FSE Bicentenary PhD Catalysis-driven molecular machinery at Manchester

About the Project

A recent series of breakthroughs (Nature 604, 80 (2022), Nat. Chem. 14, 728 (2022), J. Am. Chem. Soc. 146, 4467 (2024)) from the Leigh group demonstrate how directionally biased dynamics of molecular components can be continuously and repetitively powered by catalysis – the same mode of operation that powers motor proteins and all other machinery in the cell. In this project, we will expand on these recent findings and make molecular ratchets with new structures and chemistries that undergo directional dynamics by catalysing the fuel-to-waste reaction of different types of chemical substrates.

We shall investigate a range of systems designed to undergo directionally biased dynamics about various C-N, C-C or N-N bonds by catalysing carbodiimide hydration and other chemical transformations. We shall vary the motor-molecule structures to include or exclude power strokes (by incorporating chirality into the motor-molecule at positions where ‘matching’ of the motor chirality with the fuel chirality accelerates reaction of particular conformations of the motor) and investigate the effects of power strokes on motor performance.

We shall introduce and investigate new chemistries for molecular motors, including motors based on catalytic Mitsunobu, Swern and Wittig chemistry. Different chemistries offer the potential to produce motor-molecules with different intrinsic amounts of force that can be generated and have different motor efficiencies. The studies will serve to establish the fundamental requirements for catalysis-driven directionally biased molecular dynamics, and demonstrate how known catalytic cycles may be adapted to drive directional rotation.

The transduction of chemical energy to directionality is the fundamental process that powers biology. We envisaged that the project outputs will provide insights into how this happens how similar processes can be used to power molecular nanotechnology.

For more information and to apply visit https://www.findaphd.com/phds/project/fse-bicentenary-phd-catalysis-driven-molecular-machinery/?p178773

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