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

Abstract

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(CnHn+2N2)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.

Study details

Article type

Original Research

Disease / injury model

Vascular diseases (modeled at the molecular level)

Dose comparison

No direct dose or concentration comparison; study focuses on binding energies and activation barriers.

Outcome

Neutral

Findings

The study found that molecular hydrogen (H2) binds to heme with lower affinity than O2, NO, and CO, and that H2 can be readily displaced from heme by these diatomic molecules, especially O2 and NO, with low activation barriers. In contrast, displacement of a hydrogen atom (H) from heme by these molecules requires much higher activation energies. The results suggest that H2's antioxidant effects may be mediated by heme, but its binding is weak and easily reversible in the presence of physiological gases.