Density functional theory studies of model complexes for molybdenum-dependent nitrate reductase active sites

Molybdenum and tungsten complexes as models for the active sites of assimilatory or dissimilatory nitrate reductases (NR) were computed at the CPCM-B98/SDDp//B3LYP/Lanl2DZp* plus zero point energy level of density functional theory. The ligands were chosen on the basis of available experimental protein or small chemical model structures. A water molecule is found to bind to assimilatory NR models [(Me(2)C(2)S(2))MO(YMe)](-) (-11.5 kcal mol(-1) for M is Mo, Y is S) and may be replaced by nitrate (-4.5 kcal mol(-1)) (but a hydroxy group may not). Nature's choice of M is Mo and Y is S for NR has the largest activation energy for protein-free models (13.3 kcal mol(-1)) and the least exothermic reaction energy for the nitrate reduction (-14.9 kcal mol(-1)) compared with M is W and Y is O or Se alternatives. Water binding to dissimilatory NR model complexes [(Me(2)C(2)S(2))(2)M(YR)](-) is considerably endothermic (10.3 kcal mol(-1)); nitrate binding is only slightly so (1.5 kcal mol(-1) for RY(-) is MeS(-)). The exchange of an oxo ligand (assimilatory NR) for a dithiolato ligand (dissimilatory NR model) reduces the exothermicity (-8.6 kcal mol(-1) relative to the fivefold-coordinate reduced complex) and raises the barrier for oxygen atom transfer (OAT) in the nitrate complex (19.2 kcal mol(-1)). Not for the mono but only for the bisdithiolato complexes hydrogen bonding involving the coordinated substrate may significantly lower the OAT barrier as shown by explicitly adding water molecules. Substitution of tungsten for molybdenum generally lowers OAT activation energies and makes nitrate reduction reaction energies more negative. Bidentate carboxylato binding identified in Escherichia coli NarGHI is the preferred binding mode also for an acetato model. However, one dithiolato ligand folds when the Mo(VI) center is bare of a good pi-donor ligand, e.g., an oxo group. Computations on [(mnt)(2)Mo(IV)(YR)(PPh(3))](-) [mnt is (CN)(2)C(2)S(2) (2-)] gave a smaller nitrate reduction activation energy for RY(-) is Cl(-), compared with RY(-) is PhS(-), although experimentally only the phenyl thiolato complex and not the chloro complex was found to be a functional NR model.