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

Dinuclear Zn(II) complexes [Zn2(bpmp)($μ$-OH)](ClO4)2 (1) and [Zn2(bpmp)(H2O)2](ClO4)3 (2) (HBPMP = 2,6-bis[bis(2-pyridylmethyl)aminomethyl]-4-methylphenol) were synthesized, structurally characterized, and pH-driven changes in metal coordination obsd. The transesterification reaction of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) in the presence of the two complexes was studied both in a H2O/DMSO (70:30) mixt. and in DMSO. Complex 2 was not reactive whereas for 1 considerable rate enhancement of the spontaneous hydrolysis reaction was obsd. A detailed mechanistic study by kinetic studies, spectroscopic measurements (1H, 31P NMR spectroscopy), and ESI-MS anal. in conjunction with ab initio calcns. 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. [on SciFinder(R)]


Soumis le 12 avril 2018