Lessons on O2 and NO bonding to heme from ab initio multireference/multiconfiguration and DFT calculations

This commentary focuses on the conceptual interpretation of the bonding of O2 and NO to heme in oxyheme and nitrosylheme complexes, using high-level ab initio complete active space self-consistent field (CASSCF)/molecular mechanical (MM), gas-phase CASSCF, and CASSCF followed by second-order perturbation theory (CASPT2) calculations as well as density functional theory (DFT) calculations. The commentary shows that expanding the complex multiconfigurational (MC) wave functions into valence bond (VB)-type configurations based on localized orbitals provides significant insight into bonding and precise definitions of oxidation states. Furthermore, the VB “reading” of the wave function unifies the descriptions of DFT and MC theories, reconciling controversies and surprises. In so doing, we demonstrate the impact of the protein bulk polarity and its hydrogen-bonding capability on the bonding. The insight provided by “reading” the VB content of the MC wave functions highlights the potential of this approach as a general paradigm in future computational bioinorganic chemistry. A great deal of insight lies in this road.