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, in press.

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).

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. 2019, in press.

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.

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, in press.

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.

Milton, R. D.; Minteer, S. D. “Nitrogenase Bioelectrochemistry for Synthesis Applications”, Acc. Chem. Res. 2019, in press.

The fixation of atmospheric dinitrogen to ammonia by industrial technologies (such as the Haber Bosch process) has revolutionized humankind. In contrast to industrial technologies, a single enzyme is known for its ability to reduce or “fix” dinitrogen: nitrogenase. Nitrogenase is a complex oxidoreductase enzymatic system that includes a catalytic protein (where dinitrogen is reduced) and an electron-transferring reductase protein (termed the Fe protein) that delivers the electrons necessary for dinitrogen fixation. The catalytic protein most commonly contains a FeMo cofactor (called the MoFe protein), but it can also contain a VFe or FeFe cofactor. Besides their ability to fix dinitrogen to ammonia, these nitrogenases can also reduce substrates such as carbon dioxide to formate. Interestingly, the VFE nitrogenase can also form carbon–carbon bonds. The vast majority of research surrounding nitrogenase employs the Fe protein to transfer electrons, which is also associated with the rate-limiting step of nitrogenase catalysis and also requires the hydrolysis of adenosine triphosphate. Thus, there is significant interest in artificially transferring electrons to the catalytic nitrogenase proteins. In this Account, we review nitrogenase electrocatalysis whereby electrons are delivered to nitrogenase from electrodes. We first describe the use of an electron mediator (cobaltocene) to transfer electrons from electrodes to the MoFe protein. The reduction of protons to molecular hydrogen was realized, in addition to azide and nitrite reduction to ammonia. Bypassing the rate-limiting step within the Fe protein, we also describe how this approach was used to interrogate the rate-limiting step of the MoFe protein: metal-hydride protonolysis at the FeMo-co. This Account next reviews the use of cobaltocene to mediate electron transfer to the VFe protein, where the reduction of carbon dioxide and the formation of carbon–carbon bonds (yielding the formation of ethene and propene) was realized. This approach also found success in mediating electron transfer to the FeFe catalytic protein, which exhibited improved carbon dioxide reduction in comparison to the MoFe protein. In the final example of mediated electron transfer to the catalytic protein, this Account also reviews recent work where the coupling of infrared spectroscopy with electrochemistry enabled the potential-dependent binding of carbon monoxide to the FeMo-co to be studied. As an alternative to mediated electron transfer, recent work that has sought to transfer electrons to the catalytic proteins in the absence of electron mediators (by direct electron transfer) is also reviewed. This approach has subsequently enabled a thermodynamic landscape to be proposed for the cofactors of the catalytic proteins. Finally, this Account also describes nitrogenase electrocatalysis whereby electrons are first transferred from an electrode to the Fe protein, before being transferred to the MoFe protein alongside the hydrolysis of adenosine triphosphate. In this way, increased quantities of ammonia can be electrocatalytically produced from dinitrogen fixation. We discuss how this has led to the further upgrade of electrocatalytically produced ammonia, in combination with additional enzymes (diaphorase, alanine dehydrogenase, and transaminase), to selective production of chiral amine intermediates for pharmaceuticals. This Account concludes by discussing current and future research challenges in the field of electrocatalytic nitrogen fixation by nitrogenase.

Zinna, F.; Brun, E.; Homberg, A.; Lacour, J. “Circularly polarized luminescence from intramolecular excimers”, In Circularly Polarized Luminescence of Isolated Small Organic Molecules”, Mori, T. (Ed.), Springer: Singapore 2020.

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. 2019, in press.

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.

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.

Dereka, B.; Fureraj, I.; Rosspeintner, A.; Vauthey, E. “Halogen-Bond Assisted Photoinduced Electron Transfer”, Molecules 2019, 24, 4361.archive ouverte unige:127199 pdf texte intégral [accès libre]

The formation of a halogen-bond (XB) complex in the excited state was recently reported with a quadrupolar acceptor–donor–acceptor dye in two iodine-based liquids (J. Phys. Chem. Lett. 2017, 8, 3927–3932). The ultrafast decay of this excited complex to the ground state was ascribed to an electron transfer quenching by the XB donors. We examined the mechanism of this process by investigating the quenching dynamics of the dye in the S1 state using the same two iodo-compounds diluted in inert solvents. The results were compared with those obtained with a non-halogenated electron acceptor, fumaronitrile. Whereas quenching by fumaronitrile was found to be diffusion controlled, that by the two XB compounds is slower, despite a larger driving force for electron transfer. A Smoluchowski–Collins–Kimball analysis of the excited-state population decays reveals that both the intrinsic quenching rate constant and the quenching radius are significantly smaller with the XB compounds. These results point to much stronger orientational constraint for quenching with the XB compounds, indicating that electron transfer occurs upon formation of the halogen bond.

Soda, Y.; Bakker, E. “Quantification of Colorimetric Data for Paper-Based Analytical Devices”, ACS Sens. 2019, in press.

Colorimetric measurements by image analysis, giving RGB or HSV data, have become commonplace with optical indicator-based assays and as readout for paper-based analytical devices (PADs). Yet, most works on PADs tend to ignore the quantitative relationship between color data and concentration, which may hamper their establishment as analytical devices and make it difficult to properly understand chemical or biological reactions on the paper substrate. This Perspectives Article discusses how image color data are computed into colorimetric absorbance values that correlate linearly to dye concentration and compare well to traditional spectrophotometry. Thioflavin T (ThT), neutral red (NR) and Orange IV are used here as model systems. Absorbance meas-urements in solution correlate well to image data (and Beer's law) from the color channel of relevance if the gamma correction normally used to render the picture more natural to the human eye is removed. This approach also allows one to correct for color cast and variable background color, which may otherwise limit quantitation in field measurements. Reflectance measurements on paper color spots are equally found to correlate quantitatively between spectroscopy and imaging devices. In this way, deviations from Beer's law are identified that are explained with dye interactions on the paper substrate.

Wang, Y.; Nieto-Ortega, B.; Bürgi, T. “Transformation from [Au25(SCH2CH2CH2CH3)18]0 to Au28(SCH2CH(CH3)Ph)21 gold nanoclusters: gentle conditions is enough”, Chem. Commun. 2019, in press.

Herein we report the transformation of [Au25(SR)18]0 into Au28(SR)21 induced by ligand exchange reaction. In contrast to other reported cluster transformations, which proceed at elevated temperature and large excess of incoming ligands, the transformation reported here occurs under mild conditions (room temperature, very low thiol excess) with a chiral ligand. A difference of one methyl group between incoming and leaving thiol is sufficient to induce the transformation. To the best of our knowledge the Au28(SR)21 cluster has not been isolated before.

Zhang, X.; Sakai, N.; Matile, S. “Methyl Scanning for Mechanochemical Chalcogen-Bonding Cascade Switches”, ChemistryOpen 2020, in press.

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.

Roy Bhattacharya, S.; Bürgi, T. “Amplified vibrational circular dichroism as a manifestation of the interaction between a water soluble gold nanocluster and cobalt salt”, Nanoscale 2019, in press.

Vibrational circular dichroism (VCD) is a powerful tool for the structure determination of dissolved molecules. However, the application of VCD to nanostructures is limited up to now due to the weakness of the effect and hence the low signal intensities. Here we show that the addition of a small amount of cobalt(II) drastically enhances the VCD signals of a thiolate-protected gold cluster Au25(Capt)18 (Capt = captopril) in aqueous solution. An increase of VCD signal intensity of at least one order of magnitude is observed. The enhancement depends on the amount of CoCl2 added but almost an order of magnitude enhancement is already observed at a cluster?:?CoCl2 ratio of 1?:?1. In contrast, circular dichroism (CD) and infrared spectra hardly change. The increase in VCD intensity goes along with a qualitative change of the spectrum and the enhancement increases with time reaching a stable state only after several hours. The enhancement is due to an interaction between the cobalt(II) and the cluster, which also leads to quenching of its fluorescence. The behaviour is completely different for free captopril, where the addition of cobalt(II) salt does not affect the VCD spectrum.

Kumpulainen, T.; Panman, M. R.; Bakker, B. H.; Hilbers, M. F.; Woutersen, S.; Brouwer, A. M. “Accelerating the Shuttling in Hydrogen-Bonded Rotaxanes: Active Role of the Axle and the End Station”, J. Am. Chem. Soc. 2019, 141, 19118-19129.

The relation between the chemical structure and the mechanical behavior of molecular machines is of paramount importance for a rational design of superior nanomachines. Here, we report on a mechanistic study of a nanometer scale translational movement in two bistable rotaxanes. Both rotaxanes consist of a tetra-amide macrocycle interlocked onto a polyether axle. The macrocycle can shuttle between an initial succinamide station and a 3,6-dihydroxy- or 3,6-di-tert-butyl-1,8-naphthalimide end stations. Translocation of the macrocycle is controlled by a hydrogen-bonding equilibrium between the stations. The equilibrium can be perturbed photochemically by either intermolecular proton or electron transfer depending on the system. To the best of our knowledge, utilization of proton transfer from a conventional photoacid for the operation of a molecular machine is demonstrated for the first time. The shuttling dynamics are monitored by means of UV-Vis and IR transient absorption spectroscopies. The polyether axle accelerates the shuttling by ~70 % compared to a structurally similar rotaxane with an all-alkane thread of the same length. The acceleration is attributed to a decrease in activation energy due to an early transition state where the macrocycle partially hydrogen bonds to the ether group of the axle. The dihydroxy-rotaxane exhibits the fastest shuttling speed over a nanometer distance (τshuttling ≈ 30 ns) reported to date. The shuttling in this case is proposed to take place via so-called harpooning mechanism where the transition state involves a folded conformation due to the hydrogen bonding interactions with the hydroxyl groups of the end station.

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. 2019, in press.

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.

Caprice, K.; Aster, A.; Cougnon, F. B. L.; Kumpulainen, T. “Untying the Photophysics of Quinolinium-Based Molecular Knots and Links”, Chem. Eur. J. 2019, in press.

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.

Kumpulainen, T.; Fürstenberg, A. “SCS Photochemistry Section Meeting Fribourg, June 14, 2019”, CHIMIA 2019, 73, 840.

On June 14, 2019, nearly 50 photochemists from all over Switzerland and beyond gathered together at the Haute Ecole d'Ingénierie et d'Architecture in Fribourg (HEIA-FR) for the annual SCS Photochemistry Section meeting to discuss their latest findings in the field. The organizing committee consisting of the board of the SCS Photochemistry Section put together a program consisting of 3 invited talks, 9 oral communications and a poster session with 24 posters to revive this event which, they hope, will take place annually. In addition, the general assembly of the Section was held at the premise during the day.

Tran, G.; Mazet, C. “Ni-Catalyzed Regioselective Hydroalkoxylation of Branched 1,3-Dienes”, Org. Lett. 2019, 21, 9124-9127.archive ouverte unige:126350 pdf texte intégral [accès restreint]

A highly regioselective Ni-catalyzed hydroalkoxylation of 1,3-dienes is reported. The use of a (P,N) ligand is essential in achieving high levels of selectivity. The optimized protocol operates under particularly mild conditions, it provides access to a broad range of structurally diverse allylic ethers, and tolerates a number of sensitive functional groups.

Strakova, K.; Poblador-Bahamonde, A. I.; Sakai, N.; Matile, S. “Fluorescent Flipper Probes: Comprehensive Twist Coverage”, Chem. Eur. J. 2019, 25, 14935-14942.archive ouverte unige:126804 pdf texte intégral [accès restreint]

To image the membrane tension in living cells, planarizable push–pull probes have been introduced. The first operational probe is built around two dithieno[3,2-b:2′,3′-d]thiophenes (DTTs) that are twisted out of co-planarity and polarized with donors and acceptors at either end. In this report, the chemical space available for the twisting of “flipper probes” is assessed comprehensively. The result is, not surprisingly, that every atom matters: Removal of one methyl group in the twist region yields probes that planarize already in solution and are thus less sensitive to membrane tension. Addition of one or more carbons in the same region hinders non-interfering probe alignment along lipid tails and thus partitioning into lipid bilayer membranes as well as mechanosensitivity. However, substitution of one methyl by an isosteric trifluoromethyl group in the twist region, achieved by quite substantial multistep organic synthesis, yields excitation maxima that shift over +100 nm to the red in response to increasing order of the surrounding membrane. This record redshift comes with record changes in fluorescence intensity and lifetime, high push–pull transition dipoles and higher rotational barriers. Supported by distinct dependence on viscosity and twist of the push–pull probes, kinetic competition between dark, fully twisted and bright, fully planarized relaxed excited states emerges as unifying origin of fluorescence quantum yields.

Haribowo, A. G.; Hannich, J. T.; Michel, A. H.; Megyeri, M.; Schuldiner, M.; Kornmann, B.; Riezman, H.; Parton, R. G. “Cytotoxicity of 1-deoxysphingolipid unraveled by genome-wide genetic screens and lipidomics in Saccharomyces cerevisiae”, Mol. Biol. Cell 2019, 30, 1326-2826.

Hereditary sensory and autonomic neuropathy (HSAN) types IA and IC (IA/C) are caused by elevated levels of an atypical class of lipid named 1-deoxysphingolipid (DoxSL). How elevated levels of DoxSL perturb the physiology of the cell and how the perturbations lead to HSAN IA/C are largely unknown. In this study, we show that C26-1-deoxydihydroceramide (C26-DoxDHCer) is highly toxic to the cell, while C16- and C18-DoxDHCer are less toxic. Genome-wide genetic screens and lipidomics revealed the dynamics of DoxSL accumulation and DoxSL species responsible for the toxicity over the course of DoxSL accumulation. Moreover, we show that disruption of F-actin organization, alteration of mitochondrial shape, and accumulation of hydrophobic bodies by DoxSL are not sufficient to cause complete cellular failure. We found that cell death coincides with collapsed ER membrane, although we cannot rule out other possible causes of cell death. Thus, we have unraveled key principles of DoxSL cytotoxicity that may help to explain the clinical features of HSAN IA/C.

Laurent, Q.; Berthet, M.; Cheng, Y.; Sakai, N.; Barluenga, S.; Winssinger, N.; Matile, S. “Probing for Thiol-Mediated Uptake into Bacteria”, ChemBioChem 2019, in press.

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.

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.

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.

Romano, C.; Fiorito, D.; Mazet, C. “Remote Functionalization of α,β-Unsaturated Carbonyls by Multimetallic Sequential Catalysis”, J. Am. Chem. Soc. 2019, 141, 16983-16990.archive ouverte unige:125056 pdf texte intégral [accès restreint]

The remote functionalization of α,β-unsaturated carbonyls by an array of multimetallic sequential catalytic systems is described. The reactions are triggered by hydrometallation using [Pd–H] or [Ru–H] isomerization catalysts and driven by the formation of thermodynamically more stable 1,2-vinyl arenes. The Pd-catalyzed deconjugative isomerization was combined with a Cu-catalyzed β-borylation of the transiently generated styrenyl derivatives to deliver a range of products that would not be accessible with the use of a single catalyst. [Pd/Cu] catalytic systems were also identified for the highly enantioselective α-hydroboration and α-hydroamination of the styrenyl intermediates. Difunctionalization simultaneously at the benzylic and homobenzylic positions was achieved by combining the isomerization process with Sharpless asymmetric dihydroxylation (SAD) using [Pd/Os] or [Ru/Os] couples. Starting from a simple α,β-unsaturated ester, an isomerization/dihydroxylation/lactonization sequence gave access to a naturally occurring γ-butyrolactone in good yield, excellent diastereo- and enantioselectivity.

Stojimirovic, B.; Vis, M.; Tuinier, R.; Philipse, A. P.; Trefalt, G. “Experimental Evidence for Algebraic Double-Layer Forces”,, e-Print Archive, Physics 2019, arXiv:1910.00465.

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.

Aster, A.; Licari, G.; Zinna, F.; Brun, E.; Kumpulainen, T.; Tajkhorshid, E.; Lacour, J.; Vauthey, E. “Tuning symmetry breaking charge separation in perylene bichromophores by conformational control”, Chem. Sci. 2019, 10, 10629-10639.archive ouverte unige:126803 pdf texte intégral [accès libre]

Understanding structure–property relationships in multichromophoric molecular architectures is a crucial step in establishing new design principles in organic electronics as well as to fully understand how nature exploits solar energy. Here, we study the excited state dynamics of three bichromophores consisting of two perylene chromophores linked to three different crown-ether backbones, using stationary and ultrafast electronic spectroscopy combined with molecular dynamics simulations. The conformational space available to the bichromophores depends on the structure and geometry of the crown-ether and can be significantly changed upon cation binding, strongly affecting the excited-state dynamics. We show that, depending on the conformational restrictions and the local environment, the nature of the excited state varies greatly, going from an excimer to a symmetry-broken charge separated state. These results can be rationalised in terms of a structure–property relationship that includes the effect of the local environment.

Ngene, P.; Lambregts, S. F. H.; Blanchard, D.; Vegge, T.; Sharma, M.; Hagemann, H.; de Jongh, P. E. “The influence of silica surface groups on the Li-ion conductivity of LiBH4/SiO2 nanocomposites”, Phys. Chem. Chem. Phys. 2019, 21, 22456-22466.

Lithium borohydride is a promising lithium ion conductor for all-solid-state batteries. However, the compound only exhibits high ionic conductivity at elevated temperatures, typically above 110 °C. It was shown that the addition of oxides such as silica or alumina increases the room temperature ionic conductivity by 3 orders of magnitude. The origin of this remarkable effect is not yet well understood. Here, we investigate the influence of oxide surface groups on the ionic conductivity of LiBH4/SiO2 nanocomposites. We systematically varied the density and nature of the surface groups of mesoporous silica by heat treatment at different temperatures, or surface functionalization, and subsequently prepared LiBH4/SiO2 nanocomposites by melt infiltration. The ionic conductivity is strongly influenced by the heat treatment temperature, hence the density of the free surface silanol groups. Replacing some of the silanol groups with hydrophobic surface groups resulted in an order of magnitude reduction of the room temperature ionic conductivity, suggesting that their presence is crucial to obtain high ionic conductivity in the nanocomposites. This systematic study and insight provide a basis for further exploration of the impact of surface groups, and for the rational design of novel solid-state nanocomposite electrolytes via interface engineering.

Wang, L.; Bakker, E. “A tunable detection range of ion-selective nano-optodes by controlling solvatochromic dye transducer lipophilicity”, Chem. Commun. 2019, 55, 12539-12542.

A range of ionic solvatochromic dye (SD) transducers for use in ion-selective emulsified optical sensors are introduced and characterized. They share the same chromophore group, (E)-4-(4-(dimethylamino)styryl)pyridinium, but vary in their lipophilicities by grafted alkyl or ethoxy groups. The calibration curve is found to shift by a total of 2.7 orders of magnitude with the lipophilicity of the SD.

Bornhof, A.-B.; Vázquez-Nakagawa, M.; Rodríguez-Pérez, L.; Herranz, M. .; Sakai, N.; Martín, N.; Matile, S.; López-Andarias, J. “Anion-π Catalysis on Carbon Nanotubes”, Angew. Chem. Int. Ed. 2019, 58, 16097-16100.archive ouverte unige:125192 pdf texte intégral [accès restreint]

Induced π acidity from polarizability is emerging as the most effective way to stabilize anionic transition states on aromatic π surfaces, that is, anion–π catalysis. To access extreme polarizability, we propose a shift from homogeneous toward heterogeneous anion–π catalysis on higher carbon allotropes. According to benchmark enolate addition chemistry, multi-walled carbon nanotubes equipped with tertiary amine bases outperform single-walled carbon nanotubes. This is consistent with the polarizability of the former not only along but also between the tubes. Inactivation by π-basic aromatics and saturation with increasing catalyst concentration support that catalysis occurs on the π surface of the tubes. Increasing rate and selectivity of existing anion–π catalysts on the surface of unmodified nanotubes is consistent with transition-state stabilization by electron sharing into the tubes, i.e., induced anion–π interactions. On pristine tubes, anion–π catalysis is realized by non-covalent interfacing with π-basic pyrenes.

