Receptor Mediated Circular Dichroism Spectroscopy

受体介导的圆二色光谱

• 批准号: 1213759
• 负责人: Babak Borhan
• 金额: $ 50.55万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1213759&HistoricalAwards=false
• 关键词: Receptor; Mediated; Circular; Dichroism; Spectroscopy

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.

有了这个奖项，化学结构，动力学和机制计划正在支持Babak Borhan教授（密歇根州立大学）在手性光谱领域的研究。 在先前的NSF CAREER资助下，他的实验室已经证明卟啉镊子（通过烷基连接体连接的两个金属卟啉）可以作为手性客体分子的主体系统，在络合后导致可观察到的圆二色性（CD）光谱。 所得的光谱很容易被破译，以提取结合的手性客体分子的立体化学信息。 优点是该方法在分配相互作用卟啉的螺旋度时是非经验性的，它本质上是微尺度的，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，并且在几分钟内提供答案。 未来的工作将集中在扩大主机系统的剧目，使一个更大的子集的手性有机分子可以屈服于分析。 最重要的是，只有一个络合位点的客体分子（因此不能与镊子的两个卟啉络合）需要新的策略。 据推测，适当设计的假笼主体系统与复杂的分子，只含有一个连接位点的能力将主要采用P或M螺旋与手性客体基板相互作用后。 所得复合物是CD活性的，并将提供绝对立体化学分析所需的信息。 绝对立体化学测定的目标手性分子包括醇、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。 手性化合物家族是手性分子的一个大的子集，在有机合成、有机材料以及医药领域中有着广泛的应用。常规的、微型的、简单的、可靠的立体化学测定方法在化学和生物学的许多领域都是至关重要的，这使得大量的研究人员受益。 这里提出的研究的性质是跨学科的。 学生的训练将耦合化学合成与发色团的主机设计的基础上彻底了解分子和结构动力学。 学生还必须是熟练和知识渊博的光谱学家。 该提案也有适合成就较低的学生参与研究的内容。 在过去的十年里，该小组在密歇根州立大学组织和指导了项目种子计划。 继续招募、培训和科学地激励高中生将是重中之重。 本科生的培养也同样重要。