PARTICIPATION OF 2 CARBOXYL GROUPS IN PHOSPHODIESTER HYDROLYSIS .1. HYDROLYSIS OF BIS(2-CARBOXYPHENYL)PHOSPHATE

The energies of rotamer conformations of bis(2-carboxyphenyl) phosphate (2), where one o-carboxy group is ionized and the other is not, have been determined by semiempirical (SAM1, AM1/SM2.1) calculations in order to approximate the probability of the presence of conformations in which the o-CO2- is in position to act as a nucleophile toward phosphorus and the o-CO2H function can hydrogen bond to prostereogenic oxygens of the -(PO2-)(conformer B) or leaving phenoxide oxygen (conformer A). With simulated water phase, conformer B appears to be at the global energy minima and conformer A is somewhat less stable. The kinetics and the mechanism of hydrolysis of bis(2-carboxyphenyl) phosphate (2) have been elucidated by use of H-1 and P-31 NMR spectroscopy in acetonitrile/water 95:5 and D2O at pD up to 5.0 (39 degrees C). The hydrolysis of 2 is initiated by nucleophilic attack of the o-CO2- upon phosphate phosphorus resulting in the elimination of salicylic acid to provide salicyloyl cyclic phosphate (3) with a rate constant of 1-5 x 10(-3) s(-1) and 3 converts to salicyl monophosphate with rate constants varying between 1 and 5 x 10(-4) s(-1). The rapidity of the formation of 3 from 2 suggests the importance of both o-CO2- and o-CO2H participation {a subject of the following manuscript}.