Publications

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31
Knobloch, P.; Koliwer-Brandl, H.; Arnold, F. M.; Hanna, N.; Gonda, I.; Adenau, S.; Personnic, N.; Barisch, C.; Seeger, M. A.; Soldati, T.; Hilbi, H. “Mycobacterium marinum produces distinct mycobactin and carboxymycobactin siderophores to promote growth in broth and phagocytes”, Cell. Microbiol. 2020, in press.

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

30
Szabo, T.; Maroni, P.; Szilagyi, I. “Size-dependent aggregation of graphene oxide”, Carbon 2020, 160, 145-155.

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

29
Nazarov, A. E.; Ivanov, A. I.; Vauthey, E. “Modelling IR Spectral Dynamics upon Symmetry Breaking of a Photo-Excited Quadrupolar Dye”, J. Phys. Chem. C 2020, in press.

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

28
Doistau, B.; Jiménez, J.-R.; Guerra, S.; Besnard, C.; Piguet, C. “Key Strategy for the Rational Incorporation of Long-Lived NIR Emissive Cr(III) Chromophores into Polymetallic Architectures”, Inorg. Chem. 2020, in press.

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

Supporting Information (pdf, 4.63 MB)

27
Hopfgartner, G. “Books Review Wenkui Li, Wenying Jian, and Yunlin Fu (Eds.): Sample preparation in LC-MS bioanalysis”, Anal. Bioanal. Chem. 2020, in press.

26
Lathion, T.; Fürstenberg, A.; Besnard, C.; Hauser, A.; Bousseksou, A.; Piguet, C. “Monitoring Fe(II) Spin-State Equilibria via Eu(III) Luminescence in Molecular Complexes: Dream or Reality?”, Inorg. Chem. 2020, in press.

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

Supporting Information (pdf, 1.5 MB)

25
Galli, V.; Sadhu, K. K.; Masi, D.; Saarbach, J.; Roux, A.; Winssinger, N. “Caprin-1 Promotes Cellular Uptake of Nucleic Acids with Backbone and Sequence Discrimination”, Helv. Chim. Acta 2020, in press.

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

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

24
Forrest, T.; Zdrachek, E.; Bakker, E. “Thin Layer Membrane Systems as Rapid Development Tool for Potentiometric Solid Contact Ion-selective Electrodes”, Electroanalysis 2020, in press.

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

23
Yang, J.; Chatelet, B.; Hérault, D.; Dufaud, V.; Robert, V.; Grass, S.; Lacour, J.; Vanthuyne, N.; Jean, M.; Albalat, M.; Dutasta, J.-P.; Martinez, A. “Enantiopure encaged Verkade's superbases: Synthesis, chiroptical properties, and use as chiral derivatizing agent”, Chirality 2020, in press.

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

Supporting Information (PDF / 2 MB)

22
Hopfgartner, G. “Editorial Bioanalytical method validation: How much should we do and how should we document?”, Anal. Bioanal. Chem. 2020, in press.

21
Humeniuk, H. V.; Licari, G.; Vauthey, E.; Sakai, N.; Matile, S. “Mechanosensitive Membrane Probes:  Push-Pull Papillons”, Supramol. Chem. 2020, in press.

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

Supplemental material (pdf)

20
Stojimirovic, B.; Vis, M.; Tuinier, R.; Philipse, A. P.; Trefalt, G. “Experimental Evidence for Algebraic Double-Layer Forces”, Langmuir 2020, 36, 47-54.

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

Supporting Information (pdf / 191.56 kb)

19
Fiorito, D.; Liu, Y.; Besnard, C.; Mazet, C. “Direct Access to Chiral Secondary Amides by Copper-Catalyzed Borylative Carboxamidation of Vinylarenes with Isocyanates”, J. Am. Chem. Soc. 2020, 142, 623-632.archive ouverte unige:128621 pdf texte intégral [accès restreint]

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

Supporting Information: Experimental procedures, characterization of all new compounds, spectroscopic, spectrometric, and X-ray data for compounds 3wa, (E)-5ab, and 3ja (CCDC 1914320–1914322) (PDF / 21.13 MB)
Crystallographic information files (CIF): #1 ( 276.58 kb) / #2 (730.19 kb) / #3 (405.19 kb)

18
Oberhauser, L.; Granziera, S.; Colom, A.; Goujon, A.; Lavallard, V.; Matile, S.; Roux, A.; Brun, T.; Maechler, P. “Palmitate and Oleate Modify Membrane Fluidity and Kinase Activities of INS-1E ß-Cells Alongside Altered Metabolism-Secretion Coupling”, Biochim. Biophys. Acta, Mol. Cell Biol. Lipids 2020, 1867, 118619.archive ouverte unige:127987 pdf texte intégral [accès restreint]

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

Supplementary figures (PDF / 1 MB)

17
Brun, E.; Zhang, K.-F.; Guénée, L.; Lacour, J. “Photo-induced thiol–ene reactions for late-stage functionalization of unsaturated polyether macrocycles: regio and diastereoselective access to macrocyclic dithiol derivatives”, Org. Biomol. Chem. 2020, 18, 250-254.archive ouverte unige:128309 pdf texte intégral [accès libre]

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

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

16
Duwald, R.; Bosson, J.; Pascal, S.; Grass, S.; Zinna, F.; Besnard, C.; Di Bari, L.; Jacquemin, D.; Lacour, J. “Merging polyacenes and cationic helicenes: from weak to intense chiroptical properties in the far red region”, Chem. Sci. 2020, in press.

