Substrate sulfoxidation by a biomimetic cytochrome P450 Compound I mimic: How do porphyrin and phthalocyanine equatorial ligands compare?

Roach, Saaid; Faponle, Abayomi S.; Satpathy, Jagnyesh Kumar; Sastri, Chivukula V.; Visser, Sam P. de

doi:10.1007/s12039-021-01917-2

Cited by 2 publications

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“…Because there is no crystal structure of CyaH available, the computational model system was set up with an oxo-iron(IV)(porphyrin +· ) complex, Fe 4+ O 2– (C 20 N 4 H 12 ) − (SH) − , as the model of compound I (CpdI) of the P450 CyaH. − The nonpolar enzymatic environment was mimicked with the conductor-like polarizable continuum model (CPCM, chlorobenzene (ε = 5.62) was employed as the solvent) in the self-consistent reaction field (SCRF) calculations. The coordinate of the reagent cyanogramide D (Scheme d) was obtained from the Cambridge Crystallographic Data Center with the deposition number CCDC-1956558 .…”

Section: Computation Methodologymentioning

confidence: 99%

Theoretical Investigation on the Elusive Reaction Mechanism of Spirooxindole Formation Mediated by Cytochrome P450s: A Nascent Feasible Charge-Shift C–O Bond Makes a Difference

et al. 2021

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Spirooxindoles are pivotal biofunctional groups widely distributed in natural products and clinic drugs. However, construction of such subtle chiral skeletons is a long-standing challenge to both organic and bioengineering scientists. The knowledge of enzymatic spirooxindole formation in nature may inspire rational design of new catalysts. To this end, we presented a theoretical investigation on the elusive mechanism of the spiro-ring formation at the 3-position of oxindole mediated by cytochrome P450 enzymes (P450). Our calculated results demonstrated that the electrophilic attack of CpdI, the active species of P450, to the substrate, shows regioselectivity, i.e., the attack at the C9 position forms a tetrahedral intermediate involving an unusual feasible charge-shift C9 δ+ −O δ− bond, while the attack at the C1 position forms an epoxide intermediate. The predominant route is the first route with the charge-shift bonding intermediate due to holding a relatively lower barrier by >5 kcal mol −1 than the epoxide route, which fits the experimental observations. Such a delocalized chargeshift bond facilitates the formation of a spiro-ring mainly through elongation of the C1−C9 bond to eliminate the aromatization of the tricyclic beta-carboline. Our theoretical results shed profound mechanistic insights for the first time into the elusive spirooxindole formation mediated by P450s.

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Section: Computation Methodologymentioning

confidence: 99%

Theoretical Investigation on the Elusive Reaction Mechanism of Spirooxindole Formation Mediated by Cytochrome P450s: A Nascent Feasible Charge-Shift C–O Bond Makes a Difference

et al. 2021

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“…The reactivity of peroxides bound to a metal ion is remarkably diverse and the factors dictating the particular mode of reactivity are continuously debated. − Homolytic and heterolytic O–O bond cleavages have been observed in a variety of complexes and, among the different factors that can influence the reactivity, interactions related to the substrate–catalyst recognition event have attracted increasing interest being central in the final outcome, in particular for stereoselective processes. − Even if the mechanism of oxygen transfer continues to be a controversial subject, widely accepted is that a “Sharpless type” pathway is involved in the oxidation step (Scheme , path a) and the active species is an η 2 coordinated alkyl (or hydro) peroxo complex. The nucleophilic attack of the substrate to the electrophilic peroxo oxygen follows the antibonding σ* orbital (O 1 –O 2 ).…”

Section: Introductionmentioning

confidence: 99%

Elucidating Sulfide Activation Mode in Metal-Catalyzed Sulfoxidation Reactivity

et al. 2022

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Interest in the catalytic activation of peroxides, together with the requirement of stereoselectivity for the production of enantiopure sulfoxides, has made sulfoxidation the ideal playground for theoretical and experimental physical organic chemists investigating oxidation reactivity. Efforts have been dedicated for elucidating the catalytic pathway regarding these species and for dissecting out the dominant factors influencing the yield and stereochemistry. In this article, Ti(IV) and Hf(IV) aminotriphenolate complexes have been prepared and investigated as catalysts in the presence of peroxides in sulfide oxidation. Experimental results have been combined with theoretical calculations obtaining detailed mechanistic information on oxygen transfer processes. The study revealed that steric issues are mainly responsible for the formation of intermediates in the oxidation pathway. In particular, we could highlight the occurrence of a blended situation where the steric effects of sulfides, ligands, and oxidants influence the formation of different intermediates and reaction pathways.

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Substrate sulfoxidation by a biomimetic cytochrome P450 Compound I mimic: How do porphyrin and phthalocyanine equatorial ligands compare?

Cited by 2 publications

References 97 publications

Theoretical Investigation on the Elusive Reaction Mechanism of Spirooxindole Formation Mediated by Cytochrome P450s: A Nascent Feasible Charge-Shift C–O Bond Makes a Difference

Theoretical Investigation on the Elusive Reaction Mechanism of Spirooxindole Formation Mediated by Cytochrome P450s: A Nascent Feasible Charge-Shift C–O Bond Makes a Difference

Elucidating Sulfide Activation Mode in Metal-Catalyzed Sulfoxidation Reactivity

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