Probing Catalysis by Hydrogen Bonds

氢键探测催化

• 批准号: 6726837
• 负责人: Eric V. Anslyn
• 金额: $ 22.5万
• 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/6726837
• 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）：酶通常使用氢键