Receptor Mediated Circular Dichroism Spectroscopy

通过这一奖项，化学结构、动力学和机制计划支持密歇根州立大学Babak Borhan教授在手性光谱学领域的研究。在NSF之前的职业资助下，他的实验室已经证明，卟啉镊子(通过烷基连接物连接的两个金属卟啉)可以作为手性客体分子的主体系统，这些客体分子在络合时会产生可观察到的圆二色(CD)光谱。得到的光谱很容易破译，以提取结合的手性客体分子的立体化学信息。其优点是，该方法在指定相互作用的卟啉的螺旋度方面是非经验性的，它在性质上是微尺度的，需要微克量的手性底物，它是非破坏性的(手性材料可以回收)，几乎没有准备工作，并且在几分钟内就能提供答案。未来的工作将集中在扩大宿主系统的指纹库，以便更大的手性有机分子子集可以屈从于分析。最重要的是，只有一个络合部位的客体分子(因此不能与镊子上的两个卟啉络合)需要一个新的策略。假设适当设计的伪笼宿主系统能够复合只包含一个结合位点的分子，当与手性客体底物相互作用时，将主要采用P或M螺旋度。生成的络合物是Cd活性的，并将提供绝对立体化学分析所需的信息。用于绝对立体化学测定的目标手性分子有醇、胺、二醇、二胺、环氧醇和羟基酮、饱和和不饱和杂环分子以及具有远程立体化学的分子，仅举几例。后者是手性分子的一个大子集，在有机合成、有机材料以及医药领域有着广泛的应用。一种常规的、微规模的、简单可靠的立体化学测定方法在许多化学和生物学领域都是至关重要的，这有利于后一领域的大量研究人员。这里提出的研究的性质是跨学科的。学生培训将基于对分子和结构动力学的透彻理解，将化学合成与发色主体的设计结合起来。学生还必须是精通和知识渊博的光谱学家。该提案还包含了一些适合成绩较差的学生参与研究的内容。在过去的十年里，该组织一直在密歇根州立大学组织和指导SEED项目。继续招收、培养和科学激励高中生将是当务之急。本科生的培养同样重要。

With this award, the Chemical Structure, Dynamics and Mechanisms Program is supporting the research of Professor Babak Borhan (Michigan State University) in the area of chiroptical spectroscopy. With prior NSF CAREER funding, his laboratory has shown that porphyrin tweezers (two metalloporphyrins linked via an alkyl linker) can serve as host systems for chiral guest molecules, which upon complexation lead to an observable circular dichroic (CD) spectrum. The resultant spectrum is easily deciphered to extract stereochemical information of the bound chiral guest molecule. The advantages are that the methodology is non-empirical in assignment of helicity for the interacting porphyrins, it is micro-scale in nature requiring microgram amounts of chiral substrate, it is non-destructive (chiral material can be recovered), has little prep work, and provides the answer in a matter of minutes. Future work will focus on expanding the repertoire of host systems such that a larger subset of chiral organic molecules can succumb to analysis. Most importantly, guest molecules that only have one site of complexation (thus cannot complex with both porphyrins of the tweezer) require a new strategy. It is hypothesized that appropriately designed pseudo-cage host systems with the ability to complex molecules that contain only one site of attachment will predominantly adopt either a P or M helicity upon interaction with chiral guest substrates. The resultant complex is CD active and will provide information required for analysis of absolute stereochemistry. The target chiral molecules for absolute stereochemical determinations are alcohols, amines, diols, diamines, epoxy alcohols, and hydroxy ketones, saturated and unsaturated heterocyclic molecules, and molecules with remote stereochemistry, to name a few. The latter list of compound families is a large subset of chiral molecules that serve as chiral pool reagents for numerous applications in organic synthesis, organic materials, and the medicinal and pharmaceutical arena.A routine, microscale, easy, and reliable method for stereochemical determinations is critical in many areas of chemistry and biology, benefiting a large number of researchers in the latter areas. The nature of the research proposed here is interdisciplinary. Student training will couple chemical synthesis with the design of chromophoric hosts based on a thorough understanding of molecular and structural dynamics. The students will also have to be proficient and knowledgeable spectroscopists. The proposal also has elements that are fit for less accomplished students to participate in research. For the past ten years, the group has organized and directed the Project SEED program at Michigan State University. Continuing to recruit, train, and scientifically stimulate high school students will be a top priority. The training of undergraduate students will be no less important.