Mechanosensitive Oligodithienothiophenes: Transmembrane Anion Transport Along Chalcogen‐Bonding Cascades

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The development of fluorescent probes to image forces in cells is an important challenge in chemistry and biology. Planarizable push‐pull probes have been introduced recently for this purpose. To provide most valuable information on forces in complex systems, these mechanosensitive ‘flipper’ probes will have to be localized by molecular recognition of targets of interest. Here we report fluorescent flippers that selectively recognize gangliosides on the surface of lipid bilayer membranes by formation of dynamic covalent boronate esters. The original flipper probes were equipped with 2‐fluorophenyl boronic acids and benzoboroxoles using consecutive triazole and oxime ligation. Evaluation was done in large unilamellar vesicles composed of EYPC/SM/CL/GM 40:40‐x:20:x to obtain mixed membranes with separate liquid‐disordered (Ld) and ganglioside (GM) containing liquid‐ordered (Lo) domains. With increasing GM concentration, fluorescence intensities increased and excitation maximum shifted to the red. Deconvolution of the spectra confirmed that these changes originate from a migration of the flipper probes from Ld to Lo domains upon binding to the gangliosides and thus the planarization in the more ordered environment. Control mechanophores without boronic acids failed to show the same response, and fructose partially inhibited the ganglioside sensitivity. These results demonstrate that it is possible to selectively accumulate mechanosensitive flipper probes in Lo domains and, more generally, that probe localization in complex membranes is possible and matters.

Section: Resultsmentioning

confidence: 99%

Ganglioside‐Selective Mechanosensitive Fluorescent Membrane Probes

Straková

Soleimanpour

Diez-Castellnou

et al. 2018

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“…In the following, we answer the question which regioisomer is preferentially formed, show that fast intramolecular rearrangements influence the result, explain why this detailed question is of general interest, and apply the lessons learned to 3-alkyl-1,2diselenolanes. Recent progress with chalcogen bonding research [23] [24] confirmed that this shift of attention from sulfur to selenium is not a simple extension. Because of the longer SeÀ Se and SeÀ C bonds, ring tension from lone pair repulsion and losses of hyperconjugation are less pronounced in 1,2-diselenolanes than in 1,2-dithiolanes.…”

mentioning

confidence: 99%

The Opening of 1,2‐Dithiolanes and 1,2‐Diselenolanes: Regioselectivity, Rearrangements, and Consequences for Poly(disulfide)s, Cellular Uptake and Pyruvate Dehydrogenase Complexes

Laurent

Sakai

Matile

2019

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

“…They have been studied extensively in crystal engineering and for intramolecular conformational control in solution, including prominent use in medicinal chemistry and pioneering applications in covalent catalysis . The use of intermolecular chalcogen bonds in functional systems in solution is rare and recent, non‐covalent chalcogen‐bonding catalysis has been introduced only last year. [ ][ ][ ] The key to success was the idea that the somewhat awkwardly ‘hidden’ position of the σ holes on the side of chalcogen‐bond donors turns into an advantage as soon as transition‐state recognition in the focal point of two adjacent donors is considered .…”

Section: Methodsmentioning

confidence: 99%

Chalcogen‐Bonding Catalysis: From Neutral to Cationic Benzodiselenazole Scaffolds

Benz

Besnard

Matile

2018

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Benzodiselenazoles (BDS) are emerging as privileged structures for chalcogen‐bonding catalysis in the focal point of conformationally immobilized σ holes on strong selenium donors in a neutral scaffold. Whereas much attention has been devoted to work out the advantages of selenium compared to the less polarizable sulfur donors, high expectations concerning bidentate, rigid, and neutral scaffolds have been generated with little experimental support. Here we report design, synthesis and evaluation of the necessary catalysts to confirm that i) bidentate BDS are more effective than their monodentate analogs, ii) conformationally immobilized scaffolds are more effective than more flexible ones, iii) cationic BDS scaffolds are more effective than neutral ones, and iv) in dicationic‐bidentate BDS, contributions from chalcogen‐bonding dominate possible contributions from ion‐pairing catalysis. These conclusions result from rate enhancements found for a Ritter‐type anion‐binding reaction and an X‐ray crystal structure of dicationic BDS with a triflate anion bound with highest precision in the focal point of the σ holes.