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

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

15
Zinna, F.; Brun, E.; Homberg, A.; Lacour, J. “Circularly polarized luminescence from intramolecular excimers”, In Circularly Polarized Luminescence of Isolated Small Organic Molecules”, Mori, T. (Ed.), Springer: Singapore 2020.

14
Figuerola-Conchas, A.; Saarbach, J.; Daguer, J.-P.; Cieren, A.; Barluenga, S.; Winssinger, N.; Gotta, M. “Small-molecule modulators of the ATPase VCP/p97 affect specific p97 cellular functions”, ACS Chem. Biol. 2020, in press.

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

Supporting Information:

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

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

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

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

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

13
Rodrigues, T.; Brodier, L.; Matter, J.-M. “Investigating Neurogenesis in Birds”, In Retinal Development: Methods and Protocols”, Mao, C.-A. (Ed.), Collection “Methods in Molecular Biology” vol. 2092, Humana: New York 2020, p. 1-18.

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

12
Smith, A. M.; Borkovec, M.; Trefalt, G. “Forces between solid surfaces in aqueous electrolyte solutions”, Adv. Colloid Interface Sci. 2020, 275, 102078.

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

11
Gao, W.; Zdrachek, E.; Xie, X.; Bakker, E. “A Solid-State Reference Electrode Based on a Self-Referencing Pulstrode”, Angew. Chem. Int. Ed. 2020, in press.

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

Supporting Information (pdf / 1800.3 KB)

10
Zhang, X.; Sakai, N.; Matile, S. “Methyl Scanning for Mechanochemical Chalcogen-Bonding Cascade Switches”, ChemistryOpen 2020, 9, 18-22.archive ouverte unige:128620 pdf texte intégral [accès libre]

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

Supporting Information

9
Fedunov, R. G.; Yermolenko, I. P.; Nazarov, A. E.; Ivanov, A. I.; Rosspeintner, A.; Angulo, G. “Theory of fluorescence spectrum dynamics and its application to determining the relaxation characteristics of the solvent and intramolecular vibrations”, J. Mol. Liq. 2020, in press.

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

8
Caprice, K.; Aster, A.; Cougnon, F. B. L.; Kumpulainen, T. “Untying the Photophysics of Quinolinium-Based Molecular Knots and Links”, Chem. Eur. J. 2020, in press.

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

Supporting Information (pdf / 8 MB)

7
Laurent, Q.; Berthet, M.; Cheng, Y.; Sakai, N.; Barluenga, S.; Winssinger, N.; Matile, S. “Probing for Thiol-Mediated Uptake into Bacteria”, ChemBioChem 2020, in press.

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

Supporting Information (PDF / 1.9 MB)

6
Apichai, S.; Wang, L.; Grudpan, K.; Bakker, E. “Renewable magnetic ion-selective colorimetric microsensors based on surface modified polystyrene beads”, Anal. Chim. Acta 2020, 1094, 136-141.

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

5
Sheberstov, K. F.; Guardiola Sistare, E.; Jeannerat, D. “Everything you wanted to know about phase and reference frequency in one- and two-dimensional NMR Spectroscopy”, Magn. Reson. Chem. 2020, in press.

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

Supporting Information (ZIP / 1.6 MB)

4
Akbal, L.; Hopfgartner, G. “Supercritical fluid chromatography–mass spectrometry using data independent acquisition for the analysis of polar metabolites in human urine”, J. Chromatogr. A 2020, 1609, 460449.

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

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Baudet, K.; Kale, V.; Mirzakhani, M.; Babel, L.; Naseri, S.; Besnard, C.; Nozary, H.; Piguet, C. “Neutral Heteroleptic Lanthanide Complexes for Unravelling Host–Guest Assemblies in Organic Solvents: The Law of Mass Action Revisited”, Inorg. Chem. 2020, 59, 62-75.

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

Supporting Information (pdf, 28.1 MB)

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Sheberstov, K.; Sistaré Guardiola, E.; Pupier, M.; Jeannerat, D. “SAN plot: a Graphical representation of the signal, noise and artifacts content of spectra”, Magn. Reson. Chem. 2020, in press.

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

Supporting Information (PDF / 506.5 KB)

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Funato, K.; Riezman, H.; Muñiz, M. “Vesicular and non-vesicular lipid export from the ER to the secretory pathway”, Biochim. Biophys. Acta, Mol. Cell Biol. Lipids 2020, 1865, 158453.

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