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Designing organic molecules as platforms for reversible charge-to-spin conversion with applications in chromophore optimisation and drug discovery

Project description

A closer look at radical transformation in chemistry and biology

Chemistry and biology hinge on the interactions of molecules governed by chemical bonds. When molecules possess unpaired electrons, they transform into radicals, altering their chemical and biological characteristics. However, the demanding methods for radical formation limit their application, constraining research potential. With this in mind, the ERC-funded RadicalProtON project aims to explore reversible diradical formation in organic molecules. By leveraging a structural pattern, molecules can convert their charge and spin, becoming diradicals. The project will investigate how different molecular components influence diradical formation and explore the role of diradicals in bioactive molecules. This research promises insights into fluorescent proteins and small molecule drugs, potentially reshaping research frontiers at the intersection of chemistry and biology.

Objective

Chemistry and Biology are governed by molecules and how they interact. Crucially, what glues a molecule together are chemical bonds, made from atoms pairing all their electrons. Although preferred, this is not the only option: in the comparatively rare cases where a molecule presents unpaired electrons, it acquires a fascinating new status that transforms its chemical and biological properties, best described by the acutely apt name of radical. Despite the extraordinary toolset found in radical-bearing molecules, the rather demanding methods to radical formation currently available mean that only very specific molecular architectures can withstand them, inadvertently limiting the scope of their applicability.

The aim of this ERC project is to show that reversible diradical formation upon deprotonation is prevalent, and yet unexplored, in general donor-acceptor organic molecules and use this new knowledge to develop novel design criteria in light-emitting molecules and drug discovery.

To achieve this unique aim, I will exploit a widespread structural pattern in a novel way, enabling a molecule to reversibly convert its charge and spin and become a diradical. I will first characterise how different molecular constituents (un)favour diradical formation on isolated molecules. I will then establish, for the first time, the role that diradicals play in defining the function of the numerous bioactive molecules sharing the proposed structural pattern.

By exposing the overlooked diradical character in general families of deprotonated organic molecules, I will deliver transformative mechanistic understanding on i) the photo physical properties of fluorescent proteins and ii) the reactivity of small molecule drugs, particularly a new class of covalent inhibitors. The field of organic radicals sits at a critical crossroads between Chemistry and Biology, and as such, taking it a step forward has the potential to cross-pollinate research fields and reshape research frontiers.

Fields of science (EuroSciVoc)

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Host institution

UNIVERSIDAD DEL PAIS VASCO/ EUSKAL HERRIKO UNIBERTSITATEA
Net EU contribution
€ 1 467 111,00
Address
BARRIO SARRIENA S N
48940 Leioa
Spain

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Region
Noreste País Vasco Gipuzkoa
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 467 111,25

Beneficiaries (2)