Kim, K. T.; Angerani, S.; Chang, D.; Winssinger, N. “Coupling of DNA Circuit and Templated Reactions for Quadratic Amplification and Release of Functional Molecules”, J. Am. Chem. Soc. 2019, 141, 16288-16295.archive ouverte unige:124481 pdf texte intégral [accès restreint]

DNA-based circuitry empowers logic gated operations and amplifications but are restricted to a nucleic acid output. Templated reactions enable the translation of a nucleic acid cues into diverse small molecule outputs but are more limited in their amplification. Herein, we demonstrate the coupling of a DNA circuit to templated reactions in order to achieve high levels of amplification in the output of small molecules, in response to a nucleic acid input. We demonstrate that the coupling of the DNA circuit to templated reactions allow for the detection of fM concentration of analyte and can respond with the release of a cytotoxic drug.

Macchione, M.; Goujon, A.; Strakova, K.; Humeniuk, H. V.; Licari, G.; Tajkhorshid, E.; Sakai, N.; Matile, S. “A Chalcogen-Bonding Cascade Switch for Planarizable Push-Pull Probes”, Angew. Chem. Int. Ed. 2019, 58, 15752-15756.archive ouverte unige:125041 pdf texte intégral [accès restreint]

Planarizable push–pull probes have been introduced to demonstrate physical forces in biology. However, the donors and acceptors needed to polarize mechanically planarized probes are incompatible with their twisted resting state. The objective of this study was to overcome this “flipper dilemma” with chalcogen?bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe. This concept is explored by molecular dynamics simulations as well as chemical double?mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability, red shifts adding up to high significance, and focused mechanosensitivity. Most important, however, is the introduction of a new, general and fundamental concept that operates with non-trivial supramolecular chemistry, solves an important practical problem and opens a wide chemical space.

Pezzi, L.; De Sio, L.; Veltri, A.; Cunningham, A.; De Luca, A.; Bürgi, T.; Umeton, C.; Caputo, R. “Plasmon-mediated discrete diffraction behaviour of an array of responsive waveguides”, Nanoscale 2019, 11, 17931-17938.

We investigate the discrete diffraction phenomenon in a Polymer-Liquid Crystal-Polymer Slices (POLICRYPS) overlaying a random distribution of gold nanoparticles (AuNPs, plasmonic elements). We study the propagation of a CW green laser beam through the waveguide structure as a function of beam polarization, laser intensity and sample temperature. It turns out that the plasmonic field created at the interface between AuNPs and POLICRYPS waveguides enables and stabilizes the optical field propagation within the responsive nematic liquid crystal channels. The active role of the liquid crystal is pointed out by a polarization, temperature and beam divergence experimental analysis and evidenced by a peculiar trumpet-shaped discrete diffraction pattern. Theoretical simulations confirm that the observed optical behavior is governed by the interaction of the nematic liquid crystal with optical and plasmonic fields.

Saarbach, J.; Sabale, P. M.; Winssinger, N. “Peptide nucleic acid (PNA) and its applications in chemical biology, diagnostics, and therapeutics”, Curr. Opin. Chem. Biol. 2019, 52, 112-124.archive ouverte unige:123664 pdf texte intégral [accès restreint]

Peptide nucleic acid (PNA) stands as one of the most successful artificial oligonucleotide mimetics. Salient features include the stability of hybridization complexes (either as duplexes or triplexes), metabolic stability, and ease of chemical modifications. These features have enabled important applications such as antisense agents, gene editing, nucleic acid sensing and as a platform to program the assembly of PNA-tagged molecules. Here, we review recent advances in these areas.

Abherv, A.; Martin, K.; Hauser, A.; Avarvari, N. “Helicene Bis(pyrazol-1-yl)pyridine Ligands for Luminescent Transition-Metal Complexes”, Eur. J. Inorg. Chem. 2019, 4807-4814.

We describe herein the synthesis of 2,6-bis(pyrazol-1-yl)pyridine (1-bpp) ligands substituted by helicene units in the 4-position of the pyridine ring. The two-step procedure afforded the molecules bpp[n]helicene (n = 4, 5 and 6) and methyl-bpp[4]helicene, abbreviated as 4, 5, 6 and 4m respectively, with overall good yields. This series of ligands shows fluorescence in the violet region, with a red shift of the emission when increasing the number of aromatic rings in the helicene unit. The tridentate fluorophores have been reacted with Re(CO)5Cl and [Ru(terpy)Cl3] to prepare a series of transition metal complexes formulated as [ReI(n)(CO)3Cl] (n = 4 and 5) and [RuII(n)(terpy)](PF6)2 (n = 4, 4m, 5 and 6). The compounds [ReI(4)(CO)3Cl]·(CH2Cl2)0.5(H2O) and [RuII(4m)(terpy)](PF6)2 crystallized in the centrosymmetric space groups P21/n and P1 respectively, and thus present both M and P helicene units in their crystal structures. The absorption and emission properties of the complexes have been studied. All complexes show luminescence at 77 K in frozen DCM solution. The tricarbonyl complex [ReI(5)(CO)3Cl] shows a strong emission band with two peaks at 540 nm and 580 nm, which could be attributed to ligand-localized π–π* phosphorescence due to the extended π system of the ligand. The heteroleptic RuII complexes show emission bands above 600 nm attributed to the terpyridine-based 3MLCT state.

Front Cover: 10.1002/ejic.201901226

Cover Profile: 10.1002/ejic.201901227

Fernández Galvá, I.; Vacher, M.; Alavi, A.; Angeli, C.; Aquilante, F.; Autschbach, J.; Bao, J. J.; Bokarev, S. I.; Bogdanov, N. A.; Carlson, R. K.; Chibotaru, L. F.; Creutzberg, J.; Dattani, N.; Delcey, M. G.; Dong, S. S.; Dreuw, A.; Freitag, L.; Frutos, L. M.; Gagliardi, L.; Gendron, F.; Giussani, A.; González, L.; Grell, G.; Guo, M.; Hoyer, C. E.; Johansson, M.; Keller, S.; Knecht, S.; Kovačević, G.; Källman, E.; Li Manni, G.; Lundberg, M.; Ma, Y.; Mai, S.; Malhado, J. P.; Malmqvist, P. .; Marquetand, P.; Mewes, S. A.; Norell, J.; Olivucci, M.; Oppel, M.; Phung, Q. M.; Pierloot, K.; Plasser, F.; Reiher, M.; Sand, A. M.; Schapiro, I.; Sharma, P.; Stein, C. J.; Sørensen, L. K.; Truhlar, D. G.; Ugandi, M.; Ungur, L.; Valentini, A.; Vancoillie, S.; Veryazov, V.; Weser, O.; Wesołowski, T. A.; Widmark, P.-O.; Wouters, S.; Zech, A.; Zobel, J. P.; Lindh, R. “OpenMolcas: From source code to insight”, J. Chem. Theory Comput. 2019, 15, 5925-5964.

In this article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with post calculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory and new electronic and muonic basis sets.

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, in press.

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.

Chang, D.; Lindberg, E.; Feng, S.; Angerani, S.; Riezman, H.; Winssinger, N. “Luciferase-Induced Photouncaging: Bioluminolysis”, Angew. Chem. Int. Ed. 2019, 58, 16033-16037.archive ouverte unige:125191 pdf texte intégral [accès restreint]

Bioluminescence resonance energy transfer (BRET) has been widely used for studying dynamic processes in biological systems such as protein–protein interactions and other signaling events. Aside from acting as a reporter, BRET can also turn on functions in living systems. Herein, we report the application of BRET to performing a biorthogonal reaction in living cells; namely, releasing functional molecules through energy transfer to a coumarin molecule, a process termed bioluminolysis. An efficient BRET from Nanoluc-Halotag chimera protein (H-Luc) to a coumarin substrate yields the excited state of coumarin, which in turn triggers hydrolysis to uncage a target molecule. Compared to the conventional methods, this novel uncaging system requires no external light source and shows fast kinetics (t1/2

Soldati, T. “Editorial: Cellular Microbiology 1999–2019”, Cell. Microbiol. 2019, 21, e13106.

Gigante, A.; Duchêne, L.; Moury, R.; Pupier, M.; Remhof, A.; Hagemann, H. “Direct Solution-Based Synthesis of Na4(B12H12)(B10H10) Solid Electrolyte”, ChemSusChem 2019, 12, 4832-4837.

All-solid-state batteries (ASSBs) promise higher power and energy density compared to batteries based on liquid electrolytes. Recently, a stable 3V ASSB based on the super ionic conductor (1mS cm-1 near room temperature) Na4(B12H12)(B10H10) has demonstrated excellent cycling stability. Herein we developed a 5 steps, scalable and solution-based synthesis of Na4(B12H12)(B10H10). The use of the wet chemistry approach allows solution processing with high throughput and addresses the main drawbacks for this technology, specifically, the limited electrodes-electrolyte contact and high cost. Moreover, through the same process, we achieved a cost efficient synthesis for the expensive precursors Na2B10H10 and Na2B12H12. We investigated the mechanism of the reactions and highlighted two key parameters to tune the kinetics and selectivity: the choice of the counter cation, herein tetraethylammonium ((C2H5)4N+, TEA+), and the solvent.

Asakura, R.; Duchêne, L.; Kühnel, R.-S.; Remhof, A.; Hagemann, H.; Battaglia, C. “Electrochemical Oxidative Stability of Hydroborate-Based Solid-State Electrolytes”, ACS Appl. Energy Mater. 2019, 2, 6924-6930.

We report a robust methodology based on linear sweep voltammetry to determine experimentally the electrochemical oxidative stability of hydroborate-based solid-state electrolytes for all-solid-state batteries. To accelerate kinetics and improve the sensitivity to decomposition, we explore different solid-state electrolyte/carbon composites and employ a low scan rate of 10 μV s−1. Using LiBH4 as a model system, we show that proper selection of the conductive carbon and its ratio in the composite are important for an accurate determination of the intrinsic oxidative stability. This method is robust with respect to the choice of the current collector material and the ionic conductivity of the solid-state electrolyte. The measured oxidative stability of LiBH4 of 2.0 V vs. Li+/Li is in good agreement with the value predicted by first principles calculations. The irreversible electrochemical decomposition of LiBH4 outside the oxidative stability limit is independently confirmed by galvanostatic cycling. We apply this method to re-assess the electrochemical oxidative stability of selected, highly conductive hydroborate-based solid-state electrolytes, including Li2(CB9H10)(CB11H12), Na3(BH4)(B12H12), Na4(B12H12)(B10H10), and Na4(CB11H12)2(B12H12), and emphasize the necessity of selecting cathode materials for all-solid-state batteries based on the accurate understanding of the oxidative stability of the solid-state electrolytes.

Bakker, E. “Editorial - An Ode to You—Reviewer for ACS Sensors”, ACS Sens. 2019, 4, 1964.archive ouverte unige:122436 pdf texte intégral [accès libre]

Tran, G.; Shao, W.; Mazet, C. “Ni-Catalyzed Enantioselective Intermolecular Hydroamination of Branched 1,3-Dienes Using Primary Aliphatic Amines”, J. Am. Chem. Soc. 2019, 141, 14814-14822.archive ouverte unige:123450 pdf texte intégral [accès restreint]

A Ni-catalyzed intermolecular enantioselective hydroamination of branched 1,3-dienes is reported. The method is broadly applicable, highly regio-, chemo- and enantioselective and provides direct access to valuable chiral allylic amines starting from linear or α-branched aliphatic primary amines or secondary amines. Mechanistic studies have been conducted using 31P NMR spectroscopy for reaction progress monitoring, isotopic labeling experiments (2H) and kinetic analysis. The resting state of the catalyst is a Ni-π-allyl complex and the outer-sphere nucleophilic attack of H-bonded amine aggregates is proposed to be the rate-determining step. This hypothesis guided the identification of an improved set of reaction conditions for the enantioselective hydroamination of branched 1,3-dienes.

Perret, D.; Laty, G.; Hagemann, H. “«Elémentaire !» – The 2019 Science Contest for Schools in Geneva to Celebrate the International Year of the Periodic Table”, CHIMIA 2019, 73, 656-658.

Sels, A.; Azoulay, R.; Buma, W. J.; Koenis, M. A. J.; Nicu, V. P.; Bürgi, T. “Vibrational Circular Dichroism of Thiolate-Protected Au25 Clusters: Accurate Prediction of Spectra and Chirality Transfer within the Mixed Ligand Shell”, J. Phys. Chem. C 2019, 123, 22586-22594.

We have prepared Au25(PET)18-2x((R)-FBINAS)x (PET = 2-phenylethylthiol, (R)-FBINAS = (R)-5,5',6,6',7,7',8,8'-octafluoro-[1,1'-binaphthalene]-2,2'-dithiol) mixed ligand shell clusters via ligand exchange. Two fractions with different composition of the ligand shell were separated using size-exclusion chromatography and studied by infrared (IR) spectroscopy and vibrational circular dichroism (VCD). Both IR and VCD spectra are dominated by FBINAS vibrations although PET is more abundant on the cluster. Calculated VCD spectra on a model cluster Au25(SH)16(FBINAS)1 depend on the charge state of the cluster and the anion is in excellent agreement with the experimental spectra of the Au25(PET)18-2x(FBINAS)x samples. Calculations of Au25(SH)14(FBINAS)2 furthermore show very similar spectra for different adsorption isomers with one exception, where the two ligands share a SR-Au-SR-Au-SR staple motif. Model calculations show that it is not necessary to consider the entire cluster for obtaining reliable VCD and IR spectra but the staple motifs cannot be neglected. A band that is assigned to PET shows significant vibrational optical activity, and an anisotropy factor that depends on the composition of the ligand shell. This shows that the FBINAS molecules can transfer chirality to achiral PET within the ligand shell of the cluster.

Ruskic, D.; Hopfgartner, G. “Modifier Selectivity Effect on Differential Ion Mobility Resolution of Isomeric Drugs and Multidimensional Liquid Chromatography Ion Mobility Analysis”, Anal. Chem. 2019, 91, 11670-11677.archive ouverte unige:123631 pdf texte intégral [accès restreint]

Cluster formation in the alternating electric field during differential ion mobility is critical for separation selectivity and is governed by two factors. One is the reduced mass and the other factor is cluster binding energy between an ion and a neutral solvent molecule (modifier). Therefore, separations of isomeric analytes using a modifier can be related to the thermochemistry of the cluster formation, as subtle changes in the molecular structure will affect its charge delocalization and the binding energy with the corresponding modifier will be different. We have examined the relation between calculated Gibbs free energies of the cluster formation and experimental ion mobility measurements (CoV dispersion plots) considering the most prominent ion-modifier interactions: charge-dipole, dipole-dipole and charge-quadrupole. In order to explain selectivity effects due to the modifier, we have selected series of positional isomers of sulfonamide drugs that were analyzed in positive and negative electrospray and the diastereoisomers ephedrine and pseudoephedrine in positive mode. The following modifiers were investigated: water, linear and branched alcohols, acetonitrile, acetone, toluene and ethyl acetate. We could demonstrate a dependence of the separation selectivity of the differential mobility on the reduced mass and Gibbs free energy of the cluster formation. These results are supported by thermochemistry calculations (DFT) and interpreted by molecular modeling. Finally, we describe differential mobility spectrometry selectivity tuning for the multidimensional LCxDMS-MS separation of sulfonamide isomers in human plasma.

Hagemann, H. “Estimation of Thermodynamic Properties of Metal Hydroborates”, ChemistrySelect 2019, 4, 8989-8992.

Metal hydroborates from M(BH4)n to Mx(B12H12)y currently attract a strong interest for potential applications in the field of hydrogen storage and more recently as solid ionic conductors. While thermodynamic data for the alkali borohydrides (MBH4) are well known, experimental data for other compounds are cruelly lacking. Using a combination of theoretical (DFT) and experimental data, we calculate the lattice enthalpy for a series of borohydrides. The comparison with literature data show that these lattice enthalpies are very similar to those of the corresponding metal bromides. This similarity is at the origin of a good correlation between the formation enthalpy of bromides and borohydrides which is then used to estimate the previously unknown formation enthalpy of MII(BH4)2 (MII=divalent cation) and Ln(BH4)3 (Ln=lanthanide). The Gibbs free energy of formation of M2(B12H12) (M=alkali metal) is also estimated.

Strakova, K.; Assies, L.; Goujon, A.; Piazzolla, F.; Humeniuk, H. V.; Matile, S. “Dithienothiophenes at Work:  Access to Mechanosensitive Fluorescent Probes, Chalcogen Bonding Catalysis, and Beyond”, Chem. Rev. 2019, 119, 10977-11005.archive ouverte unige:124272 pdf texte intégral [accès restreint]

In this review, the multifunctionality of dithieno[3,2-b:2′,3′-d]thiophenes (DTTs) is covered comprehensively. This is of interest because all involved research is very recent and emphasizes timely topics such as mechanochemistry for bioimaging or chalcogen bonds for catalysis and solar cells and because the newly emerging privileged scaffold is embedded in an inspiring structural space. At the beginning, DTTs are introduced with regard to nomenclature, constitutional isomers, and optoelectronic properties. The structural space around DTTs is mapped out next with regard to heteroatom substitution in the bridge and core, covering much of the periodic table, eccentric heteroatom doping, and bridge expansions. After a brief summary of synthetic approaches to the DTT scaffold, chalcogen bonds are introduced as, together with redox switching and turn-on fluorescence, one of the three conceptual foundations of the most multifunctionality. Realized functions cover anion binding, transport (ion carriers, ion channels), catalysis, and the first fluorescent probes to image physical forces in living cells. The appearance of DTTs in many other photosystems covers push–pull systems for nonlinear optics and dye-sensitized solar cells, DTT polymers in light-emitting diodes, organic field-effect transistors and organic photovoltaics, DTT self-assembly and templated assembly into thin films and fluorescent fibers, also within cells, and the integration of DTTs into photochromes and biaromatics that violate the Hückel rule.

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, in press.

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.

Farrokhbin, M.; Stojimirović, B.; Galli, M.; Hallez, Y.; Trefalt, G. “Surfactant mediated particle aggregation in nonpolar solvents”, Phys. Chem. Chem. Phys. 2019, 21, 18866-18876.archive ouverte unige:124274 pdf texte intégral [accès libre]

The aggregation behavior of particles in nonpolar media is studied with time-resolved light scattering. At low surfactant concentrations particles are weakly charged and suspensions are not stable. The suspensions become progressively more stable with increasing surfactant concentration as particles become more highly charged. At high concentrations the particles become neutralized and aggregation is again fast. The theory of Derjaguin, Landau, Verwey, and Overbeek (DLVO) is able to predict the stability ratios quantitatively by using the experimentally measured surface charges, screening lengths and van der Waals forces.

Jiménez, J.-R.; Doistau, B.; Cruz, C. M.; Besnard, C.; Cuerva, J. M.; Campaña, A. G.; Piguet, C. “Chiral Molecular Ruby [Cr(dqp)2]3+ with Long-Lived Circularly Polarized Luminescence”, J. Am. Chem. Soc. 2019, 141, 13244-12352.archive ouverte unige:122438 pdf texte intégral [accès restreint]

The chiral resolution of a kinetically inert molecular ruby [Cr(dqp)2]3+ (1, dqp = 2,6-di(quinolin-8-yl)pyridine) displaying strong dual light emission at room temperature has been achieved. The wrapped arrangement of the six-membered dqp chelating ligands around the Cr(III) provided nonplanar helical conformations leading to the diastereoselective assembly of chiral bis-tridentate monometallic Cr(III)-helix. The PP-(+)-[Cr(dqp)2]3+ and MM-(−)-[Cr(dqp)2]3+ enantiomers could be separated and isolated by using cation-exchange chromatography and subsequent salt-metathesis with KPF6. X-ray crystallographic analysis based on Flack parameters assigned the absolute configurations of the two enantiomers. Circularly polarized luminescence (CPL) spectra showed two polarized emission bands within the NIR region corresponding to the characteristic metal-centered spin-flip Cr(2E → 4A2) and Cr(2T1 → 4A2) transitions with exceptionally high dissymmetry factors, |glum|, of 0.2 and 0.1, respectively, which are comparable to those reported for rare-earth chiral complexes. Photophysical properties also revealed an extremely long excited-state lifetime of 1.2 ms and a high quantum yield of 5.2% at room temperature in water. These properties make [Cr(dqp)2]3+ an ideal sensitizer for the preparation of enantiopure luminescent supramolecular energy-converting devices and also open up the possibility of using chiral Cr(III) chromophores for the construction of NIR-CPL materials and polarized photonic devices based on earth-abundant metals.

