Structural, kinetic, and theoretical studies on models of the zinc-containing phosphodiesterase active center: medium-dependent reaction mechanisms

Dinuclear zinc(II) complexes Zn(2)(bpmp)(mu-OH)](ClO(4))(2) (1) and Zn(2)(bpmp)(H(2)O)(2)](ClO(4))(3) (2) (H-BPMP=2,6-bisbis(2-pyridylmethyl)aminomethyl]-4-methylphenol) have been synthesized, structurally characterized, and pH-driven changes in metal coordination observed. The transesterification reaction of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) in the presence of the two complexes was studied both in a water/DMSO (70:30) mixture and in DMSO. Complex 2 was not reactive whereas for 1 considerable rate enhancement of the spontaneous hydrolysis reaction was observed. A detailed mechanistic investigation by kinetic studies, spectroscopic measurements ((1)H, (31)P NMR spectroscopy), and ESI-MS analysis in conjunction with ab initio calculations was performed on 1. Based on these results, two medium-dependent mechanisms are presented and an unusual bridging phosphate intermediate is proposed for the process in DMSO.