Imaging for Cellular Uptake, from the Schmuck Cation to the Latest Cyclic Oligochalcogenides”, Beilstein J. Org. Chem. 2020, 16, 2007-2016.open archive unige:140487 pdf full text [free access]

Recent progress with chemistry tools to deliver into living cells has seen a shift of attention from counterion-mediated uptake of cell-penetrating peptides (CPPs) and their mimics, particularly the Schmuck cation, toward thiol-mediated uptake with cell-penetrating poly(disulfide)s (CPDs) and cyclic oligochalcogenides (COCs), here exemplified by asparagusic acid. A persistent challenge in this evolution is the simultaneous and quantitative detection of cytosolic delivery and cytotoxicity in a high-throughput format. Here, we show that the combination of the HaloTag-based chloroalkane penetration assay (CAPA) with automated high-content (HC) microscopy can satisfy this need. The automated imaging of thousands of cells per condition in multiwell plates allows us to obtain quantitative data on not only the fluorescence intensity but also on the localization in a very short time. Quantitative and statistically relevant results can be obtained from dose–response curves of the targeted delivery to selected cells and the cytotoxicity in the same experiment, even with poorly optimized cellular systems.

130
Moury, R.; Gigante, A.; Remhof, A.; Roedern, E.; Hagemann, H. “Experimental investigation of Mg(B3H8)2 dimensionality, materials for energy storage applications”, Dalton Trans. 2020, 49, 12168-12173.open archive unige:140937 pdf full text [restricted access]

Mg(B3H8)2 is a crucial reaction intermediate in the thermal decomposition of the hydrogen storage material Mg(BH4)2 and is discussed as a potential solid-state Mg-ion conductor. We successfully synthesized unsolvated Mg(B3H8)2 and highlight that Mg(B3H8)2 exists mainly as a low-dimensional solid. In addition, the Mg2+ conductivity was evaluated to be 1.4.10−4 S cm−1 at 80 °C.

129
Bakker, E. “A Scientific Journey with Ionophore-based Sensors”, CHIMIA 2020, 74, 569-576.

This article describes selected historical milestones in the field of neutral ionophore-based sensors, starting with the first discovery by Wilhelm Simon and their impact to analytical sciences despite the initial difficulty to understand their function. The reader is then guided through topics in which the author has been involved over the years, from understanding thermodynamic aspects to the field of non-equilibrium potentiometry, polyion sensors, trace level potentiometry, instrumentally controlled ion sensors and finally potentiometry involving local perturbations and transient currents that allow for new readout possibilities. Discussed applications include clinical diagnostics, environmental in situ sensing/profiling and speciation analysis. The article loosely follows the content of the Simon-Widmer Award lecture of the same title presented by the author at the CH Analysis 2019 conference in Beatenberg, Switzerland.

128
Hoogendoorn, S.; van Puijvelde, G. H. M.; van der Marel, G. A.; van Koppen, C. J.; Timmers, C. M.; Overkleeft, H. S. “Fluorescent small-molecule agonists as follicle-stimulating hormone receptor imaging tools”, RSC Chem. Biol. 2020, 1, 263-272.open archive unige:141218 pdf full text [free access]

Fluorescent cell surface receptor agonists allow visualization of processes that are set in motion by receptor activation. This study describes the synthesis of two fluorescent, low molecular weight ligands for the follicle-stimulating hormone receptor (FSHR), based on a dihydropyridine (DHP) agonist. We show that both BODIPY- and Cy5-conjugated DHP (m-DHP-BDP and m-DHP-Cy5) are potent FSHR agonists, able to activate receptor signalling with nanomolar potencies and to effect receptor internalisation at higher concentrations. FSHR-dependent uptake of m-DHP-Cy5 is in stark contrast to the cellular uptake of m-DHP-BDP which was efficiently internalised also in the absence of FSHR. Our results comprise a first-in-class fluorescent low molecular weight ligand for in situ FSHR imaging and pertain the potential means for targeted delivery of drugs into the endolysosomal pathway of FSHR-expressing cells.

127
Mercier, V.; Larios, J.; Molinard, G.; Goujon, A.; Matile, S.; Gruenberg, J.; Roux, A. “Endosomal Membrane Tension Regulates ESCRT-III-Dependent Intra-Lumenal Vesicle Formation”, Nat. Cell Biol. 2020, 22, 947-959.open archive unige:140488 pdf full text [restricted access]

The plasma membrane tension strongly affects cell surface processes, such as migration, endocytosis and signalling. However, it is not known whether the membrane tension of organelles regulates their functions, notably intracellular traffic. The endosomal sorting complexes required for transport (ESCRT)-III complex is the major membrane remodelling complex that drives intra-lumenal-vesicle (ILV) formation on endosomal membranes. Here we used a fluorescent membrane-tension probe to show that ESCRT-III subunits are recruited onto endosomal membranes when the membrane tension is reduced. We find that tension-dependent recruitment is associated with ESCRT-III polymerization and membrane deformation in vitro and correlates with increased ILV formation in ESCRT-III-decorated endosomes in vivo. Finally, we find that the endosomal membrane tension decreases when ILV formation is triggered by EGF under physiological conditions. These results indicate that membrane tension is a major regulator of ILV formation and endosome trafficking, leading us to conclude that membrane tension can control organelle functions.

126
Garbo, M.; Besnard, C.; Guénée, L.; Mazet, C. “Access to Optically Active 7-Membered Rings by a 2-Step Synthetic Sequence: Cu-Catalyzed Stereoselective Cyclopropanation of Branched 1,3-Dienes/Rh-Catalyzed Stereoconvergent [5+2] Cycloaddition”, ACS Catal. 2020, 10, 9604-9611.open archive unige:140183 pdf full text [restricted access]

We report a 2-step cyclopropanation/cycloaddition catalytic sequence that provides access to optically active 7-membered rings with a carboxyl-bearing tertiary stereocenter. In the first step, the Cu-catalyzed cyclopropanation of branched dienes generates vinylcyclopropanes in high yield, regioselectivity and enantioselectivity albeit in modest cis/trans diastereoselectivity. The stereoconvergent nature of the subsequent Rh-catalyzed [5+2] cycloaddition with alkynes overrides this apparent limitation and affords preferentially one 7-membered ring out of the 8 or 16 possible stereoisomers that can be theoretically generated. The final regioselectivity and enantioselectivity are high in the majority of cases. The method is versatile and tolerates a broad range of functional groups.

125
Baghdasaryan, A.; Martin, K.; Lawson Daku, L. M.; Mastropasqua Talamo, M.; Avarvari, N.; Bürgi, T. “Ligand exchange reactions on the chiral Au38 cluster: CD modulation caused by the modification of the ligand shell composition”, Nanoscale 2020, 12, 18160-18170.open archive unige:140860 pdf full text [free access]

Ligand exchange reactions have become a highly versatile post-synthetic strategy to accurately engineer the ligand shell of atomically precise noble metal nanoclusters. Modifying the chemical structure of the exchanging ligand with chromophore substituents or adding chiral centers allow direct functionalization of the cluster with desired properties. As such, post-functionalized gold nanoclusters with unique physicochemical properties find applications in optoelectronics, catalysis and biomedicine. Herein, we successfully carried out ligand exchange reactions between the chiral Au38(2-PET)24 cluster (both racemic and enantiopure forms) and the helically chiral but configurationally labile 2-thio[4]helicene ligand (TH4). The reaction products with a composition of Au38(2-PET)24−x(TH4)x were analyzed using UV-vis spectroscopy and MALDI mass spectrometry. It was found that up to ten 2-PET ligands can be replaced with the helicene ligand on the cluster surface according to MALDI analysis. Consequently, the UV-vis and CD spectra of the cluster have been strongly affected by the ligand exchange reaction. The intensities of the CD signals of Au38(2-PET)24−x(TH4)x were drastically reduced and red shifted with respect to the reference Au38(2-PET)24 cluster. Moreover, the appearance of the other enantiomer in the HPLC chromatogram revealed the partial racemization of the cluster. DFT calculations were performed and they support the experimental observations and show that the observed chiroptical changes in UV-vis and CD spectra are exchange-site dependent. The calculations also demonstrate that charge transfer (CT) transitions occur between the Au38 cluster and the helicene ligand. Thus the ligand is directly involved in these transitions and contributes to the electronic states comprising those transitions.

124
Angulo, G.; Rosspeintner, A. “Bimolecular photo-induced electron transfer enlightened by diffusion”, J. Chem. Phys. 2020, 153, 040902.open archive unige:141044 pdf full text [restricted access]

Photochemical electron transfer between freely diffusing molecules has been studied extensively. Here, we try to elucidate how much these works have contributed to the understanding of electron transfer. To this end, we have revisited the work performed in the experimental and theoretical areas of concern from the beginning of the 20th century up to the present day. We present a critical look at the major contributions and compile the current picture of a variety of phenomena around electron transfer in solution. This is based on two main developments, besides the theory of Marcus: encounter theories of diffusion and laser techniques in time-resolved spectroscopy.

123
Doistau, B.; Jiménez, J.-R.; Piguet, C. “Beyond Chiral Organic (p-Block) Chromophores for Circularly Polarized Luminescence: The Success of d-Block and f-Block Chiral Complexes”, Front. Chem. 2020, 8, 555.open archive unige:138617 pdf full text [free access]

Chiral molecules are essential for the development of advanced technological applications in spintronic and photonic. The best systems should produce large circularly polarized luminescence (CPL) as estimated by their dissymmetry factor (glum), which can reach the maximum values of −2 ≤ glum ≤ 2 when either pure right- or left-handed polarized light is emitted after standard excitation. For matching this requirement, theoretical considerations indicate that optical transitions with large magnetic and weak electric transition dipole moments represent the holy grail of CPL. Because of their detrimental strong and allowed electric dipole transitions, popular chiral emissive organic molecules display generally moderate dissymmetry factors (10−5glum ≤ 10−3). However, recent efforts in this field show that glum can be significantly enhanced when the chiral organic activators are part of chiral supramolecular assemblies or of liquid crystalline materials. At the other extreme, chiral EuIII- and SmIII-based complexes, which possess intra-shell parity-forbidden electric but allowed magnetic dipole transitions, have yielded the largest dissymmetry factor reported so far with glum ~ 1.38. Consequently, 4f-based metal complexes with strong CPL are currently the best candidates for potential technological applications. They however suffer from the need for highly pure samples and from considerable production costs. In this context, chiral earth-abundant and cheap d-block metal complexes benefit from a renewed interest according that their CPL signal can be optimized despite the larger covalency displayed by d-block cations compared with 4f-block analogs. This essay thus aims at providing a minimum overview of the theoretical aspects rationalizing circularly polarized luminescence and their exploitation for the design of chiral emissive metal complexes with strong CPL. Beyond the corroboration that f–f transitions are ideal candidates for generating large dissymmetry factors, a special attention is focused on the recent attempts to use chiral CrIII-based complexes that reach values of glum up to 0.2. This could pave the way for replacing high-cost rare earths with cheap transition metals for CPL applications.

122
Li, H.; Duwald, R.; Pascal, S.; Voci, S.; Besnard, C.; Bosson, J.; Bouffier, L.; Lacour, J.; Sojic, N. “Near-Infrared Electrochemiluminescence in Water through Regioselective Sulfonation of Diaza [4] and [6]helicene Dyes”, Chem. Commun. 2020, 56, 9771-9774.open archive unige:140303 pdf full text [restricted access]

A series of water-soluble helicene dyes generating intense electrochemiluminescence (ECL) signal in physiological conditions is reported. Those species were prepared using diaza [4] and [6]helicenes as structural cores modified with sulfonate groups in various positions. Such functional groups improve their water solubility and induce a red-shifted emission. Efficient ECL emission up to the near-infrared is achieved in water.

121
Nuck, J.; Sugihara, K. “Mechanism of Polydiacetylene Blue-to-Red Transformation Induced by Antimicrobial Peptides”, Macromolecules 2020, 53, 6469-6475.open archive unige:140936 pdf full text [restricted access]

Thermochromic temperature of polydiacetylene has been reported to coincide with the melting temperature of its lipidic monomers, indicating that the solid-to-liquid phase transition of monomers is linked to the color change. In this work, we study a hypothesis that peptide-induced chromism is similarly mediated by the lipid phase transition as many antimicrobial peptides are known to modulate the melting temperature of lipids.

120
Straková, K.; López-Andarias, J.; Jiménez-Rojo, N.; Chambers, J. E.; Marciniak, S. J.; Riezman, H.; Sakai, N.; Matile, S. “HaloFlippers:  A General Tool for the Fluorescence Imaging of Precisely Localized Membrane Tension Changes in Living Cells”, ACS Cent. Sci. 2020, 6, 1376-1385.open archive unige:140489 pdf full text [free access]

Tools to image membrane tension in response to mechanical stimuli are badly needed in mechanobiology. We have recently introduced mechanosensitive flipper probes to report quantitatively global membrane tension changes in fluorescence lifetime imaging microscopy (FLIM) images of living cells. However, to address specific questions on physical forces in biology, the probes need to be localized precisely in the membrane of interest (MOI). Herein we present a general strategy to image the tension of the MOI by tagging our newly introduced HaloFlippers to self-labeling HaloTags fused to proteins in this membrane. The critical challenge in the construction of operational HaloFlippers is the tether linking the flipper and the HaloTag: It must be neither too taut nor too loose, be hydrophilic but lipophilic enough to passively diffuse across membranes to reach the HaloTags, and allow partitioning of flippers into the MOI after the reaction. HaloFlippers with the best tether show localized and selective fluorescence after reacting with HaloTags that are close enough to the MOI but remain nonemissive if the MOI cannot be reached. Their fluorescence lifetime in FLIM images varies depending on the nature of the MOI and responds to myriocin-mediated sphingomyelin depletion as well as to osmotic stress. The response to changes in such precisely localized membrane tension follows the validated principles, thus confirming intact mechanosensitivity. Examples covered include HaloTags in the Golgi apparatus, peroxisomes, endolysosomes, and the ER, all thus becoming accessible to the selective fluorescence imaging of membrane tension.

119
Krishnadas, K. R.; Sementa, L.; Medves, M.; Fortunelli, A.; Stener, M.; Fürstenberg, A.; Longhi, G.; Bürgi, T. “Chiral Functionalization of an Atomically Precise Noble Metal Cluster: Insights into the Origin of Chirality and Photoluminescence”, ACS Nano 2020, 14, 9687-9700.

We probe the origin of photoluminescence of an atomically precise noble metal cluster, Ag24Au1(DMBT)18, (DMBT = 2,4-dimethylbenzenethiolate) and the origin of chirality in its chirally functionalized derivatives, Ag24Au1(R/S-BINAS)x(DMBT)18-2x, with x = 1-7 (R/S-BINAS = R/S-1,1’-[binaphthalene]-2,2’-dithiol), using chiroptical spectroscopic measurements and density functional theory (DFT) calculations. Combination of chiroptical and luminescence spectroscopies to understand the nature of electronic transitions has not been applied to such molecule-like metal clusters. In order to impart chirality to the achiral Ag24Au1(DMBT)18 cluster, the chiral ligand, R/S-BINAS, was incorporated into it. A series of clusters, Ag24Au1(R/S-BINAS)x(DMBT)18-2x, with x = 1-7 were synthesized. We demonstrate that the low energy electronic transitions undergo an unexpected achiral to chiral and back to achiral transition from pure Ag24Au1(DMBT)18 to Ag24Au1(R/S-BINAS)x(DMBT)18-2x, by increasing the number of BINAS ligands. The UV/Vis, luminescence, circular dichroism and circularly polarized luminescence spectroscopic measurements, in conjunction with DFT calculations suggest that the photoluminescence in Ag24Au1(DMBT)18 and its chirally functionalized derivatives is originated from the transitions involving the whole Ag24Au1S18 framework, not merely from the icosahedral Ag12Au1 core. These results suggest that the chiroptical signatures and photoluminescence in these cluster systems cannot be solely attributed to any one of the structural components, i.e., the metal core or the protecting metal-ligand oligomeric units, but rather to their interaction, and that the ligand shell plays a crucial role. Our work demonstrates that chiroptical spectroscopic techniques such as circular dichroism and circularly polarized luminescence represent useful tools to understand the nature of electronic transitions in ligand protected metal clusters, and that this approach can be utilized for gaining deeper insights into the structure-property relationships of the electronic transitions of such molecule-like clusters.

118
Cifuentes Girard, M. F.; Ruskic, D.; Böhm, G.; Picenoni, R.; Hopfgartner, G. “Automated parallel derivatization of metabolites with SWATH-MS data acquisition for qualitative and quantitative analysis”, Anal. Chim. Acta 2020, 1127, 198-206.open archive unige:140943 pdf full text [restricted access]

For metabolite profiling chemical derivatization has been used to improve MS sensitivity and LC retention. However, for multi-analytes quantification, the number of commercially available isotopically labelled internal standards is limited. Besides, there is no single workflow which can provide large-scale metabolomics coverage in particular for polar metabolites. To overcome these limitations and to improve reproducibility a fully automated dual derivatization approach was developed. Differential Isotope Labeling (DIL) was adopted by derivatizing carbonyl, amino and phenol metabolites with two isotopic forms. Urine samples were derivatized with 12C-dansyl chloride (DnsCl) and 12C-dansylhydrazine (DnsHz). Suitable quantification standards were generated by derivatized 40 standards including amino acids, sex hormones and other highly polar metabolites with labelled 13C2-dansyl chloride and 13C2-dansylhydrazine. The derivatization of the standards and the urine sample was performed using a PAL RTC autosampler in-line to column-switching LC-HRMS analysis with data independent acquisition (SWATH-MS). The parallel reactions were completed in 15 min inside of two agitators at different conditions overlapping with the LC-MS analysis time which was of 25 min. The column switching setup is critical to remove the excess of reagents which can negatively affect the ionization efficiency and deteriorate the chromatographic performance. The combination of dual DIL with SWATH-MS acquisition enables post-identification of unknown metabolites and quantitation at precursor (MS1) and specific tag fragment (MS2) levels. The inter- and intra-batch accuracy and precision of the method fall in the range ±15% using single point calibration, and at MS1 or MS2 level providing full flexibility. The method was successfully applied to the analysis of human urine samples.

117
Verma, P.; Rosspeintner, A.; Dereka, B.; Vauthey, E.; Kumpulainen, T. “Broadband fluorescence reveals mechanistic differences in excited-state proton transfer to protic and aprotic solvents”, Chem. Sci. 2020, 11, 7963-7971.open archive unige:139631 pdf full text [free access]

Excited-state proton transfer (ESPT) to solvent is often explained according to the two-step Eigen–Weller model including a contact ion pair (CIP*) as an intermediate, but general applicability of the model has not been thoroughly examined. Furthermore, examples of the spectral identification of CIP* are scarce. Here, we report on a detailed investigation of ESPT to protic (H2O, D2O, MeOH and EtOH) and aprotic (DMSO) solvents utilizing a broadband fluorescence technique with sub-200 fs time resolution. The time-resolved spectra are decomposed into contributions from the protonated and deprotonated species and a clear signature of CIP* is identified in DMSO and MeOH. Interestingly, the CIP* intermediate is not observable in aqueous environment although the dynamics in all solvents are multi-exponential. Global analysis based on the Eigen–Weller model is satisfactory in all solvents, but the marked mechanistic differences between aqueous and organic solvents cast doubt on the physical validity of the rate constants obtained.

116
Kündig, E. P. “Tateshina: Swiss Inspiration!”, Chem. Asian J. 2020, 15, 2545-2547.open archive unige:140765 pdf full text [restricted access]

The Tateshina conference celebrates its 20th anniversary this year. Its founder, Eiichi Nakamura, modeled the conference after the Bürgenstock conference where he was a speaker in April 2000. This short account highlights this event.

