Radu Silaghi-Dumitrescu

BIOORGANOMETALLIC COMPLEXES RELEVANT TO THE “PUSH EFFECT” IN HEMOPROTEINS.

Bioorganometallic iron-aryl and iron-alkyl adducts of native hemoproteins are known to contain an S = 1/2 ferric center s-bonded to a carbon atom. Such aryl adducts of several hemoproteins have allowed extensive probing of the topology of the respective heme active sites. While spectroscopic data is available for most hemoprotein organometallic complexes, only the phenyl adduct of cytochrome P450 has been characterized by X-ray crystallography (structure shown below).

Crystal structure of the phenyl adduct of a cytochrome P450 (pdb entry 1CP4). The heme and its two axial ligands (a protein thiolate and the exogenous phenyl) are depicted as ball-and-stick. Arrow indicates the direction of the α-helix to which the thiolate (cysteinate) ligand of the heme is tethered.

Geometry optimization results for phenyl and methyl adducts of thiolate-ligated, imidazole-ligated, and non-axially ligated porphyrin models.

Molecular orbitals illustrating p bonding between iron and sulfur, in complexes examined here (ferric-methyl, ferric-phenyl) as well as in a formally ferric-peroxo complex (“ferric-peroxo”, with the axial ligand=SCH₃).

Geometry optimization results using non-hybrid density functional theory, for models of the known phenyl and methyl adducts of heme-thiolate and heme-histidine enzyme active sites, are in good agreement with previously available experimental data. These bio-organometallic complexes can be considered “s-only” mimics of dioxygen, peroxo, and superoxo complexes. A comparison of the Fe-C bond lengths in these phenyl/methyl-heme complexes as a function of the axial ligand allows a direct quantitative comparison of the trans (“push”) effect of the thiolate and histidine axial ligands in hemoproteins, without any interference from p effects. This allows us to estimate the p contribution to the trans effect in the related, previously examined, heme-dioxygen/peroxo complexes with thiolate and histidine axial ligands. The phenyl adduct also offers a previously unexplored explanation for the tilting of the axial ligands in hemoproteins.

HOMO-2 orbital of the ferric-phenyl adduct, illustrating a s interaction between a carbon-based orbital and an iron e_g orbital.