First-principles study of molecular hydrogen binding to heme in competition with O₂, NO and CO

Molecular hydrogen shows antioxidant activity and distinct efficacy towards vascular diseases, but the understanding of this is not yet satisfactory at the atomic level. In this work, we study the binding properties of H₂ to the heme group in relation with other diatomic molecules (DMs), including O₂, NO and CO, and their displacement reactions, using first-principles calculations. We carry out molecular modeling of the heme group, using iron-porphyrin with the imidazole ligand, i.e., FePIm, and smaller models of Fe(CHN₂)₂NH₃ with n = 3 and 1, and of molecular complexes of heme-DM and -H. Through analysis of optimized geometries and energetics, it is found that the order of binding strength of DMs or H to the Fe of heme is NO > O₂ > CO > H > H₂ for FePIm-based systems, while it is H > O₂ > NO > CO > H₂ for model-based systems. We calculate the activation energies for displacement reactions of H₂ and H by other DMs, revealing that the H₂ displacements occur spontaneously while the H displacements require a large amount of energy. Finally, our calculations corroborate that the rate constants increase with increasing temperature according to the Arrhenius relation.