115
Castanon, I.; Hannich, J. T.; Abrami, L.; Huber, F.; Dubois, M.; Müller, M.; van der Goot, F. G.; Gonzalez-Gaitan, M. “Wnt-controlled sphingolipids modulate Anthrax Toxin Receptor palmitoylation to regulate oriented mitosis in zebrafish”, Nat. Commun. 2020, 11, art. num 3317.open archive unige:140856 pdf full text [free access]

Oriented cell division is a fundamental mechanism to control asymmetric stem cell division, neural tube elongation and body axis extension, among other processes. During zebrafish gastrulation, when the body axis extends, dorsal epiblast cells display divisions that are robustly oriented along the animal-vegetal embryonic axis. Here, we use a combination of lipidomics, metabolic tracer analysis and quantitative image analysis to show that sphingolipids mediate spindle positioning during oriented division of epiblast cells. We identify the Wnt signaling as a regulator of sphingolipid synthesis that mediates the activity of serine palmitoyltransferase (SPT), the first and rate-limiting enzyme in sphingolipid production. Sphingolipids determine the palmitoylation state of the Anthrax receptor, which then positions the mitotic spindle of dividing epiblast cells. Our data show how Wnt signaling mediates sphingolipid-dependent oriented division and how sphingolipids determine Anthrax receptor palmitoylation, which ultimately controls the activation of Diaphanous to mediate spindle rotation and oriented mitosis.

114
García-Calvo, J.; Maillard, J.; Fureraj, I.; Strakova, K.; Colom, A.; Mercier, V.; Roux, A.; Vauthey, E.; Sakai, N.; Fürstenberg, A.; Matile, S. “Fluorescent Membrane Tension Probes for Super-Resolution Microscopy:  Combining Mechanosensitive Cascade Switching with Dynamic-Covalent Ketone Chemistry”, J. Am. Chem. Soc. 2020, 142, 12034-12038.open archive unige:138589 pdf full text [restricted access]

We report the design, synthesis, and evaluation of fluorescent flipper probes for single-molecule super-resolution imaging of membrane tension in living cells. Reversible switching from bright-state ketones to dark-state hydrates, hemiacetals, and hemithioacetals is demonstrated for twisted and planarized mechanophores in solution and membranes. Broadband femtosecond fluorescence up-conversion spectroscopy evinces ultrafast chalcogen-bonding cascade switching in the excited state in solution. According to fluorescence lifetime imaging microscopy, the new flippers image membrane tension in live cells with record red shifts and photostability. Single-molecule localization microscopy with the new tension probes resolves membranes well below the diffraction limit.

113
Klont, F.; Hopfgartner, G. “Bioanalytical research and training in academia during the COVID-19 pandemic”, Bioanalysis 2020, 12, 1209-1211.

The world is currently facing a crisis of unimaginable proportions due to the COVID-19 pandemic, and this novel coronavirus continues to pile misery on people of all ages, all across the world, and from all walks of life. In the past few months, governments have imposed unprecedented measures to halt the spread of the coronavirus, and these measures continue to impact daily lives and societies while also business operations and the economy in general. The field of bioanalysis is one of the many fields facing changes and challenges in the current crisis, which, fortunately, do not all strictly have a negative impact on laboratory operations, as was recently discussed by Pruim and Teekamp [1]. This article highlighted some of the impact on an industrial bioanalytical setting, and here we aim to complement their work by elaborating on the impact of the COVID-19 pandemic from the perspective of bioanalytical research and training in an academic laboratory.

112
Gini, A.; Paraja, M.; Galmés, B.; Besnard, C.; Poblador-Bahamonde, A. I.; Sakai, N.; Frontera, A.; Matile, S. “Pnictogen-Bonding Catalysis:  Brevetoxin-Type Polyether Cyclizations”, Chem. Sci. 2020, 11, 7086-7091.open archive unige:138455 pdf full text [free access]

Pnictogen-bond donors are attractive for use in catalysis because of deep σ holes, high multivalency, rich hypervalency, and chiral binding pockets. We here report natural product inspired epoxide-opening polyether cyclizations catalyzed by fluoroarylated Sb(V) > Sb(III) > Bi > Sn > Ge. The distinctive characteristic found for pnictogen-bonding catalysis is the breaking of the Baldwin rules, that is selective endo cyclization into the trans-fused ladder oligomers known from the brevetoxins. Moreover, tris(3,4,5-trifluorophenyl)stibines and their hypervalent stiborane catecholates afford different anti-Baldwin stereoselectivity. Lewis (SbCl3), Brønsted (AcOH) and π acids fail to provide similar access to these forbidden rings. Like hydrogen-bonding catalysis differs from Brønsted acid catalysis, pnictogen-bonding catalysis thus emerges as the supramolecular counterpart of covalent Lewis acid catalysis.

111
Nançoz, C.; Rumble, C.; Rosspeintner, A.; Vauthey, E. “Bimolecular photoinduced electron transfer in non-polar solvents beyond the diffusion limit”, J. Chem. Phys. 2020, 152, 244501.open archive unige:137602 pdf full text [free access]

Electron transfer (ET) quenching dynamics in non-polar solvents are investigated using ultrafast spectroscopy with a series of six fluorophore/quencher pairs, covering a driving force range of more than 1.3 eV. The intrinsic ET rate constants, k0, deduced from the quenching dynamics in the static regime, are of the order of 1012–1013 M−1 s−1, i.e., at least as large as in acetonitrile, and do not exhibit any marked dependence on the driving force. A combination of transient electronic and vibrational absorption spectroscopy measurements reveals that the primary product of static quenching is a strongly coupled exciplex that decays within a few picoseconds. More weakly coupled exciplexes with a longer lifetime are generated subsequently, during the dynamic, diffusion-controlled, stage of the quenching. The results suggest that static ET quenching in non-polar solvents should be viewed as an internal conversion from a locally excited state to a charge-transfer state of a supermolecule rather than as a non-adiabatic ET process.

110
Verma, P.; Rosspeintner, A.; Kumpulainen, T. “Propyl acetate/butyronitrile mixture is ideally suited for investigating the effect of dielectric stabilization on (photo)chemical reactions”, RSC Adv. 2020, 10, 23682-23689.open archive unige:141389 pdf full text [free access]

Characterization of propyl acetate/butyronitrile (PA/BuCN) mixtures by various spectroscopic techniques is described. The neat solvents have identical viscosities and refractive indices but their dielectric constants differ significantly. Detailed solvatochromic and titration data show that the mixtures do not exhibit specific solute–solvent interactions or significant dielectric enrichment effects. Therefore, the mixtures are ideally suited for investigating the effect of dielectric stabilization on (photo)chemical reactions. Dynamic Stokes shift experiments performed on two push–pull probes demonstrate that the solvation dynamics are significantly decelerated in the mixtures as compared to the neat solvents. Therefore, the mixtures allow for varying both the extent and time scale of the dielectric stabilization in a predictable manner.

109
Desfeux, C.; Besnard, C.; Mazet, C. “[n]Dendralenes as a Platform for Selective Catalysis: Ligand-Controlled Cu-Catalyzed Chemo-, Regio-, and Enantioselective Borylations”, Org. Lett. 2020, in press.open archive unige:140304 pdf full text [restricted access]

We report the development of two complementary methods for the Cu-catalyzed anti-Markovnikov borylation of one specific olefin in 2-substituted [n]dendralenes (n = 3–6). The first protocol operates with a bisphosphine ligand and occurs with high regio- and chemoselectivity for the terminal double bond, independently of the number of cross-conjugated alkenes. We show that the use of a chiral phosphanamine ligand enables the highly chemo-, regio-, and enantioselective borylation of the alkene cross-conjugated with the terminal olefin in [n]dendralenes.

108
Dera, P.; Bruffey, E.; Finkelstein, G. J.; Kelly, C.; Gigante, A.; Hagemann, H.; Severa, G. “Synthesis, Characterization, and Crystal Structures of Two New Manganese Aceto EMIM Ionic Compounds with Chains of Mn2+ Ions Coordinated Exclusively by Acetate”, ACS Omega 2020, 5, 15592-15600.

We synthesized and determined crystal structures of two manganese(II) aceto EMIM coordination compounds with simplified empirical formulas Mn4(OAc)10[EMIM]2 and Mn4(OAc)10[EMIM]2·2H2O. Both compounds feature extended chains of Mn2+ octahedrally coordinated exclusively by acetate anions, which has been observed for the first time. The EMIM moieties and water molecules participate in hydrogen bonding with acetate anions but do not directly interact with the metal cation. Both compounds have melting temperatures around 120 °C and can be considered as (non-room-temperature) ionic liquids. The structural arrangement represented by the two title compounds is robust in terms of accommodating other types of cations and allows for tuning of physical properties of the ionic liquid by means of cation substitution. Thermal analysis results obtained using TGA–DSC and VT IR suggest melting phase transitions around 120 °C, followed by structural rearrangement in the molten state taking place around 140–160 °C. Compounds I and II have a higher thermal stability range compared to [EMIM][OAc] ionic liquid, with an onset decomposition temperature above 260 °C.

107
Ricardi, N.; Ernst, M.; Macchi, P.; Wesolowski, T. A. “Embedding-theory-based simulations using experimental electron densities for the environment”, Acta Crystallogr., Sect. A: Found. Adv. 2020, 76, 571-579.open archive unige:140858 pdf full text [free access]

The basic idea of frozen-density embedding theory (FDET) is the constrained minimization of the Hohenberg–Kohn density functional EHK[ρ] performed using the auxiliary functional EFDETνABAB], where ΨA is the embedded NA-electron wavefunction and ρB(r) is a non-negative function in real space integrating to a given number of electrons NB. This choice of independent variables in the total energy EFDETνABAB] functional makes it possible to treat the corresponding two components of the total density using different methods in multi-level simulations. The application of FDET using ρB(r) reconstructed from X-ray diffraction data for a molecular crystal is demonstrated for the first time. For eight hydrogen-bonded clusters involving a chromophore (represented as ΨA) and the glycylglycine molecule [represented as ρB(r)], FDET is used to derive excitation energies. It is shown that experimental densities are suitable for use as ρB(r) in FDET-based simulations.

106
Angerani, S.; Winssinger, N. “Sense-and-release Logic-gated Molecular Network Responding to Dimeric Cell Surface Proteins”, J. Am. Chem. Soc. 2020, 142, 12333-12340.open archive unige:138561 pdf full text [restricted access]

Dimeric proteins are prominent in biology and receptor dimerization (homo- or hetero-dimerization) is central to signal transduction. Herein we report a network that responds to a membrane-associated dimeric protein with the uncaging of a powerful cytotoxic. The network is based on two ligands functionalized with PNAs (templating strand and catalyst-functionalized strand, respectively) and a substrate with the caged cytotoxic (monomethyl auristatin E: MMAE; a high-affinity tubulin ligand). In the presence of the dimeric protein, the network yields a cooperative supramolecular assembly with a hybridization architecture that enhances the templated reaction, and enables the uncaging of a substrate. The network was tested on cells that express a cancer biomarker, carbonic anhydrase IX, in response to hypoxia. The output of the network correlates with the expression of carbonic anhydrase IX, and this biomarker was harnessed to uncage a potent cytotoxic agent.

105
Buckley, C. M.; Pots, H.; Gueho, A.; Vines, J. H.; Munn, C. J.; Phillips, B. A.; Gilsbach, B.; Traynor, D.; Nikolaev, A.; Soldati, T.; Parnell, A. J.; Kortholt, A.; King, J. S. “Coordinated Ras and Rac Activity Shapes Macropinocytic Cups and Enables Phagocytosis of Geometrically Diverse Bacteria”, Curr. Biol. 2020, 30, R883-R885.open archive unige:141216 pdf full text [free access]

Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte.

104
Stojimirovic, B.; Gali, M.; Trefalt, G. “Forces between silica particles in isopropanol solutions of 1:1 electrolytes”, Phys. Rev. Res. 2020, 2, 023315.open archive unige:138566 pdf full text [free access]

Interactions between silica surfaces across isopropanol solutions are measured with colloidal probe technique based on atomic force microscope. In particular, the influence of 1:1 electrolytes on the interactions between silica particles is investigated. A plethora of different forces are found in these systems. Namely, van der Waals, double-layer, attractive non-DLVO, repulsive solvation, and damped oscillatory interactions are observed. The measured decay length of the double-layer repulsion is substantially larger than Debye lengths calculated from nominal salt concentrations. These deviations are caused by pronounced ion pairing in alcohol solutions. At separation below 10 nm, additional attractive and repulsive non-DLVO forces are observed. The former are possibly caused by charge heterogeneities induced by strong ion adsorption, while the latter originate from structuring of isopropanol molecules close to the surface. Finally, at increased concentrations the transition from monotonic to damped oscillatory interactions is uncovered.

103
Bentounsi, Y.; Seintis, K.; Ameline, D.; Diring, S.; Provost, D.; Blart, E.; Pellegrin, Y.; Cossement, D.; Vauthey, E.; Odobel, F. “Chemistry on the electrodes: post-functionalization and stability enhancement of anchored dyes on mesoporous metal oxide photoelectrochemical cells with copper-free Huisgen cycloaddition reaction”, J. Mater. Chem. A 2020, 8, 12633-12640.open archive unige:138165 pdf full text [restricted access]

Hybrid materials consisting of nanocrystalline metal oxide films coated with molecules have considerable implications for the development of optoelectronic devices. We report on a straightforward and versatile procedure to engineer stable layers made of molecules chemisorbed on the surface of mesoporous inorganic metal oxides. The procedure is based on a thermal copper-free Huisgen reaction, which is directly conducted on TiO2 or NiO nanocrystalline films, between already bound diketopyrrolopyrrole sensitizers substituted by two azido groups and a crosslinking agent consisting of a tetrapropiolate ester. The procedure is mild and simple and does not require a catalyst, since quantitative conversion is obtained by a simple heating of the photoelectrode into a solution of the crosslinking agent. The photoelectrodes were characterized by ToF-SIMS, femtosecond transient absorption spectroscopy, electrochemistry and were finally used to fabricate dye-sensitized solar cells with iodide/triiodide and cobalt trisbipyridine complexes as redox mediators. Important increased stability of the crosslinked films was demonstrated by desorption and cyclic voltammetry experiments. Transient absorption spectroscopy and photovoltaic measurements showed that the dyes keep their initial photoelectrochemical properties upon crosslinking. This bottom-up approach is certainly broadly applicable and opens the possibility to make “chemistry on the electrode” to functionalize and crosslink dyes with any component.

102
Raetz, M.; Bonner, R.; Hopfgartner, G. “SWATH-MS for metabolomics and lipidomics: critical aspects of qualitative and quantitative analysis”, Metabolomics 2020, 16, art. 71.open archive unige:140944 pdf full text [free access]

While liquid chromatography coupled to mass spectrometric detection in the selected reaction monitoring detection mode offers the best quantification sensitivity for omics, the number of target analytes is limited, must be predefined and specific methods developed. Data independent acquisition (DIA), including SWATH using quadrupole time of flight or orbitrap mass spectrometers and generic acquisition methods, has emerged as a powerful alternative technique for quantitative and qualitative analyses since it can cover a wide range of analytes without predefinition.

101
Harayama, T.; Shimizu, T. “Roles of polyunsaturated fatty acids, from mediators to membranes”, J. Lipid Res. 2020, 61, 1150-1160.

PUFAs, such as AA and DHA, are recognized as important biomolecules, but understanding their precise roles and modes of action remains challenging. PUFAs are precursors for a plethora of signaling lipids, for which knowledge about synthetic pathways and receptors has accumulated. However, due to their extreme diversity and the ambiguity concerning the identity of their cognate receptors, the roles of PUFA-derived signaling lipids require more investigation. In addition, PUFA functions cannot be explained just as lipid mediator precursors because they are also critical for the regulation of membrane biophysical properties. The presence of PUFAs in membrane lipids also affects the functions of transmembrane proteins and peripheral membrane proteins. Although the roles of PUFAs as membrane lipid building blocks were difficult to analyze, the discovery of lysophospholipid acyltransferases (LPLATs), which are critical for their incorporation, advanced our understanding. Recent studies unveiled how LPLATs affect PUFA levels in membrane lipids, and their genetic manipulation became an excellent strategy to study the roles of PUFA-containing lipids. In this review, we will provide an overview of metabolic pathways regulating PUFAs as lipid mediator precursors and membrane components and update recent progress about their functions. Some issues to be solved for future research will also be discussed.

100
Beckwith, J. S.; Rumble, C. A.; Vauthey, E. “Data analysis in transient electronic spectroscopy – an experimentalist's view”, Int. Rev. Phys. Chem. 2020, 39, 135-216.open archive unige:137443 pdf full text [restricted access]

Time-resolved electronic spectroscopy has grown into a technique that provides hundreds to thousands of electronic spectra with femtosecond time resolution. This enables complex questions to be interrogated, with an obvious cost that the data are more detailed and thus require accurate modelling to be properly reproduced. Analysis of these data comes in a variety of forms, starting with a variety of assumptions about how the data may be decomposed. Here, four different types of analysis commonly used are discussed: band-shape analysis, global kinetic analysis, lifetime distribution models, and soft-modelling. This review provides a ‘user's guide’ to these various methods of data analysis, and attempts to elucidate their successes, domains in which they may be useful, and potential pitfalls in their usage.

99
Jansod, S.; Cherubini, T.; Soda, Y.; Bakker, E. “Optical Sensing with a Potentiometric Sensing Array by Prussian Blue Film Integrated Closed Bipolar Electrodes”, Anal. Chem. 2020, 92, 9138-9145.open archive unige:141063 pdf full text [restricted access]

The simultaneous optical readout of a potentiometric sensor array of ion-selective electrodes (ISEs) based on PVC mem-branes is described here for the first time. The optical array consists of electrochromic Prussian Blue (PB) films in multiple closed ion-selective bipolar electrodes (BPEs), giving a physical separation between the optical detection and sample com-partments. The potential-dependent turnover of PB generates Prussian White (PW). A near-Nernstian response of the PB film is confirmed by spectrophotometric absorbance experiments as a function of applied potential. In the combined bipolar elec-trode cell, the overall potential is kept constant with a single potentiostat over the entire array where each PB spot indicates the potential change of an individual connected potentiometric probe. For cation-selective electrodes, the absorbance or blue intensity of the connected PB film is enhanced with increasing target cation activity. The colorimetric absorbance changes are simultaneously followed by a digital camera and analyzed by Mathematica software. A multiple cation-BPE array allows one to achieve simultaneous quantitative analysis of potassium, sodium and calcium ions, demonstrated here in highly colored fruit juices. Mass transport at the PB thin film is shown not to be rate-limiting. The measuring ranges can be tuned in a wide range by potential control. The PB film exhibits greatly improved reproducibility and stability compared to previous work with a ferroin redox probe confined in a thin solution layer.

98
Bosmani, C.; Leuba, F.; Hanna, N.; Bach, F.; Burdet, F.; Pagni, M.; Hagedorn, M.; Soldati, T. “Vacuolins and myosin VII are required for phagocytic uptake and phagosomal membrane recycling in Dictyostelium discoideum”, J. Cell Sci. 2020, 133, jcs.242974.open archive unige:141217 pdf full text [restricted access]

Flotillins are lipid rafts residents involved in membrane trafficking and recycling of plasma membrane proteins. Dictyostelium discoideum uses phagocytosis to kill, digest and feed on bacteria. It possesses three flotillin-like vacuolins that are strongly associated with membranes and gradually accumulate on maturing phagosomes. Absence of vacuolins reduced adhesion and particle recognition resulting in a drastic reduction in the uptake of various types of particles. This was caused by a block in the recycling of plasma membrane components and the absence of their specific cortex-associated proteins. In addition, absence of vacuolins also impaired phagolysosome biogenesis, without significantly impacting killing and digestion of a range of bacteria. Strikingly, both absence and overexpression of vacuolins induced a strong down-regulation of myosin VII expression, as well as its partner talin A. Episomal expression of myosin VII fully rescued defects in uptake and adhesion, but not in phagosome maturation. These results suggest a dual role for vacuolins: a novel mechanism involving membrane microdomains and myosin VII/talin A in clustering phagosomal receptors and adhesion molecules at the plasma membrane, and a role in phagolysosomal biogenesis.

