title: Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure-reactivity correlations.
abstract: Four new imidazole-based ligands, 4-((1H-imidazol-4-yl)methyl)-2-phenyl-4,5-dihydrooxyzole (L OL 1), 4-((1H-imidazol-4-yl)methyl)-2-(tert-butyl)-4,5-dihydrooxyzole (L OL 2), 4-((1H-imidazol-4-yl)methyl)-2-methyl-4,5-dihydrooxyzole (L OL 3), and N-(2,2-dimethylpropylidene)-2-(1-trityl-1H-imidazol-4-yl-)ethyl amine (L imz 1), have been synthesized. The corresponding copper(I) complexes [Cu(I)(L OL 1)(CH3CN)]PF6 (CuL OL 1), [Cu(I)(L OL 2)(CH3CN)]PF6 (CuL OL 2), [Cu(I)(L OL 3)(CH3CN)]PF6 (CuL OL 3), [Cu(I)(L imz 1)(CH3CN)2]PF6 (CuL imz 1) as well as the Cu(I) complex derived from the known ligand bis(1-methylimidazol-2-yl)methane (BIMZ), [Cu(I)(BIMZ)(CH3CN)]PF6 (CuBIMZ), are screened as catalysts for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC-H2) to 3,5-di-tert-butylquinone (3,5-DTBQ). The primary reaction product of these oxidations is 3,5-di-tert-butylsemiquinone (3,5-DTBSQ) which slowly converts to 3,5-DTBQ. Saturation kinetic studies reveal a trend of catalytic activity in the order CuL OL 3 ≈ CuL OL 1 > CuBIMZ > CuL OL 2 > CuL imz 1. Additionally, the catalytic activity of the copper(I) complexes towards the oxygenation of monophenols is investigated. As substrates 2,4-di-tert-butylphenol (2,4-DTBP-H), 3-tert-butylphenol (3-TBP-H), 4-methoxyphenol (4-MeOP-H), N-acetyl-L-tyrosine ethyl ester monohydrate (NATEE) and 8-hydroxyquinoline are employed. The oxygenation products are identified and characterized with the help of UV/Vis and NMR spectroscopy, mass spectrometry, and fluorescence measurements. Whereas the copper complexes with ligands containing combinations of imidazole and imine functions or two imidazole units (CuL imz 1 and CuBIMZ) are found to exhibit catalytic tyrosinase activity, the systems with ligands containing oxazoline just mediate a stoichiometric conversion. Correlations between the structures of the complexes and their reactivities are discussed.
authors.affiliation: Institute of Inorganic Chemistry, Christian-Albrechts-University, Max-Eyth-Straße 2, 24118, Kiel, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wendt
authors.affiliation: Institute of Inorganic Chemistry, Christian-Albrechts-University, Max-Eyth-Straße 2, 24118, Kiel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Näther
authors.affiliation: Institute of Inorganic Chemistry, Christian-Albrechts-University, Max-Eyth-Straße 2, 24118, Kiel, Germany. ftuczek@ac.uni-kiel.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Tuczek
mesh_terms: D004156:Catechol Oxidase / Q000737:chemistry / Q000378:metabolism*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D014442:Monophenol Monooxygenase / Q000737:chemistry / Q000378:metabolism*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D008024:Ligands; D009942:Organometallic Compounds; D003300:Copper; D004156:Catechol Oxidase; D014442:Monophenol Monooxygenase
keywords: Catechol oxidase; Dioxygen activation; Kinetics; Type 3 copper enzymes; Tyrosinase