Publications

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60
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, in press.

A molecular Solomon link (SL) 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 ca. 4 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 coordinated activation of the four switchable sites is controlled by the topology of the whole molecule.

59
Matile, S. “In My Element: Sulfur”, Chem. Eur. J. 2019, in press.

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.

58
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, in press.

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.

57
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, in press.

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.

56
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.

55
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, in press.

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.

54
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, in press.

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.

Results

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.

Conclusion

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.

53
Thewes, S.; Soldati, T.; Eichinger, L. “Editorial: Amoebae as Host Models to Study the Interaction With Pathogens”, Front. Cell. Infect. Microbiol. 2019, 9, 47.

52
Loewith, R.; Riezman, H.; Winssinger, N. “Sphingolipids and membrane targets for therapeutics”, Curr. Opin. Chem. Biol. 2019, 50, 19-28.open archive unige:115232 pdf full text [restricted access]

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.

51
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.

50
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. “Correction: Towards efficient initiators for two-photon induced polymerization: fine tuning of the donor/acceptor properties”, Mol. Syst. Des. Eng. 2019, 4, 449.

Correction for ‘Towards efficient initiators for two-photon induced polymerization: fine tuning of the donor/acceptor properties’ by Brigitte Holzer et al., Mol. Syst. Des. Eng., 2019, DOI: 10.1039/c8me00101d.

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

The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.

49
Jansod, S.; Bakker, E. “Tunable Optical Sensing with PVC Membrane Based Ion-Selective Bipolar Electrodes”, ACS Sens. 2019, in press.

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.

48
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.

47
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.

46
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.

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.

45
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.open archive unige:115136 pdf full text [restricted access]

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.

44
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.

43
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.

42
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.open archive unige:115269 pdf full text [restricted access]

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.

41
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.

40
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.

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.

39
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.open archive unige:114631 pdf full text [restricted access]

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.

38
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.

37
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.

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.

36
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+.

35
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.

34
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.

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.

33
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.open archive unige:114717 pdf full text [restricted access]

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.

32
Angerani, S.; Winssinger, N. “Visible Light Photoredox Catalysis Using Ruthenium Complexes in Chemical Biology”, Chem. Eur. J. 2019, in press.

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.

31
Kazan, R.; Müller, U.; Bürgi, T. “Doping of thiolate protected gold clusters through reaction with metal surfaces”, Nanoscale 2019, 11, 2938-2945.

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.

30
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.open archive unige:113756 pdf full text [restricted access]

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.

29
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, in press.

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.

28
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.

27
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.

26
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.open archive unige:114504 pdf full text [restricted access]

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.

25
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, 56-59.open archive unige:112702 pdf full text [free access]

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.

24
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.open archive unige:114615 pdf full text [restricted access]

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.

23
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.open archive unige:113057 pdf full text [restricted access]

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.

22
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.

21
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.open archive unige:115422 pdf full text [free access]

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.

20
Maechler, F. A.; Allier, C.; Roux, A.; Tomba, C. “Curvature Dependent constraints drive remodeling of epithelia”, J. Cell Sci. 2019, 132, cs222372.

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.

19
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.

18
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.

17
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.open archive unige:112884 pdf full text [free access]

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.

16
Lawson Daku, L. M. “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.

15
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 = ptert‐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.

14
McAlpine, J. B.; Chen, S.-N.; Kutateladze, A.; MacMillan, J. B.; Appendino, G.; Barison, A.; Beniddir, M. A.; Biavatti, M. W.; Bluml, S.; Boufridi, A.; Butler, M. S.; Capon, R. J.; Choi, Y. H.; Coppage, D.; Crews, P.; Crimmins, M. T.; Csete, M.; Dewapriya, P.; Egan, J. M.; Garson, M. J.; Genta-Jouve, G.; Gerwick, W. H.; Gross, H.; Harper, M. K.; Hermanto, P.; Hook, J. M.; Hunter, L.; Jeannerat, D.; Ji, N.-Y.; Johnson, T. A.; Kingston, D. G. I.; Koshino, H.; Lee, H.-W.; Lewin, G.; Li, J.; Linington, R. G.; Liu, M.; McPhail, K. L.; Molinski, T. F.; Moore, B. S.; Nam, J.-W.; Neupane, R. P.; Niemitz, M.; Nuzillard, J.-M.; Oberlies, N. H.; Ocampos, F. M. M.; Pan, G.; Quinn, R. J.; Reddy, D. S.; Renault, J.-H.; Rivera-Chávez, J.; Robien, W.; Saunders, C. M.; Schmidt, T. J.; Seger, C.; Shen, B.; Steinbeck, C.; Stuppner, H.; Sturm, S.; Taglialatela-Scafati, O.; Tantillo, D. J.; Verpoorte, R.; Wang, B.-G.; Williams, C. M.; Williams, P. G.; Wist, J.; Yue, J.-M.; Zhang, C.; Xu, Z.; Simmler, C.; Lankin, D. C.; Bisson, J.; Pauli, G. F. “Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research”, Nat. Prod. Rep. 2019, 36, 248-249.open archive unige:113449 pdf full text [free access]

Correction for ‘The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research’ by James B. McAlpine et al., Nat. Prod. Rep., 2019, DOI: 10.1039/c7np00064b.

13
Anzola, M.; Winssinger, N. “Turn On of a Ruthenium(II) Photocatalyst by DNA-Templated Ligation”, Chem. Eur. J. 2019, 25, 334-342.open archive unige:112587 pdf full text [restricted access]

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.

12
Wasnik, V. H.; Lipp, P.; Kruse, K. “Positional information readout in Ca2+ signaling”, arXiv.org, e-Print Arch., Quant. Biol. 2019, in press.

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

11
Bonner, R.; Hopfgartner, G. “SWATH data independent acquisition mass spectrometry for metabolomics”, TrAC, Trends Anal. Chem. 2019, in press.

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

10
Zdrachek, E.; Bakker, E. “Potentiometric Sensing”, Anal. Chem. 2019, 91, 2-26.

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.

9
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.open archive unige:112559 pdf full text [free access]

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.

8
Ding, J.; Cherubini, T.; Yuan, D.; Bakker, E. “Paper-supported thin-layer ion transfer voltammetry for ion detection”, Sens. Actuators, B 2019, 280, 69-76.

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

7
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.

6
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 (http://www.rhea-db.org) is a comprehensive and non-redundant resource of over 11 000 expert-curated biochemical reactions that uses chemical entities from the ChEBI ontology to represent reaction participants. Originally designed as an annotation vocabulary for the UniProt Knowledgebase (UniProtKB), Rhea also provides reaction data for a range of other core knowledgebases and data repositories including ChEBI and MetaboLights. Here we describe recent developments in Rhea, focusing on a new resource description framework representation of Rhea reaction data and an SPARQL endpoint (https://sparql.rhea-db.org/sparql) that provides access to it. We demonstrate how federated queries that combine the Rhea SPARQL endpoint and other SPARQL endpoints such as that of UniProt can provide improved metabolite annotation and support integrative analyses that link the metabolome through the proteome to the transcriptome and genome. These developments will significantly boost the utility of Rhea as a means to link chemistry and biology for a more holistic understanding of biological systems and their function in health and disease.

5
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.

4
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.

3
Banafsheh, M.; Wesolowski, T. A. “ERRATUM: Nonadditive kinetic potentials from inverted Kohn-Sham problem”, Int. J. Quantum Chem. 2019, in press.

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

2
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.open archive unige:113449 pdf full text [free access]

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.

1
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.