Probing Catalysis by Hydrogen Bonds

描述(申请人提供)：酶通常使用氢键 相互作用和一般酸催化作为其催化机制的一部分。 这两种影响是相似的，但又截然不同。简而言之 氢键催化，质子不转移，而在 一般酸催化质子转移。尽管质子转移是 最简单的反应之一，这两种形式的催化如何发挥作用 有一些方面正在辩论中。 在这项建议中，我们探讨了这两种形式的催化是如何受到 氢键几何构型、溶剂化作用和给体酸度的差异。 这首先是在D/H加扰实验的上下文中完成的，其中 氢键相互作用与关于低势垒的争论有关 氢键(LBHBs)。我们对LBHB催化理论的解释是 布朗斯特德的情节非常陡峭，这一点应该很明显。我们的第二个研究是面向 决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来 定量赋予烯烃的稳定性，然后测量它们的 能够增加烯酸的共轭酸的酸度。我们最后一次 氢键和通用酸催化的研究包括定量 咪唑、氨和胍类化合物催化磷酰化的能力 转移反应。酶通常使用这些官能团，但它们的 作为氢键或普通酸催化剂的作用还没有 被破译了。 在这里描述的所有这些项目中，我们将使用物理有机和 探索催化方面的分子识别技术。我们有 精心挑选的问题，如本文中提出的模型研究 可以回答这些问题，而文献研究的是酶 它们本身只会导致进一步的辩论。

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.