Manenschijn, H. E.; Picco, A.; Mund, M.; Rivier-Cordey, A.-S.; Ries, J.; Kaksonen, M. “Type-I myosins promote actin polymerization to drive membrane bending in endocytosis”, eLife 2019, 8, e44215.

Clathrin-mediated endocytosis in budding yeast requires the formation of a dynamic actin network that produces the force to invaginate the plasma membrane against the intracellular turgor pressure. The type-I myosins Myo3 and Myo5 are important for endocytic membrane reshaping, but mechanistic details of their function remain scarce. Here, we studied the function of Myo3 and Myo5 during endocytosis using quantitative live-cell imaging and genetic perturbations. We show that the type-I myosins promote, in a dose-dependent way, the growth and expansion of the actin network, which controls the speed of membrane and coat internalization. We found that this myosin-activity is independent of the actin nucleation promoting activity of myosins, and cannot be compensated for by increasing actin nucleation. Our results suggest a new mechanism for type-I myosins to produce force by promoting actin filament polymerization.

Rico, C. A.; Berchiche, Y. A.; Horioka, M.; Peeler, J. C.; Lorenzen, E.; Tian, H.; Kazmi, M. A.; Fürstenberg, A.; Gaertner, H.; Hartley, O.; Sakmar, T. P.; Huber, T. “High-Affinity Binding of Chemokine Analogs that Display Ligand Bias at the HIV-1 Coreceptor CCR5”, Biophys. J. 2019, 117, 903-919.

The chemokine receptor CCR5 is a drug target to prevent transmission of HIV/AIDS. We studied four analogs of the native chemokine regulated, on activation, normal T-cell-expressed, and secreted (RANTES) (CCL5) that have anti-HIV potencies of around 25 pM, which is more than four orders of magnitude higher than that of RANTES itself. It has been hypothesized that the ultrahigh potency of the analogs is due to their ability to bind populations of receptors not accessible to native chemokines. To test this hypothesis, we developed a homogeneous dual-color fluorescence cross-correlation spectroscopy assay for saturation- and competition-binding experiments. The fluorescence cross-correlation spectroscopy assay has the advantage that it does not rely on competition with radioactively labeled native chemokines used in conventional assays. We prepared site-specifically labeled fluorescent analogs using native chemical ligation of synthetic peptides, followed by bioorthogonal fluorescent labeling. We engineered a mammalian cell expression construct to provide fluorescently labeled CCR5, which was purified using a tandem immunoaffinity and size-exclusion chromatography approach to obtain monomeric fluorescent CCR5 in detergent solution. We found subnanomolar binding affinities for the two analogs 5P12-RANTES and 5P14-RANTES and about 20-fold reduced affinities for PSC-RANTES and 6P4-RANTES. Using homologous and heterologous competition experiments with unlabeled chemokine analogs, we conclude that the analogs all bind at the same binding site, whereas the native chemokines (RANTES and MIP-1α) fail to displace bound fluorescent analogs even at tens of micromolar concentrations. Our results can be rationalized with de novo structural models of the N-terminal tails of the synthetic chemokines that adopt a different binding mode as compared to the parent compound.

Wasnik, V. H.; Lipp, P.; Kruse, K. “Accuracy of position determination in Ca2+ signaling”, Phys. Rev. E 2019, 100, 022401.

A living cell senses its environment and responds to external signals. In this paper, we study theoretically the precision at which cells can determine the position of a spatially localized transient extracellular signal. To this end, we focus on the case where the stimulus is converted into the release of a small molecule that acts as a second messenger, for example, Ca2+, and activates kinases that change the activity of enzymes by phosphorylating them. We analyze the spatial distribution of phosphorylation events using stochastic simulations as well as a mean-field approach. Kinases that need to bind to the cell membrane for getting activated provide more accurate estimates than cytosolic kinases. Our results could explain why the rate of Ca2+ detachment from the membrane-binding conventional protein kinase Cα is larger than its phosphorylation rate.

Perret, D.; Laty, G.; Hagemann, H. “«Elémentaire !» – The 2019 Science Contest for Schools in Geneva to Celebrate the International Year of the Periodic Table”, CHIMIA 2019, 73, 656-658.

Wasnik, V. H.; Lipp, P.; Kruse, K. “Positional Information Readout in Ca2+ Signaling”, Phys. Rev. Lett. 2019, 123, 058102.

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

Zhang, B.; García, C.; Sels, A.; Salassa, G.; Rameshan, C.; Llorca, J.; Hradil, K.; Rupprechter, G.; Barrabés, N.; Bürgi, T. “Ligand and support effects on the reactivity and stability of Au38(SR)24 catalysts in oxidation reactions”, Catal. Commun. 2019, 130, 105768.

Thiolate protected metal nanoclusters are emerging materials for the preparation of atomically defined heterogeneous catalysts. Recently it was revealed that the ligands migrated to the support upon cluster deposition, which influences the catalytic behaviour. Here we examined the role of the protecting thiolate ligands on the cyclohexane oxidation for Au38(SR)24 supported on CeO2 and Al2O3. Sulfur containing products were detected. XANES S K-edge measurements revealed SOx species on the support during the reaction. The results indicate (i) an active and complex role of the thiolate ligand and (ii) changes of cluster (surface) structure, depending on support material and reaction conditions.

Piazzolla, F.; Minuti, L.; Temperini, A. “Metal-Free Hyperbaric Multicomponent Approach to 4-Aryl[2.2]Paracyclophanes”, Polycyclic Aromat. Compd. 2020, in press.

Herein, we report the first metal-free synthesis of 4-aryl[2.2]paracyclophanes, an important scaffold in organic ligands and material science panorama. In order to avoid the use of toxic and expensive metal catalyst, a multicomponent hyperbaric protocol has been envisaged. First, easy-to-synthesize paracyclophane-substituted butenones underwent acid-catalyzed enol acetylation in the presence of isopropenyl acetate to generate in situ acetoxy-diene intermediates, which were then reacted with methyl propiolate in a hyperbaric regioselective Diels-Alder reaction. Oxidation of the resulting cycloadducts delivered the expected products showing the potential for further functionalization.

Hopfgartner, G. “Editorial: Current developments in ion mobility spectrometry”, Anal. Bioanal. Chem. 2019, 411, 6227.

Symeonidis, M.; Suryadharma, R. N. S.; Grillo, R.; Vetter, A.; Rockstuhl, C.; Bürgi, T.; Scharf, T. “High-resolution interference microscopy with spectral resolution for the characterization of individual particles and self-assembled meta-atoms”, Opt. Express 2019, 37, 20990-21003.

We apply a high-resolution interference microscope with spectral resolution to investigate the scattering response of isolated meta-atoms in real space. The final meta-atoms consist of core-shell clusters that are fabricated using a bottom-up approach. The meta-atoms are investigated with an increasing complexity. We start by studying silica and gold spheres and conclude with the investigation of the meta-atom, which consists of a silica core sphere onto which gold nanospheres are attached. Numerical simulations entirely verify the measured data. The measuring process involves recording the intensity and phase of the total field emerging from the scattering process of an incident light at the particle in the transmitted half-space with spectral and high spatial resolution. We show that spectrally resolved high-resolution interference microscopy can be used to differentiate between nanoparticles and characterize single meta-atoms, something that is rarely accomplished.

Puszko, A. K.; Sosnowski, P.; Pułka-Ziach, K.; Hermine, O.; Hopfgartner, G.; Lepelletier, Y.; Misicka, A. “Urea moiety as amide bond mimetic in peptide-like inhibitors of VEGF-A165/NRP-1 complex”, Bioorg. Med. Chem. Lett. 2019, 29, 2493-2497.

NRP-1 is an important co-receptor of vascular endothelial growth factor receptor-2 (VEGFR-2). Many reports suggested that NRP-1 might also serve as a separate receptor for VEGF-A165 causing stimulation of tumour growth and metastasis. Therefore, compounds interfering with VEGF-A165/NRP-1 complex triggered interest in the design of new molecules, including peptides, as anti-angiogenic and anti-tumour drugs. Here, we report the synthesis, affinity and stability evaluation of the urea-peptide hybrids, based on general Lys(hArg)-AA2-AA3-Arg sequence, where hArg residue was substituted by Arg urea unit. Such substitution does not substantially affected affinity of compounds for NRP-1 but significantly increased their proteolytic stability in plasma.

Faelber, K.; Dietrich, L.; Noel, J. K.; Wollweber, F.; Pfitzner, A.-K.; Mühleip, A.; Sánchez, R.; Kudryashev, M.; Chiaruttini, N.; Lilie, H.; Schlegel, J.; Rosenbaum, E.; Hessenberger, M.; Matthaeus, C.; Kunz, S.; von der Malsburg, A.; Noé, F.; Roux, A.; van der Laan, M.; Kühlbrandt, W.; Daumke, O. “Structure and assembly of the mitochondrial membrane remodelling GTPase Mgm1”, Nature 2019, 571, 429-433.

Balanced fusion and fission are key for the proper function and physiology of mitochondria. Remodelling of the mitochondrial inner membrane is mediated by the dynamin-like protein mitochondrial genome maintenance 1 (Mgm1) in fungi or the related protein optic atrophy 1 (OPA1) in animals. Mgm1 is required for the preservation of mitochondrial DNA in yeast, whereas mutations in the OPA1 gene in humans are a common cause of autosomal dominant optic atrophy—a genetic disorder that affects the optic nerve. Mgm1 and OPA1 are present in mitochondria as a membrane-integral long form and a short form that is soluble in the intermembrane space. Yeast strains that express temperature-sensitive mutants of Mgm1 or mammalian cells that lack OPA1 display fragmented mitochondria, which suggests that Mgm1 and OPA1 have an important role in inner-membrane fusion. Consistently, only the mitochondrial outer membrane—not the inner membrane—fuses in the absence of functional Mgm1. Mgm1 and OPA1 have also been shown to maintain proper cristae architecture; for example, OPA1 prevents the release of pro-apoptotic factors by tightening crista junctions. Finally, the short form of OPA1 localizes to mitochondrial constriction sites, where it presumably promotes mitochondrial fission. How Mgm1 and OPA1 perform their diverse functions in membrane fusion, scission and cristae organization is at present unknown. Here we present crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum. Mgm1 consists of a GTPase (G) domain, a bundle signalling element domain, a stalk, and a paddle domain that contains a membrane-binding site. Biochemical and cell-based experiments demonstrate that the Mgm1 stalk mediates the assembly of bent tetramers into helical filaments. Electron cryo-tomography studies of Mgm1-decorated lipid tubes and fluorescence microscopy experiments on reconstituted membrane tubes indicate how the tetramers assemble on positively or negatively curved membranes. Our findings convey how Mgm1 and OPA1 filaments dynamically remodel the mitochondrial inner membrane.

Soldati, T.; Cardenal-Muñoz, E. “A brief historical and evolutionary perspective on the origin of cellular microbiology research”, Cell. Microbiol. 2019, 21, e13083.

Integrated with both a historical perspective and an evolutionary angle, this opinion article presents a brief and personal view of the emergence of cellular microbiology research. From the very first observations of phagocytosis by Goeze in 1777 to the exhaustive analysis of the cellular defence mechanisms performed in modern laboratories, the studies by cell biologists and microbiologists have converged into an integrative research field distinct from, but fully coupled to immunity: cellular microbiology. In addition, this brief article is thought as a humble patchwork of the motivations that have guided the research in my group over a quarter century.

Levernier, N.; Dolgushev, M.; Bénichou, O.; Voituriez, R.; Guérin, T. “Survival probability of stochastic processes beyond persistence exponents”, Nat. Commun. 2019, 10, 2990.

For many stochastic processes, the probability S(t) of not-having reached a target in unbounded space up to time t follows a slow algebraic decay at long times, S(t)∼S0/tθ. This is typically the case of symmetric compact (i.e. recurrent) random walks. While the persistence exponent θ has been studied at length, the prefactor S0, which is quantitatively essential, remains poorly characterized, especially for non-Markovian processes. Here we derive explicit expressions for S0 for a compact random walk in unbounded space by establishing an analytic relation with the mean first-passage time of the same random walk in a large confining volume. Our analytical results for S0 are in good agreement with numerical simulations, even for strongly correlated processes such as Fractional Brownian Motion, and thus provide a refined understanding of the statistics of longest first-passage events in unbounded space.

Homberg, A.; Hrdina, R.; Vishe, M.; Guénée, L.; Lacour, J. “Stereoselective deconjugation of macrocyclic α,β-unsaturated esters by sequential amidation and olefin transposition: application to enantioselective phase-transfer catalysis”, Org. Biomol. Chem. 2019, 17, 6905-6910.archive ouverte unige:120385 pdf texte intégral [accès libre]

The stereoselective synthesis of chiral macrocycles bearing two aliphatic amide functional groups is reported. After the amidation mediated by TBD, a guanidine derivative, the olefin transposition step is performed with a slight excess of t-BuOK. The products are afforded in moderate to good combined yields (up to 59%) and with an excellent syn diastereoselectivity (dr > 49:1). Introducing enantiopure α-branched substituents was possible and it resulted in mixtures of diastereomers, which could be tested as phase-transfer catalysts using the formation of a phenylalanine analog as a test reaction (up to 43% ee). A clear matched-mismatched situation was observed in the two diastereomeric series.

Dataset: 10.26037/yareta:fp326563trgt3gp3l3ofsyfiem

Rohani, S.; Ziarati, A.; Ziarani, G. M.; Badiei, A.; Burgi, T. “Engineering of highly active Au/Pd supported on hydrogenated urchin-like yolk@shell TiO2 for visible light photocatalytic Suzuki coupling”, Catal. Sci. Technol. 2019, 9, 3820-3827.

Efficient smart photocatalysts and their surface engineering are necessary for the effective conversion of light energy into chemical energy in photocatalyzed organic reactions. Herein, we designed a hydrogenated urchin-like yolk@shell TiO2 structure decorated with Au and Pd nanoparticles (HUY@S-TOH@AuPd) as a robust photocatalyst for C–C coupling reactions. The resulting architecture exhibits considerable photocatalytic performance in Suzuki coupling reactions under visible light irradiation with a turnover frequency (TOF) value as high as 7095 h−1. The beauty of this engineered structure lies on the following four points: (I) the urchin-like structure provided a large accessible surface area for high light harvesting as well as high noble metal anchoring; (II) the yolk@shell mesoporous architecture improved the absorption of light by multiple scattering; (III) the presence of Ti3+ species on the surface of TiO2 decreased the band gap of the structure to the visible region; (IV) the enriched electron density of Pd through the injection of hot electrons from Au as well as the flow of electrons from the titanium dioxide semiconductor to the metals accelerated the rate-determining step. The merging of bimetallic plasmonic nanoparticles and urchin like yolk–shell hydrogenated titanium dioxide architecture can open an avenue for designing photocatalysts with high stability and promising activity as well as high direct harvesting of visible light for a broad range of photocatalytic organic reactions.

Luscher, A.; Fröhlich, F.; Barisch, C.; Littlewood, C.; Metcalfe, J.; Leuba, F.; Palma, A.; Pirruccello, M.; Cesareni, G.; Stagi, M.; Walther, T. C.; Soldati, T.; De Camilli, P.; Swan, L. E. “Lowe Syndrome-linked endocytic adaptors direct membrane cycling kinetics with OCRL in Dictyostelium discoideum”, Mol. Biol. Cell 2019, 30, 2268-2282.

Mutations of the inositol 5-phosphatase OCRL cause Lowe Syndrome (LS), characterized by congenital cataract, low IQ and defective kidney proximal tubule resorption. A key subset of LS mutants abolishes OCRL's interactions with endocytic adaptors containing F&H peptide motifs. Converging unbiased methods examining human peptides and the unicellular phagocytic organism Dictyostelium discoideum, reveal that, like OCRL, the Dictyostelium OCRL orthologue Dd5P4 binds two proteins closely related to the F&H proteins APPL1 and Ses1/2 (also referred to as IPIP27A/B). In addition, a novel conserved F&H interactor was identified, GxcU (in Dictyostelium) and the Cdc42-GEF Frabin (in human cells). Examining these proteins in Dictyostelium discoideum, we find that, like OCRL, Dd5P4 acts at well-conserved and physically distinct endocytic stations. Dd5P4 functions in coordination with F&H proteins to control membrane deformation at multiple stages of endocytosis, and suppresses GxcU-mediated activity during fluid-phase micropinocytosis. We also reveal that OCRL/Dd5P4 acts at the contractile vacuole, an exocytic osmoregulatory organelle. We propose F&H peptide-containing proteins may be key modifiers of LS phenotypes.

Labrador, G. M.; Besnard, C.; Bürgi, T.; Poblador-Bahamonde, A. I.; Bosson, J.; Lacour, J. “Stereochemical significance of O to N atom interchanges within cationic helicenes: experimental and computational evidence of near racemization to remarkable enantiospecificity”, Chem. Sci. 2019, 10, 7059-7067.archive ouverte unige:121523 pdf texte intégral [accès libre]

Oxygen atoms of cationic dioxa and azaoxa [6]helicenes can be exchanged by amino groups to form azaoxa and diaza [6]helicenes respectively. The mild reaction conditions developed herein allow the construction of libraries of derivatives with sensitive and/or functionalized side chains. Using enantioenriched dioxa or azaoxa helicene precursors, these exchanges lead to either near racemization (es 3%) or to a remarkable enantiospecificity (es up to 97%). This unusual behavior is fully characterized via experimental and computational mechanistic evidences. Based on these investigations, the enantiospecificity of the first transformation can be improved to 57-61%.

Dataset: 10.26037/yareta:ikmm2hq375e75ebqq35mem5dsa

Raetz, M.; Duchoslav, E.; Bonner, R.; Hopfgartner, G. “Hybrid SWATH/MS and HR-SRM/MS acquisition for phospholipidomics using QUAL/QUANT data processing”, Anal. Bioanal. Chem. 2019, 411, 5681-5690.

A hybrid SWATH/MS and HR-SRM/MS acquisition approach using multiple unit mass windows and 100 u precursor selection windows has been developed to interface with a chromatographic lipid class separation. The method allows for the simultaneous monitoring of sum compositions in MS1 and up to 48 lipids in MS2 per lipid class. A total of 240 lipid sum compositions from five phospholipid classes could be monitored in MS2 (HR-SRM/MS) while there was no limitation in the number of analytes in MS1 (HR-SIM/MS). On average, 92 lipid sum compositions and 75 lipid species could be quantified in human plasma samples. The robustness and precision of the workflow has been assessed using technical triplicates of the subject samples. Lipid identification was improved using a combined qualitative and quantitative data processing based on prediction instead of library search. Lipid class specific extracted ion currents of precursors and the corresponding molecular species fragments were extracted based on the information obtained from lipid building blocks and a combinatorial strategy. The SWATH/MS approach with the post-acquisition processing is not limited to the analyzed phospholipid classes and can be applied to other analytes and samples of interest.

