Structural, Kinetic, and Theoretical Studies on Models of the Zinc‐Containing Phosphodiesterase Active Center: Medium‐Dependent Reaction Mechanisms

Dinuclear zinc(II) complexes [Zn2(bpmp)(μ‐OH)](ClO4)2(1) and [Zn2(bpmp)(H2O)2](ClO4)3(2) (H‐BPMP=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 2was not reactive whereas for 1considerable 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.