Structural and Functional Models of the Active Site of Zinc Phosphotriesterase

In an attempt to prepare structural and functional models for the active site of the hydrolytic enzyme zinc
phosphotriesterase, five new zinc complexes of the ligands 2,6-bis[N-(N-(carboxylmethyl)-N-((1-methylimidazol)methyl)amine)methyl]-4-methylphenolate (BCIMP) and the corresponding asymmetric ligand 2-(N-isopropyl-N-((1-methylimidazolyl)methyl)aminomethyl)-6-(N-carboxylmethyl-N-((1-methylimidazolyl)methyl)aminomethyl)-4-methylphenol (ICIMP) have been synthesized, viz. Na[Zn2(BCIMP)Ac2] (1), [Zn2(BCIMP)(Ph2Ac)] (2),
[Zn2(ICIMP)Ac2] (3), [Zn4(ICIMP)2(Me3Ac)2][ClO4]2 (4), and [Zn4(ICIMP)2(Ph2Ac)2][ClO4]2 (5). The X-ray structure of
complex 5 has been determined and reveals that the complex is a dimer of dimers in the solid state, which in
solution dissociates to potent structural models. Studies using NMR show that only one carboxylate coligand bridges
the dizinc units in the case of diphenyl acetate and pivalate, while the steric bulk of acetate is sufficiently small to
permit the coordination of two acetates/dizinc unit. Functional studies involving the hydrolysis/transesterification of
2-hydroxypropyl p-nitrophenyl phosphate (HPNP) show that the complex with ICIMP (compound 5) has a significantly
higher rate of catalysis than the BCIMP complex (compound 2). This is attributed to the vacant/labile coordination
site that is available in the ICIMP complex but not the BCIMP complex.