Intramolecular Phenolic H-Atom Abstraction by a N3ArOH Ligand-Supported (µ-η2:η2-Peroxo)dicopper(II) Species Relevant to the Active Site Function of oxy-Tyrosinase.

Synthetic side-on peroxide-bound dicopper(II) (SP) complexes are important for understanding the active site structure/function of many copper-containing enzymes. This work highlights the formation of new {CuII(µ-η2:η2-O22-)CuII} complexes (with electronic absorption and resonance Raman (rR) spectroscopic characterization) using tripodal N3ArOH ligands at -135 °C, which spontaneously participate in intramolecular phenolic H-atom abstraction (HAA). This results in the generation of bis(phenoxyl radical)bis(µ-OH)dicopper(II) intermediates, substantiated by their EPR/UV-vis/rR spectroscopic signatures and crystal structural determination of a diphenoquinone dicopper(I) complex derived from ligand para-C═C coupling. The newly observed chemistry in these ligand-Cu systems is discussed with respect to (a) our Cu-MeAN (tridentate N,N,N',N',N″-pentamethyldipropylenetriamine)-derived model SP species, which was unreactive toward exogenous monophenol addition (J. Am. Chem. Soc. 2012, 134, 8513-8524), emphasizing the impact of intramolecularly tethered ArOH groups, and (b) recent advances in understanding the mechanism of action of the tyrosinase (Ty) enzyme.

Kß X-ray Emission Spectroscopy of Cu(I)-Lytic Polysaccharide Monooxygenase: Direct Observation of the Frontier Molecular Orbital for H2O2 Activation.

Lytic polysaccharide monooxygenases (LPMOs) catalyze the degradation of recalcitrant carbohydrate polysaccharide substrates. These enzymes are characterized by a mononuclear Cu(I) active site with a three-coordinate T-shaped "His-brace" configuration including the N-terminal histidine and its amine group as ligands. This study explicitly investigates the electronic structure of the d10 Cu(I) active site in a LPMO using Kß X-ray emission spectroscopy (XES). The lack of inversion symmetry in the His-brace site enables the 3d/p mixing required for intensity in the Kß valence-to-core (VtC) XES spectrum of Cu(I)-LPMO. These Kß XES data are correlated to density functional theory (DFT) calculations to define the bonding, and in particular, the frontier molecular orbital (FMO) of the Cu(I) site. These experimentally validated DFT calculations are used to evaluate the reaction coordinate for homolytic cleavage of the H2O2 O-O bond and understand the contribution of this FMO to the low barrier of this reaction and how the geometric and electronic structure of the Cu(I)-LPMO site is activated for rapid reactivity with H2O2.

Fenton-like Chemistry by a Copper(I) Complex and H2O2 Relevant to Enzyme Peroxygenase C-H Hydroxylation.

Lytic polysaccharide monooxygenases have received significant attention as catalytic convertors of biomass to biofuel. Recent studies suggest that its peroxygenase activity (i.e., using H2O2 as an oxidant) is more important than its monooxygenase functionality. Here, we describe new insights into peroxygenase activity, with a copper(I) complex reacting with H2O2 leading to site-specific ligand-substrate C-H hydroxylation. [CuI(TMG3tren)]+ (1) (TMG3tren = 1,1,1-Tris{2-[N2-(1,1,3,3-tetramethylguanidino)]ethyl}amine) and a dry source of hydrogen peroxide, (o-Tol3P═O·H2O2)2 react in the stoichiometry, [CuI(TMG3tren)]+ + H2O2 → [CuI(TMG3tren-OH)]+ + H2O, wherein a ligand N-methyl group undergoes hydroxylation giving TMG3tren-OH. Furthermore, Fenton-type chemistry (CuI + H2O2 → CuII-OH + ·OH) is displayed, in which (i) a Cu(II)-OH complex could be detected during the reaction and it could be separately isolated and characterized crystallographically and (ii) hydroxyl radical (·OH) scavengers either quenched the ligand hydroxylation reaction and/or (iii) captured the ·OH produced.