About the Project
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.
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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