Beckwith, J. S.; Lang, B.; Grilj, J.; Vauthey, E. “Ion-Pair Dynamics upon Photoinduced Electron Transfer Monitored by Pump-Pump-Probe Spectroscopy”, J. Phys. Chem. Lett. 2019, 10, 3688-3693.archive ouverte unige:126819 pdf texte intégral [accès libre]

The excited-state dynamics of the radical anion of perylene (Pe) generated upon bimolecular photoinduced electron transfer (PET) with a donor was investigated using broadband pump–pump–probe spectroscopy. It was found to depend on the age of the anion, that is, on the time interval between the first pump pulse that triggers PET and the second one that excites the ensuing Pe anion (Pe•–). These differences, observed in acetonitrile but not in tetrahydrofuran, report on the evolution of the PET product from an ion pair to free ions. Two photoinduced charge recombination pathways of the ion pair to the neutral Pe*(S1) + donor state were identified: one occurring in a few picoseconds from Pe•–*(D1) and one taking place within 100–200 fs from Pe•–*(Dn>1). Both processes are sensitive to the interionic distance over different length scales and thus serve as molecular rulers.

Wang, L.; Sadler, S.; Cao, T.; Xie, X.; Moser von Filseck, J.; Bakker, E. “Simplified Fabrication for Ion-Selective Optical Emulsion Sensor with Hydrophobic Solvatochromic Dye Transducer: A Cautionary Tale”, Anal. Chem. 2019, 91, 8973-8978.archive ouverte unige:122440 pdf texte intégral [accès restreint]

It has recently been reported that polystyrene microbeads may be modified to realize plasticizer-free ion-selective optical sensors (optodes) on the basis of solvatochromic dye transducers. We show here that the functionalized microbeads, individually isolated by flow cytometry, exhibit unexpectedly poor fluorescent properties and that the sensor response is instead attributed to the supernatant. A more thorough study reveals that such optical microemulsion sensors can be made operationally functional and chemically selective, seemingly in the absence of any solvent matrix or added surfactant. Instead, it is shown that residual THF used in the fabrication of the emulsified sensors may solubilize the sensing components and give a functional optode response. To evaluate this further, the number of sensing components was stepwise simplified to assess their need. Variation of residual THF levels has no effect on the ion optode response when plasticizer is present, in support of established results. Lipophilic solvatochromic dye transducers are also shown not to require an added surfactant as their nature already endows the emulsified sensors with a stabilizing ionic surface charge. The ionophores are shown to exhibit much larger stability constants in the surfactant-free formulations than surfactant-based ones (Valionomycin: logβ>9.2 compared to 6.1; Na+-ionophore X: 6.7 vs. 4.7), which is attributed to a less polar solvent environment for the ionophore. Potassium, sodium and calcium-selective sensors were used as model systems in this study.

Kadosh, A.; Colom, A.; Yellin, B.; Roux, A.; Shemesh, T. “The tilted helix model of dynamin oligomers”, Proc. Natl. Acad. Sci. USA 2019, 116, 12845-12850.

Dynamin proteins assemble into characteristic helical structures around necks of clathrin-coated membrane buds. Hydrolysis of dynamin-bound GTP results in both fission of the membrane neck and partial disruption of the dynamin oligomer. Imaging by atomic force microscopy reveals that, on GTP hydrolysis, dynamin oligomers undergo a dynamic remodeling and lose their distinctive helical shape. While breakup of the dynamin helix is a critical stage in clathrin-mediated endocytosis, the mechanism for this remodeling of the oligomer has not been resolved. In this paper, we formulate an analytical, elasticity-based model for the reshaping and disassembly of the dynamin scaffold. We predict that the shape of the oligomer is modulated by the orientation of dynamin’s pleckstrin homology (PH) domain relative to the underlying membrane. Our results indicate that tilt of the PH domain drives deformation and fragmentation of the oligomer, in agreement with experimental observations. This model motivated the introduction of the tilted helix: a curve that maintains a fixed angle between its normal and the normal of the embedding surface. Our findings highlight the importance of tilt as a key regulator of size and morphology of membrane-bound oligomers.

Stetsiuk, O.; El-Ghayoury, A.; Hauser, A.; Avarvari, N. “Dipicolylamino-methoxy-1,2,4,5-tetrazine ligand and its metal complexes: Structural and photophysical studies”, Polyhedron 2019, 170, 232-238.

The ligand 6-methoxy-N,N-bis(pyridin-2-ylmethyl)-1,2,4,5-tetrazin-3-amine (L) has been prepared by nucleophilic substitution from 3-chloro-6-dipicolylamino-1,2,4,5-tetrazine (1). The ligand L, together with two neutral zinc(II) and cadmium(II) metal complexes, respectively formulated as [ZnLCl2] (2) and [CdLCl2]2 (3), have been crystallized and analyzed by single crystal X-ray diffraction analysis. The two metal complexes are isostructural and crystallize in the monoclinic system, space group P21/c. The structure analysis indicates that the amino nitrogen atom is involved in semi-coordination with the metal centers, thus leading to distorted coordination geometries. Photophysical studies of the ligand and its corresponding metal complexes 2 and 3 show a switch-on of the luminescence upon chelation with the diamagnetic Zn(II) and Cd(II) metal ions.

Kruve, A.; Caprice, K.; Lavendomme, R.; Wollschläger, J. M.; Schoder, S.; Schröder, H. V.; Nitschke, J. R.; Cougnon, F. B. L.; Schalley, C. A. “Ion-Mobility Mass Spectrometry for the Rapid Determination of the Topology of Interlocked and Knotted Molecules”, Angew. Chem. Int. Ed. 2019, 58, 11324-11328.archive ouverte unige:121522 pdf texte intégral [accès restreint]

A rapid screening method based on traveling-wave ion mobility spectrometry (TWIMS) combined with tandem mass spectrometry provides insight into the topology of interlocked and knotted molecules, even when they exist in complex mixtures such as interconverting dynamic combinatorial libraries. A TWIMS characterization of structure-indicative fragments generated by collision-induced dissociation (CID) together with a floppiness parameter defined merely based on parent and fragment ion arrival times provide a straightforward topology identification. To demonstrate its broad applicability, this approach is applied here six Hopf and two Solomon links, a trefoil knot, and a [3]catenate.

Tsemperouli, M.; Amstad, E.; Sakai, N.; Matile, S.; Sugihara, K. “Black Lipid Membranes: Challenges in Simultaneous Quantitative Characterization by Electrophysiology and Fluorescence Microscopy”, Langmuir 2019, 35, 8748-8757.archive ouverte unige:120388 pdf texte intégral [accès restreint]

Horizontal black lipid membranes (BLM) enable optical microscopy to be combined with the electrophysiological measurements for studying ion channels, peptide pores and ionophores. However, a careful literature review reveals that simultaneous fluorescence and electrical recording in horizontal BLM has been rarely reported for an unclear reason, whereas many works employ bright-field microscopy instead of fluorescence microscopy or perform fluorescence imaging and electrical measurements one after another separately without truly exploiting the advantage of the combined setup. In this work, the major causes related to the simultaneous electrical and fluorescence recording in horizontal BLM are identified and several solutions to counteract the issue are also proposed.

Riccardi, L.; De Biasi, F.; De Vivo, M.; Bürgi, T.; Rastrelli, F.; Salassa, G. “Dynamic Origin of Chirality Transfer between Chiral Surface and Achiral Ligand in Au38 Clusters”, ACS Nano 2019, 13, 7127-7134.

The transfer of chirality between nanomolecules is at the core of several applications in chiral technology such as sensing and catalysis. However, the origin of this phenomenon and how exactly nanoscale objects transfer chirality to molecules in their vicinity remain largely obscure. Here, we show that the transfer of chirality for the intrinsically chiral gold cluster Au38(SR)24 is site dependent; that is, it differs depending on the ligand-binding sites. This is closely related to the dynamic nature of the ligands on the cluster surface. Using a combination of NMR techniques and molecular dynamics simulations, we could assign the four symmetry-unique ligands on the cluster. The study reveals largely different conformational dynamics of the bound ligands, explaining the diverse diastereotopicities observed for the CH2 protons of the ligands. Although chirality is a structural property, our study reveals the importance of dynamics for the transfer of chirality.

Golesorkhi, B.; Fürstenberg, A.; Nozary, H.; Piguet, C. “Deciphering and quantifying linear light upconversion in molecular erbium complexes”, Chem. Sci. 2019, 10, 6876-6885.

Single-center light upconversion corresponds to the pilling up of low-energy photons via successive linear absorptions: a phenomenon commonly observed in lanthanide-doped low-phonon ionic solids or nanoparticles. Its ultimate miniaturization in molecular complexes opens challenging perspectives in term of improved reproducibility, chemical control and optical programming. However, high-energy vibrations inherent to coordination complexes severely limit the efficiency of successive excited-state absorptions (ESA) responsible for the gain in photon energy. By carefully wrapping three polyaromatic ligand strands around trivalent erbium, we managed to induce low-power room temperature near infrared (λexc = 801 nm or 966 nm) to visible green (λem = 522 nm and 545 nm) light upconversion within mononuclear coordination complexes [Er(Lk)3]3+ operating either in the solid state or in non-deuterated solution. The calculated upconversion quantum yields set the zero-level of an elemental erbium-centered molecular ESA mechanism, a values which favorably compares with cooperative upconversion (CU) previously implemented in sophisticated multisite Yb2Tb supramolecular assemblies. The various dependences of the upconverted emission on the incident excitation power imply different mechanisms, which can be tuned by molecular design.

Cheng, Y.; Zong, L.; López‐Andarias, J.; Bartolami, E.; Okamoto, Y.; Ward, T. R.; Sakai, N.; Matile, S. “Cell-Penetrating Dynamic-Covalent Benzopolysulfane Networks”, Angew. Chem. Int. Ed. 2019, 58, 9522-9526.archive ouverte unige:120447 pdf texte intégral [accès libre]

Cyclic oligochalcogenides (COCs) are emerging as promising systems to penetrate cells. Clearly better than and different to the reported diselenolanes and epidithiodiketopiperazines, we introduce the benzopolysulfanes (BPS), which show efficient delivery, insensitivity to inhibitors of endocytosis, and compatibility with substrates as large as proteins. This high activity coincides with high reactivity, selectively toward thiols, exceeding exchange rates of disulfides under tension. The result is a dynamic?covalent network of extreme sulfur species, including cyclic oligomers, from dimers to heptamers, with up to nineteen sulfurs in the ring. Selection from this unfolding adaptive network then yields the reactivities and selectivities needed to access new uptake pathways. Contrary to other COCs, BPS show high retention on thiol affinity columns. The identification of new modes of cell penetration is important because they promise new solutions to challenges in delivery and beyond.

Glöcklhofer, F.; Rosspeintner, A.; Pasitsuparoad, P.; Eder, S.; Fröhlich, J.; Angulo, G.; Vauthey, E.; Plasser, F. “Effect of Symmetric and Asymmetric Substitution on the Optoelectronic Properties of 9,10-Dicyanoanthracene”, Mol. Syst. Des. Eng. 2019, 4, 951-961.archive ouverte unige:126823 pdf texte intégral [accès restreint]

A set of substituted 9,10-dicyanoanthracenes (DCA) has been synthesized, their photophysical and electrochemical properties in liquid solution have been characterized and supplemented by high level ab initio quantum chemical calculations. Three different methoxy-group-containing substituents have been linked to the DCA core in a symmetric and asymmetric fashion to produce six different species with strong quadrupole and dipole moments, respectively. The major difference between the symmetrically and asymmetrically substituted species are the enhanced two-photon absorption intensities of the former. In most of the cases studied, the molecules show reasonably large optical transition probabilities. The fluorescence brightness of these substances makes them interesting objects for two-photon absorption applications. Additionally, all molecules can be both easily reduced and oxidized electrochemically and are therefore suitable for optoelectronic applications.

Jiménez-Rojo, N.; Riezman, H. “On the road to unraveling the molecular functions of ether lipids”, FEBS Lett. 2019, 593, 2378-2389.

Ether lipids are glycerolipids further classified into alkyl?ether and alkenyl?ether (also termed plasmalogens) lipids. The two ether lipid subclasses share the first steps of their synthesis. However, alkyl?ether and alkenyl?ether lipids differ in their structure and physico?chemical properties (featuring different head groups) and, thus, probably in their functions. Ether lipids have intermittent distribution across the evolutionary tree and defects in their synthesis have been shown to perturb cellular homeostasis and lead to disease in humans. Here, we review their structure, their interactions with other lipids, and their potential roles in cellular functions, such as membrane homeostasis and membrane trafficking. Moreover, we discuss still unclear aspects of these lipids such as their subcellular distribution, and the need to unravel their molecular functions as well as how novel tools to study lipid biology will help clarify these aspects.

Reinhardt, J. K.; Klemd, A. M.; Danton, O.; De Mieri, M.; Smieško, M.; Huber, R.; Bürgi, T.; Gründemann, C.; Hamburger, M. “Sesquiterpene Lactones from Artemisia argyi: Absolute Configuration and Immunosuppressant Activity”, J. Nat. Prod. 2019, 82, 1424-1433.

A library of extracts from plants used in Chinese Traditional Medicine was screened for inhibition of T lymphocyte proliferation. An ethyl acetate extract from aerial parts of Artemisia argyi showed promising activity and was submitted to HPLC-based activity profiling to track the active compounds. From the most active time window, three guaianolides (1, 2, and 5) and two seco-tanapartholides (3 and 4) were identified and, in a less active time window, five new sesquiterpene lactones (811, 17), along with six known sesquiterpene lactones and two known flavonoids. The absolute configurations of compounds 1, 2, 510, 1315, 17, and 18 were established by comparison of experimental with calculated electronic circular dichroism (ECD) spectra. For seco-tanapartholides B (3) and A (4), ECD yielded ambiguous results, and their absolute configurations were determined by comparing experimental and calculated vibrational circular dichroism (VCD) spectra. Compounds 15 showed significant, noncytotoxic inhibition of T lymphocyte proliferation, with IC50 values between 1.0 and 3.7 μM.

Megyeri, M.; Prasad, R.; Volpert, G.; Sliwa-Gonzalez, A.; Galih, A.; Aguilera-Romero, A.; Riezman, H.; Barral, Y.; Futerman, A. H.; Schuldiner, M. “Yeast ceramide synthases, Lag1 and Lac1, have distinct substrate specificity”, J. Cell. Sci. 2019, 132, jcs228411.

Lag1 was the first longevity assurance gene, discovered in Saccharomyces cerevisiae. Lag1 is a ceramide synthase and its homolog, Lac1, has a similar enzymatic function but no role in aging. Lag1 and Lac1 lay in an enzymatic branchpoint of the sphingolipid pathway that is interconnected by the activity of the C4-hydroxylase, Sur2. By uncoupling the enzymatic branch point and using lipidomic mass spectrometry, metabolic labeling and in vitro assays we show that Lag1 preferentially synthesizes phyto-sphingolipids. Using photo-bleaching experiments we show that the Lag1 protein is uniquely required for the establishment of a lateral diffusion barrier in the nuclear envelope, which depends on phytoceramide. Given the role of this diffusion barrier in the retention of aging factors in the mother cell, we suggest that the different specificities of the two ceramide synthases, and the specific effect of Lag1 on asymmetrical inheritance, may explain why Δlag1 cells have an increased lifespan while Δlac1 cells do not.

Bravo-Veyrat, S.; Hopfgartner, G. “A Generic Approach for High-throughput Blood Analysis”, CHIMIA 2019, 73, 416.

Tomba, C.; Petithory, T.; Pedron, R.; Airoudj, A.; Di Meglio, I.; Roux, A.; Luchnikov, V. “[Inside Back Cover] Cells at Wrinkled Interfaces: LaserAssisted Strain Engineering of Thin Elastomer Films to Form Variable Wavy Substrates for Cell Culture (Small 21/2019)”, Small 2019, 15, 1970113.

In article number 1900162, Caterina Tomba, Valeriy Luchnikov, and co?workers present a versatile approach to produce curved surfaces with dynamic and variable topographic parameters. Mid?infrared laser exposure allows for surface stiffening of an elastomer that is suitable as wavy substrate to grow cells on smooth and more realistic micro?environments. The wrinkled geometry is tuned by controlling the shape and stretching rate of the substrate and the irradiation parameters of the laser. This technique is easily accessible for further studies on cell migration and cell fate determination.

Moury, R.; Łodziana, Z.; Remhof, A.; Duchêne, L.; Roedern, E.; Gigante, A.; Hagemann, H. “Pressure-induced phase transitions in Na2B12H12, structural investigation on a candidate for solid-state electrolyte”, Acta Crystallogr., Sect. B: Struct. Sci., Cryst. Eng. Mater. 2019, B75, 406-413.

closo-Borates, such as Na2B12H12, are an emerging class of ionic conductors that show promising chemical, electrochemical and mechanical properties as electrolytes in all-solid-state batteries. Motivated by theoretical predictions, high-pressure in situ powder X-ray diffraction on Na2B12H12 was performed and two high-pressure phases are discovered. The first phase transition occurs at 0.5?GPa and it is persistent to ambient pressure, whereas the second transition takes place between 5.7 and 8.1?GPa and it is fully reversible. The mechanisms of the transitions by means of group theoretical analysis are unveiled. The primary-order parameters are identified and the stability at ambient pressure of the first polymorph is explained by density functional theory calculations. Finally, the parameters relevant to engineer and build an all-solid-state battery, namely, the bulk modulus and the coefficient of the thermal expansion are reported. The relatively low value of the bulk modulus for the first polymorph (14?GPa) indicates a soft material which allows accommodation of the volume change of the cathode during cycling.

Riggi, M.; Bourgoint, C.; Macchione, M.; Matile, S.; Loewith, R.; Roux, A. “TORC2 Controls Endocytosis Through Plasma Membrane Tension”, J. Cell Biol. 2019, 218, 2265.archive ouverte unige:120455 pdf texte intégral [accès restreint]

Target of rapamycin complex 2 (TORC2) is a conserved protein kinase that regulates multiple plasma membrane (PM)–related processes, including endocytosis. Direct, chemical inhibition of TORC2 arrests endocytosis but with kinetics that is relatively slow and therefore inconsistent with signaling being mediated solely through simple phosphorylation cascades. Here, we show that in addition to and independently from regulation of the phosphorylation of endocytic proteins, TORC2 also controls endocytosis by modulating PM tension. Elevated PM tension, upon TORC2 inhibition, impinges on endocytosis at two different levels by (1) severing the bonds between the PM adaptor proteins Sla2 and Ent1 and the actin cytoskeleton and (2) hindering recruitment of Rvs167, an N-BAR–containing protein important for vesicle fission to endocytosis sites. These results underline the importance of biophysical cues in the regulation of cellular and molecular processes.

Maillard, R.; Sethio, D.; Hagemann, H.; Lawson Daku, L. M. “Accurate Computational Thermodynamics Using Anharmonic Density Functional Theory Calculations: The Case Study of B–H Species”, ACS Omega 2019, 4, 8786-8794.

The thermal decomposition of boron–hydrogen compounds is complex and multistep and involves the formation of various intermediates. An accurate description of the thermodynamics of the reactants, products, and intermediates is required for an in-depth understanding of their reactivity. In this respect, we have proceeded to the accurate determination of the key thermodynamic functions (ΔH(T), S(T), and CP(T)) of 44 isolated B–H molecular species involved in the decomposition of B–H solids, with the inclusion of anharmonic effects. An excellent agreement is observed with available experimental data. We report the analytic expressions of these functions obtained by fitting them with NASA functions in the 200–900 K temperature range. Because the vibrational spectra of these species are their fingerprints, we also report the predicted IR and Raman spectra. The calculated anharmonic spectra show an excellent agreement with experiments and allow for a clear-cut identification of fundamentals, combinations, and overtones.

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. 2019, in press.

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.

Illuminati, S.; Annibaldi, A.; Truzzi, C.; Tercier-Waeber, M.-L.; Nöel, S.; Braungardt, C. B.; Achterberg, E. P.; Howell, K. A.; Turner, D.; Marini, M.; Romagnoli, T.; Totti, C.; Confalonieri, F.; Graziottin, F.; Buffle, J.; Scarponi, G. “In-situ trace metal (Cd, Pb, Cu) speciation along the Po River plume (Northern Adriatic Sea) using submersible systems”, Mar. Chem. 2019, 212, 47-63.

