High-valent iron(IV)-oxo intermediates are versatile oxidants in the biotransformation of various substrates by metalloenzymes and catalyze essential reactions for human health as well as in the biodegradation of toxic organic pollutants in the environment. Herein, we report a biomimetic system that efficiently reacts with halophenols through defluorination reactions and characterize various short-lived intermediates along the reaction mechanism. We study the reactivity pattern of a nonheme iron(IV)-oxo species with a series of trihalophenols (X=F, Cl, Br). A combined experimental and computational study reveals that the oxidative dehalogenation of 2,4,6-trifluorophenol is initiated with an Hatom abstraction from the phenolic group by the iron(IV)-oxo species resulting in the formation of a phenolate radical and an iron(III)-hydroxo species. This iron(III)-hydroxo species forms an adduct with the oxidized substrate with λ max at 558 nm which subsequently decays to give quinones as products.

Bisphenol A (BPA, 2,2-bis-(4-hydroxyphenyl)propane) is used as a precursor in the synthesis of polycarbonate and epoxy plastics; however, its availability in the environment is causing toxicity as an endocrine-disrupting chemical. Metabolism of BPA and their analogues (substitutes) is generally performed by liver cytochrome P450 enzymes and often leads to a mixture of products, and some of those are toxic. To understand the product distributions of P450 activation of BPA, we have performed a computational study into the mechanisms and reactivities using large model structures of a human P450 isozyme (P450 2C9) with BPA bound. Density functional theory (DFT) calculations on mechanisms of BPA activation by a P450 compound I model were investigated, leading to a number of possible products. The substrate-binding pocket is tight, and as a consequence, aliphatic hydroxylation is not feasible as the methyl substituents of BPA cannot reach compound I well due to constraints of the substrate-binding pocket. Instead, we find low-energy pathways that are initiated with phenol hydrogen atom abstraction followed by OH rebound to the phenolic ortho-or para-position. The barriers of para-rebound are well lower in energy than those for ortho-rebound, and consequently, our P450 2C9 model predicts dominant hydroxycumyl alcohol products. The reactions proceed through two-state reactivity on competing doublet and quartet spin state surfaces. The calculations show fast and efficient substrate activation on a doublet spin state surface with a rate-determining electrophilic addition step, while the quartet spin state surface has multiple high-energy barriers that can also lead to various side products including C 4 -aromatic hydroxylation. This work shows that product formation is more feasible on the low spin state, while the physicochemical properties of the substrate govern barrier heights of the rate-determining step of the reaction. Finally, the importance of the second-coordination sphere is highlighted that determines the product distributions and guides the bifurcation pathways.

Tri11 (now renamed as tri22) encoded cytochrome P 450 monooxygenase in Trichoderma brevicompactum catalyzes the C-4 C-H hydroxylation of 12, 13-epoxytrichothec-9-ene (EPT) to produce trichodermol in the biosynthetic pathway of trichodermin/harzianum A. The density functional theory (DFT)-quantum mechanics (QM) approach is applied to elucidate the hydroxylation of EPT by using a model active species of P 450 (Cpd I). The QM calculations were performed on the active site complex, to find out transition-state structure, intermediate, and product complexes for the two spin states at different potential energy surfaces. The two state reactivity rebound-free product formation resulted from the interplay of two spin states (doublet and quartet). K E Y W O R D S cytochrome P 450 monooxygenase, density functional theory, high spin state, low spin state, Trichoderma brevicompactum

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Computational docking is a globally used tool now-a-days in bioinformatics. All the drugs/ligands generate their effect only when they interact/bind with the target molecule, here DNA. The potential drugs/ligands can only be identified by the study of their relative binding energies and preferential binding modes. Due to availability of huge numbers of such drugs/ligands; the evaluation of their relative potency is a challenging task. In the present work, carbazoles and its derivatives were studied for their DNA binding abilities using computational molecular docking. All the docked ligands had planar structures which allowed them to adopt crescent shape and thus minor groove binding to DNA was preferred by most of them. Computational docking revealed that DNA binding energies of carbazoles and its analogs followed the same trend as their thermal melting values. Also the drugs/ligands preferred themselves to bind at AT-rich regions of the minor groove of the selected DNA sequences.