title: Density functional theory calculations on the mononuclear non-heme iron active site of Hmd hydrogenase: role of the internal ligands in tuning external ligand binding and driving H2 heterolysis.
abstract: DFT calculations on active-site models of the non-heme Fe site of Hmd hydrogenase are reported. Binding of several biologically relevant ligands (e.g., CN(-), CO, H(-), H(2), and O(2)) to the active site of Hmd was investigated using a method that reproduced the geometric and vibrational properties of the resting site. The results indicate that this neutral ferrous active site has higher affinity toward anionic ligands (e.g., H(-) and CN(-)) than π-acidic ligands (e.g., CO and O(2)). Natural population analysis and molecular orbital analysis revealed that this is due to extensive delocalization of electron density into the low-lying unoccupied orbitals of the CO, acyl, and pyridinol ligands present in the active site. In addition to normal d-π back-bonding, metal 3d orbital-mediated charge transfer from occupied ligand orbitals to the unoccupied orbitals of the internal ligands was observed. This charge transfer leads to systematic variations in the experimentally observed C-O stretching frequencies. Protonation of the thiolate ligand present in the active site significantly enhances these anion ligand binding affinities. In fact, the calculated vibrational frequencies indicate that CN(-) binding is possibly associated with protonation of the thiolate ligand. The high affinity for binding of the anionic H(-) ligand (where 81% of the electron density of H(-) is delocalized into the active site) is calculated to play a dominating role in the H-H bond heterolysis step during catalysis. The binding energies of these ligands relative to the substrate, H(2), highlight the importance of a proposed structural reorganization during catalysis.
authors.affiliation: Indian Association for the Cultivation of Science, 2A Raja S. C. Mullick Road, Kolkata, India 700032. icad@iacs.res.in
authors.forename: Abhishek
authors.initials: A
authors.lastname: Dey
mesh_terms: D001665:Binding Sites; D006859:Hydrogen / Q000737:chemistry*; D006864:Hydrogenase / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D019159:Nonheme Iron Proteins / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry*
chemical_list: D008024:Ligands; D019159:Nonheme Iron Proteins; D014867:Water; D006859:Hydrogen; D006864:Hydrogenase