Equilibrium of formation of the 6-carbanion of UMP, a potential intermediate in the action of OMP decarboxylase

There has been some speculation that the C-6 position in UMP may be unusually acidic, stabilizing a carbanion that is generated at this position during OMP decarboxylation. On the basis of the rate of OH- catalyzed deuterium exchange at elevated temperatures we estimate that the pKa value for ionization at C-6 of dimethyl uracil is 34 ± 2 in water. The same method yields a value of 37 ± 2 for ionization at C-2 of thiophene in good agreement with the value determined by polarographic methods. The barrier to proton release (46 kcal/mol) is even higher than that for CO2 release from orotic acid derivatives. Copyright © 2002 American Chemical Society.