プロトヘム触媒を介した分子状水素の生体内抗酸化機構：第一原理計算による解析
To elucidate the atomic-level mechanism underlying the antioxidant activity of molecular hydrogen (H₂), systematic ab initio calculations were performed on complexes of iron-protoporphyrin coordinated with imidazole, designated FeP(Im), together with reactive oxygen and nitrogen species (RONS). Two distinct bonding modes between FeP(Im) and H₂ were identified: a dihydrogen bond in the end-on asymmetric configuration and a Kubas-type interaction in the side-on symmetric configuration. Activation barriers for H₂ adsorption, dissociation, and subsequent H-atom desorption from FeP(Im) were all below 2.78 eV, substantially lower than the 4.64 eV H–H bond dissociation energy of free H₂. Mulliken charge analysis further revealed that the hydrogen bond dissociation energies of FeP(Im)–H₂ and FeP(Im)–H complexes are lower than those of the corresponding RONS–H complexes. These findings indicate that protoheme functions as an efficient in vivo catalyst, facilitating H₂-mediated scavenging of RONS and providing a quantum-chemical basis for the observed antioxidant effects of molecular hydrogen.
Protoheme (FeP(Im)) coordinates H₂ via dihydrogen or Kubas bonding with activation barriers below 2.78 eV, far less than the 4.64 eV H–H bond energy, enabling catalytic H-atom transfer to RONS and their subsequent neutralization in vivo.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/36057001