Computational Methods for Selective Catalysis

 描述(申请人提供)：该研究计划的总体目标是开发和应用最先进的计算方法，在分子水平上了解立体选择性、化学选择性和反应性，目的是设计新的、更有效的试剂和催化剂。选择性和反应活性的控制是有效合成的基本特征，但我们对基本相互作用如何扰乱这些方面的分子水平的了解还只是初步的。该计划试图量化这些基本的相互作用，以解释观察到的结果，并在此基础上建立。除了开发改进的计算和分析工具外，还将编制一份入门读物，列出这些广泛的、基本的相互作用的流行度和强度。我们确定了三个总体目标。首先，过渡态计算将用于探索机制，了解控制元素，并量化基本相互作用。在第二部分中，将开发经验建模工具并用于确定控制反应性和选择性的关键控制因素。这些知识反过来又将目标1中的研究重点放在最重要的要素上。第三，概述了一种新的反应性实验测量方法，它是正在建立的相互作用初级读物的重要组成部分。相关性这一提议的基本标志是能够通过计算设计新的反应和催化剂，以高效和合理的方式构建重要的有机结构。新的合成方法极大地增加了进入未开发的化学空间的机会，导致了造福社会的材料和药品。为了实现这一目标，调查将侧重于更好地了解支配反应性和选择性的基本相互作用。这些相同的相互作用支配着生物系统，进一步的了解将使设计针对其他生物分子的酶抑制剂和制剂能够扰乱生物功能。参与这项提议的本科生、研究生和博士后研究人员将获得宝贵的培训。

 DESCRIPTION (provided by applicant): The overall objective of this research program is to develop and apply state-of-the-art computation methods to understand stereoselectivity, chemoselectivity, and reactivity at the molecular level with the aim of designing new, more effective reagents and catalysts. The control of selectivity and reactivity are essential features f efficient synthesis, yet our molecular level understanding of how fundamental interactions perturb these aspects is only rudimentary. This program seeks to quantitate these fundamental interactions to explain the observed results and to build on this foundation. In addition to developing improved computational and analytical tools, a primer will be constructed tabulating the prevalence and strength of these widespread, fundamental interactions. We have identified three overall goals. In the first, transition state calculations will be used to probe mechanism, understand control elements, and quantitate fundamental interactions. In the second, empirical modeling tools will be developed and used to identify the key control factors governing reactivity and selectivity. This knowledge, in turn, focuses the studies in aim 1 to the most important elements. In the third, a new experimental measure of reactivity is outlined, which is an important component of the interaction primer that is being built. Relevance The fundamental hallmark of this proposal is the ability to design new reactions and catalysts via computation to construct important organic structures in an efficient and rational manner. New synthetic methods greatly increase access to untapped chemical space, leading to materials and pharmaceuticals that benefit society. To achieve this goal, investigations will focus on obtaining an improved understanding of the fundamental interactions governing reactivity and selectivity. These same interactions govern biological systems, and further understanding will enable the design of enzymatic inhibitors and agents targeting other biomolecules to disrupt biological functions. Invaluable training will be afforded to undergraduate students, graduate students, and postdoctoral researchers involved in this proposal.