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

该项目将采用蝴蝶结空腔布置，对气相和溶液相样品进行高灵敏度的连续波偏振测量。连续流动溶液相微流控装置的发展也将有助于研究对映选择性吸附在磁铁矿、均手性石英和蛭石粘土等物质表面的机理。这种选择性吸附和由此产生的手性放大被认为是生物分子均一性的潜在来源。相应地，他们的研究可能有助于揭示地球上生命化学物质的进化。空穴增强技术提供的更高的灵敏度允许对具有小量级光学旋转的构象柔性分子进行详细分析。氨基酸就是这类分子的一个很好的例子，不仅对探索生命的进化有极大的兴趣，而且对在细胞水平上理解我们体内发生的化学物质也很有兴趣。观察到的氨基酸的旋光度取决于它的电荷状态以及它的聚集状态，即它是以单体形式还是以聚合物形式存在。利用上面详述的实验装置，该项目将寻求量化诸如Clough-Lutz-Jirgensons规则等现象的起源，该规则描述了氨基酸的旋光度随pH的变化，以及对某些氨基酸观察到的非线性旋光度，其根源被认为存在于溶液中的二聚化过程。为了补充Ritchie小组采用的基于激光的方法，该项目还将利用牛津大学Baldwin和Tew小组分别拥有的核磁共振和计算专业知识。利用定量的核磁共振实验将阐明被研究样品的潜在溶液组成，而需要理论分析来确定每个分子物种的旋光度的构象依赖关系。除了这项前景光明的技术的生物学应用外，该项目还将研究腔衰荡偏振在工业和合成相关反应的实时分析和表征中的应用，在这些反应中，手性底物被消耗和破坏。考虑到不对称合成方法学在无机化学和有机化学中的流行，以及催化过程中对手性选择性的日益增长的需求，该技术提供的实时、非破坏性分析在物理科学和生命科学中具有重要意义。还将研究含手性底物的反应动力学。总而言之，该项目的总体目标是在研究中使用腔增强型偏振技术，对光学活性物质以及气相和溶液相的反应进行表征和合理化。从上面的概要可以看出，这项工作属于EPSRC关于医疗保健技术和物理科学的广泛研究主题，此外还有相应的战略优先事项，即发展物理和数学科学强国，以及通过更好地了解支配人类生物学的分子复杂性来实现健康和医疗保健的转型。

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.