EAGER: Three-wave mixing techniques to study and utilize nuclear quadrupole coupling effects in chiral molecules

自然界中的许多分子，特别是生物分子，在它们的几何结构中表现出惯用的手性。这就是说，两个分子可以有相同的原子数量、种类和几何排列，但它们是彼此的镜像，就像一个人的左手和右手一样。化学中的这种“惯用手”被称为“手性”。在化学测量中，区分“手”--也就是所谓的对映体--并量化每一种对映体的数量可能是一项艰巨的技术挑战。这一困难可能会限制我们合成和分离给定对映体的能力。在这个由化学系化学结构、动力学和机理(CSDM-A)和化学测量和成像(CMI)计划资助的项目中，密苏里科技大学的加里·格拉布斯二世教授正在使用先进的微波光谱技术来确定样品中存在的对映体的类型和浓度。微波光谱学基于微波辐射使分子结构旋转的速度来提供有关分子结构的信息。格拉布斯教授假设，如果一个分子含有一个非常重的原子，如溴或碘，就可以确定该分子的“惯用手”。这些重原子的原子核包含电荷的排列，这可以使整个分子的旋转在微波实验中比在其他情况下更能揭示其结构。如果格拉布斯教授的假设是正确的，那么可能会有新的途径来更快、更准确地合成和监测手性体系，这对制药研究特别重要。该项目还利用最先进的仪器设计和新的量子理论发展，在目前尚未探索的物理化学领域培训研究生。该项目的重点是利用最近在手性系统中发现的微波三波混频对核电四极耦合相互作用。这些实验的目的是首次为鉴定和量化混合物中对映体物种的基于核自旋的方法建立实验数据和理论理解。微波三波混频涉及利用旋转跃迁，包括沿两个分子轴的激发，同时沿第三个轴进行检测，创建非常类似于三能级脉泽系统的闭合跃迁能量路径。当非对角线核电四极相互作用在分子旋转常数的数量级上并且遵循相同的闭环路径时，发生电偶极禁止的四极促进的跃迁。然后利用微波三波混频，因为这项技术对相位而不是传统微波光谱学的能量敏感，允许首次在单个实验中确定非对角线符号，并深入了解所讨论的对映体。用同位素替代光谱分析验证了实验结果的准确性。除了技术和教育方面的影响外，这项研究还可以扩大微波光谱仪提供的分子信息的范围。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Many molecules in nature, particularly biological molecules, exhibit a handedness in their geometric structure. This is to say two molecules can have the same number and kinds of atoms and geometric arrangement, but they are mirror images of each other, as are one's left and right hands. This "handedness" in chemistry is referred to as "chirality." In chemical measurements, distinguishing between the "hands"- known as enantiomers- and quantifying the amounts of each can be a difficult technological challenge. This difficulty can limit our ability to synthesize and separate a given enantiomer. In this project, funded by the Chemical Structure, Dynamics, and Mechanism (CSDM-A) and Chemical Measurement and Imaging (CMI) Programs of the Chemistry Division, Professor Garry Grubbs II of the Missouri University of Science and Technology is using advanced microwave spectroscopy techniques to determine the type and concentration of enantiomers present in a sample. Microwave spectroscopy provides information about molecular structure based on how fast they can be made to rotate by the microwave radiation. Professor Grubbs hypothesizes that "handedness" of a molecule can be determined if that molecule contains a very heavy atom like bromine or iodine. The nuclei of these heavy atoms contain arrangements of electrical charge that can make the rotations of the overall molecule reveal more about its structure in a microwave experiment than it would otherwise. If Professor Grubbs' hypothesis is correct, there may be new paths toward faster and more accurate synthesis and monitoring of chiral systems, which is particularly important to pharmaceutical research. The project is also training graduate students in currently unexplored areas of physical chemistry using state-of-the-art instrument design as well as new quantum theory development.This project focuses on utilizing the recent discovery of microwave three-wave mixing in chiral systems on nuclear electric quadrupole coupling interactions. These experiments are designed to establish, for the first time, experimental data and theoretical understanding for nuclear spin-based methodologies for identifying and quantifying enantiomeric species in mixtures. Microwave three-wave mixing involves utilizing rotational transitions involving excitation along two molecular axes while detecting along the third axis, creating closed-loop transition energy pathways very similar to a three-level maser system. Electric dipole-forbidden, quadrupole-facilitated transitions occur when off-diagonal nuclear electric quadrupole interactions are on the order of the molecular rotation constants and follow the same closed-loop pathway. These are then leveraged using microwave three-wave mixing because of the technique's sensitivity to phase rather than energy of traditional microwave spectroscopy, allowing for the determination of the off-diagonal sign in a singular experiment for the first time as well as insight into the enantiomer in question. Isotopic substitution spectra analysis are then used to validate the veracity of the experimental results. In addition to the technological and educational impacts, this research may expand the reach of, and molecular information offered from, microwave spectroscopy.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.