On the performance of ligand field molecular mechanics for model complexes containing the peroxido-bridged [Cu2O2]2+ center

The ability of ligand field molecular mechanics (LFMM) to model accurately the structures and relative conformer energies of complexes containing the [Cu2O2](2+) unit found in oxidized copper type 3 (T3) enzymes is investigated. The consequences of ignoring the coupling between the metal centers are analyzed and predicted,to be unimportant with respect to computing molecular geometries. Angular overlap model (AOM) parameters for the peroxido bridge in [Cu2O2](2+) are derived on the basis of the mononuclear model compound [(NH3)(3)CuO2] for which good ligand field and density functional theory (DFT) calculations are also possible. Metal-ligand pi-bonding parameters are shown to play an important role with the in-plane AOM g-bonding parameter value being significantly larger than that for the out-of-plane parameter. The LFMM treatment is then extended to the model dinuclear species [(H3N)(3)CuO2Cu(NH3)(3)](2+). The planarity of the [Cu2O2](2+) moeity is implicitly obtained by defining the directions of the local Cu-O pi-bonding interactions with respect to the other copper atom, rather than the other oxygen. In conjunction with the force field parameters based on the Merck molecular force field, the model, as implemented in our DommiMOE program (Deeth, R. J.; Fey, N.; Williams-Hubbard, B. J. J. Comput Chem. 2005, 26,123-130), is applied to a set of crystallographically characterized small-molecule mimics of the T3 active site. Extensive LFMM conformational searches are carried out for these compounds, and the quality of the LFMM potential energy hypersurface is assessed by comparison with results using DFT. We find that the description of the geometries does not in fact suffer from the neglect of explicit coupling between the metal centers. Moreover, the structures and relative energies obtained by the LFMM conformational searches agree well with both experiment and the DFT values for all systems except one where the LFMM structure which is in best agreement with experiment is about 10 kcal mol(-1) higher than the lowest energy conformer. However, this discrepancy is traced to generic shortcomings in the organic force field rather than the LFMM.