On the basis of spectroscopic and crystallographic data for dopamine β-monooxygenase and peptidylglycine α-hydroxylating monooxygenase (PHM), a variety of ligand sets have been used to model the oxygen-binding Cu site in these enzymes. Calculations which employed a combination of density functional and multireference second-order perturbation theory methods provided insights into the optimal ligand set for supporting η1 superoxo coordination as seen in a crystal structure of a precatalytic Cu/O2 complex for PHM (Prigge et al. in Science 304:864-867, 2004). Anionic ligand sets stabilized η2 dioxygen coordination and were found to lead to more peroxo-like Cu-O2 complexes with relatively exergonic binding free energies, suggesting that these adducts may be unreactive towards substrates. Neutral ligand sets (including a set of two imidazoles and a thioether), on the other hand, energetically favored η1 dioxygen coordination and exhibited limited dioxygen reduction. Binding free energies for the 1:1 adducts with Cu supported by the neutral ligand sets were also higher than with their anionic counterparts. Deviations between the geometry and energetics of the most analogous models and the PHM crystal structures suggest that the protein environment influences the coordination geometry at the Cu B site and increases the lability of water bound to the preoxygenated reduced form. Another implication is that a neutral ligand set will be critical in biomimetic models in order to stabilize η1 dioxygen coordination.
- Copper peroxide
- Copper superoxide
- Density functional theory
- Dopamine β-monooxygenase
- Peptidylglycine α-hydroxylating monooxygenase