Information on the distribution and speciation of trace metals is of critical importance for our ability to interpret the links between the bioavailability and uptake of an element, and its biogeochemical cycle in coastal environments. Within the framework of the European Project “In-situ automated Monitoring of Trace metal speciation in Estuaries and Coastal zones in relation with the biogeochemical processes (IMTEC)”, the chemical speciation of Cd, Pb and Cu was carried out along the Po River plume in the period 27 October – 2 November 2002. During the cruise, five Voltammetric In-situ Profiling systems and one Multi Physical Chemical Profiler, as well as conventional voltammetric instruments, were successfully applied in order to evaluate the distribution of Cd, Pb and Cu between different fractions (free ion, dynamic, colloidal, dissolved and particulate fractions) and to assess the evolution of these fractions during estuarine mixing and in the water column. Dynamic concentrations were 0.05–0.2?nmol?L−1 Cd, 0.02–0.2?nmol?L−1 Pb, and 0.15–4.0?nmol?L−1Cu. Cd was mainly present as dynamic fraction (40–100% of the dissolved Cd). High proportions of Pb (~70%) and Cu (~80%) were present as colloids probably of biogenic origin. Principal components analysis reveals a strong influence of the Po River discharge on the spatial and vertical distributions of metal species. Almost all the metal fractions globally decreased following the salinity gradient. Metal concentrations are far below (at least one order of magnitude lower) the Environmental Quality Standard established by the Italian law. However, the Cu dynamic fraction showed concentrations likely to be toxic to sensitive phytoplankton community and to have negative effects on larva development of coastal macroinvertebrate species (toxicity data extracted from literature).

Rumble, C. A.; Vauthey, E. “Structural dynamics of an excited donor–acceptor complex from ultrafast polarized infrared spectroscopy, molecular dynamics simulations, and quantum chemical calculations”, Phys. Chem. Chem. Phys. 2019, 21, 11797-11809.archive ouverte unige:126821 pdf texte intégral [accès libre]

The structural dynamics of an electron donor/acceptor complex (DAC) consisting of benzene and tetracyanoethylene (Bz/TCNE) solvated in CH2Cl2 have been investigated using ultrafast spectroscopy and mixed quantum/classical computer simulations. Population dynamics from visible and infrared transient absorption (TRIR) spectroscopy point to complex sub-10 ps dynamics followed by charge recombination on a 55–60 ps timescale. Structural dynamics involving large-scale reorganization of Bz?+/TCNE? radical ion pairs are revealed using TRIR anisotropy measurements. A computational study combining quantum chemical calculations and classical molecular dynamics simulations was able to reproduce the experimental electronic absorption lineshape and TRIR anisotropy dynamics, allowing for a detailed investigation of the pair conformational dynamics. Contrary to the static single structure typically assumed in descriptions of DACs, we find that neither the ground nor excited state can be described using a single, well-defined species. Instead, the pair undergoes a rearrangement from disordered π-stacks to edge-to-face T-shaped structures following excitation. Translational diffusion of the radical ion pairs following excitation was found to be heterogeneous and dependent on both pair separation and orientation coordinates. Given the sensitivity of charge-transfer reactions to the arrangement of donor/acceptor pairs, the structural heterogeneity and corresponding dynamics demonstrated herein must be taken into account in future modeling of charge recombination processes in DACs.

Söderberg, M.; Dereka, B.; Marrocchi, A.; Carlotti, B.; Vauthey, E. “Ground-state Structural Disorder and Excited-state Symmetry Breaking in a Quadrupolar Molecule”, J. Phys. Chem. Lett. 2019, 10, 2944-2948.archive ouverte unige:126820 pdf texte intégral [accès libre]

The influence of torsional disorder around the ethynyl π-bridges of a linear D-π-A-π-D molecule on the nature of its S1 excited state was investigated using ultrafast time-resolved infrared spectroscopy. By tuning the pump wavelength throughout the S1←S0 absorption band, subpopulations with different extents of asymmetry could be excited. In non-polar solvents, the equilibrated S1 state is symmetric and quadrupolar independently of the initial degree of distortion. Photoexcitation of distorted molecules is followed by planarization and symmetrization of the S1 state. Excited-state symmetry breaking is only observed in polar environments, where the equilibrated S1 state has a strong dipolar character. However, neither the extent nor the rate of symmetry breaking are enhanced in an initially distorted molecule. They are only determined by the polarity and the dynamic properties of the solvent.

Khakhulin, D.; Lawson Daku, L. M.; Leshchev, D.; Newby, G. E.; Jarenmark, M.; Bressler, C.; Wulff, M.; Canton, S. E. “Visualizing the coordination-spheres of photoexcited transition metal complexes with ultrafast hard X-rays”, Phys. Chem. Chem. Phys. 2019, 21, 9277-9284.

The concept of coordination sphere (CS) is central to the rational development of hierarchical molecular assemblies in modern chemistry. Manipulating the organization around transition metal ions with covalent and supramolecular interactions is a general strategy that underlies most synthetic protocols. Achieving similar control for photoexcited molecular complexes is necessary to advance the design of light-driven functionalities. This objective calls for monitoring the ultrafast dynamics of the primary (1-CS) and the secondary (2-CS) coordination spheres on the atomic scale, which remains to date an important experimental challenge for short-lived species. In this work, transient wide-angle scattering of hard X-rays (25 keV) is employed with state-of-the-art AIMD simulations in order to visualize the 1-CS (solute-only) and the 2-CS (solvation cage) of the photoinduced high-spin (HS) state for [Fe(bpy)3]2+ (bpy = 2,2′-bipyridine) in aqueous solution. Correlating this structural information in real-space reveals the interlacing of the two CS, which in turn explains why solvation affects the photoinduced electronic and structural dynamics in this class of complexes. More generally, these results obtained for a prominent prototypical system in ultrafast X-ray sciences demonstrate the unique perspectives offered by this technique to gain the crucial knowledge about the multiscale solvation dynamics that is currently missing for controlling the solute–solvent interactions in advanced functional nano and biomaterials employed for photoconversion.

Sethio, D.; Lawson Daku, L. M.; Hagemann, H.; Kraka, E. “Quantitative Assessment of B–B–B, B–Hb–B, and B–Ht Bonds: From BH3 to B12H122–”, ChemPhysChem 2019, 20, 1967-1977.

We report the thermodynamic stabilities and the intrinsic strengths of three-center-two-electron B – B – B and B – Hb – B bonds (Hb : bridging hydrogen), and two-center-two-electron B – Ht bonds (Ht : terminal hydrogen) which can be served as a new, effective tool to determine the decisive role of the intermediates of hydrogenation/dehydrogenation reactions of borohydride. The calculated heats of formation were obtained with the G4 composite method and the intrinsic strengths of B–B–B, B–Hb –B, and B–Ht bonds were derived from local stretching force constants obtained at the B3LYP-D2/cc-pVTZ level of theory for 21 boron-hydrogen compounds, including 19 intermediates. The Quantum Theory of Atoms in Molecules (QTAIM) was used to deepen the inside into the nature of B–B–B, B–Hb –B, and B–Ht bonds. We found that all of the experimentally identified intermediates hindering the reversibility of the decomposition reactions are thermodynamically stable and possess strong B–B–B, B–Hb –B, and B–Ht bonds. This proves that thermodynamic data and intrinsic B–B–B, B–Hb –B, and B–Ht bond strengths form a new, effective tool to characterize new (potential) intermediates and to predict their role for the reversibility of the hydrogenation/dehydrogenation reactions.

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, in press.

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.

Bocekova-Gajdošíkova, E.; Epik, B.; Chou, J.; Akiyama, K.; Fukui, N.; Guénée, L.; Kündig, E. P. “Microwave-Assisted Synthesis and Transformations of Cationic CpRu(II)(naphthalene) and CpRu(II)(naphthoquinone) Complexes”, Helv. Chim. Acta 2019, 102, e190076.archive ouverte unige:117749 pdf texte intégral [accès restreint]

Details of the direct synthesis of cationic Ru(II)(η5-Cp)(η6-arene) complexes from ruthenocene using microwave heating are reported. Developed for the important catalyst precursor [Ru(II)(η5-Cp)(η6-1-4,4a,8a-naphthalene)][PF6] reaction time could be shortened from three days to 15-min. The method was extended to [Ru(II)(η6-benzene)(η5-Cp)][PF6], [Ru(II)(η5-Cp)(η6-toluene)][PF6], [Ru(II)(η5-Cp)(η6-mesitylene)][PF6], [Ru(II)(η5-Cp)(η6-hexamethylbenzene)][PF6], [Ru(II)(η5Cp)(η6-indane)][PF6], [Ru(II)(η5-Cp)(η6-2,6-dimethylnaphthalene)][PF6], and [Ru(II)(η5-Cp)(η6-pyrene)][PF6]. 1-methylnaphthalene and 2,3-dimethylnaphthalene afforded mixtures of regioisomeric complexes. [Ru(Cp)(CH3CN)3][PF6], derived from the naphthalene precursor provided access to the cationic RuCp complexes of naphthoquinone, tetralindione, 1,4-dihydroxynaphthalene, and 1,4-dimethoxynaphthalene. Reduction of the tetralindione complex afforded selectively the endo,endo diol derivative. X-Ray structures of five complexes are reported.

Wolff, F. E.; Höfener, S.; Elstner, M.; Wesołowski, T. A. “Origin of the Solvatochromism in Organic Fluorophores with Flexible Side Chains: A Case Study of Flugi-2”, J. Phys. Chem. A 2019, 123, 4581-4587.

The emission band for Flugi-2 solvated in dimethyl sulfoxide (DMSO) is obtained from the combined quantum–classical simulations in which the quantum mechanics/molecular mechanics excitation energies are evaluated at the equilibrated segment of the classical molecular dynamics trajectory on the lowest-excited-state potential energy surface. The classical force-field parameters were obtained and validated specifically for the purpose of the present work. The calculated gas-phase to DMSO solvatochromic shift amounts to −0.21 eV, which is in line with the experimentally determined difference between the maxima of the emission bands for Flugi-2 in decane and in DMSO (−0.26 eV). The used model describes rather well the effect of DMSO on the broadening of the emission band. The solvatochromic shift in DMSO originates from two competing effects. The structural deformation of Flugi-2 due to the interaction with DMSO, which results in a positive contribution, and the negative contribution of a larger magnitude due to favorable specific interactions with the solvent. The latter is dominated by a single hydrogen bond between the oxygen atom of a DMSO molecule and the N3 hydrogen atom of the Flugi-2 molecule in which the proton of N3 acts as the donor.

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.

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.

Rouster, P.; Pavlovic, M.; Cao, T.; Katana, B.; Szilagyi, I. “Stability of Titania Nanomaterials Dispersed in Aqueous Solutions of Ionic Liquids of Different Alkyl Chain Lengths”, J. Phys. Chem. C 2019, 123, 12966-12974.

Charging and aggregation of titania nanosheets (TNS) and spherical titania nanoparticles (TNP) were studied in aqueous solutions of ionic liquids (ILs). The pH and the length of the alkyl chain of the IL cations (1-methylimidazolium (MIM+), 1-ethyl-3-methylimidazolium (EMIM+) and 1-butyl-3-methylimidazolium (BMIM+)) were systematically varied in the experiments. No detectable interaction was observed between the IL cations and the positively charged TNS or TNP surfaces at low pH, where the imidazolium derivatives are the coions. For the negatively charged titania nano-objects, significant adsorption of MIM+ and EMIM+ took place leading to charge neutralization and overcharging at appropriate concentrations. The BMIM+ behaved like a simple salt constituent causing charge screening. For both TNS and TNP, the MIM+ < EMIM+ < BMIM+ counterion order was obtained in the critical coagulation concentrations indicating that MIM+ was the most effective in destabilization of the dispersions. The major interparticle forces were of electrostatic origin, however, viscous stabilization was also observed at high IL concentrations. The same aggregation mechanism and charging behavior were found for the titania nano-objects irrespectively of their shape. The results shed light on the hydrophilic nature of the surface of TNS and TNP of negative charge, in contrast to earlier findings with hydrophobic colloidal particles, where the increasing alkyl chain length gave rise to higher destabilization power. The charging properties were governed by specific adsorption of the IL constituents, while the major interparticle forces were qualitatively well-predicted by the DLVO theory.

Folz, F.; Wettmann, L.; Morigi, G.; Kruse, K. “Sound of an axon's growth”, Phys. Rev. E 2019, 99, 050401(R).

Axons are linear structures of nerve cells that can range from a few tens of micrometers up to meters in length. In addition to external cues, the length of an axon is also regulated by unknown internal mechanisms. Molecular motors have been suggested to generate oscillations with an axon-length-dependent frequency that could be used to measure an axon's extension. Here, we present a mechanism for determining the axon length that couples the mechanical properties of an axon to the spectral decomposition of the oscillatory signal.

Zhang, J.; Zhang, X.; Suarez-Alcantara, K.; Jennings, G.; Kurtz, C. A.; Lawson Daku, L. M.; Canton, S. E. “Resolving the Ultrafast Changes of Chemically Inequivalent Metal–Ligand Bonds in Photoexcited Molecular Complexes with Transient X-ray Absorption Spectroscopy”, ACS Omega 2019, 4, 6375-6381.

Photoactive transition-metal complexes that incorporate heteroleptic ligands present a first coordination shell, which is asymmetric. Although it is generally expected that the metal–ligand bond lengths respond differently to photoexcitation, resolving these fine structural changes remains experimentally challenging, especially for flexible multidentate ligands. In this work, ultrafast X-ray absorption spectroscopy is employed to capture directly the asymmetric elongations of chemically inequivalent metal–ligand bonds in the photoexcited spin-switching FeII complex [FeII(tpen)]2+ solvated in acetonitrile, where tpen denotes N,N,N′,N′-tetrakis(2-pyridylmethyl)-1,2-ethylenediamine. The possibility to correlate precisely the nature of the donor/acceptor coordinating atoms to specific photoinduced structural changes within a binding motif will provide advanced diagnostics for optimizing numerous photoactive chemical and biological building blocks.

Morstein, J.; Hill, R. Z.; Novak, A. J. E.; Feng, S.; Norman, D. D.; Donthamsetti, P. C.; Frank, J. A.; Harayama, T.; Williams, B. M.; Parrill, A. L.; Tigyi, G. J.; Riezman, H.; Isacoff, E. Y.; Bautista, D. M.; Trauner, D. “Optical control of sphingosine-1-phosphate formation and function”, Nat. Chem. Biol. 2019, 15, 623-631.

Sphingosine-1-phosphate (S1P) plays important roles as a signaling lipid in a variety of physiological and pathophysiological processes. S1P signals via a family of G-protein-coupled receptors (GPCRs) (S1P1–5) and intracellular targets. Here, we report on photoswitchable analogs of S1P and its precursor sphingosine, respectively termed PhotoS1P and PhotoSph. PhotoS1P enables optical control of S1P1–3, shown through electrophysiology and Ca2+ mobilization assays. We evaluated PhotoS1P in vivo, where it reversibly controlled S1P3-dependent pain hypersensitivity in mice. The hypersensitivity induced by PhotoS1P is comparable to that induced by S1P. PhotoS1P is uniquely suited for the study of S1P biology in cultured cells and in vivo because it exhibits prolonged metabolic stability compared to the rapidly metabolized S1P. Using lipid mass spectrometry analysis, we constructed a metabolic map of PhotoS1P and PhotoSph. The formation of these photoswitchable lipids was found to be light dependent, providing a novel approach to optically probe sphingolipid biology.

Martinent, R.; Laurent, Q.; Sakai, N.; Matile, S. “Cellular Uptake Mediated by Cyclic Oligochalcogenides”, CHIMIA 2019, 73, 304-307.archive ouverte unige:120454 pdf texte intégral [accès libre]

Cellular uptake is one of the central challenges in chemical biology and beyond. With the objective to find conceptually innovative ways to enter into cells, cyclic oligochalcogenides (COCs) are emerging as powerful tools. Increasing ring tension is shown to maximize speed and selectivity of dynamic covalent exchange chemistry on the way into cells. However, simple dynamic covalent attachment immobilizes the transporters on membrane proteins, resulting in endosomal capture. To move across the membrane into the cytosol, dynamic covalent COC opening has to produce high acidity chalcogenols that remain deprotonated in neutral water and, according to the present working hypothesis, initiate COC walking along disulfide tracks in membrane proteins, across the bilayer and into the cytosol. Compatibility of diselenolanes, the current 'lord of the rings', with the delivery of larger substrates of biological relevance is currently under investigation.

Zdrachek, E.; Bakker, E. “From Molecular and Emulsified Ion Sensors to Membrane Electrodes: Molecular and Mechanistic Sensor Design”, Acc. Chem. Res. 2019, 52, 1400-1408.archive ouverte unige:122442 pdf texte intégral [accès restreint]

Selective molecular ion probes are often insoluble in water and require a hydrophobic solvent environment for strong and selective binding, which runs counter to the desire of utilizing them in a homogeneous solution. This Account aims to guide the reader on how such molecules, often coined ionophores, can be harnessed to design exceptionally useful optical and electrochemical sensors. We start here with some historical context on the design of such ionophores and continue with the explanation of the response mechanism of optical and potentiometric sensors and the role of combined components to build a robust ion sensor. This Account is addressed to nonspecialist readers and for this reason avoids extensive use of equations or theoretical considerations. The interested reader should turn to the original literature for further reading.

Emulsified optical sensors are introduced as an initial example. Here, multiple reagents are confined in an attoliter sensing nanodroplet of the organic phase, immiscible with the aqueous sample phase. In this case, the ionophore molecules may retain their high affinity and selectivity to the target ion and the aqueous sample phase does not have to be modified. Emulsified optical sensors allow one to achieve the selective chemical sensing of ions, even with optically silent ionophores. Such ionophore-based nanodroplets are also discussed as a useful novel class of complexometric titration reagents and optical end point indicators with unique selectivities.

We then turn our attention to potentiometric sensing probes and briefly discuss the unique opportunity of a direct characterization of ion–ionophore complexation properties offered by membrane electrodes. A carbonate-selective membrane electrode containing a highly selective tweezer-type ionophore with trifluoroacetophenone functional groups is then used as an example for the construction of a robust all-solid-state sensor. This potentiometric probe, in combination with a pH electrode, can directly measure PCO2 in freshwater lakes, demonstrating a dramatically improved response time relative to traditional sensors equipped with a gas-permeable membrane.

In recent years, new sensing modes and electrode designs have been introduced to expand the application scope of ionophore-based potentiometric sensors. Membrane electrodes containing ionophores are placed under dynamic electrochemistry control to give important progress in the field. We specifically highlight our recent works by membranes that are controlled by chronopotentiometry (controlled current) for speciation analysis, by ion transfer voltammetry on thin sensing films for multianalyte detection, by exhaustive coulometry for potentially calibration-free sensors and with coulometric membrane pumps for the selective delivery of reagents.

Ortuso, R. D.; Ricardi, N.; Bürgi, T.; Wesolowski, T. A.; Sugihara, K. “The deconvolution analysis of ATR-FTIR spectra of diacetylene during UV exposure”, Spectrochim. Acta, Part A 2019, 219, 23-32.

We performed a detailed deconvolution analysis of ATR-FTIR peaks of a common diacetylene, 10,12-tricosadiynoic acid (TRCDA) during the polymerization and the blue-to-red transition. Based on the analysis and the solvent dependence on the IR signals, we found that the triple peak from CC stretching mode that has been previously suspected as a consequence of Fermi resonance is rather associated with the macromolecular assembly of TRCDA. Besides these CC triple peaks, we found that the background in the region increased during the UV exposure due to the CC signals from polymers. In addition, the anisotropic compression during polymerization was also detected, which supports the proposed interpretation of X-ray data reported previously. These results are the benefits from the deconvolution analysis.

