Probing Catalysis by Hydrogen Bonds

描述（由申请人提供）：酶通常使用氢键 相互作用和一般的酸催化作为其催化机制的一部分。 这两种效果相似，但又明显不同。用简单 氢键催化，质子不转移，而在 一般酸催化质子转移。虽然质子转移是 最简单的反应之一，这两种形式的催化作用如何仍然发挥作用， 有很多方面还在讨论中 在这个提议中，我们探讨了这两种形式的催化作用是如何受到 氢键几何形状、溶剂化作用和供体酸度的差异。 这首先在D/H加扰实验的上下文中完成，其中 氢键相互作用与低势垒的争论有关 氢键（LBHbs）。我们对LBHB催化理论的解释是： 很陡的布朗斯台德曲线应该很明显我们的第二项研究是 在确定氢键和金属配位如何影响碳 酸度我们将使用烯醇化酶和消旋酶的合成模拟物， 定量赋予烯醇化物的稳定性，然后测量它们的 增加烯醇化物的共轭酸的酸度的能力。我们最后 氢键和一般酸催化的研究涉及定量 咪唑鎓、铵和胍鎓催化磷酰化反应的能力 转移反应酶通常使用这些官能团，但它们的 作用，作为氢键或作为一般的酸催化剂还没有被 解密 在本文描述的所有这些项目中，我们将使用物理有机和 分子识别技术来探测催化作用。我们有 仔细选择的问题，模型研究，如本文提出的 可以回答这些问题，而文献研究的酶 这只会引发进一步的争论。

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.