Electronic structure of iron(II)–porphyrin nitroxyl complexes: Molecular mechanism of fungal nitric oxide reductase (P450nor)

Density functional calculations are employed to investigate key intermediates of the catalytic cycle of fungal nitric oxide reductase (P450nor). The formal Fe(II)–nitroxyl species Fe(II)NO/(−) can principally exist in the two spin‐states S = 0 and S = 1. In the S = 0 case, a very covalent FeNO σ bond is present, which leads to an electronic structure description that is actually intermediate between Fe(I)NO and Fe(II)NO − . In contrast, the S = 1 case shows a ferrous Fe(II)NO complex with the extra electron being stored in the π system of the porphyrin ligand. Importantly, the Fe(II)NO/(−) species are very basic. The electronic structures and spectroscopic properties of the corresponding N‐ and O‐protonated forms are very different, and unequivocally show that the Mb–HNO adduct (Mb‐Myoglobin) prepared by farmer and coworkers is in fact N‐protonated. The presence of an axial thiolate ligand enables a second protonation leading to the corresponding Fe(IV)NHOH − species, which is identified with the catalytically active intermediate I of P450nor. This species reacts with a second molecule of NO by initial electron transfer from NO to Fe(IV) followed by addition of NO + forming an NN bond. This is accompanied by an energetically very favorable intramolecular proton transfer leading to the generation of a quite stable Fe(III)N(OH)(NOH) complex. This way, the enzyme is able to produce dimerized HNO under very controlled conditions and to prevent loss of this ligand from Fe(III). The energetically disfavoured tautomer Fe(III)N(OH 2 )(NO) is the catalytically productive species that spontaneously cleaves the NOH 2 bond forming N 2 O and H 2 O in a highly exergonic reaction. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1338–1351, 2006