Ab initio molecular dynamics studies of a synthetic biomimetic model of galactose oxidase

Very recently, highly efficient biomimetic models of the mononuclear copper enzyme galactose oxidase were synthesized which are able to reproduce the structural, spectroscopic, and functional properties of the native system e xceptionally well. We have characterized an inactive and an active form of one of these biomimetic compounds using unrestricted dynamical density func tional calculations. The peculiar nonsquare planar O2N2-coordination geomet ry of the copper ion in the catalytically inactive (EPR-active) form induce s a complex energy-level diagram that cannot be related to crystal-field mo dels: The highest occupied orbitals are located on the pi-system of the aro matic ligands and are essentially spin-paired while the unpaired electron i s localized mainly in a lower-lying d(x2-y2) orbital of the copper. Using a b initio molecular dynamics simulations, we determined for the first time t he structure of the active form complexed with a substrate analog. Our calc ulations reveal that upon substrate binding one of the phenolate ligands is pushed away from the copper center into an axial position and the electron ic structure rearranges to an unusual antiferromagnetic diradical state. As in the inactive form, the unpaired alpha-spin density is located in the co pper d(x2-y2) orbital. The unpaired beta-spin density, instead, is localize d on the axial ligand in agreement with the ligand-based radical mechanism that has been proposed for galactose oxidase. (C) 1999 John Wiley & Sons, I nc. Int J Quant Chem 73: 209-218, 1999.