A Skeletal Editing Approach to Silicon-Switch Molecules

Summary

A fully funded 3.5-year combined synthetic/digital chemistry PhD studentship. The project will be ideally suited to anybody wanting to further develop their synthetic chemistry skills alongside valuable modern techniques including machine learning/AI, automation, and cheminformatics.

Background

Replacing a carbon atom with a silicon atom to develop a new drug molecule is known as a “silicon-switch”, and this approach has been used to increase potency and lifetime in bioactive molecules.^1,2 While conceptually simple, to access these molecules is synthetically challenging, with no general way to directly transform a carbon atom to a silicon atom in a molecule. Skeletal editing is an approach that has simplified such transformations, with many examples of single-atom transformations,^3-5 yet there is no equivalent reactivity reported for silicon.

This studentship will combine transition metal catalysis and digital chemistry to afford the first carbon-to-silicon skeletal editing reaction. The successful candidate will develop their synthetic chemistry skills, gaining valuable experience in handling air/moisture-sensitive chemicals, and analytical techniques such as NMR spectroscopy and X-ray diffraction. Alongside this, the successful candidate will be trained in modern digital chemistry techniques (quantum mechanics/DFT, AI/machine learning, and cheminformatics) to accelerate reaction discovery and optimisation. With access to the Continuum Flow Laboratory at Heriot-Watt University, the successful PhD student will be able to gain hands-on experience with flow and automation technologies.

For informal inquiries, please contact Dr Dominic Willcox ([email protected]).