Synlett 2017; 28(12): 1407-1421
DOI: 10.1055/s-0036-1588778
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© Georg Thieme Verlag Stuttgart · New York

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

Tina L. Amyes, John P. Richard*
  • Department of Chemistry, University at Buffalo, SUNY, Buffalo, NY 14260-3000, USA   Email: jrichard@buffalo.edu
Further Information

Publication History

Received: 07 February 2017

Accepted after revision: 15 March 2017

Publication Date:
10 April 2017 (eFirst)

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