Solution Structures of Natural and Synthetic Chiral Oligomers and Polymers from Ab Initio Simulations of Raman Optical Activity Data

了解溶液中分子的三维结构对于理解它们的物理和化学性质是必不可少的。这对生命系统中发现的大分子如多肽、蛋白质和碳水化合物尤其重要；但对于聚合物技术和纳米技术等领域的大合成分子(超分子化学)的设计和应用也很重要。然而，结构化学和生物学中使用的核心技术，即晶体和纤维X射线衍射，不能应用于溶液；主要溶液技术，即核磁共振，其应用往往受到许多大分子在溶液中固有的灵活性的影响(尽管它对处于‘固定’折叠状态的蛋白质等非常有价值)。在拟议的研究中，新的拉曼光学活性(ROA)光谱技术将应用于这一问题。水(天然生物介质)中的大多数生物分子可以用ROA来研究，ROA是对其三维结构的一个尖锐的探头。ROA在这种情况下特别尖锐的原因之一是它对手性敏感，这意味着在右旋和左旋螺丝中，在分子结构中，手性是敏感的，这些分子拥有的一种特性。例如，蛋白质只由氨基酸的‘L对映体’而不是镜像的‘D-对映体’的多肽链构成，自然界中发现的碳水化合物几乎总是由‘D-对映体’而不是葡萄糖等碱性糖环的‘L对映体’构成。ROA的工作原理是通过一束激光穿过手性分子的溶液，并使用非常灵敏的仪器检测从样品散射的光中微小的右圆或左圆偏振成分。以光谱的形式呈现的ROA测量能够提供关于分子的结构和三维形状的有价值的新信息。RoA是我们格拉斯哥实验室的先驱，我们是这类光谱学的世界领先专家。直到最近，结构信息主要是通过将光谱模式与覆盖一系列先前确定的模型结构的分子光谱中观察到的光谱模式(通常来自晶体或纤维X射线衍射)进行比较来间接从ROA光谱中推断出来的。然而，由于从头算量子化学计算技术的发展，从理论上模拟各种可能的模型结构的ROA光谱成为可能，从而使直接从实验观察的光谱推导出详细的溶液结构成为可能。我们建议进一步发展这些计算技术，并通过模拟观察到的一系列寡肽和多肽、蛋白质和碳水化合物的ROA光谱来举例说明它们。一些合成的手性聚合物也将被研究，这些聚合物可能是纳米科学的结构和功能构建块(通常是受到生物大分子的同质性和功能的启发)。总体目标是开发通用方法，用于可靠地提取手性低聚物和聚合物的详细溶液结构和动态行为，包括天然和合成的。

Knowledge of the three-dimensional structures of molecules in solution is essential for understanding their physical and chemical properties. This is especially important for the large molecules such as peptides, proteins and carbohydrates found in living systems; but it is also important for the design and application of large synthetic molecules ('supramolecular chemistry') in areas such as polymer technology and nanotechnology. However, the core technique used in structural chemistry and biology, namely crystal and fibre X-ray diffraction, cannot be applied to solutions; and the application of the main solution technique, namely nuclear magnetic resonance (NMR), is often compromised by the intrinsic flexibility of many large molecules in solution (although it is immensely valuable for, inter alia, proteins in their 'fixed' folded states). In the proposed research, the novel spectroscopic technique of Raman optical activity (ROA) will be applied to this problem. Most biological molecules in water (the natural biological medium) may be studied using ROA, which is an incisive probe of their three-dimensional structure. One of the reasons for the special incisiveness of ROA in this situation is that it is sensitive to chirality, meaning handedness as in right- and left-handed screws, in molecular structure, a property possessed by these molecules. For example, proteins are constructed from polypeptide chains of exclusively the 'L-enantiomers' of amino acids rather than the mirror-image 'D-enantiomers', and carbohydrates found in nature are nearly always built from the 'D-enantiomers' rather than the 'L-enantiomers' of basic sugar rings such as glucose. ROA works by passing a laser light beam through a solution of the chiral molecules and detecting tiny right- or left-circularly polarized components in the light scattered away from the sample using very sensitive instruments. The ROA measurements, presented in the form of a spectrum, are able to provide valuable new information about the structure and three-dimensional shape of the molecule. ROA was pioneered in our Glasgow laboratory, and we are leading world experts in this type of spectroscopy. Until recently, structural information has mainly been deduced indirectly from ROA spectra by comparing spectral patterns with those observed in the spectra of molecules covering a range of previously determined model structures (usually from crystal or fibre X-ray diffraction). However, thanks to developments in 'ab initio' quantum-chemical computational techniques, it is becoming possible to simulate ROA spectra theoretically for various possible model structures, thereby enabling detailed solution structures to be deduced directly from experimentally observed spectra. We propose to further develop these computational techniques and exemplify them by simulating the observed ROA spectra of a range of oligo- and polypeptides, proteins and carbohydrates. Some synthetic chiral polymers, which are attracting much current interest as possible structural and functional building blocks for nanoscience (often inspired by the homochirality and function of biological macromolecules), will also be studied. The overall aim is to develop generic methods for the reliable extraction of detailed solution structures and dynamic behaviour of chiral oligomers and polymers, both natural and synthetic.