Intramolecular Ligand Hydroxylation:  Mechanistic High-Pressure Studies on the Reaction of a Dinuclear Copper(I) Complex with Dioxygen

We provide a mechanistic study of a monooxygenase model system and detail low-temperature stopped-flow kinetics studies in acetone as solvent, employing both the use of rapid-scanning diode-array observation and variable high-pressure (20−100 MPa) techniques. The dicopper(I) complex employed is [Cu2(H-XYL-H)]2+ (1), with the H-XYL-H ligand wherein a m-xylyl group links two bis[2-(2-pyridyl)ethyl]amine units. This reacts with O2 reversibly (k 1/k - 1) giving a peroxo−dicopper(II) intermediate [Cu2(H-XYL-H)(O2)]2+ (2), which thereupon irreversibly (k 2) reacts by oxygen atom insertion (i.e., hydroxylation) of the xylyl group, producing [Cu2(H-XYL-O-)(OH)]2+ (3). Activation parameters are as follows: k 1, ΔH ⧧ = 2.1 ± 0.7 kJ/mol, ΔS ⧧ = −174 ± 3 J/(K mol); k - 1, ΔH ⧧ = 80.3 ± 0.8 kJ/mol, ΔS ⧧ = 77 ± 3 J/(K mol); k 2, ΔH ⧧ = 58.2 ± 0.2 kJ/mol, ΔS ⧧ = −5.8 ± 0.9 J/(K mol). These values are similar to values obtained in a previous study in dichloromethane. At low temperatures and higher concentrations, the situation in acetone is complicated by a pre-equilibrium of 1 to an isomer form. The present study provides the first determination of activation volumes for individual steps in copper monooxygenase reactions. The data and analysis provide that ΔV ⧧(k 1) = −15 ± 2.5 cm3/mol and ΔV ⧧(k - 1) = +4.4 ± 0.5 cm3/mol for formation and dissociation of 2, respectively, while ΔV ⧧(k 2) = −4.1 ± 0.7 cm3/mol; a volume profile for the overall reaction has been constructed. The significance of the findings in the present study is described, and the results are compared to those for other systems.