Enzyme-like acceleration for the hydrolysis of a DNA model promoted by a dinuclear Zn(II) catalyst in dilute aqueous ethanol

Article abstract of DOI:10.1021/ja805801j

The rates and products of cleavage of methyl (2-chloro-4-nitrophenyl) phosphate (2) promoted by a dinuclear Zn(II) complex (3) of 1,3-bis-N,N′(1,5,9-triazacyclododecyl)propane along with 1 equiv of ethoxide were investigated in ethanol solution containing small amounts of water (8 mM ≤ [H₂O] ≤ 2.1 M) at 25 °C and ^s_spH 7.9. The kinetics of decomposition of 5 × 10^-5 M 2 in the presence of varying [3] (0.03 mM ≤ [3] ≤ 0.12 mM) in ethanol containing 28 mM water show very strong saturation binding which is analyzed to give fitted values for the complex dissociation constant (K_d) and maximum catalytic rate constant (k_cat^max) of 3.2 × 10^-8 M and 1.47 × 10^-3 s^-1. Product analysis indicates that the reaction in ethanol containing 28 mM and 2.1 M water produces 46% and 93% of the hydrolysis product (methyl phosphoric acid), with the remainder being ethanolysis product (ethyl methyl phosphate). Analysis of the kinetics of the reaction at 28 mM water indicates that second order rate constant for the catalytic reaction, given as k_cat^max/K_d, is 4.6 × 10⁴ M^-1 s^-1, is a factor of 8.4 × 10¹⁰ larger than the second order rate constant (k₂^EtO) for the ethoxide promoted reaction of 2 in ethanol (5.5 ± 0.3) × 10^-7 M^-1 s^-1. A more detailed analysis that considers the relative acidities of water and ethanol in ethanol solvent indicates that at ^s_spH 7.9, the ethanolysis is accelerated by 2.3 × 10¹⁴ times relative to the computed ethoxide reaction at that ^s_spH, while the hydrolysis isaccelerated by ≥1.6 × 10¹⁷ times relative to the background hydroxide reaction, suggesting that complex 3 promotes the hydrolysis at least 1000 times more effectively than ethanolysis. Copyright