Developments and applications of cavity ring-down polarimetry for the detection and characterisation of optically active biological compounds.

This project will employ a bow-tie cavity arrangement to conduct high-sensitivity continuous-wave polarimetry on both gas- and solution-phase samples. The development of a continuous-flow solution-phase microfluidic setup will also facilitate the study of enantioselective adsorption mechanisms on the surfaces of substances such as magnetite, homochiral quartz, and vermiculite clays. This selective adsorption and the resulting chiral amplification have been posited as potential sources of biomolecular homochirality. Correspondingly, their study could help reveal new insights into the evolution of the chemicals of life on Earth.
The increased sensitivity afforded by cavity-enhanced techniques allows for the detailed analysis of conformationally flexible molecules possessing small-magnitude optical rotations. Amino acids are good examples of such molecules and are of extreme interest, not only for probing the evolution of life, but also for understanding the chemistry occurring within our bodies on a cellular level. The observed optical rotation of an amino acid will vary depending on its charge state, as well as its state of aggregation, i.e., whether it exists in monomeric or polymeric form. Using the experimental setup detailed above, this project will seek to quantify the origins of phenomena such as the Clough-Lutz-Jirgensons rule, which describes the variation of an amino acid's optical rotation with pH, in addition to non-linear optical rotations observed for certain amino acids, the origin of which is thought to lie in dimerization processes in solution. To compliment the laser-based methodologies employed in the Ritchie Group, this project will also leverage the NMR and computational expertise of the Baldwin and Tew groups at the University of Oxford, respectively. Utilisation of quantitative NMR experiments will shed light on the underlying solution composition of the samples under study, while theoretical analyses are required to determine the conformational dependence of the optical rotation of each molecular species.
In addition to the biological applications of this promising technique, this project will also investigate the utility of cavity ring-down polarimetry in real-time analysis and characterisation of industrially and synthetically relevant reactions in which chiral substrates are consumed and destroyed. Bearing in mind the prevalence of asymmetric synthetic methodologies in both Inorganic and Organic Chemistry, and the ever-increasing demand for chiral selectivity in catalytic processes, the real-time, non-destructive analysis that this technique provides has relevance across the Physical and Life Science. The dynamics of reactions containing chiral substrates will also be studied. In summary, the overall objective of this project is to employ cavity-enhanced polarimetric techniques in the study, characterisation and rationalisation of both optically-active substances and reactions across the gas and solution phases. As is evident from the above outline, this work falls within the EPSRC's broad research themes of healthcare technologies and the physical sciences, in addition to the corresponding strategic priorities of developing a physical and mathematical sciences powerhouse as well as the transformation of health and healthcare through greater understanding of the molecular complexity governing human biology.