97
Jajcevic, K.; Sugihara, K. “Lipid Nanotubes as an Organic Template for an Electrically-Conductive Gold Nanostructure Network”, J. Phys. Chem. B 2020, 124, 5761-5769.open archive unige:140935 pdf full text [restricted access]

We demonstrate an approach to fabricate a gold nanowire network that presents a macroscopic electrical conductivity based on a lipid nanotube (LNT) template with attached gold nanoparticles. The poor electrical conductivity that we have previously faced was overcome by centrifugation and resuspension of gold nanoparticle solution for removing stabilizing agents, which increased the density of gold nanoparticles on the LNTs. An additional electroless metal plating further enhanced their contacts at nanoscale. Thanks to these procedures the sheet resistance was improved by 11 orders of magnitude. As a proof of principle, transparent conductive films were fabricated with these gold nanowires, which exhibited sheet resistance of maximum 70 Ω/? and transmittance of 50-75% in visible light.

96
Moser von Filseck, J.; Barberi, L.; Talledge, N.; Johnson, I. E.; Frost, A.; Lenz, M.; Roux, A. “Anisotropic ESCRT-III architecture governs helical membrane tube formation”, Nat. Commun. 2020, 11, 1516.open archive unige:141214 pdf full text [free access]

ESCRT-III proteins assemble into ubiquitous membrane-remodeling polymers during many cellular processes. Here we describe the structure of helical membrane tubes that are scaffolded by bundled ESCRT-III filaments. Cryo-ET reveals how the shape of the helical membrane tube arises from the assembly of two distinct bundles of helical filaments that have the same helical path but bind the membrane with different interfaces. Higher-resolution cryo-EM of filaments bound to helical bicelles confirms that ESCRT-III filaments can interact with the membrane through a previously undescribed interface. Mathematical modeling demonstrates that the interface described above is key to the mechanical stability of helical membrane tubes and helps infer the rigidity of the described protein filaments. Altogether, our results suggest that the interactions between ESCRT-III filaments and the membrane could proceed through multiple interfaces, to provide assembly on membranes with various shapes, or adapt the orientation of the filaments towards the membrane during membrane remodeling.

95
Sansen, T.; Sanchez Fuentes, D.; Rathar, R.; Colom, A.; El Alaoui, F.; Viaud, J.; Macchione, M.; de Rossi, S.; Matile, S.; Gaudin, R.; Bäcker, V.; Carretero-Genevrier, A.; Picas, L. “Mapping Cell Membrane Organization and Dynamics Using Soft Nano-Imprint Lithography”, ACS Appl. Mater. Interfaces 2020, 12, 29000-29012.open archive unige:138225 pdf full text [restricted access]

Membrane shape is a key feature of many cellular processes, including cell differentiation, division, migration, and trafficking. The development of nanostructured surfaces allowing for the in situ manipulation of membranes in living cells is crucial to understand these processes, but this requires complicated and limited-access technologies. Here, we investigate the self-organization of cellular membranes by using a customizable and bench top method allowing to engineer 1D SiO2 nanopillar arrays of defined sizes and shapes on high-performance glass compatible with advanced microscopies. As a result of this original combination, we provide a mapping of the morphology-induced modulation of the cell membrane mechanics, dynamics and steady-state organization of key protein complexes implicated in cellular trafficking and signal transduction.

94
Ferling, I.; Dunn, J. D.; Ferling, A.; Soldati, T.; Hillmann, F.; Goldman, G. H. “Conidial Melanin of the Human-Pathogenic Fungus Aspergillus fumigatus Disrupts Cell Autonomous Defenses in Amoebae”, mBio 2020, 11, 165rv13.open archive unige:140846 pdf full text [free access]

The human-pathogenic fungus Aspergillus fumigatus is a ubiquitous saprophyte that causes fatal lung infections in immunocompromised individuals. Following inhalation, conidia are ingested by innate immune cells and can arrest phagolysosome maturation. How this virulence trait could have been selected for in natural environments is unknown. Here, we found that surface exposure of the green pigment 1,8-dihydroxynaphthalene-(DHN)-melanin can protect conidia from phagocytic uptake and intracellular killing by the fungivorous amoeba Protostelium aurantium and delays its exocytosis from the nonfungivorous species Dictyostelium discoideum. To elucidate the antiphagocytic properties of the surface pigment, we followed the antagonistic interactions of A. fumigatus conidia with the amoebae in real time. For both amoebae, conidia covered with DHN-melanin were internalized at far lower rates than were seen with conidia lacking the pigment, despite high rates of initial attachment to nonkilling D. discoideum. When ingested by D. discoideum, the formation of nascent phagosomes was followed by transient acidification of phagolysosomes, their subsequent neutralization, and, finally, exocytosis of the conidia. While the cycle was completed in less than 1 h for unpigmented conidia, the process was significantly prolonged for conidia covered with DHN-melanin, leading to an extended intracellular residence time. At later stages of this cellular infection, pigmented conidia induced enhanced damage to phagolysosomes and infected amoebae failed to recruit the ESCRT (endosomal sorting complex required for transport) membrane repair machinery or the canonical autophagy pathway to defend against the pathogen, thus promoting prolonged intracellular persistence in the host cell and the establishment of a germination niche in this environmental phagocyte.

93
Grillo, R.; Beutel, D.; Cataldi, U.; Rockstuhl, C.; Bürgi, T. “Self-Assembled Arrays of Gold Nanorod-Decorated Dielectric Microspheres with a Magnetic Dipole Response in the Visible Range for Perfect Lensing and Cloaking Applications”, ACS Appl. Nano Mater. 2020, 3, 6107-6117.open archive unige:140519 pdf full text [restricted access]

Photonic nanostructures made of a dielectric sphere covered with many metallic nanospheres fabricated by self-assembly constitute a basic building block for optical metamaterials with a magnetic response in the visible. However, they suffer from limited degrees of freedom to tune their response. Once the involved materials are chosen, the response is mostly determined. To overcome such limitation, we design, fabricate, and characterize here a bottom-up metamaterial where metallic nanorods are used instead of nanospheres. Nanorods offer the ability to tune the spectral position of the resonances by changing their aspect ratio. Building blocks consisting of dielectric spheres covered with metallic nanorods are fabricated and characterized. They are also deposited in densely pack arrays on a substrate using a blade coating deposition of the dielectric spheres first and a subsequent deposition of the metallic nanorods. Full-wave optical simulations support the spectroscopic characterization. These simulations also indicate a dominant magnetic dipolar response of the building blocks. These arranged core-shell structures are promising materials for applications such as perfect lensing and cloaking.

92
Licari, G.; Strakova, K.; Matile, S.; Tajkhorshid, E. “Twisting and Tilting of a Mechanosensitive Molecular Probe Detects Order in Membranes”, Chem. Sci. 2020, 11, 5637-5649.open archive unige:137073 pdf full text [free access]

Lateral forces in biological membranes affect a variety of dynamic cellular processes. Recent synthetic efforts have introduced fluorescent “flippers” as environment-sensitive planarizable push–pull probes that can detect lipid packing and membrane tension, and respond to lipid-induced mechanical forces by a shift in their spectroscopic properties. Herein, we investigate the molecular origin of the mechanosensitivity of the best known flipper, Flipper-TR, by an extended set of molecular dynamics (MD) simulations in membranes of increasing complexity and under different physicochemical conditions, revealing unprecedented details of the sensing process. Simulations enabled by accurate refinement of Flipper-TR force field using quantum mechanical calculations allowed us to unambiguously correlate the planarization of the two fluorescent flippers to spectroscopic response. In particular, Flipper-TR conformation exhibits bimodal distribution in disordered membranes and a unimodal distribution in highly ordered membranes. Such dramatic change was associated with a shift in Flipper-TR excitation spectra, as supported both by our simulated and experimentally-measured spectra. Flipper-TR sensitivity to phase-transition is confirmed by a temperature-jump protocol that alters the lipid phase of an ordered membrane, triggering an instantaneous mechanical twisting of the probe. Simulations show that the probe is also sensitive to surface tension, since even in a naturally disordered membrane, the unimodal distribution of coplanar flippers can be achieved if a sufficiently negative surface tension is applied to the membrane. MD simulations in ternary mixtures containing raft-like nanodomains show that the probe can discriminate lipid domains in phase-separated complex bilayers. A histogram-based approach, called DOB-phase classification, is introduced that can differentiate regions of disordered and ordered lipid phases by comparing dihedral distributions of Flipper-TR. Moreover, a new sensing mechanism involving the orientation of Flipper-TR is elucidated, corroborating experimental evidence that the probe tilt angle is strongly dependent on lipid ordering. The obtained atomic-resolution description of Flipper-TR mechanosensitivity is key to the interpretation of experimental data and to the design of novel mechanosensors with improved spectroscopic properties.

91
Abdou, M.; Gil-Díaz, T.; Schäfer, J.; Catrouillet, C.; Bossy, C.; Dutruch, L.; Blanc, G.; Cobelo-García, A.; Massa, F.; Castellano, M.; Magi, E.; Povero, P.; Tercier-Waeber, M.-L. “Short-term variations of platinum concentrations in contrasting coastal environments: The role of primary producers”, Mar. Chem. 2020, 222, 103782.open archive unige:136526 pdf full text [restricted access]

Short-term variations of Pt concentrations and primary production indicators were compared in three contrasting coastal sites during spring bloom: (i) the Gironde Estuary mouth (SW France), (ii) the semi-enclosed Arcachon Bay (SW France), and (iii) the urbanized Genoa Harbor (NW Italy). At each site, surface seawater sampling and physical-chemical measurements were combined to study diel cycles (over 25 h) of dissolved Pt concentrations in seawater (PtD) and master variables reflecting primary production activity (chlorophyll-a, phaeopigments, and particulate organic carbon, POC concentrations). Plankton nets were used in all sites, providing for the first time plankton Pt concentrations (PtPK) over a whole diel cycle (Gironde Estuary mouth) and spot sampling (Arcachon Bay and Genoa Harbor) in the coastal zone. Bivalves (wild oysters or mussels), reflecting organisms at higher trophic levels, were also collected at all sites. The POC/Chl-a ratios in the collected particulate material suggested high contribution of phytoplankton to the particulate matter in the productive Gironde Estuary mouth. At this site, phytoplankton activity partly controlled Pt cycling and particle/dissolved Pt partitioning during daytime. During the night, zooplankton grazing may release Pt into the dissolved phase. These processes are partly masked by external factors such as tide or local Pt sources, especially in more confined and/or urbanized coastal water bodies such as the Arcachon Bay and the Genoa Harbor. Platinum levels in plankton and bivalves from these contrasting sites along the Atlantic and Mediterranean coasts tended to reflect the general Pt levels in seawater. These results clearly suggest that (i) Pt contamination of coastal waters and marine organisms has become a common feature in urbanized sites and (ii) Pt transfer to the marine food chain starts at the basic level of primary producers. By concentrating Pt (Bioconcentration Factor: BCF ~ 104), phytoplankton may serve as a biomonitor to assess Pt contamination in coastal environments.

90
Trefalt, G.; Szilágyi, I.; Borkovec, M. “Schulze-Hardy rule revisited”, Colloid Polym. Sci. 2020, 298, 961-967.open archive unige:140948 pdf full text [restricted access]

The classical Schulze-Hardy rule suggests that the critical coagulation concentration (CCC) decreases as the inverse sixth power of the counterion valence. While this dependence can be derived from the theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO), this derivation relies on unrealistic assumptions. In particular, one cannot assume that the electrolytes are symmetric, since one normally works with the better soluble asymmetric electrolytes. For such electrolytes, however, it is essential to distinguish between multivalent counterions and coions. For multivalent counterions, one must consider their strong tendency towards adsorption to the oppositely charged substrates, which leads to low charge densities. In this situation, the CCC increases with the surface charge density, inducing the strong decrease of the CCC with valence. For multivalent coions, the substrates are typically highly charged. In this case, the CCC decreases with increasing ionic valence and is in fact inversely proportional to the valence. This dependence is referred to as the inverse Schulze-Hardy rule.

89
Szakacs, Z.; Tasior, T.; Gryko, D.; Vauthey, E. “Change of Quadrupole Moment upon Excitation and  Symmetry Breaking in Multibranched Donor-Acceptor Dyes”, ChemPhysChem 2020, 21, 1718-1730.open archive unige:139636 pdf full text [free access]

Upon photoexcitation, a majority of quadrupolar dyes, developed for large two-photon absorption, undergo excited-state symmetry breaking (ES-SB) and behave as dipolar molecules. We investigate how the change of quadrupole moment upon S 1  

88
Ricardi, N.; Ernst, M.; Macchi, P.; Wesolowski, T. A. “Frozen-Density Embedding Theory based simulations with experimental electron densities”, arXiv.org, e-Print Arch., Phys. 2020, arXiv:2005.13409.open archive unige:141198 pdf full text [free access]

The basic idea of Frozen-Density Embedding Theory (FDET) is the constrained minimisation of the Hohenberg-Kohn density functional EHK[ρ] performed using the auxiliary functional EF D ETvABA,ρB], where ΨA is the embedded NA-electron wave-function and ρB(r) a non-negative function in real space integrating to a given number of electrons NB. This choice of independent variables in the total energy functional EF D ETvABA,ρB] makes it possible to treat the corresponding two components of the total density using different methods in multi-level simulations. We demonstrate, for the first time, the applications of FDET using ρB(r) reconstructed from X-ray diffraction data on a molecular crystal. For eight hydrogen-bonded clusters involving a chromophore (represented with ΨA) and the glycylglycine molecule (represented as ρB(r)), FDET is used to derive excitation energies. It is shown that experimental densities are suitable to be used as ρB(r) in FDET based simulations.

87
Dunne#, P.; Adachi#, T.; Dev, A. A.; Sorrenti, A.; Giacchetti, L.; Bonnin, A.; Bourdon, C.; Mangin, P. H.; Coey, J.; Doudin, B.; Hermans, T. M. “Liquid flow and control without solid walls”, Nature 2020, 581, 58-62.open archive unige:140859 pdf full text [restricted access]

When miniaturizing fluidic circuitry, the solid walls of the fluid channels becomeincreasingly important because they limit the flow rates achievable for a givenpressure drop, and they are prone to fouling. Approaches for reducing the wallinteractions include hydrophobic coatings, liquid-infused porous surfaces, nanoparticle surfactant jamming, changes to surface electronic structure, electrowetting, surface tension pinning and use of atomically flat channels. A better solution may be to avoid the solid walls altogether. Droplet microfluidics andsheath flow achieve this but require continuous flow of the central liquid and thesurrounding liquid. Here we demonstrate an approach in which aqueous liquidchannels are surrounded by an immiscible magnetic liquid, both of which arestabilized by a quadrupolar magnetic field. This creates self-healing, non-clogging,anti-fouling and near-frictionless liquid-in-liquid fluidic channels. Manipulation of thefield provides flow control, such as valving, splitting, merging and pumping. The latteris achieved by moving permanent magnets that have no physical contact with theliquid channel. We show that this magnetostaltic pumping method can be used totransport whole human blood with very little damage due to shear forces. Haemolysis (rupture of blood cells) is reduced by an order of magnitude compared withtraditional peristaltic pumping, in which blood is mechanically squeezed through aplastic tube. Our liquid-in-liquid approach provides new ways to transport delicateliquids, particularly when scaling channels down to the micrometre scale, with noneed for high pressures, and could also be used for microfluidic circuitry.

Short video: https://www.youtube.com/watch?v=Dnm4Twk60G4

86
Galli, M.; Saringer, S.; Szilagyi, I.; Trefalt, G. “A Simple Method to Determine Critical Coagulation Concentration from Electrophoretic Mobility”, arXiv.org, e-Print Archive, Soft Condensed Matter. 2020, arXiv:2003.12513.

Critical coagulation concentration (CCC) is a key parameter of particle dispersions, since it provides the threshold limit of electrolyte concentrations, above which the dispersions are destabilized due to rapid particle aggregation. A computational method is proposed to predict CCC values using solely electrophoretic mobility data without the need to measure aggregation rates of the particles. The model relies on the DLVO theory; contributions from repulsive double-layer forces and attractive van der Waals forces are included. Comparison between the calculated and previously reported experimental CCC data for the same particles shows that the method performs well in the presence of mono and multivalent electrolytes provided DLVO interparticle forces are dominant. The method is validated for particles of various compositions, shapes, and sizes.

85
Gooding, J. J.; Mazur, A.; Bakker, E.; Kelley, S.; Sailor, M.; Merkx, M.; Mao, L.; Clark, H.; Maboudian, R.; Long, Y. “Remembering NJ”, ACS Sens. 2020, 5, 887-888.open archive unige:141064 pdf full text [restricted access]

It is with great sadness that we inform you of the sudden passing of our beloved colleague NJ Tao. NJ was our friend. He was not only an amazing scientist and editor, but also one of the kindest and gentlest people you will ever meet.

We will miss him dearly.

84
Trefalt, G.; Cao, T.; Sugimoto, T.; Borkovec, M. “Heteroaggregation between charged and neutral particles”, Langmuir 2020, 36, 5303-5311.open archive unige:136255

Experimentally determined heteroaggregation rates between charged and neutral colloidal particles are reported for the first time. Different positively and negatively charged polystyrene latex particles are investigated. The neutral particles are obtained through adsorption of an appropriate amount of oppositely charged additives, such as aliphatic oligoamines, iron cyanide complexes, or alkyl sulfates. Heteroaggregation rates were measured with time-resolved multi-angle light scattering. One observes that heteroaggregation between charged and neutral particles is always fast and diffusion controlled. These experimental values are compared with calculations of the Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory, whereby one finds that this heteroaggregation process is highly sensitive to charge regulation conditions. The comparison with experiments shows unambiguously that the surface of the neutral particles regulates strongly, and probably behaves close to a constant potential surface. This observation is in line with direct force measurements on similar systems, and further agrees with the fact that for neutral surfaces the capacitance of the diffuse layer is expected to be much smaller than the one of the inner layer.

83
Truttmann, V.; Herzig, C.; Illes, I.; Limbeck, A.; Pittenauer, E.; Stöger-Pollach, M.; Allmaier, G.; Bürgi, T.; Barrabés, N.; Rupprechter, G. “Ligand engineering of immobilized nanoclusters on surfaces: ligand exchange reactions with supported Au11(PPh3)7Br3”, Nanoscale 2020, 12, 12809-12816.open archive unige:140861 pdf full text [free access]

The properties of gold nanoclusters, apart from being size-dependent, are strongly related to the nature of the protecting ligand. Ligand exchange on Au nanoclusters has been proven to be a powerful tool for tuning their properties, but has so far been limited to dissolved clusters in solution. By supporting the clusters previously functionalized in solution, it is uncertain that the functionality is still accessible once the cluster is on the surface. This may be overcome by introducing the desired functionality by ligand exchange after the cluster deposition on the support material. We herein report the first successful ligand exchange on supported (immobilized) Au11 nanoclusters. Dropcast films of Au11(PPh3)7Br3 on planar oxide surfaces were shown to react with thiol ligands, resulting in clusters with a mixed ligand shell, with both phosphines and thiolates being present. Laser ablation inductively coupled plasma mass spectrometry and infrared spectroscopy confirmed that the exchange just takes place on the cluster dropcast. Contrary to systems in solution, the size of the clusters did not increase during ligand exchange. Different structures/compounds were formed depending on the nature of the incoming ligand. The feasibility to extend ligand engineering to supported nanoclusters is proven and it may allow controlled nanocluster functionalization.

82
Voci, S.; Zinna, F.; Arrico, L.; Grass, S.; Bouffier, L.; Lacour, J.; Di Bari, L.; Sojic, N. “Chiroptical Detection of a Model Ruthenium Dye in Water by Circularly Polarized-Electrochemiluminescence”, Chem. Commun. 2020, 56, 5989-5992.open archive unige:137072 pdf full text [restricted access]

We demonstrate the possibility to detect selectively the two singleenantiomers of a model [Ru(bpy)3]2+-based dye by circularlypolarized-electrochemiluminescence (CP-ECL). This new aspect ofthe ECL emission combines the chiral information intrinsic to CPLmethods with an electrogeneration of the excited state. Thus, itopens the possibility to perform ECL-based bioassays or microscopywith efficient chiral dyes.

