No abstract
Mechanistic studies on the aliphatic ligand hydroxylation in a copper complex of tridentate ligand 1a {N,N-bis[2-(2-pyridyl)ethyl]-2-phenylethylamine} by O2 have been performed in order to shed light on the structure and reactivity of the active oxygen species of our functional model for copper monooxygenases (Itoh, S.; et al. J. Am. Chem. Soc. 1995, 117, 4714). When the copper complex [CuII(1a)(ClO4)2] was treated with an equimolar amount of benzoin and triethylamine in CH2Cl2 under O2 atmosphere, efficient hydroxylation occurred selectively at the benzylic position of the ligand to provide oxygenated product 2a {N,N-bis[2-(2-pyridyl)ethyl]-2-phenyl-2-hydroxyethylamine} quantitatively. An isotope labeling experiment using 18O2 confirms that the oxygen atom of the OH group in 2a originates from molecular oxygen. Spectroscopic analyses using UV−vis, resonance Raman, and ESR on the reaction of [CuI(1a)]+ and O2 at low temperature show that a μ-η2:η2-peroxodicopper(II) complex is an initially formed intermediate. Kinetic analysis on the peroxo complex formation indicates that the reaction of the Cu(I) complex and the monomeric superoxocopper(II) species is rate-determining for the formation of the μ-η2:η2-peroxodicopper(II) intermediate. When ligand 1a is replaced by 1,1,2,2-tetradeuterated phenethylamine derivative 1a- d 4, a relatively small kinetic deuterium isotope effect (k H/k D = 1.8 at −40 °C) is observed for the ligand hydroxylation step. The rate of the hydroxylation step is rather insensitive to the p-substituent of the ligand [(PyCH2CH2)2NCH2CH2Ar, 1a Ar = C6H5; 1b Ar = p-CH3C6H4, 1c Ar = p-ClC6H4, and 1d Ar = p-NO2C6H4)], but it varies depending on the solvent (THF > acetone > CH3OH > CH2Cl2). The p-substituent, the solvent, and the kinetic deuterium isotope effects suggest that O−O bond homolysis of the μ-η2:η2-peroxodicopper(II) intermediate is involved as a rate-determining step in the aliphatic ligand hydroxylation process. Based on the results of the kinetics and the crossover experiments, we propose a mechanism involving intramolecular C−H bond activation in a bis-μ-oxodicopper(III) type intermediate for the ligand hydroxylation reaction.
The electronic effect of the thioether linkage between Tyr 272 and Cys 228 (the novel organic cofactor) of galactose oxidase has been examined by using model compounds, 2-(methylthio)-p-cresol (1H), 2-(methylthio)-4,6-dimethylphenol (2H), and 2-(methylthio)-4-methyl-6-[[bis[2-(2-pyridyl)ethyl]amino]methyl]phenol (3H), the physicochemical properties of which are compared to those of 2-[[bis[2-(2-pyridyl)ethyl]amino]methyl]-4-methylphenol (4H) and p-cresol (5H). (1)H NMR and electrochemical studies indicate that the methylthio group has essentially an electron-donating nature. On the other hand, the lower pK(a) values of 1H and 2H as compared to that of 5H suggest that the methylthio group also has a 2ppi-3dpi electron conjugative effect, stabilizing the negative charge on the phenolate oxygen. Furthermore, the electron-sharing conjugative effect of the substituent in the radical state has been clearly demonstrated by ESR studies and semiempirical molecular orbital calculations. Dimer copper(II) complexes [Cu(II)(2)(3(-)())(2)](PF(6))(2) (7) and [Cu(II)(2)(4(-)())(2)](PF(6))(2) (8) were prepared, and the crystal structures were determined by the X-ray diffraction method. Electrochemical analyses of the monomeric species [Cu(II)(3(-)())(py)](PF(6)) (9) and [Cu(II)(4(-)())(py)](PF(6)) (10) generated in situ by adding an external ligand such as pyridine (py) reveal that the methylthio substituent in the copper complex shows electronic effects similar to those of the free ligand stabilizing the phenoxyl radical state of the cofactor moiety in the Cu(II) complex.
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