Structural, Kinetic and Theoretical Studies on modeling Zn-containing phosphodiesterase Active Center: medium-dependent Reaction Mechanisms
Résumé
Dinuclear zinc(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) 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 (1H, 31P 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.