81
Dereka, B.; Svechkarev, D.; Rosspeintner, A.; Aster, A.; Lunzer, M.; Liska, R.; Mohs, A. M.; Vauthey, E. “Solvent tuning of photochemistry upon excited-state symmetry breaking”, Nat. Commun. 2020, 11, 1925.open archive unige:135135 pdf full text [free access]

The nature of the electronic excited state of many symmetric multibranched donor–acceptor molecules varies from delocalized/multipolar to localized/dipolar depending on the environment. Solvent-driven localization breaks the symmetry and traps the exciton in one branch. Using a combination of ultrafast spectroscopies, we investigate how such excited-state symmetry breaking affects the photochemical reactivity of quadrupolar and octupolar A–(π-D)2,3 molecules with photoisomerizable A–π–D branches. Excited-state symmetry breaking is identified by monitoring several spectroscopic signatures of the multipolar delocalized exciton, including the S2 ← S1 electronic transition, whose energy reflects interbranch coupling. It occurs in all but nonpolar solvents. In polar media, it is rapidly followed by an alkyne–allene isomerization of the excited branch. In nonpolar solvents, slow and reversible isomerization corresponding to chemically-driven symmetry breaking, is observed. These findings reveal that the photoreactivity of large conjugated molecules can be tuned by controlling the localization of the excitation.

80
Hoogendoorn, S.; Aye, Y. “Empowering Global Chemical Biology at the Dawn of the New Decade”, ACS Chem. Biol. 2020, 15, 1287-1291.open archive unige:137445 pdf full text [restricted access]

On January 22-24 2020, scientific luminaries across the far-flung corners of chemical biology gathered in Geneva, Switzerland, to deliver their latest and greatest discoveries in the field. Generously supported by the Swiss National Science Foundation (SNSF), our academic partners, and industrial and journal sponsors, this chemical biology symposium in our opinion will remain memorable for several years to come, not only because of the diversity in scientific topics delivered by our invited eminent speakers as detailed herein, but it is also one-of-a-kind conference which reflected multidimensional balance—balance in age and gender, across these speakers. Such a remarkable speaker line-up doubt-less attracted >200 attendees from academia and industry in and around Switzerland and beyond, representing a huge swathe of subfields of science interfacing chemistry and biology. Poster presenta-tions from students and postdocs further spotlighted the exciting diversity in the field: spanning from biosynthesis, optochemical genetics, genetic code expansion, lipid chemical biology, redox perturba-tion, microfluidics screening, membrane signaling, immune modulation, DNA circuits, to synthetic and computational biology. This notable heterogeneity in scientific topics also went hand-in-hand with the diverse representations of student/postdoc trainees from 56 institutions covering 14 countries world-wide, allowing us to witness science as a truly global enterprise.

79
Pham, A.-T.; Matile, S. “Peptide Stapling with Anion-π Catalysts”, Chem. Asian J. 2020, 15, 1562-1566.open archive unige:135871 pdf full text [free access]

We report design, synthesis and evaluation of a series of naphthalenediimides (NDIs) that are bridged with short peptides. Reminiscent of peptide stapling technologies, the macrocycles are conveniently accessible by a chromogenic nucleophilic aromatic substitution of two bromides in the NDI core with two thiols from cysteine sidechains. The dimension of core-bridged NDIs matches that of one turn of an α helix. NDI-stapled peptides exist as two, often separable atropisomers. Introduction of tertiary amine bases in amino-acid sidechains above the π-acidic NDI surface affords operational anion-π catalysts. According to an enolate chemistry benchmark reaction, anion-π catalysis next to peptides occurs with record chemoselectivity but weak enantioselectivity. Catalytic activity drops with increasing distance of the amine base to the NDI surface, looser homocysteine bridges, mismatched, shortened and elongated α-helix turns, and acyclic peptide controls. Elongation of isolated turns into short α helices significantly increases activity. This increase is consistent with remote control of anion-π catalysis from the α-helix macrodipole.

78
Voci, S.; Duwald, R.; Grass, S.; Hayne, D. J.; Bouffier, L.; Francis, P. S.; Lacour, J.; Sojic, N. “Self-Enhanced Multicolor Electrochemiluminescence by Competitive Electron-transfer Processes”, Chem. Sci. 2020, 11, 4508-4515.open archive unige:135646 pdf full text [free access]

Controlling electrochemiluminescence (ECL) color(s) is crucial for many applications ranging from multiplexed bioassays to ECL microscopy. This can only be achieved through the fundamental understanding of high-energy electron-transfer processes in complex and competitive reaction schemes. Recently, this field has generated huge interest, but the effective implementation of multicolor ECL is constrained by the limited number of ECL-active organometallic dyes. Herein, the first self-enhanced organic ECL dye, a chiral red-emitting cationic diaza [4]helicene connected to a dimethylamino moiety by a short linker, is reported. This molecular system integrates bifunctional ECL features (i.e. luminophore and coreactant) and each function may be operated either separately or simultaneously. This unique level of control is enabled by integrating but decoupling both molecular functions in a single molecule. Through this dual molecular reactivity, concomitant multicolor ECL emission from red to blue with tunable intensity is readily obtained in aqueous media. This is done through competitive electron-transfer processes between the helicene and a ruthenium or iridium dye. The reported approach provides a general methodology to extend to other coreactant/luminophore systems, opening enticing perspectives for spectrally distinct detection of several analytes, and original analytical and imaging strategies.

Dataset: https://doi.org/10.26037/yareta:ptypzp365nhjrlfjzlakr2biqu

77
Penezić, A.; Tercier-Waeber, M.-L.; Abdou, M.; Bossy, C.; Dutruch, L.; Bakker, E.; Schäfer, J. “Spatial variability of arsenic speciation in the Gironde Estuary: Emphasis on dynamic (potentially bioavailable) inorganic arsenite and arsenate fractions”, Mar. Chem. 2020, 223, 103804.open archive unige:136352 pdf full text [restricted access]

Inorganic arsenic (As) speciation and behaviour were studied in the Gironde Estuary, a major European estuary in the south west of France. For the first time ever, the dynamic (potentially bioavailable) fraction of inorganic arsenite, As(III), and arsenate, As(V), were quantified in this estuary, using an antifouling gel-integrated gold microelectrode interrogated by square wave anodic stripping voltammetry (GIME-SWASV). The concentrations of dissolved As(III) and As(V) were determined by hydrid generation-flow injection-atomic absorption spectrometry (HG-FI-AAS) and inductively coupled plasma-mass spectrometry (ICP-MS) in collected samples following filtration through 0.2 μm, as well as 0.02 μm pore size filters. The concentrations of arsenite in the dynamic fraction, As(III)dyn, ranged from 1.3 to 3.3 nM, contributing almost completely to the dissolved arsenite, As(III)diss, which ranged between 0.9 and 3.1 nM in the 0.2 μm fraction, and between 1.2 and 3.7 nM in the 0.02 μm fraction. Concentrations of arsenate in the dynamic fraction, As(V)dyn, ranged from 0.9 to 22.9 nM, and contributed to the dissolved arsenate, As(V)diss, by 4–73% in the 0.2 μM fraction, and by 5–90% in the 0.02 μm fraction. The concentrations of As(V)diss in the 0.2 μm fraction were between 14.5 and 36.2 nM, and between 15.2 and 34.9 nM in the 0.02 μm fraction.

The impact of this work is two-fold. Measurements of As species with different techniques allowed one to validate the on-board GIME voltammetric measurements. In addition, determination of As species in different fractions, as well as combining the obtained results with the conducted measurements of dissolved Mn and Fe, particulate suspended matters, and master physicochemical parameters (T, pH, O2, redox E), helped to broaden the understanding of biotic and abiotic processes governing the distribution of arsenic, especially its potentially bioavailable forms, in the Gironde Estuary.

76
Streuff, J.; Echavarren, A. M.; González, J. M.; Oestreich, M.; Gansäuer, A.; Barluenga, S.; Winssinger, N. “Kilian Muñiz (1970-2020)”, Angew. Chem. Int. Ed. 2020, 59, 7648.open archive unige:135617 pdf full text [restricted access]

Kilian Muñiz passed away unexpectedly on March 16th, 2020, at the age of only 49. Kilian was a leading figure in the field of catalytic (di-)amination reactions. He will be remembered as one of the finest, most passionate chemists, a dear colleague, and, most of all, as a close friend.

75
Deorukhkar, N.; Lathion, T.; Guénée, L.; Besnard, C.; Piguet, C. “The Tyranny of Arm-Wrestling Methyls on Iron(II) Spin State in Pseudo-Octahedral [Fe(didentate)3] Complexes”, Chemistry 2020, 2, 231-252.open archive unige:134727 pdf full text [free access]

The connection of a sterically constrained 3-methyl-pyrazine ring to a N-methyl-benzimidazole unit to give the unsymmetrical α,α’-diimine ligand L5 has been programmed for the design of pseudo-octahedral spin-crossover [Fe(L5)3]2+ units, the transition temperature (T1/2) of which occurs in between those reported for related facial tris-didentate iron chromophores fitted with 3-methyl-pyridine-benzimidazole in a LaFe helicate (T1/2 ~ 50 K) and with 5-methyl-pyrazine-benzimidazole L2 ligands (T1/2 ~350 K). A thorough crystallographic analysis of [Fe(L5)3](ClO4)2 (I), [Ni(L5)3](ClO4)2 (II), [Ni(L5)3](BF4)2?H2O (III), [Zn(L5)3](ClO4)2 (IV), [Ni(L5)3](BF4)2?1.75CH3CN (V), and [Zn(L5)3](BF4)2?1.5CH3CN (VI) shows the selective formation of pure facial [M(L5)3]2+ cations in the solvated crystals of the tetrafluoroborate salts and alternative meridional isomers in the perchlorate salts. Except for a slightly larger intra-strand interannular twist between the aromatic heterocycles in L5, the metric parameters measured in [Zn(L5)3]2+ are comparable to those reported for [Zn(L2)3]2+, where L2 is the related unconstrained ligand. This similitude is reinforced by comparable ligand-field strengths (?oct) and nephelauxetic effects (as measured by the Racah parameters B and C) extracted from the electronic absorption spectra recorded for [Ni(L5)3]2+ and [Ni(L2)3]2+. In this context, the strictly high-spin behavior observed for [Fe(L5)3]2+ within the 5–300 K range contrasts with the close to room-temperature spin-crossover behavior of [Fe(L2)3]2+ (T1/2 = 349(5) K in acetonitrile). This can be unambiguously assigned to an intraligand arm wrestling match operating in bound L5, which prevents the contraction of the coordination sphere required for accommodating low-spin FeII. Since the analogous 3-methyl-pyridine ring in [Fe(L3)3]2+ derivatives are sometimes compatible with spin-crossover properties, the consequences of repulsive intra-strand methyl–methyl interactions are found to be amplified in [Fe(L5)3]2+ because of the much lower basicity of the 3-methyl-pyrazine ring and the resulting weaker thermodynamic compensation. The decrease of the stability constants by five orders of magnitude observed in going from [M(L2)3]2+ to [M(L5)3]2+ (M = NiII and ZnII) is diagnostic for the operation of this effect, which had been not foreseen by the authors.

74
Farrera-Soler, L.; Daguer, J.-P.; Raunft, P.; Barluenga, S.; Imberty, A.; Winssinger, N. “PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins”, Bioorg. Med. Chem. 2020, 28, 115458.open archive unige:134730 pdf full text [restricted access]

Selections from dynamic combinatorial libraries (DCL) benefit from the dynamic nature of the library that can change constitution upon addition of a selection pressure, such as ligands binding to a protein. This technology has been predominantly used with small molecules interacting with each other through reversible covalent interaction. However, application of this technology in biomedical research and drug discovery has been limited by the reversibility of covalent exchange and the analytical deconvolution of small molecule fragments. Here we report a supramolecular approach based on the use of a constant short PNA tag to direct the combinatorial pairing of fragment. This PNA tag yields fast exchange kinetics, while still delivering the benefits of cooperativity, and provides favourable properties for analytical deconvolution by MALDI. A selection from >6,000 assemblies of glycans (mono-, di-, tri-saccharides) targeting AFL, a lectin from pathogenic fungus, yielded a 95 nM assembly, nearly three orders of magnitude better in affinity than the corresponding glycan alone (41 µM).

73
Liu, Y.; Mazet, C. “A Catalytic Dual Isomerization/Allylboration Sequence for the Stereoselective Construction of Congested Secondary Homoallylic Alcohols”, J. Org. Chem. 2020, 85, 5638-5650.open archive unige:134731 pdf full text [restricted access]

A catalytic sequence for the diastereo- and enantioselective preparation of homoallylic alcohols with an adjacent quaternary (stereo)center is reported. The one-pot process relies on the use of a single (achiral or chiral) iridium complex to catalyze the concomitant isomerization of primary allylic alcohols and homoallylboronates into (chiral) aldehydes and allylboronates respectively. In the same flask, a chiral Brønsted acid is added next to engage the isomerization products into a stereocontrolled allylboration reaction. Structural variations have been performed on both the allylic alcohols and the homoallylboronates. This mild process affords an array of stereochemically congested and complex chiral secondary homoallylic alcohols in high yield, excellent diastereoselectivity and usually high enantioselectivity.

72
Huang, J.; Zajforoushan Moghaddam, S.; Maroni, P.; Thormann, E. “Swelling behavior, interaction, and electrostatic properties of chitosan/alginate dialdehyde multilayer films with different outermost layer”, Langmuir 2020, 36, 3782-3791.

In this study, self-cross-linked chitosan/alginate dialdehyde multilayer films, capped with either alginate dialdehyde (6 layers) or chitosan (7 layers), are fabricated using the layer-by-layer method. The disruption of the electrostatic equilibrium when exposing the fabricated layers to acidic and alkaline conditions causes swelling within the film and independently in the outermost layer, showing dependence on the ionic strength. Spectroscopic ellipsometry and quartz crystal microbalance with dissipation monitoring are employed to examine the swelling behavior. Atomic force microscopy colloidal probe measurements are conducted to assess the surface forces between the multilayer films at different pH and ionic strengths. Finally, the electrostatic properties of the multilayer films are examined at different pH and ionic strengths using zeta potential measurements. The results suggest that stimuli-responsiveness and overall swelling behavior of the polysaccharide multilayer films significantly depend on the outermost layer, an effect that should expectedly become more pronounced the thinner the film becomes.

71
Mateus, R.; Holtzer, L.; Seum, C.; Hadjivailiou, Z.; Dubois, M.; Jülicher, F.; Gonzalez-Gaitan, M. “Wtn-controlled sphingolipids modulate Anthrax Toxin Receptor palmitoylation to regulate oriented mitoses in zebrafish”, Science Direct 2020, 30, 4292-4302.e7.open archive unige:140856 pdf full text [free access]

Secreted growth factors can act as morphogens that form spatial concentration gradients in developing organs, thereby controlling growth and patterning. For some morphogens, adaptation of the gradients to tissue size allows morphological patterns to remain proportioned as the organs grow. In the zebrafish pectoral fin, we found that BMP signaling forms a two-dimensional gradient. The length of the gradient scales with tissue length and its amplitude increases with fin size according to a power-law. Gradient scaling and amplitude power-laws are signatures of growth control by time derivatives of morphogenetic signaling: cell division correlates with the fold change over time of the cellular signaling levels. We show that Smoc1 regulates BMP gradient scaling and growth in the fin. Smoc1 scales the gradient by means of a feedback loop: Smoc1 is a BMP agonist and BMP signaling represses Smoc1 expression. Our work uncovers a layer of morphogen regulation during vertebrate appendage development.

70
Kim, K. T.; Winssinger, N. “Enhanced SNP-sensing using DNA-templated reactions through confined hybridization of minimal substrates (CHOMS)”, Chem. Sci. 2020, 11, 4150-4157.open archive unige:135618 pdf full text [free access]

DNA or RNA templated reactions are attractive for nucleic acid sensing and imaging. As for any hybridization-based sensing, there is a tradeoff between sensitivity (detection threshold) and resolution (single nucleotide discrimination). Longer probes afford better sensitivity but compromise single nucleotide resolution due to the small thermodynamic penalty of a single mismatch. Herein we report a design that overcomes this tradeoff. The reaction is leveraged on the hybridization of a minimal substrate (covering 4 nucleotides) which is confined by two guide DNAs functionalized respectively with a ruthenium photocatalyst. The use of a catalytic reaction is essential to bypass the exchange of guide DNAs while achieving signal amplification through substrate turnover. The guide DNAs restrain the reaction to a unique site and enhance the hybridization of short substrates by providing two π-stacking interactions. The reaction was shown to enable the detection of SNPs and SNVs down to 50 pM with a discrimination factor ranging from 24 to 309 (median 82, 27 examples from 3 oncogenes). The clinical diagnostic potential of the technology was demonstrated with the analysis of RAS amplicons obtained directly from cell culture.

69
Mottet, M.; Soldati, T. “AI842, AI843, AI844 and AI177 antibodies do not recognize a FLAG-tagged protein by immunofluorescence in D. discoideum cells”, Antib. Rep. 2020, 3, e126.open archive unige:134087 pdf full text [free access]

The recombinant antibodies AI842, AI843, AI844 and AI177 failed to detect by immunofluorescence a C-terminally FLAG-tagged LmpA fusion protein expressed in Dictyostelium discoideum.

68
Bisio, A.; Schito, A. M.; Pedrelli, F.; Danton, O.; Reinhardt, J. K.; Poli, G.; Tuccinardi, T.; Bürgi, T.; De Riccardis, F.; Giacomini, M.; Calzia, D.; Panfoli, I.; Schito, G. C.; Hamburger, M.; De Tommasi, N. “Antibacterial and ATP Synthesis Modulating Compounds from Salvia tingitana”, J. Nat. Prod. 2020, 83, 1027-1042.open archive unige:140931 pdf full text [restricted access]

A surface extract of the aerial parts of Salvia tingitana afforded a nor-sesterterpenoid (1) and eight new sesterterpenoids (29), along with five known sesterterpenoids, five labdane and one abietane diterpenoid, one sesquiterpenoid, and four flavonoids. The structures of the new compounds were established by 1D and 2D NMR spectroscopy, HRESIMS, and VCD data and Mosher’s esters analysis. The antimicrobial activity of compounds was evaluated against 30 human pathogens including 27 clinical strains and three isolates of marine origin for their possible implications on human health. The methyl ester of salvileucolide (10), salvileucolide-6,23-lactone (11), sclareol (15), and manool (17) were the most active against Gram-positive bacteria. The compounds were also tested for the inhibition of ATP production in purified mammalian rod outer segments. Terpenoids 101115, and 17 inhibited ATP production, while only 17 inhibited also ATP hydrolysis. Molecular modeling studies confirmed the capacity of 17 to interact with mammalian ATP synthase. A significant reduction of ATP production in the presence of 17 was observed in Enterococcus faecalis and E. faecium isolates.

67
Paraja, M.; Hao, X.; Matile, S. “Polyether Natural Product Inspired Cascade Cyclizations: Autocatalysis on π-Acidic Aromatic Surfaces”, Angew. Chem. Int. Ed. 2020, 59, 15093-15097.open archive unige:139856 pdf full text [restricted access]

Anion-π catalysis functions by stabilizing anionic transition states on aromatic π surfaces, thus providing a new approach to molecular transformation. The delocalized nature of anion–π interactions suggests that they serve best in stabilizing long-distance charge displacements. Aiming therefore for an anionic cascade reaction that is as charismatic as the steroid cyclization is for conventional cation-π biocatalysis, reported here is the anion-π-catalyzed epoxide-opening ether cyclizations of oligomers. Only on π-acidic aromatic surfaces having a positive quadrupole moment, such as hexafluorobenzene to naphthalenediimides, do these polyether cascade cyclizations proceed with exceptionally high autocatalysis (rate enhancements kauto/kcat >104 m−1). This distinctive characteristic adds complexity to reaction mechanisms (Goldilocks-type substrate concentration dependence, entropy-centered substrate destabilization) and opens intriguing perspectives for future developments.

