Probing Catalysis by Hydrogen Bonds

氢键探测催化

• 批准号: 6466268
• 负责人: Eric V. Anslyn
• 金额: $ 25.16万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6466268
• 关键词: Schiff bases; acidity /alkalinity; catalyst; chemical conjugate; chemical kinetics; chemical structure function; chemical synthesis; enzyme activity; enzyme mechanism; enzyme model; enzyme substrate complex; ethers; hydrogen bond; intermolecular interaction; isomerase; metal complex; model design /development; molecular shape; phosphopyruvate hydratase; protonation; statistics /biometry; synthetic protein; thermodynamics

DESCRIPTION (provided by applicant): Enzymes often use hydrogen-bonding interactions and general-acid catalysis as part of their catalytic machinery. The two effects are similar, but distinctly different. In simple hydrogen-bonding catalysis, the proton is not transferred, while in general-acid catalysis the proton is transferred. Although proton transfer is one of the simplest reactions, how these two forms of catalysis function still has facets that are under debate. In this proposal we explore how these two forms of catalysis are influenced by hydrogen bond geometry, solvation, and differences in acidity of the donor. This is first done within the context of a D/H scrambling experiment where the hydrogen-bonding interaction is relevant to the debate about low barrier hydrogen bonds (LBHBs). Our interpretation of the theory of LBHB catalysis is that very steep Bronsted plots should be evident. Our second study is oriented at determining how hydrogen bonds and metal coordinations influence carbon acidity. We will use synthetic mimics of enolase and racemase enzymes to quantitate the stabilization imparted to enolates, and then measure their ability to increase the acidity of the enolate's conjugate acids. Our last study of hydrogen-bonding and general-acid catalysis involves quantitating the ability of imidazoliums, ammoniums, and guanidiniums to catalyze a phosphoryl transfer reaction. Enzymes commonly use these functional groups, but their role, as hydrogen-bonding or as general-acid catalysts have not been deciphered. In all these projects described herein, we will use physical organic and molecular recognition techniques to probe aspects of catalysis. We have carefully chosen problems where model studies such as those presented herein can answer the questions, while the literature studies on the enzymes themselves have only lead to further debate.

描述（由申请人提供）：酶经常使用氢键 相互作用和一般酸催化是其催化机械的一部分。 这两个效果相似，但截然不同。简单 氢键结催化，质子未转移 一般 - 酸催化质子被转移。虽然质子转移是 最简单的反应之一，这两种形式的催化功能如何仍然 有正在辩论的方面。 在此提案中，我们探讨了这两种形式的催化如何受到 氢键的几何形状，溶剂化和供体酸度的差异。 这首先是在D/H争夺实验的背景下完成的 氢键相互作用与关于低障碍的争论有关 氢键（LBHB）。我们对LBHB催化理论的解释是 那个非常陡峭的布朗斯特地块应该很明显。我们的第二项研究是定向的 在确定氢键和金属配位如何影响碳时 酸度。我们将使用烯醇酶和种族酶的合成模仿来 量化赋予体能的稳定性，然后测量其 能够增加烯烃缀合酸的酸度。我们的最后一个 氢键和一般酸催化的研究涉及定量 咪唑，铵和鸟嘌呤的能力催化磷酸 转移反应。酶通常使用这些功能组，但 角色，作为氢键或作为一般酸催化剂的作用 解密。 在本文所述的所有这些项目中，我们将使用物理有机和 分子识别技术，用于探测催化的方面。我们有 精心选择的问题，例如在此提出的模型研究中 可以回答问题，而文献研究酶 自己只会导致进一步的辩论。