Charge Description of Base-Catalyzed Alcoholysis of Aryl Phosphodiesters: A Ribonuclease Model

Article abstract of DOI:10.1021/ja00223a031

The release of substituted phenol from aryl uridine-3'-phosphates is catalyzed by bases and involves cyclization to form the 2',3'-cyclic nucleotide.The rate constants for imidazole and hydroxide ion catalysis (k_im and k_OH, respectively) obey the Broensted equations (25 deg C and 0.25 M ionic strength) log k_im = -0.59 pK^ArOH + 1.40 (n = 7, r = 0.955) and log k_OH = -0.54 pK^ArOH + 6.68 (n = 9, r = 0.967).General-base-catalyzed release of 4-nitrophenol from the 4-nitrophenyl ester (k_B) obeys the Broensted relationship log k_B = 0.67 pK^BH - 7.50 (n = 7, r = 0.989).Charge changes on base and leaving group atoms as determined from the corresponding β and β_eq values do not balance.Comparison with data in the literature indicates that the difference in charge may be assigned to the attacking oxygen (2'-hydroxyl) rather than to the phosphoryl oxygens in the O...PO2... group of atoms.Both P-O bond forming and bond fission components of the reaction are considered to be only weakly advanced in a transition state that lies on a concerted pathway.