RUI: Solvent Effects on Organic Reactions

RUI：溶剂对有机反应的影响

• 批准号: 0307260
• 负责人: Steven Bachrach
• 金额: $ 26.53万
• 依托单位: Trinity University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0307260&HistoricalAwards=false
• 关键词: RUI; Solvent; Effects; Organic; Reactions

With the support of the Organic Dynamics Program in the Chemistry Division, Professor Steven M. Bachrach at Trinity University will explore computational approaches towards incorporating the effects of solvents within quantum mechanical calculations of organic reactions. Modern computational techniques have become quite reliable in predicting gas phase properties; however, much of chemistry and all of biochemistry occurs within a solvent. In this proposal, Professor Bachrach will examine a number of different approaches towards accounting for solvation, including continuum fields and explicit consideration of a small number of solvent molecules. These techniques will be applied to a number of important chemical problems. Nucleophilic substitution at sulfur and selenium is critical for the activation of some novel anti-tumor and antibiotic agents. Gas phase studies suggest an addition-elimination mechanism, so these studies will be extended to determine the mechanism in the more biologically relevant aqueous environment. In particular, the activation step for the powerful anti-tumor agent calichaemicin and the antibiotic leinamycin will be examined with the hope that mechanistic insight may help to create more effective analogues with better pharmacokinetic properties. Hydrogen bonding solvents that will activate carbonyl species used in the Diels-Alder reaction will be examined. And, finally, solution NMR experiments will be used as an alternate approach to addressing the strength of aromaticity, which remains one of the cornerstone principles of organic chemistry. The principal broader aim of the proposal is to train undergraduate students in the science of computational chemistry and to motivate these students towards a career in the sciences. The Organic and Macromolecular Chemistry Program in the Chemistry Division supports Professor Steven M. Bachrach who will undertake the project at Trinity University, which has a long history of attracting undergraduate students to the research program, including many women and students of Hispanic origin, groups that have been underrepresented in the sciences. Professor Bachrach will expose these students to the challenges, excitement and opportunities for careers in chemistry. Another societal benefit that may develop from the proposed research is added insight toward the activation of some novel antitumor and antibiotic agents. Greater understanding of how these compounds are "turned on" can provide guidance towards developing analogues that may serve as new drug treatments.

在化学系有机动力学项目的支持下，史蒂文·M·Trinity大学的Bachrach将探索将溶剂效应纳入有机反应量子力学计算的计算方法。现代计算技术在预测气相性质方面已经变得相当可靠;然而，大部分化学和所有生物化学都发生在溶剂中。在本提案中，Bachrach教授将研究多种不同的溶剂化方法，包括连续场和对少量溶剂分子的明确考虑。这些技术将应用于许多重要的化学问题。硫原子和硒原子上的亲核取代对于一些新的抗肿瘤和抗生素的活化是至关重要的。气相研究表明，添加-消除机制，因此这些研究将扩展到确定更多的生物相关的水环境中的机制。特别是，强大的抗肿瘤剂calichaemicin和抗生素雷那霉素的活化步骤将进行检查，希望机制的洞察力可能有助于创造更有效的类似物具有更好的药代动力学特性。将检查将活化在Diels-Alder反应中使用的羰基物种的氢键溶剂。最后，溶液NMR实验将被用作解决芳香性强度的替代方法，这仍然是有机化学的基石原则之一。该提案的主要更广泛的目标是培养计算化学科学的本科生，并激励这些学生从事科学事业。化学系的有机和高分子化学项目支持Steven M. Bachrach将在Trinity大学开展该项目，该大学在吸引本科生参加研究项目方面有着悠久的历史，其中包括许多女性和西班牙裔学生，这些群体在科学领域的代表性不足。Bachrach教授将让这些学生接触化学职业的挑战、兴奋和机会。从拟议的研究中可能产生的另一个社会效益是对一些新型抗肿瘤和抗生素药物的激活增加了洞察力。更好地了解这些化合物是如何“打开”的，可以为开发可能作为新药治疗的类似物提供指导。