Substituent Effects on Carbon Acidity in Aqueous Solution and at Enzyme Active Sites

Abstract

Methods are described for the determination of pK _as for weak carbon acids in water. The application of these methods to the determination of the pK _as for a variety of carbon acids including nitriles, imidazolium cations, amino acids, peptides and their derivatives and, α-iminium cations is presented. The substituent effects on the acidity of these different classes of carbon acids are discussed, and the relevance of these results to catalysis of the deprotonation of amino acids by enzymes and by pyridoxal 5′-phosphate is reviewed. The procedure for estimating the pK _a of uridine 5′-phosphate for C-6 deprotonation at the active site of orotidine 5′-phosphate decarboxylase is described, and the effect of a 5-F substituent on carbon acidity of the enzyme-bound substrate is discussed.

1 Introduction

2 The Carbon Acidity of Ethyl Thioacetate

3 The Carbon Acidity of Carboxylic Acid Derivatives

4 The Carbon Acidity of Imidazolium Cations

5 The α-Carbon Acidity of Amino Acids, Peptides and Their Derivatives

6 Electrophilic Catalysis of Deprotonation of Amino Acids: The α-Carbon Acidity of Iminium Cations

7 pK _as for Carbon Acids at Enzyme Active Sites

8 Concluding Remarks

Key Words

proton transfer - carbon acids - imidazole carbenes - enolates - pyridoxal - enzyme - catalysis

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