Synthetic organic chemistry @ Queen's University, Belfast
We are an organic chemistry research group, interested in using synthesis as a tool to investigate and solve problems. Central to this research is the concept of molecular recognition; by understanding and controlling the interactions between molecules we can design catalysts, sensors and therapeutics in a targeted manner.
Selective, catalytic synthesis is vitally import to society, reducing the waste and energy requirements for the production of complex molecules and intermediates.
In general, asymmetric synthesis requires the formation of diastereomeric transition states that differ in energy sufficiently to give a bias towards a single enantiomeric product. One strategy to achieve this is by exploiting ion-pairing interactions between a charged, prochiral reaction intermediate and a homochiral catalyst ion bearing a complementary charge. The catalyst thus directs facial selectivity in the subsequent reaction, leading to enantioselectivity in the process overall. However, despite decades of research in this area, the range of available catalysts is limited.
In the Knipe lab we are interested in developing new chiral scaffolds that will direct asymmetry in such processes, and in discovering new catalytic reactions that are amenable to this strategic approach.
We are also interested in developing multifunctional catalysts to access new modes of reactivity and levels of selectivity.
Nature achieves its exquisite levels of selectivity and efficiency through a modular approach to synthesis: with just a few key building blocks (amino acids, nucleic acids and carbohydrates) it achieves a range of function that spans all of biology. In the context of proteins, this reactivity is made possible by the flexibility of these oligomers to adopt an almost infinite number of three-dimensional structures. In combination with evolutionary pressure and a timescale of aeons this leads to high levels of activity, despite the relatively limited 'alphabet' of catalytically-active proteinogenic amino acids.
In the Knipe group we seek to emulate Nature's strategy for functional molecules by developing un-natural folded, oligomeric molecules ('foldamers') that are imbued with a range of functions including: (i) catalytic activity; (ii) stimulus response/sensory activity and (iii) complementarity to protein surfaces for chemical biology applications.