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

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

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

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

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

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

Zhang, X.; Liu, L.; López-Andarias, J.; Wang, C.; Sakai, N.; Matile, S. “Anion-π Catalysis: Focus on Nonadjacent Stereocenters”, Helv. Chim. Acta 2018, in press.

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

Kaksonen, M.; Roux, A. “Mechanisms of clathrin-mediated endocytosis”, Nat. Rev. Mol. Cell Biol. 2018, in press.

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

Harayama, T.; Riezman, H. “Understanding the diversity of membrane lipid composition”, Nat. Rev. Mol. Cell Biol. 2018, in press.

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

Bruderer, T.; Varesio, E.; Hidasi, A. O.; Duchoslav, E.; Burton, L.; Bonner, R.; Hopfgartner, G. “Metabolomic spectral libraries for data-independent SWATH liquid chromatography mass spectrometry acquisition”, Anal. Bioanal. Chem. 2018, 410, 1873-1884.

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

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

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

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

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

Kim, K. T.; Chang, D.; Winssinger, N. “Double-Stranded RNA-specific Templated Reaction with Triplex Forming PNA”, Helv. Chim. Acta 2018, in press.

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

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

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

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

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

Bauer, C. . R.; Duwald, R.; Labrador, G.; Pascal, S.; Moneva Lorente, P.; Bosson, J.; Lacour, J.; Rochaix, J.-D. “Specific labeling of mitochondria of Chlamydomonas with cationic helicene fluorophores”, Org. Biomol. Chem. 2018, 16, 919-923.

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

Radiom, M.; Maroni, P.; Wesolowski, T. A. “Size extensivity of elastic properties of alkane fragments”, J. Mol. Model. 2018, 24, article 36.

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

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

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

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

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

Ray, S. K.; Homberg, A.; Vishe, M.; Besnard, C.; Lacour, J. “Efficient Synthesis of Ditopic Polyamide Receptors for Cooperative Ion Pair Recognition in Solution and Solid States”, Chem. Eur. J. 2018, in press.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Piguet, C.; Babel, L.; Baudet, K.; Hoang, T. N. Y.; Nozary, H. “A Rational Approach to Metal Loading of Organic Multi-Site Polymers: Illusion or Reality?”, Chem. Eur. J. 2018, in press.

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

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

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

Fakis, M.; Beckwith, J.; Seintis, K.; Martinou, E.; Nançoz, C.; Karakostas, N.; Petsalakis, I. D.; Pistolis, G.; Vauthey, E. “Energy Transfer and Charge Separation Dynamics in Photoexcited Pyrene-Bodipy Molecular Dyads”, Phys. Chem. Chem. Phys. 2018, 20, 837-849.

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

Vasylevskyi, S.; Regeta, K.; Ruggi, A.; Petoud, S.; Piguet, C.; Fromm, K. “cis- and trans-9,10-di(1H-imidazol-1-yl)-anthracene based coordination polymers of ZnII and CdII: synthesis, crystal structures and luminescence properties”, Dalton Trans. 2018, 47, 596-607.

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

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

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

Smith, A. M.; Maroni, P.; Borkovec, M. “Attractive Non-DLVO Forces Induced by Adsorption of Monovalent Organic Ions”, Phys. Chem. Chem. Phys. 2018, 20, 158-164.

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

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

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

Vishe, M.; Lathion, T.; Pascal, S.; Yushchenko, O.; Homberg, A.; Brun, E.; Vauthey, E.; Piguet, C.; Lacour, J. “Excimer-Based On-Off Bis(pyreneamide) Macrocyclic Chemosensors”, Helv. Chim. Acta 2018, 101, archive unige:101609 pdf full text [restricted access]

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

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

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

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

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

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

Babel, L.; Guénée, L.; Besnard, C.; Eliseeva, S. V.; Petoud, S.; Piguet, C. “Cooperative loading of multisite receptors with lanthanide containers: an approach for organized luminescent metallopolymers”, Chem. Sci. 2018, 9, archive unige:101289 pdf full text [free access]

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

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

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

Fuchs, K.; Kiss, A.; Bize, P. E.; Duran, R.; Denys, A.; Hopfgartner, G.; Borchard, G.; Jordan, O. “Mapping of drug distribution in the rabbit liver tumor model by complementary fluorescence and mass spectrometry imaging”, J. Controlled Release 2018, 269, 128-135.

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

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

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

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

Compound: Sunitinib: PubChem CID 5329102.

