Insights into the Electronic Nature of the Iron Porphyrin Framework: A Computational Study

Abstract

Density functional theory, a quantum mechanical based electronic structure method, is used to investigate iron porphyrin systems. Specific interest in the electronic structure of the heme group in myoglobin and hemoglobin has motivated investigations of the geometry and electronic nature of the deoxy-heme system, as well as binding energies for O2 and subsequent NO oxidation of the oxyheme complex. Specifically, the size of iron within the porphyrin ring in different spin states of the iron porphyrin complex is analyzed using the quantum theory of atoms in molecules (QTAIM). It is shown that the bonding interaction between the iron atom and the axial ligand has a more significant role in the domed structure of the high-spin state, counter to previous explanations of the atomic volume of iron contributing to increased doming in the high-spin ground state. The performance of contemporary density functional approximations is assessed, with specific interest on the effects of including Hartree-Fock exchange when investigating iron porphyrin systems. Varied amount of Hartree-Fock exchange are employed in popular hybrid and range-separated type functionals. It is found that increasing Hartree-Fock exchange improves the ability of the functional to correctly predict the high-spin ground state, however, inhibits the prediction of favourable dioxygen binding to the system. Binding of oxygen to heme and subsequent nitric oxide oxidation of the oxyheme species is of significant interest to aid in advancing the field of cell-free blood substitutes, as well as understanding analogous systems to assist in protein design, development of catalysts, and designing therapeutics. The mechanism of NO oxidation is explored and the effect of replacing the proximal histidine, which tethers heme to the protein backbone, with other amino acid ligands is probed. The binding energies of dioxygen to the system, and resulting superoxide character of the dioxygen ligand are reported. Substitution of the amino acid group is found to have little effect on the NO affinity of the oxyheme system, however, electronic differences suggest modification of the reaction mechanism may be possible and requires further study.