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

Chemistry. 2007;13(32):9093-106. doi: 10.1002/chem.200700104.

Abstract

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-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 ((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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Enzyme Activation
  • Hydrogen-Ion Concentration
  • Kinetics
  • Magnetic Resonance Spectroscopy / methods
  • Magnetic Resonance Spectroscopy / standards
  • Models, Biological*
  • Models, Molecular
  • Molecular Structure
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Phosphoric Diester Hydrolases / chemistry*
  • Reference Standards
  • Ribonucleases / chemistry*
  • Sensitivity and Specificity
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Spectrophotometry, Ultraviolet / methods
  • Stereoisomerism
  • Zinc / chemistry*

Substances

  • Organometallic Compounds
  • Ribonucleases
  • Phosphoric Diester Hydrolases
  • Zinc