Characterization of the transition state for the hydride transfer in a model of the flavoprotein reductase class of enzymes

The transition state structure for the hydride transfer between 1,4-dihydronicotinamide and the flavin isoalloxazine moiety has been characterized by means of the AM1 and PM3 semiempirical methods. The distance between the initially H-bonded carbon atom of 1,4-dihydronicotinamide and the nitrogen atom of the flavin isoalloxazine moiety is found to be 2.67 Å with both methods. The transferring hydrogen is located closer to the nitrogen atom than to the carbon atom, with an almost linear arrangement. Finally, an insight into the electronic nature of the transfer is obtained from Mulliken atomic charge population and Bader analyses: the former shows an atomic charge of 0.18 a.u. for the formally termed hydride, while from the latter, bond critical points for the breaking (C4'-H) and forming (H-N5) bonds have been located and electronic charge density and laplacian contour maps have been built. Finally, mechanistic implications of the overall results are discussed.