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

Methods are described for the determination of ps for weak carbon acids in water. The application of these methods to the determination of the ps 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 p 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.