Theoretical studies of biological nitrogen fixation. I. Density functionalmodeling of the Mo-site of the FeMo-cofactor

The Mo-site and its ligand environment of the FeMo-cofactor (FeMo-co) were studied using the hybrid density functional method B3LYP. The structure and stability of the model complex (S-ligand)(3)(N-ligand)Mo[(S)-OCH(CH3)C(O)O -] along with its various protonated and reduced/oxidized forms, were calcu lated. Several hypotheses were tested: (i) ligand environment of the Mo-sit e, (ii) monodentate vs bidentate coordination of the Mo-bound homocitrate l igand, (iii) substrate coordination to the Mo center, and (iv) Mo-His inter action. It was found that the decoordination of one of the homocitrate (lac tate in the model) "legs", the bidentate --> monodentate rearrangement, doe s not occur spontaneously upon either single/double protonation or one-elec tron reduction. However, it could occur only upon substrate coordination to the Mo-center of the single-protonated forms of the complex. It was shown that one-electron reduction, single-protonation, and substrate coordination facilitate the bidentate <-> monodentate rearrangement of the homocitrate (lactate) ligand of FeMo-co. It was demonstrated that the smallest acceptab le model of His ligand in FeMo-co is methylimidazolate (MeIm(-)). Our studi es suggest that the epsilon -N Of the FeMo-co-bound His residue is not prot onated, and as a consequence the cluster is tightly bound to the protein ma trix via a strong Mo-N-delta bond.