Theoretical Studies on Models for the Oxo-Transfer Reaction of Dioxomolybdenum Enzymes

Abstract

Patterned after synthetic model systems for dioxomolybdenum enzymes, our theoretical model system produces an energy profile and structures for the various species and oxidation states in the catalytic cycle. A key step in this cycle is the oxo-transfer reaction. Here, our substrate, PMe(3), approaches [Mo(VI)O(2)](2+) at an O-Mo-O-P dihedral angle of 90 degrees, i.e. perpendicular to the MoO(2) plane, crosses over a barrier of 14 kcal/mol, and rotates to an O-Mo-O-P dihedral angle of 0 degrees to form an intermediate, [Mo(IV)O(OPMe(3))](2+), which is 69 kcal/mol more stable than the reactants. The direction of the substrate's attack leaves the two d electrons of this Mo(IV) system in an orbital which is delta with respect to the remaining spectator Mo-O bond, a configuration which allows this O to form a formal triple Mo-O bond. The displacement of the product, OPR(3), by water, H(2)O, proceeds via an associative mechanism with a barrier of only 19 kcal/mol. In our model, [Mo(IV)O(OH(2))](2+) then reacts with [Mo(VI)O(2)](2+) to form [Mo(V)O(OH)](2+), a process which is exothermic by 14 kcal/mol. The addition of O(2) then oxidizes [Mo(V)O(OH)](2+) to [Mo(VI)O(2)](2+) to complete our model catalytic cycle.

Experimental and theoretical study of a truly functional biomimetic molybdenum oxotransferase analogue system

“…In the oxo(phosphoryl) complex 3a the Mo-O2 bond is now a single bond (2.223 Å ), the P-O2 bond has formed (1.550 Å ), the O2-P-C1 angle has relaxed to 114.2°, the P-O2-Mo-O1 torsion angle is reduced to -53.6°and the Mo-O1 bond is shortened (formal triple bond) according to the spectator oxygen effect (Table S3) [3]. The results described for our system are fully compatible with previous computational studies of model systems [10][11][12][13][14][15][16][17][18].…”

Mechanism of Nitrate Reduction by Desulfovibrio desulfuricans Nitrate Reductase—A Theoretical Investigation

“…For example, it has been shown that sulfite oxidation by sulfite oxidase enzymes, which can be viewed as a reverse reaction of nitrate reduction, proceeds through attack of the lone pair of electrons of the sulfur atom on one of the oxo ligands at the molybdenum. [16] Other computational studies of phosphine oxidation [17,18] have led to similar results. Two DFT investigations concerning DMSO reductase [24,25] and trimethylamine N-oxide reductase [25] have been published, in which model systems of the general form Mo IV OR(S 2 C 2 R' 2 ) 2 were used.…”

Structural Basis of Eukaryotic Nitrate Reduction: Crystal Structures of the Nitrate Reductase Active Site

“…Three of these residues (Asp271, Arg89, and His91) are completely conserved throughout the entire SO family, possibly indicating a conserved mechanism for the oxo-transfer reaction catalyzed by NR and SO. The position of the reaction intermediate ( Figure 6D) was chosen by a planarity restrain for the nitrogen, nitrateoxygen, Mo, and the apical oxygen bonds according to the stereochemistry and reaction of model compounds (Pietsch and Hall, 1996), and reasonable distances to adjacent atoms were also considered. The resulting coordination of the bound nitrate involves Asp271 and Asn272.…”