We are interested in designing and synthesising organic molecules to investigate the basis of catalysis, and to apply these principles to designing our own, artificial catalysts. This means that we design and make model compounds that have particular interactions, then study them mechanistically to evaluate the effect of that interaction. This approach is also applied to biological catalysts, to dissect and quantify the most important features that are involved in making them so efficient. Perhaps the most challenging is to apply our understanding to design new artificial catalysts based on these principles that we have been discovering. We have been particularly successful in creating metal ion complexes that are highly reactive under mild conditions, and are working on developing a deeper understanding of their properties, and how we can improve them.
The focus of this project will be to disentangle the key features that lead to efficient catalysis of phosphate ester cleavage. It will involve a series of diverse applications ranging from synthetic preparation of modified recognition moieties, characterisation of the assembly of secondary structure, and reaction mechanism investigations that will provide a full insight into all aspects of creating an artificial catalyst that is conceptually based on natural systems.
The aim is to generate a reaction centre that is reactive enough to catalyse the cleavage of natural phosphate di-ester substrates at a practical rate in vivo. Most ambitiously, we would like to harness the intrinsic recognition features of the targets to help achieve and control this activity. To manage this, we need to dissect and quantify the effect of different local features on the activity of metal ion complexes, and to explore the impact that catalysis has on the transition state. We will test the impact of introducing substitutions which allow delivery of specific local solvating groups that can enhance the intrinsic reactivity of the system. This polyfunctional behaviour mimics active sites; it will be important to explore a range of structures to be able to dissect the contributions of several (possibly competing) interactions. We will also probe how these interactions affect the transition state so that we can simultaneously assay for activity with a close analogue of RNA and explore how the transition state varies through the charge development at the leaving group.
The candidate will have a degree that qualifies them for PhD study and which should involve a substantial experience of chemistry. The candidate should be interested in understanding how chemical reactions work, and be interested in designing and making organic compounds which help us achieve that for the phosphate reactions we are interested in. They will also be interested in designing and carrying out mechanistic experiments to discover how the compounds behave, and in interpreting the results mechanistically. Well qualified candidates who are interested in these aspects of organic chemistry, biological chemistry, supramolecular chemistry or physical organic chemistry will be suitable.
Funding Notes
You should have, or expect to achieve, a first class or upper second class MChem or MSc degree in a relevant subject.
If you have the correct qualifications and access to your own funding, either from your home country or your own finances, your application to work with this supervisor will be considered.
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