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

Introduction

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.

Limitations of Current Methods

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.

Project Aim

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.

Methodology

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.

1. I will first characterise how different molecular constituents (un)favour diradical formation on isolated molecules.
2. 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.

Expected Outcomes

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.

Conclusion

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.