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

本项目将采用蝴蝶结腔安排进行高灵敏度的连续波偏振气相和溶液相样品。连续流动的溶液相微流体装置的发展也将促进对映体选择性吸附机制的研究，如磁铁矿，纯手性石英，蛭石粘土的物质的表面上。这种选择性吸附和由此产生的手性放大已被假定为生物分子同手性的潜在来源。相应地，他们的研究有助于揭示地球上生命化学物质进化的新见解。腔增强技术提供的更高灵敏度允许对具有小幅度旋光度的构象柔性分子进行详细分析。氨基酸是这种分子的很好的例子，并且非常感兴趣，不仅用于探测生命的进化，而且用于理解我们体内在细胞水平上发生的化学反应。观察到的氨基酸的旋光度将根据其电荷状态以及其聚集状态而变化，即，无论其以单体或聚合物形式存在。使用上述实验装置，该项目将寻求量化现象的起源，例如Clough-Lutz-Jirgensons规则，该规则描述了氨基酸的旋光度随pH值的变化，以及观察到的某些氨基酸的非线性旋光度，其起源被认为是在溶液中的二聚化过程中。为了补充里奇小组采用的基于激光的方法，该项目还将分别利用牛津大学鲍德温和图小组的NMR和计算专业知识。利用定量核磁共振实验将揭示所研究样品的基本溶液组成，而理论分析需要确定每个分子种类的旋光度的构象依赖性。除了这种有前途的技术的生物应用外，本计画亦将探讨光腔衰荡旋光术在真实的应用。时间分析和表征工业和合成相关的反应，其中手性底物被消耗和破坏。考虑到无机和有机化学中不对称合成方法的普遍性，以及催化过程中对手性选择性的需求不断增加，该技术提供的实时，非破坏性分析在物理和生命科学中具有相关性。还将研究含有手性底物的反应的动力学。总之，该项目的总体目标是采用腔增强偏振技术的研究，表征和合理化的光学活性物质和反应的气体和溶液相。从上述概述中可以明显看出，这项工作福尔斯属于EPSRC的医疗保健技术和物理科学的广泛研究主题，此外，还包括发展物理和数学科学强国的相应战略重点，以及通过更好地理解人类生物学的分子复杂性来改造健康和医疗保健。

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.