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

Abstract

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 exceptionally well. We have characterized an inactive and an active form of one of these biomimetic compounds using unrestricted dynamical density functional calculations. The peculiar nonsquare planar O N -coordination geometry of the copper ion in the catalytically 2 2 Ž . inactive EPR-active form induces a complex energy-level diagram that cannot be related to crystal-field models: The highest occupied orbitals are located on the -system of the aromatic ligands and are essentially spin-paired while the unpaired electron is localized mainly in a lower-lying d 2 2 orbital of the copper. Using ab initio molecular x yy dynamics simulations, we determined for the first time the structure of the active form complexed with a substrate analog. Our calculations reveal that upon substrate binding one of the phenolate ligands is pushed away from the copper center into an axial position and the electronic structure rearranges to an unusual antiferromagnetic diradical state. As in the inactive form, the unpaired ␣-spin density is located in the copper d 2 2x yy orbital. The unpaired ␤-spin density, instead, is localized on the axial ligand in agreement with the ligand-based radical mechanism that has been proposed for galactose oxidase.

Role of the electronic properties of azurin active site in the electron‐transfer process

“…This behavior is consistent with previous theoretical findings for other biological Cu(II) complexes, which were suggested as an indication of the strong Coulombic repulsion between the electron in the formally d 9 ion 57, 58. By a closer inspection of the α‐ and β‐orbital levels, one notes that the α orbitals of copper are more stabilized than the corresponding β ones.…”

Ten Years of a Biomimetic Approach to the Copper(II) Radical Site of Galactose Oxidase

“… Proposed mechanisms for the catalytic oxidation of alcohols by [Cu(L 12 · )] (A), and simplified models of [Cu(L 2 )] (B) and [Cu(L 54 )] (C) [adapted from ref 46. (A), ref 102,103. (B) and ref 104.…”

“…Theoretical approaches to the oxidation of methoxide by [Cu(L 2 · )]102,103 and [Cu(L 54 · )]104 (in their Cu II ‐phenoxyl radical form) have been undertaken. Ab initio molecular dynamics studies on [Cu(L 2 · )] have shown that the methoxide adduct is a five‐coordinate distorted pyramidal phenoxylcopper(II) complex 102,103. The methoxide binds in the equatorial plane with a short Cu–O bond (1.93 Å), whereas the phenoxyl becomes an axial ligand with a much longer Cu–O bond (2.54 Å).…”

Green Oxidation Catalysts: Computational Design of High‐Efficiency Models of Galactose Oxidase

“…A number of recent quantum‐chemical investigations have aimed at a full atomistic characterization of the enzymatic reaction mechanism, thereby complementing the available experimental data 16–19. We have recently performed a mechanistic analysis of the functional biomimetic compound developed by Wang et al4 (MIM0 in Scheme )18 in direct comparison with its natural target 17. This study identified the delocalization of the unpaired spin density during the rate‐determining H‐abstraction step (Scheme , C → D ) as the crucial determinant for the efficiency of the process.…”

“…23 Geometries were converged up to a residual nuclear gradient of 0.001 atomic units. In CPMD calculations, the Kohn–Sham orbitals were expanded in plane waves with an energy cutoff of 80 Ry, which has been shown to be sufficiently accurate for these compounds 17. In ADF calculations we used DZP (H, N, O) and TZP (Cu, Ti, Ru, Rh, Pd) basis sets.…”