title: Simplest Monodentate Imidazole Stabilization of the oxy-Tyrosinase Cu2 O2 Core: Phenolate Hydroxylation through a Cu(III) Intermediate.
abstract: Tyrosinases are ubiquitous binuclear copper enzymes that oxygenate to Cu(II) 2 O2 cores bonded by three histidine Nτ-imidazoles per Cu center. Synthetic monodentate imidazole-bonded Cu(II) 2 O2 species self-assemble in a near quantitative manner at -125 °C, but Nπ-ligation has been required. Herein, we disclose the syntheses and reactivity of three Nτ-imidazole bonded Cu(II) 2 O2 species at solution temperatures of -145 °C, which was achieved using a eutectic mixture of THF and 2-MeTHF. The addition of anionic phenolates affords a Cu(III) 2 O2 species, where the bonded phenolates hydroxylate to catecholates in high yields. Similar Cu(III) 2 O2 intermediates are not observed using Nπ-bonded Cu(II) 2 O2 species, hinting that Nτ-imidazole ligation, conserved in all characterized Ty, has functional advantage beyond active-site flexibility. Substrate accessibility to the oxygenated Cu2 O2 core and stabilization of a high oxidation state of the copper centers are suggested from these minimalistic models.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Linus
authors.initials: L
authors.lastname: Chiang
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA, 94305, USA.
authors.forename: William
authors.initials: W
authors.lastname: Keown
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA, 94305, USA.
authors.forename: Cooper
authors.initials: C
authors.lastname: Citek
authors.affiliation: Department Chemistry and Biochemistry, California State University, Chico, CA, 95929, USA.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Wasinger
authors.affiliation: Department of Chemistry, Stanford University, Stanford, CA, 94305, USA. stack@stanford.edu.
authors.forename: T Daniel P
authors.initials: TD
authors.lastname: Stack
mesh_terms: D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000378:metabolism*; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D011789:Quantum Theory
chemical_list: D056831:Coordination Complexes; D007093:Imidazoles; D010636:Phenols; D003300:Copper; C029899:imidazole; D014442:Monophenol Monooxygenase; C030973:cupric oxide
keywords: Nτ imidazole ligation; coordination chemistry; copper dioxygen; extreme solution temperatures