Toluene Dioxygenase-Catalyzed -Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides.

Molecular docking studies of quinoline and 2-chloroquinoline substrates at the active site of toluene dioxygenase (TDO), were conducted using Autodock Vina, to identify novel edge-to-face interactions and to rationalize the observed stereoselective -dihydroxylation of carbocyclic rings and formation of isolable -dihydrodiol metabolites. These docking results of quinoline and pyridine substrates, with TDO, also provided support for the postulated -dihydroxylation of electron-deficient pyridyl rings, to give transient -dihydrodiol intermediates and the derived hydroxyquinolines. 2-Chloroquinoline -dihydrodiol metabolites were used as precursors in the chemoenzymatic synthesis of enantiopure arene oxide and arene dioxide derivatives of quinoline, in the context of its possible mammalian metabolism and carcinogenicity.