66
Mateus, R.; Holtzer, L.; Seum, C.; Hadjivasiliou, Z.; Dubois, M.; Jülicher, F.; Gonzalez-Gaitan, M. “BMP Signaling Gradient Scaling in the Zebrafish Pectoral Fin”, Cell Reports 2020, 30, 4292-4302.e7.open archive unige:141202 pdf full text [free access]

Secreted growth factors can act as morphogens that form spatial concentration gradients in developing organs, thereby controlling growth and patterning. For some morphogens, adaptation of the gradients to tissue size allows morphological patterns to remain proportioned as the organs grow. In the zebrafish pectoral fin, we found that BMP signaling forms a two-dimensional gradient. The length of the gradient scales with tissue length and its amplitude increases with fin size according to a power-law. Gradient scaling and amplitude power-laws are signatures of growth control by time derivatives of morphogenetic signaling: cell division correlates with the fold change over time of the cellular signaling levels. We show that Smoc1 regulates BMP gradient scaling and growth in the fin. Smoc1 scales the gradient by means of a feedback loop: Smoc1 is a BMP agonist and BMP signaling represses Smoc1 expression. Our work uncovers a layer of morphogen regulation during vertebrate appendage development.

65
Sosnowski, P.; Hopfgartner, G. “Application of 3D printed tools for customized open port probe-electrospray mass spectrometry”, Talanta 2020, 215, 120894.open archive unige:134728 pdf full text [free access]

Three dimensional printed open port probe (3DP-OPP) and air displacement based liquid handler, were designed and optimized using fused deposition modeling (FDM) and stereolitography (SLA) 3D printing. The performance of the devices were investigated for the analysis of solid and liquid samples with electrospray ionization mass spectrometry (ESI-MS). Direct analysis in less than 1 min and without any sample preparation, enabled detection of pesticides (azoxtystrobin/imazalil) on fruits peel surface and illegal substances (MDMA/MDEA) in home-made pills. Conjunction of OPP in the overspill mode with a customized autosampler, equipped with disposable pipette tips, enables direct quantitative analysis of drugs of abuse in urine and plasma, with minimized carry-over and reduced matrix effect compared to flow injection analysis.

64
Cadoux, C.; Milton, R. D. “Recent Enzymatic Electrochemistry for Reductive Reactions”, ChemElectroChem 2020, 7, 1974-1986.open archive unige:140941 pdf full text [restricted access]

Enzymatic electrochemistry is the coupling of oxidoreductase enzymes to electrodes, where electrons are transferred between the electrode and an enzyme's cofactor(s). In addition to enzymatic electrochemistry enabling mechanistic study [such as the determination of cofactor reduction potential(s)], enzymatic electrocatalysis also enables substrate reduction or oxidation by exploiting the catalytic properties of enzymes. This Minireview illustrates some recent examples, in which electrodes are coupled with enzymes that catalyze the reduction of substrates such as dinitrogen (N2), carbon dioxide (CO2) and protons (H+), performed by metalloenzymes such as nitrogenases, formate dehydrogenases and hydrogenases. We review some strategies to achieve electron transfer (such as mediated and direct electron transfer), as well as some key results of recent studies.

63
Homberg, A.; Lacour, J. “From reactive carbenes to chiral polyether macrocycles in two steps – synthesis and applications made easy?”, Chem. Sci. 2020, 11, 6362-6369.open archive unige:138227 pdf full text [free access]

Chiral polyether macrocycles are versatile molecules. For their preparation, original two-step procedures were recently developed and present the advantage of high concentration conditions and simple starting reagents (stable diazo reagents, small cyclic ethers, aliphatic or aromatic amines). Enantiopure materials are readily afforded by CSP-HPLC on semi preparative scale. Flexibility and adaptability in the macrocyclic design is provided by a large selection of amines to choose from while ring size and chemical nature is controlled by the choice of 5 to 7-membered cyclic ether precursors. Such macrocycles have been used already as asymmetric catalysts, mono and ditopic receptors, fluorescent sensors and probes, and chiroptical reversible switches.

62
Soda, Y.; Robinson, K. J.; Cherubini, T. J.; Bakker, E. “Colorimetric absorbance mapping and quantitation on paper-based analytical devices”, Lab Chip 2020, 20, 1441-1448.open archive unige:134649 pdf full text [free access]

A wide range of microfluidic paper-based analytical devices (μPADs) have been developed in the last decade. Despite this, the quality of colorimetric analysis has not substantially improved as the data is vulnerable to heterogeneous color distribution (e.g., coffee ring effects), non-uniform shapes of colored detection area, and noise from the underlying paper structure. These limitations are here addressed by a colorimetric method to quantify freely discharged dye on paper substrate, without the need for a defined channel or hydrophobic barrier. For accurate quantification, colorimetric absorbance values are calculated for each pixel based on the recorded RGB values and noise from the paper structure eliminated, to extract accurate absorbance information at the pixel level. Total analyte quantity is then calculated through the conversion of absorbance values into quantity values for each pixel followed by integration across the entire image. The resulting quantity is shown to be independent of the shape of the applied colored dye spot, with a cross, circle or rod shape all giving the same quantity information. The approach is applied to a capillary-based potassium-selective sensor, where the sample solution is loaded with the dye thioflavin T (ThT) obtained by quantitative exchange with K+ in a sensing capillary, which is discharged onto a bare paper substrate without any channels. The resulting dye quantity is successfully obtained by flatbed scanner and smartphone. The successful automated computation of colorimetric data on μPADs will help realize simpler paper-based assay and reaction systems that should be more applicable to addressing real world analytical problems.

61
Levernier, N.; Bénichou, O.; Voituriez, R.; Guérin, T. “Kinetics of rare events for non-Markovian stationary processes and application to polymer dynamics”, Phys. Rev. Res. 2020, 2, 012057(R).

How much time does it take for a fluctuating system, such as a polymer chain, to reach a target configuration that is rarely visited—typically because of a high energy cost? This question generally amounts to the determination of the first-passage time statistics to a target zone in phase space with lower occupation probability. Here, we present an analytical method to determine the mean first-passage time of a generic non-Markovian random walker to a rarely visited threshold, which goes beyond existing weak-noise theories. We apply our method to polymer systems, to determine (i) the first time for a flexible polymer to reach a large extension, and (ii) the first closure time of a stiff inextensible wormlike chain. Our results are in excellent agreement with numerical simulations and provide explicit asymptotic laws for the mean first-passage times to rarely visited configurations.

60
Lamrabet, O.; Melotti, A.; Burdet, F.; Hanna, N.; Perrin, J.; Nitschke, J.; Pagni, M.; Hilbi, H.; Soldati, T.; Cosson, P. “Transcriptional Responses of Dictyostelium discoideum Exposed to Different Classes of Bacteria”, Front. Microbiol. 2020, 11, art. 410.open archive unige:136123 pdf full text [free access]

Dictyostelium discoideum amoebae feed by ingesting bacteria, then killing them in phagosomes. Ingestion and killing of different bacteria have been shown to rely on largely different molecular mechanisms. One would thus expect that D. discoideum adapts its ingestion and killing machinery when encountering different bacteria. In this study, we investigated by RNA sequencing if and how D. discoideum amoebae respond to the presence of different bacteria by modifying their gene expression patterns. Each bacterial species analyzed induced a specific modification of the transcriptome. Bacteria such as Bacillus subtilis, Klebsiella pneumoniae, or Mycobacterium marinum induced a specific and different transcriptional response, while Micrococcus luteus did not trigger a significant gene regulation. Although folate has been proposed to be one of the key molecules secreted by bacteria and recognized by hunting amoebae, it elicited a very specific and restricted transcriptional signature, distinct from that triggered by any bacteria analyzed here. Our results indicate that D. discoideum amoebae respond in a highly specific, almost non-overlapping manner to different species of bacteria. We additionally identify specific sets of genes that can be used as reporters of the response of D. discoideum to different bacteria.

59
Chang, D.; Kim, K. T.; Lindberg, E.; Winssinger, N. “Smartphone DNA or RNA-Sensing Using Semisynthetic Luciferase-Based Logic Device”, ACS Sens. 2020, 5, 807-813.open archive unige:132816 pdf full text [restricted access]

Detection of specific oligonucleotide sequences is central to numerous applications and technologies amenable to point-of-care diagnostics or end users are needed. Here we report a technology making use of a bioluminescent readout and smartphone quantification. The sensor is a semisynthetic luciferase (H-Luc-PNA conju-gate) that is turned on by a strand-displacement reaction. We demonstrated sensing of three different microRNAs (miRs), as representative cancer biomarker, and demonstrate the possibility to integrate an AND gate to sense two sequences simultaneously.

58
Kraikaew, P.; Jeanneret, S.; Soda, Y.; Cherubini, T.; Bakker, E. “Ultrasensitive Seawater pH Measurement by Capacitive Readout of Potentiometric Sensors”, ACS Sens. 2020, 5, 650-654.open archive unige:141065 pdf full text [restricted access]

Potentiometric pH probes remain the gold standard for the detection of pH but are not sufficiently sensitive to reliably detect ocean acidification at adequate frequency. Here, potentiometric probes are made dramatically more sensitive by placing a capacitive electronic component in series to the pH probe while imposing a constant potential over the measurement circuit. Each sample change now triggers a capacitive current transient that is easily identified between the two equilibrium states, and is integrated to reveal the accumulated charge. This affords dramatically higher precision than with traditional potentiometric probes. pH changes down to 0.001 pH units are easily distinguished in buffer and seawater samples, at a precision (standard deviation) of 28 μpH and 67 µpH, respectively, orders of magnitude better than what is possible with potentiometric pH probes.

57
López-Andarias, J.; Saarbach, J.; Moreau, D.; Cheng, Y.; Derivery, E.; Laurent, Q.; González-Gaitán, M.; Winssinger, N.; Sakai, N.; Matile, S. “Cell-Penetrating Streptavidin:  A General Tool for Bifunctional Delivery with Spatiotemporal Control, Mediated by Transport Systems such as Adaptive Benzopolysulfane Networks”, J. Am. Chem. Soc. 2020, 142, 4784-4792.open archive unige:132259 pdf full text [restricted access]

In this report, cell-penetrating streptavidin (CPS) is introduced to exploit the full power of streptavidin–biotin biotechnology in cellular uptake. For this purpose, transporters, here cyclic oligochalcogenides (COCs), are covalently attached to lysines of wild-type streptavidin. This leaves all four biotin binding sites free for at least bifunctional delivery. To maximize the standards of the quantitative evaluation of cytosolic delivery, the recent chloroalkane penetration assay (CAPA) is coupled with automated high content (HC) imaging, a technique that combines the advantages of fluorescence microscopy and flow cytometry. According to the resulting HC-CAPA, cytosolic delivery of CPS equipped with four benzopolysulfanes was the best among all tested CPSs, also better than the much smaller TAT peptide, the original cell-penetrating peptide from HIV. HaloTag-GFP fusion proteins expressed on mitochondria were successfully targeted using CPS carrying two different biotinylated ligands, HaloTag substrates or anti-GFP nanobodies, interfaced with peptide nucleic acids, flipper force probes, or fluorescent substrates. The delivered substrates could be released from CPS into the cytosol through desthiobiotin–biotin exchange. These results validate CPS as a general tool which enables unrestricted use of streptavidin–biotin biotechnology in cellular uptake.

56
Plank, M.; Perepelkina, M.; Müller, M.; Vaga, S.; Zou, X.; Bourgoint, C.; Berti, M.; Saarbach, J.; Haesendonckx, S.; Winssinger, N.; Aebersold, R.; Loewith, R. “Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9”, Mol. Cell. Proteomics 2020, 19, 655-671.open archive unige:137142 pdf full text [free access]

Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases.

55
Maroni, P.; Gvaramia, M.; Kosior, D.; Kubiak, K.; Scarratt, L.; Smith, A. M.; Merkel, D. G.; Bottyán, L.; Borkovec, M. “Structuring of colloidal silica nanoparticle suspensions near water–silica interfaces probed by specular neutron reflectivity”, Phys. Chem. Chem. Phys. 2020, 22, 6449-6456.open archive unige:132164 pdf full text [free access]

Structuring of aqueous suspensions of colloidal silica nanoparticles near an isolated planar silica–water interface is studied by specular neutron reflectivity. The reflectivity data clearly show that the suspensions develop a damped, oscillatory concentration profile in the normal direction to the interface. The wavelengths of these oscillations agree well with those independently determined by direct force measurements in the slit-geometry. The reflectivity data further demonstrate that the oscillatory structure persists over several layers and that the first particle layer is separated from the interface by a particle-free region.

54
Saarbach, J.; Barluenga, S.; Winssinger, N. “PNA-Encoded Synthesis (PES) and DNA Display of Small Molecule Libraries”, In Peptide Nucleic Acids” Chapter 7, Nielsen, P. (Ed.), Collection “Methods in Molecular Biology” vol. 2105, Humana: New York, NY 2020, p. 119-139.open archive unige:139639 pdf full text [restricted access]

DNA-encoded library technologies have emerged as a powerful platform to rapidly screen for binders to a protein of interest. These technologies are underpinned by the ability to encode a rich diversity of small molecules. While large libraries are accessible by cycles of mix and split synthesis, libraries based on single chemistries tend to be redundant. Furthermore, the quality of libraries generally decreases with the number of synthetic transformations performed in its synthesis. An alternative approach is to use hybridization to program the combinatorial assembly of fragment pairs onto a library of DNA templates. A broad molecular diversity is more easily sampled since it arises from the pairing of diverse fragments. Upon identification of productive fragment pairs, a focused library covalently linking the fragments is prepared. This focused library includes linker of different length and geometry and offers the opportunity to enrich the selected fragment set with close neighbors. Herein we describe detailed protocols to covalently link diverse fragments and screen fragment-based libraries using commercially available microarray platform.

53
Hanna, N.; Kicka, S.; Chiriano, G.; Harrison, C.; Sakouhi, H. O.; Trofimov, V.; Kranjc, A.; Nitschke, J.; Pagni, M.; Cosson, P.; Hilbi, H.; Scapozza, L.; Soldati, T. “Identification of Anti-Mycobacterium and Anti-Legionella Compounds With Potential Distinctive Structural Scaffolds From an HD-PBL Using Phenotypic Screens in Amoebae Host Models”, Front. Microbiol. 2020, 11, art. 266.open archive unige:136484 pdf full text [free access]

Tubercular Mycobacteria and Legionella pneumophila are the causative agents of potentially fatal respiratory diseases due to their intrinsic pathogenesis but also due to the emergence of antibiotic resistance that limits treatment options. The aim of our study was to explore the antimicrobial activity of a small ligand-based chemical library of 1255 structurally diverse compounds. These compounds were screened in a combination of three assays, two monitoring the intracellular growth of the pathogenic bacteria, Mycobacterium marinum and L. pneumophila, and one assessing virulence of M. marinum. We set up these assays using two amoeba strains, the genetically tractable social amoeba Dictyostelium discoideum and the free-living amoeba Acanthamoeba castellanii. In summary, 64 (5.1%) compounds showed anti-infective/anti-virulence activity in at least one of the three assays. The intracellular assays hit rate varied between 1.7% (n = 22) for M. marinum and 2.8% (n = 35) for L. pneumophila with seven compounds in common for both pathogens. In parallel, 1.2% (n = 15) of the tested compounds were able to restore D. discoideum growth in the presence of M. marinum spiked in a lawn of food bacteria. We also validated the generality of the hits identified in the A. castellaniiM. marinum anti-infective screen using the D. discoideumM. marinum host–pathogen model. The characterization of anti-infective and antibacterial hits in the latter infection model revealed compounds able to reduce intracellular growth more than 50% at 30 μM. Moreover, the chemical space and physico-chemical properties of the anti-M. marinum hits were compared to standard and candidate Mycobacterium tuberculosis (Mtb) drugs using ChemGPS-NP. A principle component analysis identified separate clusters for anti-M. marinum and anti-L. pneumophila hits unveiling the potentially new physico-chemical properties of these hits compared to standard and candidate M. tuberculosis drugs. Our studies underscore the relevance of using a combination of low-cost and low-complexity assays with full 3R compliance in concert with a rationalized focused library of compounds to identify new chemical scaffolds and to dissect some of their properties prior to taking further steps toward compound development.

52
Delarue Bizzini, L.; Bürgi, T.; Mayor, M. “The Enantiomers of Trinorbornane and Derivatives Thereof”, Helv. Chim. Acta 2020, 103, e2000019.open archive unige:140934 pdf full text [restricted access]

Herein, we report the synthesis of the enantiomers of trinorbornane, a tetracyclic saturated hydrocarbon with the chemical formula C 11 H 16 . The preparation of these rigid carbon scaffolds was enabled by the successful chiral separation of its tricyclic precursor, thus allowing the enantiomers to be synthesized via a reductive radical cyclization rection. Assignment of the absolute conformation of the enantiomers was achieved via VCD experiments. Further we report an alternative cyclization procedure providing access to hydroxyl and phenyl sulfone functionalized trinorbornanes.

51
Paraja, M.; Matile, S. “Primary Anion-π Catalysis of Epoxide-Opening Ether Cyclizations into Rings of Different Sizes:  Access to New Reactivity”, Angew. Chem. Int. Ed. 2020, 59, 6273-6277.open archive unige:134081 pdf full text [free access]

The concept of anion–π catalysis focuses on the stabilization of anionic transition states on aromatic π surfaces. Recently, we demonstrated the occurrence of epoxide-opening ether cyclizations on aromatic π surfaces. Although the reaction proceeded through unconventional mechanisms, the obtained products are the same as those from conventional Brønsted acid catalysis, and in agreement with the Baldwin selectivity rules. Different mechanisms, however, should ultimately lead to new products, a promise anion–π catalysis has been reluctant to live up to. Herein, we report non-trivial reactions that work with anion–π catalysis, but not with Brønsted acids, under comparable conditions. Namely, we show that the anion–π templated autocatalysis and epoxide opening with alcoholate–π interactions can provide access to unconventional ring chemistry. For smaller rings, anion–π catalysis affords anti-Baldwin oxolanes, 2-oxabicyclo[3.3.0]octanes, and the expansion of Baldwin oxetanes by methyl migration. For larger rings, anion–π templated autocatalysis is thought to alleviate the entropic penalty of folding to enable disfavored anti-Baldwin cyclizations into oxepanes and oxocanes.

50
Chen, W.; Egly, J.; Poblador-Bahamonde, A. I.; Maisse-Francois, A.; Bellemin-Laponnaz, S.; Achard, T. “Synthesis, characterization, catalytic and biological application of half-sandwich ruthenium complexes bearing hemilabile (κ2-C,S )-thioether-functionalised NHC ligands”, Dalton Trans. 2020, 49, 3243-3252.open archive unige:132257 pdf full text [restricted access]

A series of cationic Ru(II)(η6-p-cymene) complexes with thioether-functionalised N-heterocyclic carbene ligands have been prepared and fully characterized. Steric and electronic influence of the R thioether substituent on the coordination of the sulfur atom was investigated. The molecular structure of three of them has been determined by means of X-ray diffractrometry and confirmed the bidentate (κ2-C,S) coordination mode of the ligand. Interestingly, only a single diastereomer, as an enantiomeric couple, was observed in the solid state for complexes 1c, 1i and 1j. DFT calculations established a low energy inversion barrier between the two diastereomers through a sulfur pyramidal inversion pathway with R donating group while a dissociative/associative mechanism is more likely with R substituents that contain electron withdrawing group, thus suggesting that the only species observed by the 1H-NMR correspond to an average resonance position of a fluxional mixtures of isomers. All these complexes were found to catalyse the oxydant-free double dehydrogenation of primary amine into nitrile. Ru complex bearing NHC-functionalised S-tBu group was further investigated in a wide range of amines and was found more selective for alkyl amine substrates than for benzylamine derivatives. Finally, preliminary results of the biological effects on various human cancer cells of four selected Ru complexes are reported.

