The catalytic ability of a dinuclear Zn2+ complex of 1,3-bis-N-1-(1,5,9-triazacyclododecyl) propane (3) in promoting the cleavage of an RNA model, 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP, 1), and a DNA model, methyl p-nitrophenyl phosphate (MNPP, 4), was studied in methanol solution in the presence of added CH3O- at 25 degrees C. The di-Zn2+ complex (Zn-2:3), in the presence of 1 equiv of added methoxide, exhibits a second-order rate constant of (2.75 +/-0.10) x 10(5) M-1 s(-1) for the reaction with 1 at (s)(s)pH 9.5, this being 10(8)-fold larger than the k(2) value for the CH3O- promoted reaction (k(OCH3) = (2.56 +/- 0.16) x 10(-3) M-(1) s(-1)). The complex is also active toward the DNA model 4, exhibiting Michaelis-Menten kinetics with a K-M and k(max) of 0.37 +/- 0.07 mM and (4.1 +/- 0.3) x 10(-2) s(-1), respectively. Relative to the background reactions at sspH 9.5, Zn(2:)3 accelerates cleavage of each phosphate diester by a remarkable factor of 10(12)-fold. A kinetic scheme common to both substrates is discussed. The study shows that a simple model system comprising a dinuclear Zn2+ complex and a medium effect of the alcohol solvent achieves a catalytic reactivity that approaches enzymatic rates and is well beyond anything seen to date in water for the cleavage of these phosphate diesters.