Oxidative biotransformations of phenol substrates catalysed by toluene dioxygenase: A molecular docking study

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

“…Molecular docking studies of TDO-catalyzed cisdihydroxylations of mono-and di-substituted benzene substrates were conducted in other laboratories, using the GOLD program (Vila et al, 2016a(Vila et al, ,b, 2017. AutoDock and AutoDock Vina programs have similarly been used in our laboratories, to study TDO-catalyzed cis-dihydroxylation of other types of monocyclic arenes, e.g., substituted phenols and anilines and tricyclic heteroarenes, e.g., dibenzofuran and dibenzothiophene (Hoering et al, 2016;Boyd et al, 2017Boyd et al, , 2019. Relative free binding energies (kcal/mol −1 ) and relative proximity of arene bonds to dioxygen, within the TDO active site (Å), were determined by applying the AutoDock Vina program to monocyclic arenes (toluene, chlorobenzene) and mono-and bicyclic-azarenes in the current study.…”

“…2.6-2.8 Å and observed distances ca. 2.70-2.86 Å, from X-ray crystallographic analysis, using a range of model systems (Hoering et al, 2016;Boyd et al, 2019). Keyhole pictures, looking through the rear face of the component aromatic ring, showed both edge to face-T (Supplementary Figures 4A 3 ,B 3 ,C 3 ), and face tilted-T dockings (Supplementary Figures 4A 2 ,B 2 ,C 2 ) of quinoline 1 with TDO.…”

Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, cis-Dihydroxylation and Epoxidation

“…The interaction between dioxygen and Fe(III) during the catalysis of the cis-dihydroxylation is considered to involve a hydroperoxide (Fe-OOH) [29]. Attractive interactions between substrates and proximate amino acids (Phe-216, His-222, Ile-276, Leu-272, Ile-324, Val-309, Leu-272, Figure 1A) allow the preferred binding orientation to be predicted; it matched both with the regio-and stereo-selectivity observed during TDO-catalyzed cis-dihydroxylation of toluene and other substituted benzene substrates to form cis-dihydrodiols (Scheme 1a) [72,[74][75][76][77][78][79]. A similar in situ docking approach, applied earlier to other arene and heteroarene substrates [71,72], was used to determine the preferred binding orientations of thiophene 1a (Figure 1A,B) and 2-phenylthiophene 1g (Figure 2A,B).…”

“…The Autodock Vina program was used for docking toluene A (R = Me, Scheme 1a) and other arene and heteroarene substrates within the active site of toluene dioxygenase [71,72]. An X-ray crystal structure of the TDO showed the toluene substrate bound at the active site by proximate amino acids but without dioxygen complexed to Fe(III) [73].…”

“…An X-ray crystal structure of NDO displayed dioxygen coordinated with Fe(III) and indole substrate bonded at the active site [74]. The O 2 -Fe(III) complex of NDO was then inserted into the TDO active site employing the reported procedure [72]. The interaction between dioxygen and Fe(III) during the catalysis of the cis-dihydroxylation is considered to involve a hydroperoxide (Fe-OOH) [29].…”