A structural and catalytic model for zinc phosphoesterases

Abstract

A structural model for the active site of phosphoesterases, enzymes that degrade organophosphate neurotoxins, has been synthesised. The ligand [2-((2-hydroxy-3-(((2-hydroxyethyl)(pyridin-2-ylmethyl)amino)methyl)-5-methylbenzyl)(pyridin-2-ylmethyl)amino)acetic acid] (H₃L1) and two Zn(II) complexes have been prepared and characterised as [Zn₂(HL1)(CH₃COO)](PF₆)·H₂O and Li[Zn₂(HL1)]₄(PO₄)₂(PF₆)₃·(CH₃OH). The ligand (H₃L1) and complex [Zn₂(HL1)(CH₃COO)](PF₆)·H₂O were characterised through ¹H NMR, ¹³C NMR, mass spectroscopy and microanalysis. The X-ray crystal structure of Li[Zn₂(HL1)]₄(PO₄)₂(PF₆)₃·(CH₃OH) revealed a tetramer of dinuclear complexes, bridged by two phosphate molecules and bifurcating acetic acid arms. Functional studies of the zinc complex with the substrate bis(4-nitrophenyl)phosphate (bNPP) determined the complex with HL1²⁻ to be a competent catalyst with k_cat = 1.26 ± 0.06 × 10⁻⁶ s⁻¹.