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Synthetic Supramolecular Systems at Work

English title Synthetic Supramolecular Systems at Work
Applicant Matile Stefan
Number 204175
Funding scheme Project funding
Research institution Département de Chimie Organique Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Organic Chemistry
Start/End 01.10.2021 - 30.09.2025
Approved amount 1'680'000.00
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Keywords (8)

Mechanochemistry; Lipid Bilayer Membranes; Unorthodox interactions; Supramolecular Catalysis; Dynamic Covalent Exchange; Cellular Uptake; Fluorescent Membrane Tension Probes; Multistep Organic Synthesis

Lay Summary (French)

Lead
Utiliser de nouvelles façons d'entrer en contact au niveau moléculaire promet des solutions innovatrices aux défis importants en chimie, science et société. Avec cette vision, des outils chimiques seront créés pour réaliser des réactions difficiles, pour visualiser les forces physiques en biologie et pour gérer l’entrée dans les cellules.
Lay summary

Offrir aux molécules de nouvelles façons d'entrer en contact permet l'accès à de nouvelles structures et activités qui, à leur tour, peuvent ouvrir de nouvelles approches à d’importants défis. Ce paradigme émergeant sera développé autour de trois thèmes. Le premier concerne des transformations moléculaires. L'accent est mis sur l'intégration de contacts moléculaires innovants dans des systèmes catalytiques de plus en plus sophistiqués, tels que des membranes lipidiques ou des nanotubes de carbone sur des électrodes. Cela promet un accès facilité à des réactions autrement impossibles et riches en régio- et stéréochimie, jusqu’à, par exemple, l'autocatalyse asymétrique de cyclisations en cascade des polyéthers. Le deuxième thème se concentre sur des outils mécanochimiques pour l’imagerie microscopique des forces physiques. La sensibilité aux forces de compression est complémentée par celle d'étirement. Ces nouveaux outils chimiques sont difficiles à construire et répondent à une forte demande des sciences de la vie et des matériaux. Le troisième thème tourne autour de l’entrée dans les cellules, un obstacle persistant en biologie et médecine. De manière générale, la capacité à créer de nouvelles molécules est d'une importance fondamentale en chimie organique, centrale notamment pour l'économie suisse. Le potentiel de la chimie supramoléculaire translationnelle dans la synthèse organique est peu exploité et promet d’avancer ce domaine si utile pour notre société.

Direct link to Lay Summary Last update: 01.10.2021

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
185898 NCCR Chemical Biology - Visualisation and Control of Biological Processes Using Chemistry (phase III) 01.12.2018 National Centres of Competence in Research (NCCRs)
175486 Synthetic Biosupramolecular Systems at Work 01.10.2017 Project funding
182895 NCCR MSE: Molecular Systems Engineering (phase II) 01.07.2018 National Centres of Competence in Research (NCCRs)

Abstract

The objective of this research is to create synthetic supramolecular systems with significant functions. The general expectation is that introducing new ways to get into contact on the molecular level will provide access to new structures and functions that ultimately will allow us to address scientific and societal challenges that are otherwise beyond reach. The general themes of current interest are:Theme 1: Systems catalysis with unorthodox interactions Theme 2: Fluorescent probes to image physical forces in biologyTheme 3: Expansion and inhibition of thiol-mediated uptakeTheme 1 builds on the introduction of catalysis with anion-p interactions, chalcogen bonds and pnictogen bonds by this group. The next milestone will be to integrate the realized unorthodox catalysts into catalytic systems. Systems of interest are p-materials, proteins, and lipid bilayer membranes. Initial focus with catalytic p-systems, for instance, will be on non-covalent interfacers for primary anion-p catalysis of polyether cascade cyclization on carbon nanotubes and related giant, polarizable aromatics. The resulting “substrate-binding sites” should open the door to p-systems on conducting surfaces, in flow reactors, also for voltage-gated anion-p catalysis and, perhaps, automation. The envisioned new reactivities include control over the Baldwin rules or Soai-like asymmetric anion-p autocatalysis. Deliverables for Theme 1 include catalytic systems that integrate unorthodox interactions and exhibit emergent properties that are not accessible with the respective small-molecule catalysts.Theme 2 builds on fluorescent flipper probes to image physical forces in biology that have been introduced, and commercialized, by this group. Upcoming milestones include targeted release and selective excitation of the original probes, heteroatom permutations, the most demanding functionalization in the core to pull rather than press, and the search for completely new scaffolds. Deliverables are flippers that enable the biology community to image membrane tension changes with engineered (e.g. photocleavable) original flippers in any membrane of interest, and the exploration of new systems (e.g., X-bridged (X = sulfonimines, phosphole oxides, diketophosphepines) and core-substituted flippers, Kyoto FLAPers).Theme 3 builds on CPDs (cell-penetrating poly(disulfide)s) and COCs (cyclic oligochalcogenides) introduced by this group to initiate or inhibit thiol-mediated uptake into cells. Upcoming milestones include increasingly extreme COC chemistry and amplification of the best COCs in oligo-COCs along modular peptide scaffolds or spaced by molecular rulers. Further topics of interest include adaptive networks, templated ring-opening polymerization, molecular walkers, metallo-COCs, phosphorothioate DNA and target identification. Deliverables for Theme 3 include new delivery agents, potential antivirals (also SARS-CoV-2) - and new, adventurous COC chemistry.
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