Caprice, K.; Pupier, M.; Bauzá, A.; Frontera, A.; Cougnon, F. B. L. “Synchronized On/Off Switching of Four Binding Sites for Water in a Molecular Solomon Link”, Angew. Chem. Int. Ed. 2019, 58, 8053-8057.archive ouverte unige:118702 pdf texte intégral [accès restreint]

A molecular Solomon link adopts different conformations in acetonitrile (1) and in water (2). Contrary to expectations, the main driving force of the transformation is not the change in medium polarity, but the cooperative binding of about four molecules of water, forming a tiny droplet in the central cavity of 2. Mechanistic studies reveal that the four binding sites can simultaneously switch between an inactive state (unable to bind water) and an active state (able to bind water) during the transformation. Spatial and temporal coordination of switching events is commonly observed in biological systems but has been rarely achieved in artificial systems. Here, the concerted activation of the four switchable sites is controlled by the topology of the whole molecule.

Duchêne, L.; Lunghammer, S.; Burankova, T.; Liao, W.-C.; Embs, J. P.; Copéret, C.; Wilkening, H. M. R.; Remhof, A.; Hagemann, H.; Battaglia, C. “Ionic Conduction Mechanism in the Na2(B12H12)0.5(B10H10)0.5 closo-Borate Solid-State Electrolyte: Interplay of Disorder and Ion–Ion Interactions”, Chem. Mater. 2019, 31, 3449-3460.

The conduction mechanism of Na2(B12H12)0.5(B10H10)0.5, a particularly promising solid-state electrolyte for sodium-ion batteries, is elucidated. We find from electrochemical impedance spectroscopy that the temperature-dependent conductivity is characterized by three distinct regimes of conductivity. In the first regime, at temperatures below −50 °C, conductivity remains low before a glasslike transition identified by X-ray diffraction and calorimetry causes a faster increase of sodium conductivity through site disordering. The second regime of faster diffusion above −50 °C is characterized by an apparent activation energy of 0.6 eV, higher than expected from the local microscopic barrier of 0.35 eV observed by, e.g., 23Na nuclear magnetic resonance spin-lattice relaxation. This mechanism of so-called correlated ion diffusion originates from the coupling of the cation and anion motion due to short-range ion–ion interactions combined with background energy fluctuations, which we can associate through quasi-elastic neutron scattering experiment to fast librations of the anions. In the third regime, at temperatures above 70 °C, the thermal energy increases above the background energy fluctuations and the activation energy decreases to 0.34 eV, reflecting the local energy barrier for noncorrelated ion diffusion. We discuss the link between this behavior and the different frustrations responsible for the high conductivity of closo-borate electrolytes and show that our interpretation can also explain the complex conductivity behavior observed in related compounds.

Matile, S. “In My Element: Sulfur”, Chem. Eur. J. 2019, 25, 6460.archive ouverte unige:117134 pdf texte intégral [accès restreint]

The In My Element series celebrates the personal accounts from Chemistry – A European Journal Editorial Board members for the 2019 International Year of the Periodic Table. In this contribution, Stefan Matile gives his story on sulfur.

Tomba, C.; Petithory, T.; Pedron, R.; Airoudj, A.; Di Meglio, I.; Roux, A.; Luchnikov, V. “Laser–Assisted Strain Engineering of Thin Elastomer Films to Form Variable Wavy Substrates for Cell Culture”, Small 2019, 15, 1900162.

Endothelial and epithelial cells usually grow on a curved environment, at the surface of organs, which many techniques have tried to reproduce. Here a simple method is proposed to control curvature of the substrate. Prestrained thin elastomer films are treated by infrared laser irradiation in order to rigidify the surface of the film. Wrinkled morphologies are produced upon stress relaxation for irradiation doses above a critical value. Wrinkle wavelength and depth are controlled by the prestrain, the laser power, and the speed at which the laser scans the film surface. Stretching of elastomer substrates with a “sand clock”?width profile enables the generation of a stress gradient, which results in patterns of wrinkles with a depth gradient. Thus, different combinations of topography changes on the same substrate can be generated. The wavelength and the depth of the wrinkles, which have the characteristic values within a range of several tens of µm, can be dynamically regulated by the substrate reversible stretching. It is shown that these anisotropic features are efficient substrates to control polarization of cell shapes and orientation of their migration. With this approach a flexible tool is provided for a wide range of applications in cell biophysics studies.

Pulcu, G. S.; Galenkamp, N. S.; Qing, Y.; Gasparini, G.; Mikhailova, E.; Matile, S.; Bayley, H. “Single-Molecule Kinetics of Growth and Degradation of Cell-Penetrating Poly(disulfide)s”, J. Am. Chem. Soc. 2019, 141, 12444-12447.archive ouverte unige:122434 pdf texte intégral [accès restreint]

The delivery of therapeutic agents into target cells is a challenging task. Cell penetration and intracellular targeting were recently ad-dressed with biodegradable poly(disulfide)s (CPDs). Cellular localization is determined by the length of these polymers, emphasizing the significance of initial chain length and the kinetics of intracellular depolymerization for targeted delivery. In the present study, the kinetics of CPD polymer growth and degradation were monitored in a single-molecule nanoreactor. The chain lengths achievable un-der synthetic conditions with high concentrations of dithiolanes, were then predicted by using the rate constants. For example, CPDs comprising 40 units are generated in 1 s at pH 7.4 and 0.3 s at pH 8.4 at dithiolane concentrations of 200 mM. The rate constants for degradation suggest that the main depolymerization pathway in the cell is by monomer removal by self-cyclization, rather than by intra-chain cleavage by endogenous thiols.

Zech, A.; Dreuw, A.; Wesolowski, T. A. “Extension of frozen-density embedding theory for non-variational embedded wavefunctions”, J. Chem. Phys. 2019, 150, 121101.

In the original formulation, frozen-density embedding theory [T. A. Wesolowski and A. Warshel, J. Phys. Chem. 97, 8050–8053 (1993); T. A. Wesołowski, Phys. Rev. A 77, 012504 (2008)] concerns multi-level simulation methods in which variational methods are used to obtain the embedded NA-electron wavefunction. In this work, an implicit density functional for the total energy is constructed and used to derive a general expression for the total energy in methods in which the embedded NA electrons are treated non-variationally. The formula is exact within linear expansion in density perturbations. Illustrative numerical examples are provided.

Johnson, D. A.; Williams, A. F. “The Gestation and Growth of the Periodic Table”, CHIMIA 2019, 73, 144-151.

The development of ideas of chemical periodicity from Lavoisier to Mendeleyev's first periodic table of 1869 is surveyed. Although his first periodic table contained a number of errors and weaknesses, his remarkable predictions of the properties of several then unknown elements, together with his capacity to adapt the table to new discoveries, slowly led to its general acceptance. The theory of atomic structure slowly developed to a point where it could rationalise the structure of the table which had, however, been established solely on the basis of experimental observations. Chemistry has played the central role, up to and including the final modification of Seaborg to introduce the actinides – although this had been foreseen by Alfred Werner! Finally we discuss the many physical forms in which the table has been presented.

Piguet, C. “Set Aside when Building the Periodic Table 150 Years ago, are Rare Earths any better considered by Chemists in the 21st century?”, CHIMIA 2019, 73, 165-172.archive ouverte unige:116053 pdf texte intégral [accès libre]

A hundred and fifty years ago, the Rare Earths posed a serious problem to Mendeleyev because of their very similar chem. properties, although their at. mass dispersions pointed to different elements.  This difficulty persisted for several decades and only the emergence of the at. theory provided some legitimacy for their consideration as a full series of 15 elements resulting from the filling of the 4f orbitals (La-?4f0 to Lu-?4f14)?, to which scandium and yttrium were added for the sake of chem. similarities.  However, it is difficult to give up bad habits and major advances in transition metal chem. started systematically with d-?block cations prior to extension to f-?block analogs, and this despite the broader perspectives often brought by the latter.  The technol.-?oriented society put in place for economic reasons during the last five decades has reactivated scientific interest in the Rare Earths, which have now become essential for many applications in telecommunications, lasers, magnetic materials and optical devices.

Zinna, F.; Voci, S.; Arrico, L.; Brun, E.; Homberg, A.; Bouffier, L.; Funaioli, T.; Lacour, J.; Sojic, N.; Di Bari, L. “Circularly Polarized-Electrochemiluminescence from a Chiral Bispyrene Organic Macrocycle”, Angew. Chem. Int. Ed. 2019, 58, 6952-6956.archive ouverte unige:117369 pdf texte intégral [accès restreint]

The first observation of circular polarization of electrochemiluminescence (ECL) from a purely organic derivative is reported. A bis-pyrene scaffold mounted on a constrained polyether macrocycle displaying intense excimer fluorescence and highly circularly polarized (CP) photoluminescence has been selected for this purpose. Such compound displays an ECL dissymmetry factor of ca. |8×10-3|, in good agreement with the corresponding photoluminescence value. This observation is the first step towards the molecular engineering of bespoke suitable dyes acting both as ECL and CP-ECL reporters for (bio)analysis by bringing a new level of information when dealing with chiral environments. In addition, it provides an extra-dimension to the ECL phenomenon and opens the way to chiral detection and discrimination.

Diop, E. H. A.; Queiroz, E. F.; Marcourt, L.; Kicka, S.; Rudaz, S.; Diop, T.; Soldati, T.; Wolfender, J.-L. “Antimycobacterial activity in a single-cell infection assay of ellagitannins from Combretum aculeatum and their bioavailable metabolites”, J. Ethnopharmacol. 2019, 238, 111832.

Ethnopharmacological relevance

The water decoction of Combretum aculeatum aerial parts is traditionally used in Senegal to treat tuberculosis (TB). The extract shows significant antimycobacterial activity in a validated single-cell infection assay.

Aim of the study

The main aim of this study was to identify the antimycobacterial compounds in the water decoction of Combretum aculeatum. Since the traditional preparations are used orally, a bioactivity assessment of the possible bioavailable human metabolites was also performed.

Materials and methods

The Combretum aculeatum water decoction extract was first fractionated by flash chromatography. The fractions were submitted to an antibiotic assay against Mycobacterium marinum and to a single-cell infection assay involving Acanthamoeba castellanii as a host. Using these approaches, it was possible to correlate the antimycobacterial activity with two zones of the chromatogram. In parallel with this liquid chromatography (LC)-based activity profiling, high-resolution mass spectrometry (UHPLC-HRMS/MS) revealed the presence of ellagitannin (Et) derivatives in the active zones of the chromatogram. Isolation of the active compounds was performed by preparative chromatography. The structures of the isolated compounds were elucidated by nuclear magnetic resonance (NMR). Additionally, the main human metabolites of commercially available Ets were biologically evaluated in a similar manner.


The in vitro bioassay-guided isolation of the Combretum aculeatum water extract led to the identification of three Ets (13) and ellagic acid (4). The major compounds 2 and 3 (α- and β-punicalagin, respectively), exhibited anti-infective activity with an IC50 of 51.48?μM. In view of the documented intestinal metabolism of these compounds, some metabolites, namely, urolithin A (5), urolithin B (6) and urolithin D (7), were investigated for their antimycobacterial activity in the two assays. Urolithin D (7) exhibited the strongest anti-infective activity, with an IC50 of 345.50?μM, but this was moderate compared to the positive control rifampin (IC50 of 6.99?μM). The compounds assayed had no observable cytotoxicity towards the amoeba host cells at concentrations lower than 200?μg/mL.


The observed antimycobacterial properties of the traditional water decoction of Combretum aculeatum might be related to the activity of Ets derivatives (13) and their metabolites, such as ellagic acid (4) and urolithin D (7). Despite the relatively weak activity of these metabolites, the high consumption of tannins achieved by taking the usual traditional decoction doses should lead to an important increase in the plasmatic concentrations of these active and bioavailable metabolites. These results support to some extent the traditional use of Combretum aculeatum to treat tuberculosis.

Thewes, S.; Soldati, T.; Eichinger, L. “Editorial: Amoebae as Host Models to Study the Interaction With Pathogens”, Front. Cell. Infect. Microbiol. 2019, 9, 47.

Loewith, R.; Riezman, H.; Winssinger, N. “Sphingolipids and membrane targets for therapeutics”, Curr. Opin. Chem. Biol. 2019, 50, 19-28.archive ouverte unige:115232 pdf texte intégral [accès restreint]

Lipids and membranes are often strongly altered in various diseases and pathologies, but are not often targeted for therapeutic advantage. In particular, the sphingolipids are particularly sensitive to altered physiology and have been implicated as important players in not only several rare hereditary diseases, but also other major pathologies, including cancer. This review discusses some potential targets in the sphingolipid pathway and describes how the initial drug compounds have been evolved to create potentially improved therapeutics. This reveals how lipids and their interactions with proteins can be used for therapeutic advantage. We also discuss the possibility that modification of the physical properties of membranes could also affect intracellular signaling and be of therapeutic interest.

Delgado, T.; Afshani, J.; Hagemann, H. “Spectroscopic Study of a Single Crystal of SrAl2O4:Eu2+:Dy3+”, J. Phys. Chem. C 2019, 123, 8607-8613.

The extraordinary long phosphorescence of SrAl2O4:Eu2+:Dy3+ has been widely studied in powder samples because of its broad range of applications in this form and despite the fact that the bulk material shows higher intensity emission and longer afterglow. However, the investigation of SrAl2O4:Eu2+:Dy3+ crystals that, unlike the powder, do not contain surface defects, would allow a better insight into the mechanism that governs the long-lasting phosphorescence of this co-doped material. Thus, a SrAl2O4:Eu2+:Dy3+ single crystal was studied in detail by absorption spectroscopy and photoluminescence, including a novel estimation of its extinction coefficient. In addition, thermoluminescence measurements and wavelength-dependent quantum efficiency measurements have been performed to improve the understanding of the role of both europium and dysprosium ions in the corresponding persistent phosphorescence mechanism.

Jansod, S.; Bakker, E. “Tunable Optical Sensing with PVC Membrane Based Ion-Selective Bipolar Electrodes”, ACS Sens. 2019, 4, 1008-1016.archive ouverte unige:122437 pdf texte intégral [accès restreint]

We show here that the response of ion-selective membrane electrodes (ISEs) based on traditional PVC membranes can be directly translated into a colorimetric readout by a closed bipolar electrode (BPE) arrangement. Because the resulting optical response is based on the turnover of the redox probe, ferroin, dissolved in a thin layer compartment, it directly indicates the potential change at the ISE in combination with a reference electrode. This class of probes measures ion activity, analogous to their ISE counterparts. Unlike other ion optodes, the response if also fully tunable over a wide concentration range by the application of an external potential and occurs in a compartment that is physically separate from the sample. To allow for the electrical charge to pass across the ion-selective electrodes, the membranes are doped with inert lipophilic electrolyte, ETH 500, but are otherwise of established composition. The observed response behavior corre-lates well to theory. A wide range of ion-selective membranes are confirmed to work with this readout principle, demon-strating the detection of potassium, sodium, calcium and carbonate ions. The corresponding sigmodal calibration curve is used for the quantitative analysis in a range of samples including commercial beverages and river and lake samples. The data are successfully correlated with atomic emission spectroscopy and direct potentiometry.

Akbarimoosavi, M.; Rohwer, E.; Rondi, A.; Hankache, J.; Geng, Y.; Decurtins, S.; Hauser, A.; Liu, S.-X.; Feurer, T.; Cannizzo, A. “Tunable Lifetimes of Intramolecular Charge-Separated States in Molecular Donor–Acceptor Dyads”, J. Phys. Chem. C 2019, 123, 8500-8511.

We report ultrafast transient UV–vis absorption and electrochemical spectroscopies on the photoinduced charge separation dynamics in a recently synthesized family of metal-free donor–acceptor systems, where two redox-active molecules are fused into a compact and planar structure upon annulation of a tetrathiafulvalene and a benzothiadiazole as electron donor and acceptor, respectively. We found extraordinary tunability of the lifetime of the photoinduced charge separation by more than 2 orders of magnitude (from 6 to 900 ps) upon small changes of the peripheral residues on the acceptor and the polarity of the environment. Contrary to expectations, the lifetime of the charge separation state decreases in more polar environments and with more electronegative acceptors. This study proves that such fused donor–acceptor systems give rise to a new class of electronically versatile materials whose physicochemical properties can be tuned via a targeted substitution or a suitable choice of local electrostatics.

Christmann, J.; Hagemann, H. “New Insights into the Influence of the 4f55d1 State in the 4f6 Electronic Configuration of Sm2+ in Crystal Hosts”, J. Phys. Chem. A 2019, 123, 2881-2887.

The use of the Sm2+ luminescence properties in numerous applications appeals for a better understanding of its electronic structure. This work compares luminescence data and crystal field parameters from 31 Sm2+-containing compounds to assess the effects of the crystal field on its energy levels. In particular, the relationship between the 5D07F0 and 5D07F1 transition energies are analyzed and compared with previously published data for the isoelectronic Eu3+. It appears that for Sm2+, in contrast to Eu3+, the energy of the 5D0 state cannot be considered to be constant and implies the involvement of an extra state (presumably the 4f55d1 level) in the mixing of the 4f6 states. On the other side, the total crystal field strength is correlated with the splitting of the 7F1 states for both Sm2+ and Eu3+ in lower symmetry environments. The plot of the 5D07F0 energy as a function of the 7F1 splitting clearly evidences the mixing of the 4f6 state with the environment-sensitive 4f55d1 state for Sm2+, what is finally confirmed by the discrepancy of the ratio between the 5D1 and 7F1 splittings from its theoretical value in the absence of any mixing with the 4f55d1 state.

Gao, W.; Jeanneret, S.; Yuan, D.; Cherubini, T.; Wang, L.; Xie, X.; Bakker, E. “Electrogenerated Chemiluminescence for Chronopotentiometric Sensors”, Anal. Chem. 2019, 91, 4889-4895.archive ouverte unige:122441 pdf texte intégral [accès restreint]

We introduce here a general strategy to read out chronopotentiometric sensors by electrogenerated chemiluminescence (ECL). The potentials generated in chronopotentiometry in a sample compartment are used to control the ECL in a separate detection compartment. A three-electrode cell is used to monitor the concentration changes of the analyte, while luminol-H2O2 system is responsible for ECL. The principle was shown to be feasible by theoretical simulations, indicating that the sampled times at a chosen potential, rather than traditional transition times, similarly give linear behavior between concentration and square root of sampled time. With the help of a voltage adapter, the experimental combination between chronopotentiometry and ECL was successfully implemented. As an initial proof of concept, the ferro/ferricyanide redox couple was investigated. The square root of time giving maximum light output changed linearly with ferrocyanide concentration in the range from 0.70 mM to 4.81 mM. The method was successfully applied to the visual detection of car-bonate alkalinity from 0.06 mM to 0.62 mM using chronopotentiometry at an ionophore-based hydrogen ion-selective membrane electrode. The measurements of carbonate in real samples including river water and commercial mineral water were successfully demonstrated.

Williams, A. F. “Editorial”, CHIMIA 2019, 73, 141.

Bartolami, E.; Basagiannis, D.; Zong, L.; Martinent, R.; Okamoto, Y.; Laurent, Q.; Ward, T. R.; Gonzalez-Gaitan, M.; Sakai, N.; Matile, S. “Diselenolane-Mediated Cellular Uptake:  Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein-Coated Quantum Dots”, Chem. Eur. J. 2019, 25, 4047-4051.archive ouverte unige:115136 pdf texte intégral [accès restreint]

Cyclic oligochalcogenides are emerging as powerful tools to penetrate cells. With disulfide ring tension maximized, selenium chemistry had to be explored next to enhance speed and selectivity of dynamic covalent exchange on the way into the cytosol. We show that diseleno lipoic acid (DiSeL) delivers a variety of relevant substrates. DiSeL‐driven uptake of artificial metalloenzymes enables bioorthogonal fluorophore uncaging within cells. Binding of a bicyclic peptide, phalloidin, to actin fibers evinces targeted delivery to the cytosol. Automated tracking of diffusive compared to directed motility and immobility localizes 79 % of protein‐coated quantum dots (QDs) in the cytosol, with little endosomal capture (0.06 %). These results suggest that diselenolanes might act as molecular walkers along disulfide tracks in locally denatured membrane proteins, surrounded by adaptive micellar membrane defects. Miniscule and versatile, DiSeL tags are also readily available, stable, soluble, and non‐toxic.