49
Ziarati, A.; Badiei, A.; Luque, R.; Dadras, M.; Burgi, T. “Visible Light CO2 Reduction to CH4 Using Hierarchical Yolk@shell TiO2-xHx Modified with Plasmonic Au-Pd Nanoparticles”, ACS Sustainable Chem. Eng. 2020, 8, 3689-3696.open archive unige:140932 pdf full text [restricted access]

Engineering of advanced semiconductor photocatalysts for CO2 conversion to solar fuels is a promising strategy to solve the greenhouse effect and energy crisis. Herein, hierarchical urchin like yolk@shell TiO2-xHx decorated with core/shell Au-Pd plasmonic nanoparticles (HUY@S-TOH/AuPd) have been prepared using a multi-step process and employed as advanced visible light active photocatalyst in CO2 conversion to CH4 with rate of 47 µmol/gcat.h (up to 126 µmol/gcat after 7h). Different engineered sites in this structure for high gas adsorption, powerful visible light activation and intense electron transformation are responsible for the observed high photocatalytic CO2 conversion efficiency. The present smart designing process can produce a considerable cooperation, not only to disclose the architectural engineering to improvement of photo-conversion efficiency, but also as a viable and appropriate photocatalytic process to sustainable energy production.

48
Bierwagen, J.; Delgado, T.; Jiranek, G.; Yoon, S.; Gartmann, N.; Walfort, B.; Pollnau, M.; Hagemann, H. “Probing traps in the persistent phosphor SrAl2O4:Eu2+,Dy3+,B3+ - A wavelength, temperature and sample dependent thermoluminescence investigation”, J. Lumin. 2020, 222, 117113.open archive unige:140938 pdf full text [restricted access]

Wavelength-dependent thermoluminescence (TL) experiments were performed on SrAl2O4:Eu, SrAl2O4:Eu,B, SrAl2O4:Eu,Dy and SrAl2O4:Eu,Dy,B polycrystalline samples. Excitation at 445 nm allows to selectively excite one of the two different Eu2+ ions substituting for Sr in the crystal, whereas excitation at 375 nm excites both Eu2+ ions. Incorporation of boron generates the deepest traps which contribute to the very long afterglow in this material, while dysprosium increases significantly (by a factor of about 4–8) the total number of traps involved in the afterglow of this persistent phosphor. Increasing the temperature at which the samples are irradiated (loaded) from 173 K to 248 K reveals that many new traps can only be occupied or activated at higher temperatures, leading to a strong increase of the integrated TL intensity, in particular for the Dy-containing samples. Boron does not appear to contribute to these thermally-activated traps significantly responsible for the long afterglow of SrAl2O4:Eu,Dy,B. The results of this study reveal that the diversity of traps leading to the long afterglow is much larger than previously reported in the literature. We propose that boron stabilizes F centers (which absorb in the far UV), while the presence of dysprosium induces an excitation-induced charge-transfer reaction Eu2+ + Dy3+ → Eu3+ + Dy2+. However, the principal traps responsible for the efficient afterglow are temperature-activated and appear to be associated with the green emitting Eu2+ ion on the Sr2 site coupled to a nearby dysprosium ion.

47
Gao, W.; Xie, X.; Bakker, E. “Direct Potentiometric Sensing of Anion Concentration (Not Activity)”, ACS Sens. 2020, 5, 313-318.open archive unige:136736 pdf full text [restricted access]

Potentiometric probes used in direct potentiometry are attractive sensing tools. They give information on ion activities, which is often uniquely useful. If, instead, concen-trations are desired as sensor output, the ionic strength of the sample must be precisely known, which is often not possible. Here, for the first time, direct potentiometry can be made to report concentrations, rather than activities. It is demonstrat-ed for the detection of monovalent anionic species by using a self-referencing Ag/AgI pulstrode as reference element in-stead of a traditional reference electrode. This reference pul-strode releases a discrete quantity of iodide ions from the electrode and the resulting reference potential varies with the activity coefficient of iodide. The effects of activity coefficient on the indicator and reference electrode are therefore com-pensated and the observed cell potential may now be de-scribed in a nernstian manner against anion concentration, rather than activity. Theoretical simulations and experimental results support the validity of this approach. For most mono-valent anions of practical relevance, the potential difference between this approach and from a traditional activity coeffi-cient calculation is less than 0.5 mV. The concept is validated with an all-solid-state nitrate sensor as well as a commercial fluoride-selective electrode, giving nernstian responses in different ionic strength backgrounds against concentration without the need for correcting activity coefficients or liquid junction potentials.

46
Baghdasaryan, A.; Besnard, C.; Lawson Daku, L. M.; Delgado, T.; Burgi, T. “Thiolato Protected Copper Sulfide Cluster with the Tentative Composition Cu74S15(2-PET)45”, Inorg. Chem. 2020, 59, 2200-2208.open archive unige:140933 pdf full text [restricted access]

Ligand protected copper nanoclusters with precise compositions have attracted considerable attention due to their unique photoluminescent properties. However, the acquisition of structural information, knowledge of the factors affecting the stability, and high quantum yields are prerequisites for assessing their applications in biomedicine as fluorescent contrast agents, biosensors, and probes for cells. Despite all the effort, only finite examples of single crystal structures of CuNCs are reported. Herein, we report the phosphine-free synthesis and structure determination of 2-PET protected CuNCs. The structure analysis established by single crystal X-ray diffraction reveals the formation of binary Cu74S15(2-PET)45 sulfide cluster. A similar phenomenon has been observed for several other chalcogenide-bridged copper clusters. The synthesized cluster possesses a rod-like structure, protected with 45 thiol ligands on the surface. Fifteen independent bridged-sulfur atoms couple to the copper atoms inside the core. Calculations for both a neutral and negatively charged cluster showed no major differences in their geometrical structures. Further analysis of frontier MO levels of the closed-shell anion predicts the HOMO–LUMO transition to be intramolecular L7 → L1 charge transfer, where “L7” and “L1” abbreviations refer to the corresponding sulfur layer in the structure. For the neutral cluster, the calculated spin density is delocalized over the two moieties. On the basis of TDDFT+TB calculations, the onset of the measured absorption spectrum could be satisfactorily reproduced.

45
Sethio, D.; Martins, J. B. L.; Lawson Daku, L. M.; Hagemann, H.; Kraka, E. “Modified Density Functional Dispersion Correction for Inorganic Layered MFX Compounds (M = Ca, Sr, Ba, Pb and X = Cl, Br, I)”, J. Phys. Chem. A 2020, 124, 1619-1633.open archive unige:140939 pdf full text [restricted access]

MFX (M = Ca, Ba, Sr, Pb and X = Cl, Br, I) compounds have received considerable attention due to their technological application as X-ray detectors, pressure sensors and optical data storage materials, when doped with rare-earth ions. MFX compounds belong to the class of layered materials with a tetragonal Matlockite crystal structure, characterized by weakly stacked double-halide layers along the crystallographic $c$-axis. These layers predominantly determine phase transitions, elastic and mechanical properties. However, the correct description of the lattice parameter $c$ is a challenge for most standard DFT functionals, which tend to overestimate the lattice parameter $c$. Because of the weak interactions between the halide layers dispersion corrected functionals seem to be a better choice. We investigated 11 different inorganic layered MFX compounds for which experimental data is available, with standard and dispersion-corrected functionals to assess their performance in reproducing the lattice parameter $c$, structural and vibrational properties of the MFX compounds. Our results revealed that these functionals do not describe the weak interactions between the halide layers in a balanced way. Therefore, we modified Grimme's popular DFT-D2 dispersion correction scheme in two different ways by (i) replacing the dispersion coefficients and van der Waals radii with those of noble gas atoms, or (ii) increasing the van der Waals radii of the MFX atoms up to 40 percent. Comparison with the available experimental data revealed that the latter approach applied to the PBE (Perdew-Burke-Ernzerhof)-D2 functional with 30 percent increased van der Waals radii, which we coined PBE-D2* (Stextsubscript{rvdw}1.30) is best suited to fine-tune the description of the weak interlayer interactions in MFX compounds, thus significantly improving the description of their structural and vibrational properties. Work is in progress applying this new, computationally inexpensive scheme to other inorganic layered compounds and periodic systems with weakly stacked layers.

44
Zdrachek, E.; Bakker, E. “Potentiometric Sensor Array with Multi-Nernstian Slope”, Anal. Chem. 2020, 92, 2926-2930.open archive unige:136525 pdf full text [restricted access]

The sensitivity of potentiometric sensors functioning in equilibrium mode is limited by the value predicted according to the Nernst equation and inversely proportional to the charge of the analyte ion. Therefore, an increased ion charge results in a dramatic decrease of sensor sensitivity. We propose an approach to allow one to increase the sensitivity of potentiometric measurements by using a combined electrochemical cell composed of several identical ion-selective electrodes immersed into separate sample solutions of equal composition. The combination of n electrodes demonstrating individually a Nernstian slope in one elec-trochemical cell allows to amplify the signal and associated response slope by n times. The proposed approach is shown to provide a double and triple Nernstian slope for potassium-, calcium-, nitrate and carbonate-selective electrodes by combining two or three identical electrodes, correspondingly. Each ion-selective electrode functions in an equilibrium mode, hence ensuring response sta-bility and reproducibility.

43
Kosior, D.; Morga, M.; Maroni, P.; Cieśla, M.; Adamczyk, Z. “Formation of Poly-L-lysine Monolayers on Silica: Modeling and Experimental Studies”, J. Phys. Chem. C 2020, 124, 4571-4581.

Modification of solid substrates by poly-L-lysine (PLL) layers has been widely employed in order to improve their biocompatibility, for promoting protein and cell immobilization for fabrication of biosensor arrays and antibacterial coatings. However, despite many studies conducted in the literature there is deficiency in a quantitative description of PLL adsorption processes. It is postulated that this becomes feasible applying direct experimental techniques combined with through theoretical modeling. In this work the kinetic of PLL adsorption on silica for various ionic strengths was determined in situ under controlled flow conditions using the optical reflectometry and the streaming potential methods. Both, the initial adsorption rates and longer time kinetic runs, were acquired and quantitatively interpreted in terms of the convective-diffusion and the random sequential adsorption theoretical modeling based on the coarse grained Monte-Carlo approach. This unique combination of experimental and theoretical approaches enabled to gain a new insight into the mechanism of macroion adsorption controlled by the electrostatic interactions, which affect both the molecule conformations and the blocking effects. Beside significance for basic science, the results obtained in this work can be exploited for developing reliable procedures for preparing stable PLL monolayers of well controlled coverage and electrokinetic properties.

42
Gooding, J. J.; Mazur, A.; Bakker, E.; Kelley, S.; Tao, N.; Sailor, M.; Merkx, M.; Mao, L.; Clark, H. “Editorial - Happy 5th Anniversary for ACS Sensors”, ACS Sens. 2020, 5, 1-2.open archive unige:141066 pdf full text [restricted access]

41
Christmann, J.; Mansouri, A.; Grinderslev, J. B.; Jensen, T. R.; Hagemann, H. “Probing the local symmetry of Tb3+ in borohydrides using luminescence spectroscopy”, J. Lumin. 2020, 221, 117065.open archive unige:140502 pdf full text [restricted access]

Rare-earth borohydrides have recently attracted a strong interest as potential hydrogen storage materials. While the local structure of the BH4 ion can be probed using vibrational spectroscopy, the local structure of the rare-earth ion can be studied using luminescence spectroscopy. This is reported here for Tb(BH4)3 and its solvate with S(CH3)2. The spectra clearly show smaller CF splittings for the unsolvated compound. These experimental data are compared with recent DFT+U calculations of the energy levels and CF splittings for Tb(BH4)3 and show that these calculations significantly overestimate the experimental results.

40
Cao, T.; Trefalt, G.; Borkovec, M. “Measuring slow heteroaggregation rates in the presence of fast homoaggregation”, J. Colloid Interface Sci. 2020, 566, 143-152.open archive unige:134082 pdf full text [restricted access]

Homoaggregation and heteroaggregation involving amidine and sulfate latex particles in the presence of the anionic surfactant octyl sulfate (OS) is studied by light scattering. This surfactant causes a charge reversal of the amidine particles. This reversal induces a rapid homoaggregation near the charge reversal point. In the presence of the same surfactant, the sulfate particles remain negatively charged and stable. The heteroaggregation process is probed in mixed suspensions of amidine and sulfate latex particles with multi-angle time-resolved dynamic light scattering. This technique allows differentiating between the contributions of homoaggregation and heteroaggregation, and permits to measure the heteroaggregation rate. By optimally choosing the sizes of the particles, one can optimize the contrast and extract heteroaggregation stability ratio over a wide range. The heteroaggregation rate is fast at low OS concentrations, where the two particles are oppositely charged. This rate slows down at higher OS concentrations due to double layer repulsion between the negatively charged particles. However, the onset of this slow heteroaggregation occurs at lower OS concentrations than for homoaggregation. The reason for this shift is that the double layer repulsion between two OS-decorated amidine particles is weaker than between one sulfate particle and one OS-decorated amidine particle. These measurements compare favorably with calculations with the theory by Derjaguin, Landau, Verwey, and Overbeek (DLVO). These calculations suggest that constant potential boundary conditions are more appropriate than the ones of constant charge. In the system studied, the present light scattering technique permits to extract heteroaggregation stability ratios over almost three orders of magnitude. This study is the first of its kind, where such a large range is being probed.

39
Golesorkhi, B.; Nozary, H.; Fürstenberg, A.; Piguet, C. “Erbium complexes as pioneers for implementing linear light-upconversion in molecules”, Mater. Horiz. 2020, 7, 1279-1296.open archive unige:132163 pdf full text [free access]

Since the non-linear optical (NLO) response of matter to incident excitation light does not require long-lived intermediate excited states working as relays, the conversion of low-energy photons into high energy light beams using second-harmonic generation (second-order NLO process) or two-photon absorption (third-order NLO process) can be implemented either in low-phonon macroscopic solids or in molecules containing high-energy vibrations. However, harnessing the very weak non-linear absorption coefficients requires (very) intense excitation sources, typically lasers, for getting reasonable emitted intensities. In contrast, the piling of successive near-infrared photons to get visible emission using linear optics, i.e. upconversion, is much more efficient, but it depends on the existence of intermediate excited states possessing long residence lifetimes. Therefore, upconversion usually occurs in low-phonon ionic solids or nanoparticles doped with pertinent activators. The recent recognition that trivalent erbium coordination complexes possessing high-frequency oscillators may act as dual visible/near-infrared activators, which implies the existence of at least one long-lived intermediate excited state in these complexes, paved the way for the implementation of the first upconversion processes within isolated molecules. Beyond a justification for using trivalent lanthanides, and especially erbium, for the manipulation of the energy of photons in molecules using linear optics, this tutorial review summarizes the current level of developments in the field of molecular-based upconversion and discusses some forthcoming challenges.

38
Knobloch, P.; Koliwer-Brandl, H.; Arnold, F. M.; Hanna, N.; Gonda, I.; Adenau, S.; Personnic, N.; Barisch, C.; Seeger, M. A.; Soldati, T.; Hilbi, H. “Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes”, Cell. Microbiol. 2020, 22, e13163.open archive unige:136124 pdf full text [restricted access]

Mycobacterium marinum is a model organism for pathogenic Mycobacterium species, including Mycobacterium tuberculosis, the causative agent of tuberculosis. These pathogens enter phagocytes and replicate within the Mycobacterium-containing vacuole (MCV), possibly followed by vacuole exit and growth in the host cell cytosol. Mycobacteria release siderophores called mycobactins to scavenge iron, an essential, yet poorly soluble and available micro-nutrient. To investigate the role of M. marinum mycobactins, we purified by organic solvent extraction and identified by mass spectrometry the lipid-bound mycobactin (MBT) and the water-soluble variant carboxymycobactin (cMBT). Moreover, we generated by specialized phage transduction a defined M. marinum ΔmbtB deletion mutant predicted to be defective for mycobactin production. The M. marinum ΔmbtB mutant strain showed a severe growth defect in broth and phagocytes, which was partially complemented by supplying the mbtB gene on a plasmid. Furthermore, purified Fe-MBT or Fe-cMBT improved the growth of wild-type as well as ΔmbtB mutant bacteria on minimal plates, but only Fe-cMBT promoted the growth of wild-type M. marinum during phagocyte infection. Finally, the intracellular growth of M. marinum ΔmbtB in Acanthamoeba castellanii amoebae was restored by co-infection with wild-type bacteria. Our study identifies and characterizes the M. marinum MBT and cMBT siderophores and reveals the requirement of mycobactins for extra- and intracellular growth of the pathogen.

37
Leuba, F.; Soldati, T. “AI842, AI843, AI844 and AI177 antibodies do not recognize a FLAG-tagged protein expressed in D. discoideum by western blot”, Antib. Rep. 2020, 3, e111.open archive unige:131083 pdf full text [free access]

The recombinant antibodies AI842, AI843, AI844 and AI177 do not detect by western blot an N-terminal FLAG-tagged RavZ protein expressed in Dictyostelium discoideum.

36
Klont, F.; Jahn, S.; Grivet, C.; König, S.; Bonner, R.; Hopfgartner, G. “SWATH data independent acquisition mass spectrometry for screening of xenobiotics in biological fluids: Opportunities and challenges for data processing”, Talanta 2020, 211, 120747.open archive unige:136523 pdf full text [restricted access]

SWATH data independent acquisition (DIA) mass spectrometry (MS) has become an established technique in MS-based ‘omics’ research and is increasingly used for the screening of xenobiotics (e.g. drugs, drug metabolites, pesticides, toxicants). Such xenobiotic screening methods are mostly applied for tentative compound identification purposes based on spectral library searching, while additional data processing techniques are scarcely used thereby leaving the full potential of these methods often unused. Here we present an analytical workflow for screening xenobiotics in human samples using SWATH/MS based on which we highlight opportunities for unlocking unused potential of these methods. The workflow was applied to urine samples from subjects who tested positive for THC and/or cocaine during roadside drug testing with the goal of confirming the positive roadside drug tests and identifying compounds that relate to illicit drug use (e.g. cutting agents, tobacco components) or associate with corresponding lifestyle choices (e.g. nasal decongestants, painkillers). These goals could only be reached by complementing spectral library search procedures with additional multivariate data analyses due to inherent incompleteness of the spectral library that was employed. Such incompleteness represents a common challenge for applications where limited or no metadata is available for study samples, for example in toxicology, doping control in sports, and workplace or roadside drug testing. It furthermore sets the stage for employing additional data processing techniques as is outlined in the presented work.

35
Levernier, N.; Kruse, K. “Spontaneous formation of chaotic protrusions in a polymerizing active gel layer”, New J. Phys. 2020, 22, 013003.open archive unige:141204 pdf full text [free access]

The actin cortex is a thin layer of actin filaments and myosin motors beneath the outer membrane of animal cells. It determines the cells' mechanical properties and forms important morphological structures. Physical descriptions of the cortex as a contractile active gel suggest that these structures can result from dynamic instabilities. However, in these analyses the cortex is described as a two-dimensional layer. Here, we show that the dynamics of the cortex is qualitatively different when gel fluxes in the direction perpendicular to the membrane are taken into account. In particular, an isotropic cortex is then stable for arbitrarily large active stresses. If lateral contractility exceeds vertical contractility, the system can either from protrusions with an apparently chaotic dynamics or a periodic static pattern of protrusions.