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

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

Egea, J.; Fabregat, I.; Frapart, Y.; Ghezzi, P.; Görlach, A.; Kietzmann, T.; Kubaichuk, K.; Knaus, U.; Lopez, M.; Olaso-Gonzalez, G.; Petry, A.; Schulz, R.; Vina, J.; Winyard, P.; Abbas, K.; Ademowo, O.; Afonso, C.; Andreadou, I.; Antelmann, H.; Antunes, F.; Aslan, M.; Bachschmid, M.; Barbosa, R.; Belousov, V.; Berndt, C.; Bernlohr, D.; Bertrán, E.; Bindoli, A.; Bottari, S.; Brito, P.; Carrara, G.; Casas, A.; Chatzi, A.; Chondrogianni, N.; Conrad, M.; Cooke, M.; Costa, J.; Cuadrado, A.; My-Chan Dang, P.; De Smet, B.; Debelec-Butuner, B.; Dias, I.; Dunn, J.; Edson, A.; El Assar, M.; El-Benna, J.; Ferdinandy, P.; Fernandes, A.; Fladmark, K.; Förstermann, U.; Giniatullin, R.; Giricz, Z.; Görbe, A.; Griffiths, H.; Hampl, V.; Hanf, A.; Herget, J.; Hernansanz-Agustín, P.; Hillion, M.; Huang, J.; Ilikay, S.; Jansen-Dürr, P.; Jaquet, V.; Joles, J.; Kalyanaraman, B.; Kaminskyy, D.; Karbaschi, M.; Kleanthous, M.; Klotz, L.; Korac, B.; Korkmaz, K.; Koziel, R.; Kračun, D.; Krause, K.; Křen, V.; Krieg, T.; Laranjinha, J.; Lazou, A.; Li, H.; Martínez-Ruiz, A.; Matsui, R.; McBean, G.; Meredith, S.; Messens, J.; Miguel, V.; Mikhed, Y.; Milisav, I.; Milković, L.; Miranda-Vizuete, A.; Mojović, M.; Monsalve, M.; Mouthuy, P.; Mulvey, J.; Münzel, T.; Muzykantov, V.; Nguyen, I.; Oelze, M.; Oliveira, N.; Palmeira, C.; Papaevgeniou, N.; Pavićević, A.; Pedre, B.; Peyrot, F.; Phylactides, M.; Pircalabioru, G.; Pitt, A.; Poulsen, H.; Prieto, I.; Rigobello, M.; Robledinos-Antón, N.; Rodríguez-Mañas, L.; Rolo, A.; Rousset, F.; Ruskovska, T.; Saraiva, N.; Sasson, S.; Schröder, K.; Semen, K.; Seredenina, T.; Shakirzyanova, A.; Smith, G. L.; Soldati, T.; Sousa, B. C.; Spickett, C. M.; Stancic, A.; Stasia, M. J.; Steinbrenner, H.; Stepanić, V.; Steven, S.; Tokatlidis, K.; Tuncay, E.; Turan, B.; Ursini, F.; Vacek, J.; Vajnerova, O.; Valentová, K.; Van Breusegem, F.; Varisli, L.; Veal, E. A.; Yalçın, A. S.; Yelisyeyeva, O.; Žarković, N.; Zatloukalová, M.; Zielonka, J.; Touyz, R. M.; Papapetropoulos, A.; Grune, T.; Lamas, S.; Schmidt, H. H. H. W.; Di Lisa, F.; Daiber, A. “Corrigendum to “European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)”  [Redox Biol. 13 (2017) 94–162]”, Redox Biol. 2018, 14, 694-696.

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

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

The authors would like to apologise for any inconvenience caused.

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

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

Shinde, A. B.; Baboota, R. K.; Denis, S.; Loizides-Mangold, U.; Peeters, A.; Espeel, M.; Malheiro, A. R.; Riezman, H.; Vinckier, S.; Vaz, F. M.; Brites, P.; Ferdinandusse, S.; Van Veldhoven, P. P.; Baes, M. “Mitochondrial disruption in peroxisome deficient cells is hepatocyte selective but is not mediated by common hepatic peroxisomal metabolites”, Mitochondrion 2018, 39, 51-59.

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

Coll Crespi, M.; Crespo, G. A.; Xie, X.; Touilloux, R.; Tercier-Waeber, M.; Bakker, E. “Agarose hydrogel containing immobilized pH buffer microemulsion without increasing permselectivity”, Talanta 2018, 177, archive unige:101844 pdf full text [restricted access]

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

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

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

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

Fluorinated tripodal compounds were recently reported to be efficient transmembrane transporters for a series of inorganic anions. In particular, this class of receptors has been shown to be suitable for the effective complexation of chloride, nitrate, bicarbonate and sulfate anions via hydrogen bonding. The potentiometric properties of urea and thiourea-based fluorinated tripodal receptors are explored here for the first time, in light of the need for reliable sensors for chloride monitoring in undiluted biological fluids. The ion selective electrode (ISE) membranes with tren-based tris-urea bis(CF3) tripodal compound (ionophore I) were found to exhibit the best selectivity for chloride over major lipophilic anions such as salicylate (log K pot Cl-/Sal- =+1.0) and thiocyanate (log K pot Cl-/SCN- =+0.1). Ionophore I-based ISEs were successfully applied for chloride determination in undiluted human serumas well as artificial serum sample, the slope of the linear calibration at the relevant background of interfering ions being close to Nernstian (49.8±1.7 mV). The results of potentiometric measurements were confirmed by argentometric titration. Moreover, the ionophore I-based ISE membrane was shown to exhibit a very good long-term stability of potentiometric performance over the period of 10 weeks. Nuclear magnetic resonance (NMR) titrations, potentiometric sandwich membrane experiments and density functional theory (DFT) computational studies were performed to determine the binding constants and suggest 1:1 complexation stoichiometry for the ionophore I with chloride as well as salicylate.

Banafsheh, M.; Wesolowski, T. A. “Nonadditive kinetic potentials from inverted Kohn-Sham problem”, Int. J. Quantum Chem. 2018, 118, e25410.

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