Recent Computational Insights into the Oxygen Activation by Copper-Dependent Metalloenzymes

Direct Benzene Hydroxylation with Dioxygen Induced by Copper Complexes: Uncovering the Active Species by DFT Calculations

“…However, by approaching the copper atoms (“closed” conformation), a stable binuclear Cu I (μ-OOH)Cu II species affords the more stable species Cu II (μ-O • )(μ-OH)Cu II , which is the reactive intermediate responsible for substrate hydroxylation. 11b , 26 This is the same active species 7 we found for the hydroxylation of benzene promoted by Tp Br3 Cu, proving for first time that it can also operate in synthetic systems. As for the enzyme, neither Cu II –superoxo nor Cu II (hydroperoxo) is reactive toward substrate hydroxylation.…”

“…Very recently, a thorough computational study has afforded a new perspective for O 2 activation and substrate hydroxylation by binuclear copper monooxygenases . As in our system, the proposed active species for substrate hydroxylation has a Cu II (μ-O • )­(μ-OH)­Cu II nature.…”

“…Very recently, a thorough computational study has afforded a new perspective for O 2 activation and substrate hydroxylation by binuclear copper monooxygenases. 26 As in our system, the proposed active species for substrate hydroxylation has a Cu II (μ-O • )(μ-OH)Cu II nature. Scheme 4 compares the key steps for the formation of such species for binuclear copper monooxygenases with our results for Tp Br3 Cu.…”

“…Although these enzymes contain two copper­(I) cofactors very far away (about 11 Å, “open” conformation), this study showed that in the presence of cosubstrate ascorbate hydrogen-atom abstraction leads to the formation of a Cu­(II)–OOH intermediate that is inert toward H abstraction from the substrate. However, by approaching the copper atoms (“closed” conformation), a stable binuclear Cu I (μ-OOH)­Cu II species affords the more stable species Cu II (μ-O • )­(μ-OH)­Cu II , which is the reactive intermediate responsible for substrate hydroxylation. , This is the same active species 7 we found for the hydroxylation of benzene promoted by Tp Br3 Cu, proving for first time that it can also operate in synthetic systems. As for the enzyme, neither Cu II –superoxo nor Cu II (hydroperoxo) is reactive toward substrate hydroxylation .…”

Theoretical perspective on mononuclear copper-oxygen mediated C–H and O–H activations: A comparison between biological and synthetic systems

“…In addition to pMMO, the copper-oxygen species in lytic polysaccharide monooxygenases (LPMOs, Fig. 1(b)) can activate the C-H bond of polysaccharides (BDE of cellulose: 100 kcal/mol) [42], resulting in the degradation of polysaccharides such as chitin and cellulose [15,31,[43][44][45][46][47][48][49][50][51][52]]. In the "uncoupled" binuclear copper enzymes, including peptidylglycine α-hydroxylating monooxygenase (PHM), dopamine β-monooxygenase (DβM), and tyramine β-monooxygenase (TβM), two copper sites (CuM and CuH) are separated by a distance of ~11 Å without bridging ligands (Fig.…”