Antioxidation activity of molecular hydrogen via protoheme catalysis in vivo: an insight from ab initio calculations

Abstract

Recently, molecular hydrogen has been found to exhibit antioxidation activity through many clinical experiments, but the mechanism has not been fully understandable at atomic level. In this work, we perform systematic ab initio calculations of protoheme-hydrogen complexes to clarify the antioxidation mechanism of molecular hydrogen. We make molecular modeling of iron–protoporphyrin coordinated by imidazole, FeP(Im), and its hydrogen as well as dihydrogen complexes, together with reactive oxygen/nitrogen species (RONS). We carry out structural optimization and Mulliken charge analysis, revealing the two kinds of bonding characteristics between FeP(Im) and H 2 : dihydrogen bonding in the end-on asymmetric configuration and Kubas bonding in the side-on symmetric configuration of H 2 molecule. The activation barriers for adsorption and dissociation of H 2 on and further desorption of H atom from FeP(Im) are found to be below 2.78 eV at most, which is remarkably lower than the H–H bond breaking energy of 4.64 eV in free H 2 molecule. We find that the hydrogen bond dissociation energies of FeP(Im)–H2 and –H complexes are lower than those of RONS–H complexes, indicating the decisive role of protoheme as an effective catalyst in RONS antioxidation by molecular hydrogen in vivo.

Study details

Article type

Original Research

Disease / injury model

Oxidative stress and RONS-related pathologies (general, not specific to a single disease)

Dose-dependent effect

No

Outcome

Positive

Findings

Ab initio calculations reveal that protoheme (iron–protoporphyrin coordinated by imidazole) acts as an effective catalyst for the antioxidation activity of molecular hydrogen in vivo. The bond dissociation energies for protoheme–hydrogen complexes are lower than those for RONS–H complexes, indicating that protoheme enables molecular hydrogen to scavenge a broader range of reactive oxygen/nitrogen species (RONS) than H2 alone, which primarily scavenges hydroxyl radicals. The study elucidates the atomic-level mechanism of H2 antioxidation via protoheme catalysis.