34
Szabo, T.; Maroni, P.; Szilagyi, I. “Size-dependent aggregation of graphene oxide”, Carbon 2020, 160, 145-155.

Graphene oxides (GO) of highly polydisperse size distribution were prepared by the Brodie method and their dispersion stability was characterized. Exfoliation and fractionation led to well-defined particle populations in the Nano, classical Colloidal (submicron) and Micrometer size ranges, as revealed by atomic force microscopy and light scattering measurements. Time-resolved dynamic light scattering experiments revealed that aggregation processes are fully impeded in the intermediate pH regime of 3–13 in the absence of electrolytes. While the resistance against salt-induced aggregation increases with the pH due to the progressive ionization of the surface functional groups of GO sheets, their dispersions are inherently unstable at supramillimolar concentrations of strong acids and submolar concentrations of bases, in line with the DLVO theory. However, the aggregation behavior quantified by the critical coagulation concentrations (CCCs) shows surprisingly substantial platelet size dependence. The CCC of Nano Brodie-GO reaches 360 mm at pH = 12, which is one of the highest values ever reported for GO aqueous dispersions. These results provide useful quantitative information to design processable GO dispersions of pH- and size-tunable stability for future applications.

33
Nazarov, A. E.; Ivanov, A. I.; Vauthey, E. “Modeling Infrared Spectral Dynamics upon Symmetry Breaking of a Photo-Excited Quadrupolar Dye”, J. Phys. Chem. C 2020, 124, 2357-2369.open archive unige:132980 pdf full text [free access]

A significant number of quadrupolar dyes with a D-π-A-π-D or A-π-D-π-A structure,where D and A are electron donor and acceptor groups, were shown to undergosymmetry breaking (SB) upon optical excitation. During this process, the electronicexcitation, originally distributed evenly over the molecule, concentrates on one D-π-Abranch, and the molecule becomes dipolar. This process can be monitored by timeresolved infra-red (TRIR) spectroscopy and causes significant spectral dynamics. Atheoretical model of excited-state SB developed earlier ( Ivanov, A. I.J. Phys. Chem.C,2018,122, 29165-29172) is extended to account for the temporal changes takingplace in the IR spectrum upon SB. This model can reproduce the IR spectral dynamicsobserved in the−C≡C−stretching region with a D-π-A-π-D dye in two polar solventsusing a single set of molecular parameters. This approach allows estimating the degreeof asymmetry of the excited state in different solvents as well as its change during SB.Additionally, the relative contribution of the different mechanisms responsible for thesplitting of the symmetric and antisymmetric−C≡C−stretching bands, which areboth IR active upon SB, can be determined.

32
Doistau, B.; Jiménez, J.-R.; Guerra, S.; Besnard, C.; Piguet, C. “Key Strategy for the Rational Incorporation of Long-Lived NIR Emissive Cr(III) Chromophores into Polymetallic Architectures”, Inorg. Chem. 2020, 59, 1424-1435.open archive unige:129610 pdf full text [restricted access]

The CrIIIN6 chromophores are particularly appealing for low-energy sensitization via energy transfer processes since they show extremely long excited state lifetimes reaching the millisecond range in the technologically crucial near-infrared domain. However, their properties were barely harnessed in multimetallic structures because of the lack of both monitoring methods and accessible synthetic pathways. We herein report a remedy to monitor and control the formation of CrIII-containing assemblies in solution via the design of a CrIIIN6 inert “complex-as-ligand” that can be included into polymetallic architectures. As a proof of concept, these CrN6 building blocks were reacted in solution with ZnII or FeII to give extended trinuclear linear Cr–M–Cr assemblies, the structure of which could be addressed by NMR spectroscopy despite the presence of two slowly relaxing CrIII paramagnetic centers. In addition to long CrIII excited state lifetimes and weak sensitivity to oxygen quenching, these polymetallic assemblies display controlled CrIII to MII energy transfers, which pave the way for use of the “complex-as-ligand” strategy for introducing photophysically active CrIII probes into light-converting polymetallic devices.

Supporting Information (pdf, 4.63 MB)

31
Hopfgartner, G. “Books Review Wenkui Li, Wenying Jian, and Yunlin Fu (Eds.): Sample preparation in LC-MS bioanalysis”, Anal. Bioanal. Chem. 2020, 412, 803-804.open archive unige:140945 pdf full text [restricted access]

30
Butler, R. E.; Smith, A. A.; Mendum, T. A.; Chandran, A.; Wu, H.; Lefrançois, L.; Chambers, M.; Soldati, T.; Stewart, G. R. “Mycobacterium bovis uses the ESX-1 Type VII secretion system to escape predation by the soil-dwelling amoeba Dictyostelium discoideum”, ISME J. 2020, 14, 919-930.open archive unige:136125 pdf full text [free access]

Mycobacterium bovis is the causative agent of bovine tuberculosis and the predominant cause of zoonotic tuberculosis in people. Bovine tuberculosis occurs in farmed cattle but also in a variety of wild animals, which form a reservoir of infection. Although direct transmission of tuberculosis occurs between mammals, the low frequency of contact between different host species and abundant shedding of bacilli by infected animals suggests an infectious route via environmental contamination. Other intracellular pathogens that transmit via the environment deploy strategies to survive or exploit predation by environmental amoebae. To explore if M. bovis has this capability, we investigated its interactions with the soil and dung-dwelling amoeba, Dictyostelium discoideum. We demonstrated that M. bovis evades phagocytosis and destruction by D. discoideum and actively transits through the amoeba using the ESX-1 Type VII Secretion System as part of a programme of mechanisms, many of which have been co-opted as virulence factors in the mammalian host. This capacity of M. bovis to utilise an environmental stage between mammalian hosts may enhance its transmissibility. In addition, our data provide molecular evidence to support an evolutionary role for amoebae as training grounds for the pathogenic M. tuberculosis complex.

29
Lathion, T.; Fürstenberg, A.; Besnard, C.; Hauser, A.; Bousseksou, A.; Piguet, C. “Monitoring Fe(II) Spin-State Equilibria via Eu(III) Luminescence in Molecular Complexes: Dream or Reality?”, Inorg. Chem. 2020, 59, 1091-1103.open archive unige:129611 pdf full text [restricted access]

The modulation of light emission by Fe(II) spin-crossover processes in multifunctional materials has recently attracted major interest for the indirect and noninvasive monitoring of magnetic information storage. In order to approach this goal at the molecular level, three segmental ligand strands, L4L6, were reacted with stoichiometric mixtures of divalent d-block cations (M(II) = Fe(II) or Zn(II)) and trivalent lanthanides (Ln(III) = La(III) or Eu(III)) in acetonitrile to give C3-symmetrical dinuclear triple-stranded helical [LnM(Lk)3]5+ cations, which can be crystallized with noncoordinating counter-anions. The divalent metal M(II) is six-coordinate in the pseudo-octahedral sites produced by the facial wrapping of the three didentate binding units, the ligand field of which induces variable Fe(II) spin-state properties in [LnFe(L4)3]5+ (strictly high-spin), [LnFe(L5)3]5+ (spin-crossover (SCO) around room temperature), and [LnFe(L6)3]5+ (SCO at very low temperature). The introduction of the photophysically active Eu(III) probe in [EuFe(Lk)3]5+ results in europium-centered luminescence modulated by variable intramolecular Eu(III) → Fe(II) energy-transfer processes. The kinetic analysis implies Eu(III) → Fe(II) quenching efficiencies close to 100% for the low-spin configuration and greater than 95% for the high-spin state. Consequently, the sensitivity of indirect luminescence detection of Fe(II) spin crossover is limited by the resulting weak Eu(III)-centered emission intensities, but the dependence of the luminescence on the temperature unambiguously demonstrates the potential of indirect lanthanide-based spin-state monitoring at the molecular scale.

Supporting Information (pdf, 1.5 MB)

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Stankevicins, L.; Ecker, N.; Terriac, E.; Maiuri, P.; Schoppmeyer, R.; Vargas, P.; Lennon-Duménil, A.-M.; Piel, M.; Qu, B.; Hoth, M.; Kruse, K.; Lautenschläger, F. “Deterministic actin waves as generators of cell polarization cues”, Proc. Natl. Acad. Sci. USA 2020, 117, 826-835.open archive unige:141205 pdf full text [restricted access]

Dendritic cells “patrol” the human body to detect pathogens. In their search, dendritic cells perform a random walk by amoeboid migration. The efficiency of pathogen detection depends on the properties of the random walk. It is not known how the dendritic cells control these properties. Here, we quantify dendritic cell migration under well-defined 2-dimensional confinement and in a 3-dimensional collagen matrix through recording their long-term trajectories. We find 2 different migration states: persistent migration, during which the dendritic cells move along curved paths, and diffusive migration, which is characterized by successive sharp turns. These states exhibit differences in the actin distributions. Our theoretical and experimental analyses indicate that this kind of motion can be generated by spontaneous actin polymerization waves that contribute to dendritic cell polarization and migration. The relative distributions of persistent and diffusive migration can be changed by modification of the molecular actin filament nucleation and assembly rates. Thus, dendritic cells can control their migration patterns and adapt to specific environments. Our study offers an additional perspective on how dendritic cells tune their searches for pathogens.

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Galli, V.; Sadhu, K. K.; Masi, D.; Saarbach, J.; Roux, A.; Winssinger, N. “Caprin-1 Promotes Cellular Uptake of Nucleic Acids with Backbone and Sequence Discrimination”, Helv. Chim. Acta 2020, 103, e1900255.open archive unige:129366 pdf full text [free access]

The cellular delivery of oligonucleotides has been a major obstacle in the development of therapeutic antisense agents. PNAs (Peptide Nucleic Acid) are unique in providing a modular peptidic backbone that is amenable to structural and charge modulation. While cationic PNAs have been shown to be taken up by cells more efficiently than neutral PNAs, the generality of uptake across different nucleobase sequences has never been tested. Herein, we quantified the relative uptake of PNAs across a library of 10 000 sequences for two different PNA backbones (cationic and neutral) and identified sequences with high uptake and low uptake. We used the high uptake sequence as a bait for target identification, leading to the discovery that a protein, caprin-1, binds to PNA with backbone and sequence discrimination. We further showed that purified caprin-1 added to cell cultures enhanced the cellular uptake of PNA as well as DNA and RNA.

Supporting Information: PDF (1 MB) / XSLX (1.7 MB)

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Patel, J.; Cai, R.; Milton, R.; Chen, H.; Minteer, S. D. “Pyrene-Based Noncovalent Immobilization of Nitrogenase on Carbon Surfaces”, ChemBioChem 2020, 21, 1729-1732.open archive unige:140942 pdf full text [restricted access]

Early work with viologen-mediated nitrogenase bio-electrochemistry focused on bio-electrocatalysis with the enzyme in solution, but biocatalyst immobilization at electrode surfaces is favorable as it provides a high effective concentration of biocatalyst at the electrode surface. We have used a pyrene–peptide linker as a method for immobilizing nitrogenase on carbon electrode surfaces for nitrogenase bio-electrocatalysis.

25
Forrest, T.; Zdrachek, E.; Bakker, E. “Thin Layer Membrane Systems as Rapid Development Tool for Potentiometric Solid Contact Ion-selective Electrodes”, Electroanalysis 2020, 32, 799-804.open archive unige:136739 pdf full text [restricted access]

The use of thin membrane layer ion selective electrodes (of ∼200 nm thickness) as rapid diagnosis tool is proposed. While conventional solid contact systems (with a membrane of ∼250 μm thickness) may exhibit a satisfactory stability for regular laboratory use, a signal degradation can still be distinguished over a longer period of time but this requires tedious and time consuming tests. By diminishing the thickness of the membrane by a factor of 103 approximately, diffusion processes happen faster, and the lifetime is significantly reduced. This would ordinarily be a strong drawback but not if the aim is to detect a membrane deterioration in a shorter time frame. This characteristic makes thin membrane systems an ideal tool for rapid complications identification in the development process of conventional solid contact electrodes. The approach is demonstrated here in the development of an all new solid contact probe for anions. PEDOT−C14, a conducting polymer, was used for the first time in a solid contact electrode with an anion exchange membrane for the detection of nitrate. The thin layer configuration was used to optimise the polymerisation parameters as well as the membrane composition without having to run week long trials. A stable conventional solid contact electrode was in the end successfully developed and exhibited a lower detection limit of 10−5.5 M for nitrate with a stable Nernstian response for several days.

24
Yang, J.; Chatelet, B.; Hérault, D.; Dufaud, V.; Robert, V.; Grass, S.; Lacour, J.; Vanthuyne, N.; Jean, M.; Albalat, M.; Dutasta, J.-P.; Martinez, A. “Enantiopure encaged Verkade's superbases: Synthesis, chiroptical properties, and use as chiral derivatizing agent”, Chirality 2020, 32, 139-146.open archive unige:129075 pdf full text [restricted access]

Verkade's superbases, entrapped in the cavity of enantiopure hemicryptophane cages, have been synthesized with enantiomeric excess (ee) superior to 98%. Their absolute configuration has been determined by using electronic circular dichroism (ECD) spectroscopy. These enantiopure encaged superbases turned out to be efficient chiral derivatizing agents for chiral azides, underlining that the chirality of the cycloveratrylene (CTV) macrocycle induces different magnetic and chemical environments around the phosphazide functions.

Supporting Information (PDF / 2 MB)

23
Hopfgartner, G. “Editorial Bioanalytical method validation: How much should we do and how should we document?”, Anal. Bioanal. Chem. 2020, 412, 531-532.open archive unige:140947 pdf full text [restricted access]

22
Humeniuk, H. V.; Licari, G.; Vauthey, E.; Sakai, N.; Matile, S. “Mechanosensitive Membrane Probes:  Push-Pull Papillons”, Supramol. Chem. 2020, 33, 106-111.open archive unige:131618 pdf full text [free access]

Design, synthesis and evaluation of push-pull N,N′-diphenyl-dihydrodibenzo[a,c]phenazines are reported. Consistent with theoretical predictions, donors and acceptors attached to the bent mechanophore are shown to shift absorption maxima to either red or blue, depending on their positioning in the chromophore. Redshifted excitation of push-pull fluorophores is reflected in redshifted emission of both bent and planar excited states. The intensity ratios of the dual emission in more and less polar solvents imply that excited-state (ES) planarization decelerates with increasing fluorophore macrodipole, presumably due to attraction between the wings of closed papillons. ES planarization of highly polarisable papillons is not observed in lipid bilayer membranes. All push-pull papillon amphiphiles excel with aggregation-induced emission (AIE) from bent ES as micelles in water and mechanosensitivity in viscous solvents. They are not solvatochromic and only weakly fluorescent (QY < 4%).

Supplemental material (pdf)

21
Stojimirovic, B.; Vis, M.; Tuinier, R.; Philipse, A. P.; Trefalt, G. “Experimental Evidence for Algebraic Double-Layer Forces”, Langmuir 2020, 36, 47-54.open archive unige:136351 pdf full text [free access]

According to textbook wisdom electric double-layer forces decay exponentially with separation distance. Here we present experimental evidence of algebraically decaying double-layer interactions. We show that algebraic interactions arise in both strongly overlapping as well as counterion-only regimes. In both of these cases the disjoining pressure profile assumes an inverse square distance dependence. At small separation distances another algebraic regime is recovered. In this regime the pressure decays as the inverse of separation distance.

Supporting Information (pdf / 191.56 kb)

20
Fiorito, D.; Liu, Y.; Besnard, C.; Mazet, C. “Direct Access to Chiral Secondary Amides by Copper-Catalyzed Borylative Carboxamidation of Vinylarenes with Isocyanates”, J. Am. Chem. Soc. 2020, 142, 623-632.open archive unige:128621 pdf full text [restricted access]

A Cu-catalyzed borylative carboxamidation reaction has been developed using vinylarenes and isocyanates. Alkynes, branched 1,3-dienes and bicyclic alkenes were also found to be competent coupling partners. Using a chiral phosphan-amine ligand, an enantioselective variant of this transformation was developed, affording a set of α-chiral amides with unprecedented levels of enantioselectivity. The synthetic utility of the method was demonstrated through a series of representative stereoretentive post-catalytic derivatizations.

19
Oberhauser, L.; Granziera, S.; Colom, A.; Goujon, A.; Lavallard, V.; Matile, S.; Roux, A.; Brun, T.; Maechler, P. “Palmitate and Oleate Modify Membrane Fluidity and Kinase Activities of INS-1E ß-Cells Alongside Altered Metabolism-Secretion Coupling”, Biochim. Biophys. Acta, Mol. Cell Biol. Lipids 2020, 1867, 118619.open archive unige:127987 pdf full text [restricted access]

Chronic exposure to elevated levels of glucose and free fatty acids impairs beta-cell function, leading to insulin secretion defects and eventually beta-cell failure. Using a semi-high throughput approach applied to INS-1E beta-cells, we tested multiple conditions of chronic exposure to basal, intermediate and high glucose, combined with saturated versus mono- and polyunsaturated fatty acids in order to assess cell integrity, lipid metabolism, mitochondrial function, glucose-stimulated calcium rise and secretory kinetics. INS-1E beta-cells were cultured for 3 days at different glucose concentrations (5.5, 11.1, 25 mM) without or with BSA-complexed 0.4 mM saturated (C16:0 palmitate), monounsaturated (C18:1 oleate) or polyunsaturated (C18:2 linoleate, C18:3 linolenate) fatty acids, resulting in 0.1–0.5 μM unbound fatty acids. Accumulation of triglycerides in cells exposed to fatty acids was glucose-dependent, oleate inducing the strongest lipid storage and protecting against glucose-induced cytotoxicity. The combined chronic exposure to both high glucose and either palmitate or oleate altered mitochondrial function as well as glucose-induced calcium rise. This pattern did not directly translate at the secretory level since palmitate and oleate exhibited distinct effects on the first and the second phases of glucose-stimulated exocytosis. Both fatty acids changed the activity of kinases, such as the MODY-associated BLK. Additionally, chronic exposure to fatty acids modified membrane physicochemical properties by increasing membrane fluidity, oleate exhibiting larger effects compared to palmitate. Chronic fatty acids differentially and specifically exacerbated some of the glucotoxic effects, without promoting cytotoxicity on their own. Each of the tested fatty acids functionally modified INS-1E beta-cell, oleate inducing the strongest effects.

Supplementary figures (PDF / 1 MB)

18
Brun, E.; Zhang, K.-F.; Guénée, L.; Lacour, J. “Photo-induced thiol–ene reactions for late-stage functionalization of unsaturated polyether macrocycles: regio and diastereoselective access to macrocyclic dithiol derivatives”, Org. Biomol. Chem. 2020, 18, 250-254.open archive unige:128309 pdf full text [free access]

Double hydrothiolation of bis enol ether macrocycles was achieved under photo-mediated conditions. The thiol–ene reactions afford a fully regioselective anti-Markovnikov post-functionalization. Thanks to the use of ethanedithiol as reagent, moderate to excellent diastereoselectivity was accomplished leading to macrocycles containing four defined stereocenters in only three steps from 1,4-dioxane, tetrahydrofuran (THF) or tetrahydropyran (THP).

Supplementary Information (PDF) / Crystal Structure data (CIF)

17
Duwald, R.; Bosson, J.; Pascal, S.; Grass, S.; Zinna, F.; Besnard, C.; Di Bari, L.; Jacquemin, D.; Lacour, J. “Merging polyacenes and cationic helicenes: from weak to intense chiroptical properties in the far red region”, Chem. Sci. 2020, 11, 1165-1169.open archive unige:129838 pdf full text [free access]

A series of helical tetracenes and pentacenes was synthesized from cationic [6] and [4]helicene precursors. These colorful acenes fluoresce in the far red region. While [4]helicene-based pentacenes exhibit chiroptical properties mainly in the UV region, [6]helicene-derived tetracenes show enhanced ECD in the visible range, in addition to clear CPL responses. This difference is rationalized using first principles.