Kozhuharov, S.; Maroni, P.; Borkovec, M. “In situ Imaging of Single Polyelectrolyte Chains with the Atomic Force Microscope”, CHIMIA 2019, 73, 17-20.

This article discusses the possibilities offered by modern atomic force microscopes (AFMs) with ultra-small cantilevers to perform in situ imaging of single adsorbed polyelectrolytes in aqueous solutions. We demonstrate that such AFM techniques permit high quality images of single polyelectrolyte molecules to be obtained. These images can then be used to qualitatively address differences in the adsorbed conformations for different polyelectrolyte architectures. Moreover, such images can be also analyzed quantitatively. As an example, we discuss the determination of the persistence length of adsorbed polyelectrolytes.

Klinkert, K.; Levernier, N.; Gross, P.; Gentili, C.; von Tobel, L.; Pierron, M.; Busso, C.; Herrman, S.; Grill, S. W.; Kruse, K.; Gönczy, P. “Aurora A depletion reveals centrosome-independent polarization mechanism in Caenorhabditis elegans”, eLife 2019, 8, e44552.

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

Bosmani, A.; Guarnieri-Ibáñez, A.; Lacour, J. “Configurational Lability of Imino-Substituted Ethano Tröger Bases. Insight on the Racemization Mechanism”, Helv. Chim. Acta 2019, 102, e1900021.archive ouverte unige:115269 pdf texte intégral [accès restreint]

Polycyclic indoline‐benzodiazepines are afforded in one step by the reaction of Tröger bases with N‐sulfonyl‐1,2,3‐triazoles under Rh(II) catalysis. After α‐imino carbene formation, the process involves a cascade of [1,2]‐Stevens rearrangement, Friedel‐Crafts, Grob fragmentation and aminal formation reactions. It is highly diastereoselective (d.r.>49:1, four stereocenters incl. two bridgehead N atoms). However and in contrast with other reported carbene additions to these moieties, full racemization occurs when enantiopure Tröger Bases are used as substrates. To pinpoint the origin of this unexpected behavior, key elemental steps of the mechanism were evaluated and tested. Interestingly, it is not only the initial ring‐opening but also the latter reversible Mannich reaction of the imino‐substituted ethano Tröger base intermediate that is responsible for the loss of enantiospecificity.

Sharma, M.; Sethio, D.; Lawson Daku, L. M.; Hagemann, H. “Theoretical Study of Halogenated B12HnX(12-n)2- (X=F, Cl, Br)”, J. Phys. Chem. A 2019, 123, 1807-1813.

The closoborane and their derivatives have attracted high interest owing to their superionic conductivity. Very recently, high ionic conductivities have been reported for compounds containing the closoborane ion B12H122-. In this work, we address halogen substituted ions B12HnX12-n2- (n = 0-3, 6, 9-12 and X = F, Cl, Br) using DFT calculations to probe the structures, the chemical stability and the electrochemical stability as well as spectroscopic properties in view of potential future applications. Considering the theoretical reaction n/12 B12H122- + (12-n)/12 B12X122- --> B12HnX12-n2-, it appears that for X = Cl and Br the compounds with n=6 are stabilized by about 100kJ/mol. The calculation of the vertical detachment energy (which is indirectly related to the electrochemical stability) shows an increasing stability with increasing halogen content. These results suggest that for practical applications, it is likely that a partially halogenated ion offers the best compromise. The calculations of vibrational properties and NMR chemical shifts also reveal several systematic trends which are discussed and compared to available literature values.

Holzer, B.; Lunzer, M.; Rosspeintner, A.; Licari, G.; Tromayer, M.; Naumov, S.; Lumpi, D.; Horkel, E.; Hametner, C.; Ovsianikov, A.; Liska, R.; Vauthey, E.; Fröhlich, J. “Towards efficient initiators for two-photon induced polymerization: fine tuning of the donor/acceptor properties”, Mol. Syst. Des. Eng. 2019, 4, 437-448.archive ouverte unige:126822 pdf texte intégral [accès libre]

In this work we present the design, synthesis and systematic investigation of the optical properties of symmetric triphenylamine (TPA)-substituted thiophenes. The use of electron-donating (–OMe, –tBu, –Me, –TMS), -neutral (–H) or -withdrawing (–F, –CN, –SO2Me) substituents gives rise to D–A–D based two-photon absorption (2PA) chromophores. The photophysical properties of these compounds, including one-photon absorption and 2PA using two-photon-excited fluorescence, were investigated in different organic solvents with varying polarity. The maximum 2PA cross sections prove to be strongly dependent on the nature of the TPA substituent and range between ∼173 GM (Goeppert-Mayer units) and 379 GM. Although most of the investigated substances also exhibit high fluorescence quantum yields, two-photon absorption screening tests of an acrylate monomer formulation revealed the efficiency of these materials as 2PA photoinitiators. These results are supported by quantum chemical calculations of the spin density distribution indicating that the mechanism of polymerization initiation using acrylate monomer is favored by strong localization of the unpaired electrons in the triplet state on the C2 carbon of the thiophene moiety.


The authors regret that in the published article, affiliations b and c were inadvertently switched.

Goujon, A.; Colom, A.; Straková, K.; Mercier, V.; Mahecic, D.; Manley, S.; Sakai, N.; Roux, A.; Matile, S. “Mechanosensitive Fluorescent Probes to Image Membrane Tension in Mitochondria, Endoplasmic Reticulum and Lysosome”, J. Am. Chem. Soc. 2019, 141, 3380-3384.archive ouverte unige:114631 pdf texte intégral [accès restreint]

Measuring forces inside cells is particularly challenging. With the development of quantitative microscopy, fluorophores which allow the measurement of forces became highly desirable. We have previously introduced a mechanosensitive flipper probe, which responds to the change of plasma membrane tension by changing its fluorescence lifetime and thus allows tension imaging by FLIM. Herein, we describe the design, synthesis, and evaluation of flipper probes that selectively label intracellular organelles, i.e., lysosomes, mitochondria, and the endoplasmic reticulum. The probes respond uniformly to osmotic shocks applied extracellularly, thus confirming sensitivity toward changes in membrane tension. At rest, different lifetimes found for different organelles relate to known differences in membrane organization rather than membrane tension and allow colabeling in the same cells. At the organelle scale, lifetime heterogeneity provides unprecedented insights on ER tubules and sheets, and nuclear membranes. Examples on endosomal trafficking or increase of tension at mitochondrial constriction sites outline the potential of intracellularly targeted fluorescent tension probes to address essential questions that were previously beyond reach.

Buff, M.; Drab, E.; Sugihara, K. “Effect of the nonspecific binding in differential impedance biosensing”, Biointerphases 2019, 14, 011004.

The detection limits of impedance biosensors are dictated by the presence of background nonspecific binding, yet almost all the detection limits reported in the literature are determined using a clean buffer solution without confronting this real challenge. In this work, the authors employed the simplest “differential” impedance biosensor, composed of poly-l-lysine-polyethylene glycol-biotin-coated gold electrodes for the detection of streptavidin in the presence of 0.1% fetal calf serum, and studied the effect of the nonspecific binding on the performance of the differential impedance biosensing. The lowest streptavidin concentration detected by the system (5 μg/ml) was 1 order of magnitude higher (worse) than that from a previously demonstrated impedance biosensor where avidin was detected in the absence of background proteins. Interestingly, the origin of the differential signal was not due to the electrochemical properties of streptavidin itself but was that of the serum, where the coverage of the electrode by streptavidin indirectly modulated the electrical signal by suppressing the accessibility of the serum to the electrode.

Buckley, C. M.; Heath, V. L.; Gueho, A.; Bosmani, C.; Knobloch, P.; Sikakana, P.; Personnic, N.; Dove, S. K.; Michell, R. H.; Meier, R.; Hilbi, H.; Soldati, T.; Insall, R. H.; King, J. “PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection”, PLoS Pathog. 2019, 15, e1007551.

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

Šutka, A.; Järvekülg, M.; Gross, K. A.; Kook, M.; Käämbre, T.; Visnapuu, M.; Trefalt, G.; Šutka, A. “Visible light to switch-on desorption from goethite”, Nanoscale 2019, 11, 3794-3798.archive ouverte unige:114882 pdf texte intégral [accès libre]

Switching adsorption–desorption by visible light could provide the possibility for a wide range of applications that require controlled release-on-demand. Here, we demonstrate a visible-light controlled desorption behavior in aqueous suspensions for the first time. We observed cationic dye adsorption on amphoteric goethite α-FeOOH in the dark and release during visible light exposure at a pH value slightly over the isoelectric point of goethite. During this process, the dye does not degrade. Desorption is triggered by local heating due to light absorption in narrow band gap goethite, α-FeOOH.

Delgado, T.; Ajoubipour, S.; Afshani, J.; Yoon, S.; Walfort, B.; Hagemann, H. “Spectroscopic properties of Dy3+- and Dy3+, B3+- doped SrAl2O4”, Opt. Mater. 2019, 89, 268-275.

The dysprosium and boron effect on the emission properties of europium-doped SrAl2O4 samples has recently attracted considerable attention due to their high brightness and long afterglow. Here, the influence of both cations, Dy3+ and B3+, on the spectroscopic properties of the europium free samples SrAl2O4:Dy3+ and SrAl2O4:Dy3+, B3+ has been investigated in order to get more insights concerning the mechanism by which they enhance the afterglow. Unique features have been observed in their excitation and emission spectra that show on one hand the lattice defects induced by the replacement of Sr2+ by Dy3+ and proves the existence of different crystallography sites for the Dy3+ ions and on the other hand, the local distortion of the energy levels of Dy3+ ions in the presence of B3+.

Colmont, M.; Lemoine, K.; Roussel, P.; Kabbour, H.; Olchowka, J.; Henry, N.; Hagemann, H.; Mentré, O. “Identification and optical features of the Pb4Ln2O7 series (Ln = La, Gd, Sm, Nd); genuine 2D-van der Waals oxides ”, Chem. Commun. 2019, 55, 2944-2947.

We report on the identification and survey of the Pb4Ln2O7 series (Ln = La, Gd, Sm and Nd) which turn out to be real van der Waals 2D oxides. In the neutral layers, strong covalent Pb–O bonds together with external stereoactive Pb2+ lone pairs, which act as sensitizers, lead to an ideal matrix for enhanced and tunable luminescence by lanthanide emitters, tested here for Sm3+ and Eu3+ doping. DFT calculations and preliminary ex-solution experiments validate the weak bonding between the layers separated by 3.5 Å and suggest a indirect to direct crossover realized by isolating the layers.

Soda, Y.; Citterio, D.; Bakker, E. “Equipment-Free Detection of K+ on Microfluidic Paper-based Analytical Devices Based on Exhaustive Replacement with Ionic Dye in Ion-selective Capillary Sensors”, ACS Sens. 2019, 4, 670-677.archive ouverte unige:114491 pdf texte intégral [accès libre]

A distance-based analysis of potassium ion (K+) is introduced that is performed on a microfluidic paper-based analyti-cal device (µPAD) coupled to an ion-selective capillary sensor. The concept is based on two sequential steps, the selec-tive replacement of analyte ion with an ionic dye, and the detection of this dye in a distance-based readout on paper. To achieve the first step, the capillary sensor holds a poly (vinyl chloride) (PVC) membrane film layer plasticized by dioctyl sebacate (DOS) that contains the potassium ionophore valinomycin, a lipophilic cation-exchanger and the ion-ic indicator Thioflavin T (ThT) on its inner wall. Upon introduction of the sample, K+ in the aqueous sample solution is quantitatively extracted into the film membrane and replaced with ThT. To convert the ion exchange signal into a distance-based analysis, this solution was dropped onto the inlet area of a µPAD to flow the ThT along a channel de-fined by wax printing, resulting in the electrostatic binding of ThT to the cellulose carboxylic groups. The initial amount of K+ determines the amount ThT in the aqueous solution after ion-exchange, and consequently the distance of ThT-colored area reflects the sample K+ concentration. The ion exchange reaction was operated in a so-called “ex-haustive sensing mode” and gave a distinct response in a narrow range of K+ concentration (1~6 mM) that cannot be achieved by the classical optode sensing mode. The absence of hydrogen ions from the equilibrium competition of the capillary sensor contributed to a complete pH-independence, unlike conventional optodes that contain a pH sensitive indicator. A very high selectivity for K+ over Na+ and Ca2+ has been confirmed in separate solutions and mixed solu-tions tests. K+ measurements in pooled serum samples at concentrations between 2~6 mM are successfully demon-strated on a temperature controlled support.

Smith, A. M.; Maroni, P.; Trefalt, G.; Borkovec, M. “Unexpectedly Large Decay Lengths of Double Layer Forces in Solutions of Symmetric, Multivalent Electrolytes”, J. Phys. Chem. B 2019, 123, 1733-1740.archive ouverte unige:114717 pdf texte intégral [accès restreint]

Double layer forces acting between micron-sized silica particles are measured with the atomic force microscope (AFM) in solutions of symmetric, multivalent electrolytes. In particular, the following 2:2 electrolytes, CuSO4, MgSO4, and the 3:3 electrolyte LaFe(CN)6 were investigated. For the multivalent electrolytes, the measured decay lengths are substantially larger than the ones expected on the basis of simple Debye-Hückel (DH) theory. These deviations can be explained quantitatively by the formation of neutral ion pairs. The measured surface charge density decreases in magnitude with increasing valence. Both effects are caused by ion-ion correlations, which are not included in the classical DH theory. However, this theory remains applicable provided one considers the formation of ion pairs in solution and an effective surface charge density. This effective charge is substantially smaller in magnitude than the one of the bare surface. This reduction results from adsorption of counter-ions, which becomes stronger with increasing valence. These observations reveal that DH theory is applicable even in the presence of multivalent ions, provided the effective parameters are chosen appropriately.

Angerani, S.; Winssinger, N. “Visible Light Photoredox Catalysis Using Ruthenium Complexes in Chemical Biology”, Chem. Eur. J. 2019, 25, 6661-6672.archive ouverte unige:117368 pdf texte intégral [accès restreint]

The development of bioorthogonal reactions have had a transformative impact in chemical biology and the quest to expand this toolbox continues. Herein we review recent applications of ruthenium?catalyzed photoredox reactions used in chemical biology.

Levernier, N.; Kruse, K. “Spontaneous formation of chaotic protrusions in a polymerizing active gel layer”,, e-Print Archive, Physics 2019, arXiv:1901.08332v2.

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.

Kazan, R.; Müller, U.; Bürgi, T. “Doping of thiolate protected gold clusters through reaction with metal surfaces”, Nanoscale 2019, 11, 2938-2945.archive ouverte unige:119357 pdf texte intégral [accès libre]

A new technique is introduced for doping gold nanoclusters by using a metal surface such as Ag, Cu and Cd as a source of heteroatoms. The importance of the thiol ligand in the doping process is examined by following the reactions with MALDI-TOF mass spectrometry in the presence and the absence of the thiols on the surface. The doping reactions depend greatly on the type of the cluster and the availability of the ligand which is a crucial element for alloying. The thiol acts as a messenger exchanging the metal atoms between the cluster and the metal surface as revealed by the XPS studies performed on the metal surfaces.

Homberg, A.; Poggiali, D.; Vishe, M.; Besnard, C.; Guénée, L.; Lacour, J. “One-Step Synthesis of Diaza Macrocycles by Rh(II)-Catalyzed [3 + 6 + 3 + 6] Condensations of Morpholines and α-Diazo-β-ketoesters”, Org. Lett. 2019, 21, 687-691.archive ouverte unige:113756 pdf texte intégral [accès restreint]

Selective formation of oxonium ylides from morpholines and α-diazo-β-ketoesters was achieved. This was applied to the high-concentration (0.5 M) dirhodium-catalyzed (0.1 mol %) [3 + 6 + 3 + 6] synthesis of 18-membered ring diaza macrocycles (46%–72%). Late-stage functionalization of these derivatives is demonstrated. Mechanistic evidence for a novel (undesired) diazo decomposition pathway is also reported.

Koliwer-Brandl, H.; Knobloch, P.; Barisch, C.; Welin, A.; Hanna, N.; Soldati, T.; Hilbi, H. “Distinct Mycobacterium marinum phosphatases determine pathogen vacuole phosphoinositide pattern, phagosome maturation and escape to the cytosol”, Cell. Microbiol. 2019, 21, e13008.

The causative agent of tuberculosis, Mycobacterium tuberculosis, and its close relative Mycobacterium marinum manipulate phagocytic host cells, thereby creating a replication?permissive compartment termed the Mycobacterium?containing vacuole (MCV). The phosphoinositide (PI) lipid pattern is a crucial determinant of MCV formation and is targeted by mycobacterial PI phosphatases. In this study, we establish an efficient phage transduction protocol to construct defined M. marinum deletion mutants lacking one or three phosphatases, PtpA, PtpB and/or SapM. These strains were defective for intracellular replication in macrophages and amoebae, and the growth defect was complemented by the corresponding plasmid?borne genes. Fluorescence microscopy of M. marinum?infected Dictyostelium discoideum revealed that MCVs harboring mycobacteria lacking PtpA, SapM or all three phosphatases accumulate significantly more phosphatidylinositol?3?phosphate (PtdIns3P) compared to MCVs containing the parental strain. Moreover, PtpA reduced MCV acidification by blocking the recruitment of the V?ATPase, and all three phosphatases promoted bacterial escape from the pathogen vacuole to the cytoplasm. In summary, the translocated M. marinum phosphatases PtpA, PtpB and SapM determine the MCV PI pattern, compartment acidification and phagosomal escape.

Ziarati, A.; Badiei, A.; Grillo, R.; Burgi, T. “3D Yolk@Shell TiO2–x/LDH Architecture: Tailored Structure for Visible Light CO2 Conversion”, ACS Appl. Mater. Interfaces 2019, 11, 5903-5910.

CO2 photoconversion into hydrocarbon solar fuels by engineered semiconductors is considered as a feasible plan to address global energy requirements in times of global warming. In this regard, three-dimensional yolk@shell hydrogenated TiO2/Co–Al layered double hydroxide (3D Y@S TiO2–x/LDH) architecture was successfully assembled by sequential solvothermal, hydrogen treatment, and hydrothermal preparation steps. This architecture revealed a high efficiency for the photoreduction of CO2 to solar fuels, without a noble metal cocatalyst. The time-dependent experiment indicated that the production of CH3OH was almost selective until 2 h (up to 251 μmol/gcat. h), whereas CH4 was produced gradually by increasing the time of reaction to 12 h (up to 63 μmol/gcat. h). This significant efficiency can be ascribed to the engineering of 3D Y@S TiO2–x/LDH architecture with considerable CO2 sorption ability in mesoporous yolk@shell structure and LDH interlayer spaces. Also, oxygen vacancies in TiO2–x could provide excess sites for sorption, activation, and conversion of CO2. Furthermore, the generated Ti3+ ions in the Y@S TiO2 structure as well as connecting of structure with LDH plates can facilitate the charge separation and decrease the band gap of nanoarchitecture to the visible region.

Melot, R.; Craveiro, M. V.; Bürgi, T.; Baudoin, O. “Divergent Enantioselective Synthesis of (Nor)illudalane Sesquiterpenes via Pd0-Catalyzed Asymmetric C(sp3)–H Activation”, Org. Lett. 2019, 21, 812-815.

A divergent enantioselective synthesis of (nor)illudalane sesquiterpenes was designed by using a Pd0-catalyzed asymmetric C(sp3)–H arylation as a key step to control the isolated, highly symmetric quaternary stereocenter of the target molecules. A matched combination of chiral substrate and catalyst proved optimal to reach good levels of stereoselectivity. This approach enabled the synthesis of three (nor)illudalanes, including (S)-deliquinone and (S)-russujaponol F, which are synthesized for the first time in enantioenriched form.

