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

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[Formula: see text]: dihydrogen bonding in the end-on asymmetric configuration and Kubas bonding in the side-on symmetric configuration of H[Formula: see text] molecule. The activation barriers for adsorption and dissociation of H[Formula: see text] 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[Formula: see text] molecule. We find that the hydrogen bond dissociation energies of FeP(Im)-H[Formula: see text] 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.