Formation and stability of organic zwitterions in aqueous solution: Enolates of the amino acid glycine and its derivatives

Second-order rate constants for carbon deprotonation of glycine zwitterion, N-protonated glycine methyl ester, betaine methyl ester, and betaine by de uterioxide ion in D2O have been determined by following deuterium exchange into these carbon acids in buffered solutions at 25 degrees C and I = 1.0 ( KCl) by H-1 NMR spectroscopy. The data were used to calculate the following carbon acidities for glycine zwitterion and its derivatives in aqueous sol ution: +H3NCH2CO2-, pK(a) = 28.9 +/- 0.5; +H3NCH2CO2Me, pK(a) = 21.0 +/- 1. 0; +Me3NCH2CO2Me, pK(a) = 18.0 +/- 1.0; +Me3NCH2CO2-, pK(a) = 27.3 +/- 1.2. The rate constants for deprotonation of glycine methyl eater by Bronsted b ase catalysts are correlated by beta = 0.92. Two important differences betw een structure-reactivity relationships for deprotonation of neutral alpha-c arbonyl carbon acids and cationic esters are attributed to the presence of the positively charged ammonium substituent at the latter carbon acids: (1) The smaller negative deviation of log k(DO) from the Bronsted correlation for deprotonation of +H3NCH2CO2Me than for deprotonation of ethyl acetate i s attributed to stabilization of the transition state for enolization by el ectrostatic interactions between DO- and the positively charged ammonium su bstituent. (2) The positive deviation of log k(HO) for deprotonation of cat ionic esters from the rate-equilibrium correlation for deprotonation of neu tral alpha-carbonyl carbon acids is attributed to both transition-state sta bilization by these same electrostatic interactions and movement of negativ e charge at the product enolate away from oxygen and onto the alpha-carbon. This maximizes the stabilizing interaction of this negative charge with th e positively charged ammonium substituent and leads to a reduction in the M arcus intrinsic barrier to proton transfer, as a result, of the decreased r esonance stabilization of the enolate. The implications of these results fo r enzymatic catalysis of racemization of amino acids is discussed.