Understanding Phosphoryl Transfer through Physical Organic Chemistry

The transfer of phosphate groups is at the heart of many biological processes. However, unless it is catalysed, they are among the slowest known biochemical reactions. To understand how biological catalysts manage to acclerate these reactions so efficiently requires an insight into the transition state structure - this is the species that must be stabilised to allow the reaction to proceed rapidly. We have defined some of the background characteristics of closely relevant phosphate esters, and need to extend these studies to reveal more detail. Then, using model systems, we shall investigate how specific interactions speed up the reaction and how they affect the probes we use to characterise the transition state. These studies will inform the interpretation of structural and kinetic data of biological catalysts, and help direct the design of more effective artificial catalysts that can be used within a biological context. Such catalysts have valuable potential as robust tools for use in molecular biology, particularly in manipulating DNA if they can be made efficient enough. The same approach and modifications shall be made with Zn based complexes that are already effective for cleaving RNA model compounds; the models will aid their development, and the analysis will establish where to focus further improvements.