Supplementary information (PDF) / Crystal structure data (CIF)

16
Zinna, F.; Brun, E.; Homberg, A.; Lacour, J. “Circularly polarized luminescence from intramolecular excimers”, In Circularly Polarized Luminescence of Isolated Small Organic Molecules” Chapter 12, Mori, T. (Ed.), Springer: Singapore 2020, p. 273-292.open archive unige:138295 pdf full text [restricted access]

In this chapter, examples of circularly polarized luminescence (CPL) stemming from intramolecularly formed excimers will be reviewed. Emission from excimers has peculiar photophysical properties with respect to fluorescence of regular monomers. In addition, if the fluorophoric couple forming the excimer in the excited state is mounted on a chiral scaffold, a strong CPL can be usually observed. Examples of chiral scaffolds include oligopeptides, macrocycles, binaphthyl, and diaminocyclohexane derivatives. CPL from excimers has mainly been observed from pyrenes but other molecules are also able to give rise to such phenomenon, e.g., perylenes and 1,8-naphthalene monoimide. Excimer CPL can provide important information about the conformation of a molecule in the excited state and how it evolves depending on the environment (e.g., solvent and temperature) or external stimuli (e.g., light irradiation and cation addition). Moreover, thanks to the peculiar photophysical nature of excimers, the degree of circular polarization associated with excimer emission is usually much larger than the one associated with the absorption (electronic circular dichroism, ECD) for the same molecule. This allows to study chiroptical emission properties of molecules which are ECD-silent (ground state cryptochirality). As a whole, excimer CPL is an interesting and useful strategy to develop organic molecular systems endowed with bright and highly polarized luminescence.

15
Figuerola-Conchas, A.; Saarbach, J.; Daguer, J.-P.; Cieren, A.; Barluenga, S.; Winssinger, N.; Gotta, M. “Small-molecule modulators of the ATPase VCP/p97 affect specific p97 cellular functions”, ACS Chem. Biol. 2020, 15, 243-253.open archive unige:129089 pdf full text [free access]

VCP/p97 belongs to the AAA+ ATPase family and has an essential role in several cellular processes ranging from cell division to protein homeostasis. Compounds targeting p97 inhibit the main ATPase domain and cause cell death. Here, using PNA-encoded chemical libraries, we have identified two small molecules that target the regulatory domain of p97, comprising the N-terminal and the D1 ATPase domains, and do not cause cell death. One molecule, NW1028, inhibits the degradation of a p97-dependent reporter, whereas the other, NW1030, increases it. ATPase assays show that NW1028 and NW1030 do not affect the main catalytic domain of p97. Mapping of the binding site using a photo-affinity conjugate points to a cleft at the interface of the N-terminal and the D1 ATPase domains. We have therefore discovered two new compounds that bind to the reg-ulatory domain of p97 and modulate specific p97 cellular functions. Using these compounds, we have revealed a role for p97 in the regulation of mitotic spindle orientation in HeLa cells.

Supporting Information:

Supplementary figures and synthetic procedures as well as analysis of the synthesized compounds (PDF / 4.27 MB)

Video 1: HeLa K cells expressing H2B-mCherry (red, to mark chromosomes) and α-tubulin-mEGFP (green, to mark microtubules) treated with 10 μM DBeQ (AVI / 1.91 MB)

Video 2: HeLa K cells expressing H2B-mCherry (red, to mark chromosomes) and α-tubulin-mEGFP (green, to mark microtubules) treated with 10 μM NW1028 (AVI / 90.02 kb)

Video 3: HeLa K cells expressing H2B-mCherry (red, to mark chromosomes) and α-tubulin-mEGFP (green, to mark microtubules) treated with 10 μM NW1030 (AVI / 112.48 kb)

Video 4: HeLa K cells expressing H2B-mCherry (red, to mark chromosomes) and α-tubulin-mEGFP (green, to mark microtubules) treated with 10 μM DMSO (AVI / 90.9 kb)

14
Rodrigues, T.; Brodier, L.; Matter, J.-M. “Investigating Neurogenesis in Birds”, In Retinal Development: Methods and Protocols”, Mao, C.-A. (Ed.), Collection “Methods in Molecular Biology” vol. 2092, Humana: New York 2020, p. 1-18.

The macula and fovea make human vision unique among mammals. An understanding of the genetic network underlying the development and maintenance of this highly specialized region is instrumental to address issues about human macula-related retinopathies. The pigeon retina, unlike currently available animal models, shares numerous key characteristics of the primate macula and represents a promising new model for the study of retinal development. We provide key elements to take advantage of this new model for the study of retina and brain development. This includes precise embryo staging, transfection of genetic material (reporter plasmid, expression vectors, siRNAs) using in ovo and ex vivo electroporation, live imaging, high-resolution confocal imaging, and data layout and instructions for data analysis.

13
Smith, A. M.; Borkovec, M.; Trefalt, G. “Forces between solid surfaces in aqueous electrolyte solutions”, Adv. Colloid Interface Sci. 2020, 275, 102078.open archive unige:136316 pdf full text [restricted access]

This review addresses experimental findings obtained with direct force measurements between two similar or dissimilar solid surfaces in aqueous electrolyte solutions. Interpretation of these measurements is mainly put forward in terms of the classical theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO). This theory invokes a superposition of attractive van der Waals forces and repulsive double layer forces. DLVO theory is shown to be extremely reliable, even in the case of multivalent ions. However, such a description is only successful, when appropriate surface charge densities, charge regulation characteristics, and ion pairing or complexation equilibria in solution are considered. Deviations from DLVO theory only manifest themselves at distances of typically below few nm. More long-ranged non-DLVO forces can be observed in some situations, particularly, in concentrated electrolyte solutions, in the presence of strongly adsorbed layers, or for hydrophobic surfaces. The latter forces probably originate from patch-charge surface heterogeneities, which can be induced by ion-ion correlation effects, charge fluctuations, or other types of surface heterogeneities.

12
Gao, W.; Zdrachek, E.; Xie, X.; Bakker, E. “A Solid-State Reference Electrode Based on a Self-Referencing Pulstrode”, Angew. Chem. Int. Ed. 2020, 59, 2294-2298.open archive unige:136738 pdf full text [restricted access]

The design of solid-state reference electrodes without a liquid junction is important to allow miniature and cost-effective electrochemical sensors. To address this, a pulse control is proposed using an Ag/AgI element as reliable solid-state reference electrode. It involves the local release of iodide by a cathodic current that is immediately followed by an electromotive force (EMF) measurement that serves as the reference potential. The recapture of iodide ions is achieved by potentiostatic control. This results in intermittent potential values that are reproducible to less than one millivolt (SD=0.27 mV, n=50). The ionic strength is shown to influence the activity coefficient of released iodide in accordance with the extended Debye–Hückel equation, resulting in a predictable change of the potential reading. The principle is applied to potentiometric potassium detection with a valinomycin-based ion-selective electrode (ISE), demonstrating a completely solid-state sensor configuration.

Supporting Information (pdf / 1800.3 KB)

11
Zhang, X.; Sakai, N.; Matile, S. “Methyl Scanning for Mechanochemical Chalcogen-Bonding Cascade Switches”, ChemistryOpen 2020, 9, 18-22.open archive unige:128620 pdf full text [free access]

Chalcogen-bonding cascade switching was introduced recently to produce the chemistry tools needed to image physical forces in biological systems. In the original flipper probe, one methyl group appeared to possibly interfere with the cascade switch. In this report, this questionable methyl group is replaced by a hydrogen. The deletion of this methyl group in planarizable push-pull probes was not trivial because it required the synthesis of dithienothiophenes with four different substituents on the four available carbons. The mechanosensitivity of the resulting demethylated flipper probe was nearly identical to that of the original. Thus methyl groups in the switching region are irrelevant for function, whereas those in the twisting region are essential. This result supports the chalcogen-bonding cascade switching concept and, most importantly, removes significant synthetic demands from future probe development.

Supporting Information

10
Fedunov, R. G.; Yermolenko, I. P.; Nazarov, A. E.; Ivanov, A. I.; Rosspeintner, A.; Angulo, G. “Theory of fluorescence spectrum dynamics and its application to determining the relaxation characteristics of the solvent and intramolecular vibrations”, J. Mol. Liq. 2020, 298, 112016.open archive unige:141196 pdf full text [restricted access]

A general analytical expression for the transient fluorescence spectrum is derived. The formation of a wave packet in the excited state of a fluorophore is described, assuming that the pump pulse has a Gaussian time-profile. The expression explicitly connects the relaxation characteristics of the medium with the spectral dynamics of a fluorophore. Fitting the expression to experimental spectral dynamics allows obtaining the solvent relaxation function. So far this approach was applicable for the analysis of experimental data when the pump pulse does not populate excited sublevels of intramolecular high-frequency vibrational modes. Here, the approach is generalized to include vibrational relaxation in the excited electronic state. In this case, fitting to the experimental spectral dynamics provides reliable information not only on the solvent relaxation, but also on the relaxation time constants of intramolecular high-frequency vibrational modes. This approach is applied to the excited state dynamics of coumarin 153 in multiple solvents, obtained from broadband fluorescence upconversion spectroscopy.

9
Caprice, K.; Aster, A.; Cougnon, F. B. L.; Kumpulainen, T. “Untying the Photophysics of Quinolinium-Based Molecular Knots and Links”, Chem. Eur. J. 2020, 26, 1576-1587.open archive unige:129606 pdf full text [restricted access]

Today, complex molecular knots and links are still difficult to synthesize and the properties arising from their topology are mostly unknown. Here, we report on a comparative photophysical study carried out on a family of closely related quinolinium-based knots and links to determine the impact exerted by topology on the molecular backbone. Our results indicate that topology has a negligible influence on the behavior of loosely braided molecules, which mostly behave like their unbraided equivalents. On the other hand, tightly braided molecules display distinct features. Their higher packing density results in a pronounced ability to resist deformation, a significant reduction in the solvent-accessible surface area and favors close-range π-π interactions between the quinolinium-units and neighboring aromatics. Finally, the sharp alteration in behavior between loosely and tightly braided molecules sheds light upon the factors contributing to braiding tightness.

Supporting Information (pdf / 8 MB)

8
Laurent, Q.; Berthet, M.; Cheng, Y.; Sakai, N.; Barluenga, S.; Winssinger, N.; Matile, S. “Probing for Thiol-Mediated Uptake into Bacteria”, ChemBioChem 2020, 21, 69-73.open archive unige:129267 pdf full text [restricted access]

Cellular uptake mediated by cyclic oligochalcogenides (COCs) is emerging as a conceptually innovative method to penetrate mammalian cells. Their mode of action is based on dynamic covalent oligochalcogenide exchange with cellular thiols. To test thiol-mediated uptake in bacteria, five antibiotics have been equipped with up to three different COCs: One diselenolane and two dithiolanes. We found that the COCs do not activate antibiotics in Gram-negative bacteria. In Gram-positive bacteria, the COCs inactivate antibiotics that act in the cytoplasm and reduce the activity of antibiotics that act on the cell surface. These results indicate that thiol-mediated uptake operates in neither of the membranes of bacteria. COCs are likely to exchange with thiols on the inner, maybe also on the outer membrane, but do not move on. Concerning mammalian cells, the absence of a COC-mediated uptake into bacteria observed in this study disfavors trivial mechanisms, such as passive diffusion, and supports the existence of more sophisticated, so far poorly understood uptake pathways.

Supporting Information (PDF / 1.9 MB)

7
Apichai, S.; Wang, L.; Grudpan, K.; Bakker, E. “Renewable magnetic ion-selective colorimetric microsensors based on surface modified polystyrene beads”, Anal. Chim. Acta 2020, 1094, 136-141.open archive unige:136735 pdf full text [restricted access]

Magnetic ion-selective colorimetric microspheres based on surface modification of polystyrene beads (0.8 μm diameter) are reported for the first time. The common components of ion-selective optode sensing (chromoionophore, ion-exchanger and ionophore) and magnetic nanoparticles are adsorbed onto the surface of the polystyrene particles using a simple mixed solvent method. The average diameter of the magnetic microspheres is evaluated by dynamic light scattering as 0.79 ± 0.06 μm. The reversible microsensors are circulated by flow and accumulated at a single spot by an applied magnet to become observable by digital camera. Hue signals are extracted from the recorded images to quantify the ratio of protonated and deprotonated form of the chromoionophore, which is the basis for optode response. The resulting magnetic microsensors respond to K+ with excellent selectivity over the range of 10−6 M to 10−2 M and a response time of t99 < 2.6±0.5 min above 10−5 M. The use of solvatochromic dyes as pH independent transducers was not successful in this application.

6
Abdou, M.; Schäfer, J.; Gil-Díaz, T.; Tercier-Waeber, M.-L.; Catrouillet, C.; Massa, F.; Castellano, M.; Magi, E.; Povero, P.; Blanc, G. “Spatial variability and sources of platinum in a contaminated harbor – tracing coastal urban inputs”, Environ. Chem. 2020, 17, 105.open archive unige:136355 pdf full text [restricted access]

Biogeochemical cycles that include processes to control platinum (Pt) distribution remain widely unknown in aquatic environments, especially in coastal systems. Dissolved Pt concentrations in coastal seawater (PtD) and in suspended particulate matter (SPM, PtP) were measured, together with master variables comprising dissolved oxygen, dissolved and particulate organic carbon, chlorophyll-a, turbidity, and ammonium levels, along two longitudinal profiles in the industrial Genoa Harbor (north-west Italy). Concentrations and spatial distribution of PtD and PtP levels reflect distinct concentration gradients that were attributed to different Pt sources such as hospital, domestic and industrial wastewater, atmospheric deposition, and/or road runoff. Concentrations reaching up to 0.18 ng L-1 PtD and 14 ng g-1 PtP reflect the impact of Pt urban inputs to coastal sites. These first data highlight considerable anthropogenic contamination in a confined harbor compared with the proposed reference value for the westernMediterranean surface seawater measured at external sites. Identified correlations between Pt levels and human pollution signals suggest the potential use of Pt as a new tracer of anthropogenic inputs that can be applied to other urbanised coastal systems. Biogeochemical processes that induce changes in the partitioning and fate of Pt in coastal seawater reflect a spatial variability and highlight the need for comprehensive environmental monitoring at an appropriate spatial scale.

5
Sheberstov, K. F.; Guardiola Sistare, E.; Jeannerat, D. “Everything you wanted to know about phase and reference frequency in one- and two-dimensional NMR Spectroscopy”, Magn. Reson. Chem. 2020, 58, 376-389.open archive unige:132660 pdf full text [restricted access]

The fundamental concept of phase is discussed in this tutorial aimed at providing students with an explanation of the delays and processing parameters they may find in NMR pulse programs. We consider the phase of radio-frequency pulses, receiver, magnetization and how all these parameters are related to phases and offsets of signals in spectra. The impact of the off-resonance effect on the phase of the magnetization is discussed before presenting an overview of how adjustment of the time reference of the free induction decay (FID) avoids first-order correction of the phase of spectra. The main objective of this tutorial is to show how the relative phase of a pulse and the receiver can be used to change the reference frequency along direct and indirect dimensions of NMR experiments. Unusual applications of phase incrementation with non-90 degree angles will be illustrated on 1D and 2D NMR spectra.

Supporting Information (ZIP / 1.6 MB)

4
Akbal, L.; Hopfgartner, G. “Supercritical fluid chromatography–mass spectrometry using data independent acquisition for the analysis of polar metabolites in human urine”, J. Chromatogr. A 2020, 1609, 460449.open archive unige:136524 pdf full text [restricted access]

The application of supercritical fluid chromatography with mass spectrometric (MS) detection (SFC–MS) was compared towards generic reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) for the analysis of urine with regards of ionization performance and analyte identification. The different chromatographic conditions were characterized with a selected set of 51 metabolites from different classes reported in the Human Metabolome DataBase (HMDB) and previously detected in human urine and/or plasma. SFC using a diol column with a gradient of carbon dioxide (CO2) and methanol with 10?mM ammonium hydroxide as modifier was able to retain and separate 20 polar analytes co-eluting in the RPLC eluent front. In the conditions investigated and compared to HILIC where many metabolites were also co-eluting, SFC showed a different ratio between elution domain and analysis time. Similar peak width and symmetry were observed, while retention time variability was slightly lower compared to that of HILIC (0.15% versus 0.24% and 1.26% for RPLC and HILIC, respectively). In SFC–MS, a significant signal enhancement (2–150 times, average of about 10 times) was measured after post-column make-up addition (MeOH/H2O, 95/5, v/v + 25?mM ammonium acetate) for 28 analytes. Nine analytes measured by LC–MS could not be detected in SFC–MS. Applicability of SFC–MS for metabolomics was investigated with the analysis of urine samples using data independent acquisition (DIA) and more specifically Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH/MS). Using a metabolomics library, 74 metabolites from human urine could be identified in positive mode in a single SFC–MS analysis of 15 min.

3
Baudet, K.; Kale, V.; Mirzakhani, M.; Babel, L.; Naseri, S.; Besnard, C.; Nozary, H.; Piguet, C. “Neutral Heteroleptic Lanthanide Complexes for Unravelling Host–Guest Assemblies in Organic Solvents: The Law of Mass Action Revisited”, Inorg. Chem. 2020, 59, 62-75.open archive unige:128831 pdf full text [restricted access]

The binding of lanthanide containers [Ln(β-diketonate)3dig] [dig = 1-methoxy-2-(2-methoxyethoxy)ethane] to aromatic tridentate N-donor ligands (L) in dichloromethane produces neutral nine-coordinate heteroleptic [LLn(β-diketonate)3] complexes, the equilibrium reaction quotients of which vary with the total concentrations of the reacting partners. This problematic drift prevents the determination of both reliable thermodynamic stability constants and intrinsic host–guest affinities. The classical solution theory assigns this behavior to changes in the activity coefficients of the various partners in nonideal solutions, and a phenomenological approach attempts to quantitatively attribute this effect to some partition of the solvent molecules between bulk-innocent and contact-noninnocent contributors to the chemical potential. This assumption eventually predicts an empirical linear dependence of the equilibrium reaction quotient on the concentration of the formed [LLn(β-diketonate)3] complexes, a trend experimentally supported in this contribution for various ligands L differing in lipophilicity and nuclearity and for lanthanide containers grafted with diverse β-diketonate coligands. Even if the origin of the latter linear dependence is still the subject of debate, this work demonstrates that this approach can be exploited by experimentalists for extracting reliable thermodynamic constants suitable for analyzing and comparing host–guest affinities in organic solvents.

Supporting Information (pdf, 28.1 MB)

2
Sheberstov, K.; Sistaré Guardiola, E.; Pupier, M.; Jeannerat, D. “SAN plot: a Graphical representation of the signal, noise and artifacts content of spectra”, Magn. Reson. Chem. 2020, 58, 466-472.open archive unige:132183 pdf full text [free access]

The signal-to-noise ratio is an important property of NMR spectra. It allows to compare the sensitivity of experiments, the performance of hardware, etc. Its measurement is usually done in a rudimentary manner involving manual operation of selecting separately a region of the spectrum with signal and noise respectively, applying some operation and returning the SNR. We introduce here a simple method based on the analysis of the distribution of point intensities in one- and two-dimensional spectra. The Signal/Artifact/Noise plots, (SAN plots) allows one to present in a graphical manner qualitative and quantitative information about spectra. It will be shown that besides measuring signal and noise levels, SAN plots are also quite useful to visualize and compare artifacts within a series of spectra. Some basic properties of the SAN plots are illustrated with simple application.

Supporting Information (PDF / 506.5 KB)

1
Funato, K.; Riezman, H.; Muñiz, M. “Vesicular and non-vesicular lipid export from the ER to the secretory pathway”, Biochim. Biophys. Acta, Mol. Cell Biol. Lipids 2020, 1865, 158453.open archive unige:141212 pdf full text [restricted access]

The endoplasmic reticulum is the site of synthesis of most glycerophospholipids, neutral lipids and the initial steps of sphingolipid biosynthesis of the secretory pathway. After synthesis, these lipids are distributed within the cells to create and maintain the specific compositions of the other secretory organelles. This represents a formidable challenge, particularly while there is a simultaneous and quantitatively important flux of membrane components stemming from the vesicular traffic of proteins through the pathway, which can also vary depending on the cell type and status. To meet this challenge cells have developed an intricate system of interorganellar contacts and lipid transport proteins, functioning in non-vesicular lipid transport, which are able to ensure membrane lipid homeostasis even in the absence of membrane trafficking. Nevertheless, under normal conditions, lipids are transported in cells by both vesicular and non-vesicular mechanisms. In this review we will discuss the mechanism and roles of vesicular and non-vesicular transport of lipids from the ER to other organelles of the secretory pathway.