Laurent, Q.; Sakai, N.; Matile, S. “The Opening of 1,2-Dithiolanes and 1,2-Diselenolanes:  Regioselectivity, Rearrangements, and Consequences for Poly(disulfide)s, Cellular Uptake and Pyruvate Dehydrogenase Complexes”, Helv. Chim. Acta 2019, 102, e1800209.archive ouverte unige:114504 pdf texte intégral [accès restreint]

The thiol‐mediated opening of 3‐alkyl‐1,2‐dithiolanes and diselenolanes is described. The thiolate nucleophile is shown to react specifically with the secondary chalcogen atom, against steric demand, probably because the primary chalcogen atom provides a better leaving group. Once released, this primary chalcogen atom reacts with the obtained secondary dichalcogenide to produce the constitutional isomer. Thiolate migration to the primary dichalcogenide equilibrates within ca. 20 ms at room temperature at a 3 : 2 ratio in favor of the secondary dichalcogenide. The clarification of this focused question is important for the understanding of multifunctional poly(disulfide)s obtained by ring opening disulfide exchange polymerization of 3‐alkyl‐1,2‐dithiolanes, to rationalize the cellular uptake mediated by 3‐alkyl‐1,2‐diselenolanes as molecular walkers and, perhaps, also of the mode of action of pyruvate dehydrogenase complexes. The isolation of ring‐opened diselenolanes is particularly intriguing because dominant selenophilicity disfavors ring opening strongly.

Oppermann, M.; Bauer, B.; Rossi, T.; Zinna, F.; Helbing, J.; Lacour, J.; Chergui, M. “Ultrafast broadband circular dichroism in the deep ultraviolet”, Optica 2019, 6, 56-60.archive ouverte unige:112702 pdf texte intégral [accès libre]

The measurement of chirality and its temporal evolution are crucial for the understanding of a large range of biological functions and chemical reactions. Steady-state circular dichroism (CD) is a standard analytical tool for measuring chirality in chemistry and biology. Nevertheless, its push into the ultrafast time domain and in the deep-ultraviolet has remained a challenge, with only some isolated reports of subnanosecond CD. Here, we present a broadband time-resolved CD spectrometer in the deep ultraviolet (UV) spectral range with femtosecond time resolution. The setup employs a photoelastic modulator to achieve shot-to-shot polarization switching of a 20 kHz pulse train of broadband femtosecond deep-UV pulses (250–370 nm). The resulting sequence of alternating left- and right-circularly polarized probe pulses is employed in a pump-probe scheme with shot-to-shot dispersive detection and thus allows for the acquisition of broadband CD spectra of ground- and excited-state species. Through polarization scrambling of the probe pulses prior to detection, artifact-free static and transient CD spectra of enantiopure [Ru(bpy)3]2+ are successfully recorded with a sensitivity of <2×10−5 OD (≈0.7  mdeg). Due to its broadband deep-UV detection with unprecedented sensitivity, the measurement of ultrafast chirality changes in biological systems with amino-acid residues and peptides and of DNA oligomers is now feasible.

Feskov, S. V.; Rogozina, M. V.; Ivanov, A. I.; Aster, A.; Koch, M.; Vauthey, E. “Magnetic field effect on ion pair dynamics upon bimolecular photoinduced electron transfer in solution”, J. Chem. Phys. 2019, 150, 024501.archive ouverte unige:114615 pdf texte intégral [accès restreint]

The dynamics of the ion pairs produced upon fluorescence quenching of the electron donor 9,10-dimethylanthracene (DMeA) by phthalonitrile have been investigated in acetonitrile and tetrahydrofuran using transient absorption spectroscopy. Charge recombination to both the neutral ground state and the triplet excited state of DMeA is observed in both solvents. The relative efficiency of the triplet recombination pathway decreases substantially in the presence of an external magnetic field. These results were analyzed theoretically within the differential encounter theory, with the spin conversion of the geminate ion pairs described as a coherent process driven by the hyperfine interaction. The early temporal evolution of ion pair and triplet state populations with and without magnetic field could be well reproduced in acetonitrile, but not in tetrahydrofuran where fluorescence quenching involves the formation of an exciplex. A description of the spin conversion in terms of rates, i.e., incoherent spin transitions, leads to an overestimation of the magnetic field effect.

Lee, L. M.; Tsemperouli, M.; Poblador-Bahamonde, A. I.; Benz, S.; Sakai, N.; Sugihara, K.; Matile, S. “Anion Transport with Pnictogen Bonds in Direct Comparison with Chalcogen and Halogen Bonds”, J. Am. Chem. Soc. 2019, 141, 810-814.archive ouverte unige:113057 pdf texte intégral [accès restreint]

In this Communication, we introduce transmembrane anion transport with pnictogen-bonding compounds and compare their characteristics with chalcogen- and halogen-bonding analogues. Tellurium-centered chalcogen bonds are at least as active as antimony-centered pnictogen bonds, whereas iodine-centered halogen bonds are 3 orders of magnitude less active. Irregular voltage-dependent single-channel currents, high gating charges, and efficient dye leakage support for the formation of bulky, membrane-disruptive supramolecular amphiphiles due to “too strong” binding of anions to tris(perfluorophenyl)stibanes. In contrast, the chalcogen-bonding bis(perfluorophenyl)tellanes do not cause leakage and excel as carriers with nanomolar activity, with P(Cl/Na) = 10.4 for anion/cation selectivity and P(Cl/NO3) = 4.5 for anion selectivity. The selectivities are lower with pnictogen-bonding carriers because their membrane-disturbing 3D structure also affects weaker binders (P(Cl/Na) = 2.1, P(Cl/NO3) = 2.5). Their 2D structure, directionality, hydrophobicity, and support from proximal anion−π interactions are suggested to contribute to the unique power of chalcogen bonds to transport anions across lipid bilayer membranes.

Machado, S.; Mercier, V.; Chiaruttini, N. “LimeSeg: a coarse-grained lipid membrane simulation for 3D image segmentation”, BMC Bioinf. 2019, 20, 2.

3D segmentation is often a prerequisite for 3D object display and quantitative measurements. Yet existing voxel-based methods do not directly give information on the object surface or topology. As for spatially continuous approaches such as level-set, active contours and meshes, although providing surfaces and concise shape description, they are generally not suitable for multiple object segmentation and/or for objects with an irregular shape, which can hamper their adoption by bioimage analysts.

Feng, S.; Harayama, T.; Chang, D.; Hannich, J. T.; Winssinger, N.; Riezman, H. “Lysosome-targeted photoactivation reveals local sphingosine metabolism signatures”, Chem. Sci. 2019, 10, 2253-2258.archive ouverte unige:115422 pdf texte intégral [accès libre]

Lipids are essential components of eukaryotic cell membranes and play crucial roles in cellular signaling and metabolism. While increasing evidence shows that the activities of lipids are dependent upon subcellular localization, tools to study local lipid metabolism and signaling are limited. Herein, we report an approach that enabled us to selectively deliver photo-caged lipids into lysosomes and thereafter to quickly release the lipid molecules by illumination. On combining this method with genetic techniques and lipidomics, we were able to investigate the localization-dependent metabolism of an important intermediate of sphingolipid metabolism, sphingosine. Our data reveal a distinct metabolic pattern of lysosomal sphingosine. In general, this method has the potential to serve as a platform to study lysosomal metabolism and signaling of various lipids and metabolites in living cells.

Maechler, F. A.; Allier, C.; Roux, A.; Tomba, C. “Curvature Dependent constraints drive remodeling of epithelia”, J. Cell Sci. 2019, 132, jcs222372.

Epithelial tissues function as barriers that separate the organism from the environment. They usually have highly curved shapes, such as tubules or cysts. However, the processes by which the geometry of the environment and the cell's mechanical properties set the epithelium shape are not yet known. In this study, we encapsulated two epithelial cell lines, MDCK and J3B1A, into hollow alginate tubes and grew them under cylindrical confinement forming a complete monolayer. MDCK monolayers detached from the alginate shell at a constant rate, whereas J3B1A monolayers detached at a low rate unless the tube radius was reduced. We showed that this detachment is driven by contractile stresses in the epithelium and can be enhanced by local curvature. This allows us to conclude that J3B1A cells exhibit smaller contractility than MDCK cells. Monolayers inside curved tubes detach at a higher rate on the outside of a curve, confirming that detachment is driven by contraction.

Sundukova, M.; Prifti, E.; Bucci, A.; Kirillova, K.; Serrao, J.; Reymond, L.; Umebayashi, M.; Hovius, R.; Riezman, H.; Johnsson, K.; Heppenstall, P. A. “A Chemogenetic Approach for the Optical Monitoring of Voltage in Neurons”, Angew. Chem. Int. Ed. 2019, 58, 2341-2344.

Optical monitoring of neuronal voltage using fluorescent indicators is a powerful approach for the interrogation of the cellular and molecular logic of the nervous system. Herein, a semisynthetic tethered voltage indicator (STeVI1) based upon nile red is described that displays voltage sensitivity when genetically targeted to neuronal membranes. This environmentally sensitive probe allows for wash‐free imaging and faithfully detects supra‐ and sub‐threshold activity in neurons.

Babič, A.; Vorobiev, V.; Trefalt, G.; Crowe, L. A.; Helm, L.; Vallée, J.-P.; Allémann, E. “MRI micelles self-assembled from synthetic gadolinium-based nano building blocks”, Chem. Commun. 2019, 55, 945-948.

A synthetic nano building block endowed with amphiphilic properties and chelated gadolinium is presented. Spontaneous self-assembly into small 12 nm corona-core stealth Gd-micelles with inherently high gadolinium loading occurs in water. Gd-Micelles are a new blood pool contrast agent with high relaxivity for magnetic resonance imaging.

Kicka, S.; Hanna, N.; Chiriano, G.; Harrison, C.; Ouertatani Sakouhi, H.; Trofimov, V.; Kranjc, A.; Hilbi, H.; Cosson, P.; Scapozza, L.; Soldati, T. “Identification of novel anti-bacterial compounds from a chemically highly diverse pathways-based library using phenotypic screens in amoebae host models”, bioRxiv 2019, in press.archive ouverte unige:112884 pdf texte intégral [accès libre]

Legionella pneumophila and tubercular Mycobacteria are the causative agents of potentially fatal diseases due to their pathogenesis but also to the emergence of antibiotic resistance that limits treatment strategies. The aim of our study is to explore the antimicrobial activity of a small ligand-based chemical library of 1,255 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 an additional anti-virulence plaque assay for M. marinum. We set up these assays using two amoeba strains, the genetically tractable Dictyostelium discoideum and the free-living amoeba Acanthamoeba castellanii. In summary, sixty-four compounds showed anti-infective/anti-virulence activity in at least one of the 3 assays. The intracellular assays hit rate varied between 1.7% (n=22) for M. marinum and 2.8% (n=35) for L pneumophila with 7 compounds in common between both pathogens. In parallel, 1.2 % (n= 15) of the tested compounds were able to restore D. discoideum growth in presence of M. marinum spiked in a lawn of Klebsiella pneumoniae. We also validated the generality of the hit compounds identified using the A. castellanii-M. marinum anti-infective screen in the powerful D. discoideum-M. 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. Our studies underline the relevance of using a combination of low-cost and low-complexity assays with full 3R compliance associated with a rationalized focused library of compounds to help identifying new chemical scaffolds and dissect some of their properties prior to run further compounds development steps.

Lawson Daku, L. “Spin-state dependence of the structural and vibrational properties of solvated iron(II) polypyridyl complexes from AIMD simulations: II. aqueous [Fe(tpy)2]Cl2”, Phys. Chem. Chem. Phys. 2019, 21, 650-661.

We report a detailed ab initio molecular dynamics (AIMD) study of the structural and vibrational properties of aqueous [Fe(tpy)2]2+ (tpy = 2,2′:6′,2′′-ter-pyridine) in the low-spin (LS) and high-spin (HS) states, which extends our previous work on aqueous [Fe(bpy)3]2+ (bpy = 2,2′-bipyridine) [L. M. Lawson Daku and A. Hauser, J. Phys. Chem. Lett., 2010, 1, 1830–1835; L. M. Lawson Daku, Phys. Chem. Chem. Phys., 2018, 20, 6236–6253]. Upon the LS → HS change of states, the axial and distal Fe–N bonds of aqueous [Fe(tpy)2]2+ are predicted to lengthen by 0.226 Å and 0.206 Å, respectively, in excellent agreement with experiments [X. Zhang et al., J. Phys. Chem. C, 2015, 119, 3312–3321; G. Vankó et al., J. Phys. Chem. C, 2015, 119, 5888–5902]. The lengthening of the Fe–N bonds results from their weakening, which also gives rise to an increased thermal fluctuation of the molecular structure. As with [Fe(bpy)3]2+, the first hydration shell of [Fe(tpy)2]2+ consists in a chain of hydrogen-bonded water molecules wrapped around the ligands. The predicted hydration number of [Fe(tpy)2]2+ in both spin states is ≈15 while it was found for [Fe(bpy)3]2+ to increase from ≈15 to ≈17 on passing from the LS to the HS state. Due to the ≈0.2 Å lengthening of the Fe–N bonds in both complexes upon the LS → HS transition, the water molecules can get closer to the Fe atom: by ≈0.4 Å for [Fe(tpy)2]2+ and by ≈0.2 Å for [Fe(bpy)3]2+. This difference is ascribed to the fact that the bpy ligands with their trigonal coordination motif provides a bulkier environment to the Fe atom than the tpy ligands with their tetragonal coordination motif. In other words, upon the tpy → bpy substitution, the bulkier environment provided by the bpy ligands repels the hydration shell, the displacement being greater in the HS state than in the LS state. As a consequence of their chemical similarity, the calculated LS and HS IR spectra of aqueous [Fe(tpy)2]2+ closely resemble those of aqueous [Fe(bpy)3]2+, the LS → HS transition translating into a global increase in intensity. The present work taken with the one on aqueous [Fe(bpy)3]2+ enhances our understanding of the spin-state dependence of the structural and vibrational properties of Fe(II) polypyridyl complexes in water, highlighting the strong interpenetration between their coordination sphere and their hydration shell.

O'Toole, N.; Lecourt, C.; Suffren, Y.; Hauser, A.; Khrouz, L.; Jeanneau, E.; Brioude, A.; Luneau, D.; Desroches, C. “Photogeneration of Manganese(III) from Luminescent Manganese(II) Complexes with Thiacalixarene Ligands: Synthesis, Structures and Photophysical Properties”, Eur. J. Inorg. Chem. 2019, 73-78.

The photophysical properties of the compound [(ThiaSO2)(MnII)2(DMF)4(H2O)2] (2), ThiaSO2 = p?tert?butylsulfonylcalix[4]arene, are presented and compared to the ones of [(ThiaSO2)2(MnII)4F]K (1). The orange luminescence of 2 is attributed, as for 1, to the MnII centred 4T16A1 transition and shows, for this type of complex, the weak influence of the Mn2+ coordination and ThiaSO2 conformation on this luminescence, the temperature and pressure dependence and quenching by molecular dioxygen of which are reported for 2. The latter is attributed to energy transfer from the 4T1 state exciting dioxygen to its 1Σ+g state and is responsible for the photosynthesis of the [(ThiaSO2)(MnIII)(DMF)2]Na (3) complex in DMF solution from 1 or 2. This reaction was studied by UV/Visible and EPR spectroscopy. The molecular structure and EPR spectroscopy of 3 are also presented.

Anzola, M.; Winssinger, N. “Turn On of a Ruthenium(II) Photocatalyst by DNA-Templated Ligation”, Chem. Eur. J. 2019, 25, 334-342.archive ouverte unige:112587 pdf texte intégral [accès restreint]

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

Bonner, R.; Hopfgartner, G. “SWATH data independent acquisition mass spectrometry for metabolomics”, TrAC, Trends Anal. Chem. 2019, 120, 115278.

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

Zdrachek, E.; Bakker, E. “Potentiometric Sensing”, Anal. Chem. 2019, 91, 2-26.archive ouverte unige:113818 pdf texte intégral [accès restreint]

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

Goujon, A.; Straková, K.; Sakai, N.; Matile, S. “Streptavidin Interfacing as a General Strategy to Localize Fluorescent Membrane Tension Probes in Cells”, Chem. Sci. 2019, 10, 310-319.archive ouverte unige:112559 pdf texte intégral [accès libre]

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

Ding, J.; Cherubini, T.; Yuan, D.; Bakker, E. “Paper-supported thin-layer ion transfer voltammetry for ion detection”, Sens. Actuators, B 2019, 280, 69-76.archive ouverte unige:109948 pdf texte intégral [accès libre]

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

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

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

Lombardot, T.; Morgat, A.; Axelsen, K. B.; Aimo, L.; Hyka-Nouspikel, N.; Niknejad, A.; Ignatchenko, A.; Xenarios, I.; Coudert, E.; Redaschi, N.; Bridge, A. “Updates in Rhea: SPARQLing biochemical reaction data”, Nucleic Acids Res. 2019, 47, D596-D600.

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

Palermo, G.; Guglielmelli, A.; Pezzi, L.; Cataldi, U.; De Sio, L.; Caputo, R.; De Luca, A.; Bürgi, T.; Tabiryan, N.; Umeton, C. “A command layer for anisotropic plasmonic photo-thermal effects in liquid crystal”, Liq. Cryst. 2019, 45, 2214-2220.

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

Saad, M. M.; Michalet, S.; Fossou, R. K.; Putnik-Delić, M.; Crèvecoeur, M.; Meyer, J.; De Malézieux, C.; Hopfgartner, G.; Maksimovic, I.; Perret, X. “Loss of NifQ leads to accumulation of porphyrins and altered metal-homeostasis in nitrogen-fixing symbioses”, Mol. Plant-Microbe Interact. 2019, 32, 208-216.

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

McAlpine, J. B.; Chen, S.-N.; Kutateladze, A.; MacMillan, J. B.; Appendino, G.; Barison, A.; Beniddir, M. A.; Biavatti, M. W.; Bluml, S.; Boufridi, A.; Butler, M. S.; Capon, R. J.; Choi, Y. H.; Coppage, D.; Crews, P.; Crimmins, M. T.; Csete, M.; Dewapriya, P.; Egan, J. M.; Garson, M. J.; Genta-Jouve, G.; Gerwick, W. H.; Gross, H.; Harper, M. K.; Hermanto, P.; Hook, J. M.; Hunter, L.; Jeannerat, D.; Ji, N.-Y.; Johnson, T. A.; Kingston, D. G. I.; Koshino, H.; Lee, H.-W.; Lewin, G.; Li, J.; Linington, R. G.; Liu, M.; McPhail, K. L.; Molinski, T. F.; Moore, B. S.; Nam, J.-W.; Neupane, R. P.; Niemitz, M.; Nuzillard, J.-M.; Oberlies, N. H.; Ocampos, F. M. M.; Pan, G.; Quinn, R. J.; Reddy, D. S.; Renault, J.-H.; Rivera-Chávez, J.; Robien, W.; Saunders, C. M.; Schmidt, T. J.; Seger, C.; Shen, B.; Steinbeck, C.; Stuppner, H.; Sturm, S.; Taglialatela-Scafati, O.; Tantillo, D. J.; Verpoorte, R.; Wang, B.-G.; Williams, C. M.; Williams, P. G.; Wist, J.; Yue, J.-M.; Zhang, C.; Xu, Z.; Simmler, C.; Lankin, D. C.; Bisson, J.; Pauli, G. F. “The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research”, Nat. Prod. Rep. 2019, 36, 35-107.archive ouverte unige:113449 pdf texte intégral [accès libre]

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


The authors regret that there were errors within references 83–85 within the version of the article published on 13th July 2018.

Carlini, L.; Mahecic, D.; Kleele, T.; Roux, A.; Manley, S. “Membrane bending energy and tension govern mitochondrial division”, bioRxiv, Biophys. 2019, in press.

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