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

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.