Reversible dioxygen binding and aromatic hydroxylation in O2-reactions with substituted xylyl dinuclear copper(I) complexes: Syntheses and low-temperature kinetic/thermodynamic and spectroscopic investigations of a copper monooxygenase model system

Article abstract of DOI:10.1021/ja00083a018

The binding and subsequent reactivity of dioxygen (O₂) upon binding to copper ion centers is of fundamental interest in chemical and biological processes. We provide here a detailed account of the reaction of O₂ with dicopper(I) complexes, involving O₂-reversible binding, followed by the stoichiometric aromatic hydroxylation of the ligand. Thus, tricoordinated dicopper(I) complexes [Cu₂(R-XYL)]²⁺ (R = H, MeO, t-Bu, F, CN, NO₂; 1a-f) possess dinucleating meta-substituted xylylene ligands with two chelating tridentate bis[2-(2-pyridyl)ethyl]amine (PY2) moieties and a 5-R substituent. Upon reaction with O₂, dioxygen adducts [Cu₂(R-XYL)(O₂)]²⁺ (2a,c-f) form reversibly, and these subsequently yield 2-xylylene-hydroxylated products [Cu₂(R-XYL-O^-)(OH)]²⁺ (3a-f), which are phenoxo- and hydroxo-bridged copper(II) complexes. The products 3 have been characterized via the X-ray structure of the parent complex 3a, and by their UV-visible, infrared, and room-temperature magnetic properties. Incorporation of the O-atom from dioxygen into the phenolic products has been proven by isotopic labeling experiments, except in the case of 3f, where workup results in an exchange reaction causing loss of the oxygen label. In reactions of O₂ with 1 in dichloromethane at room temperature, 10-25% yields of unhydroxylated complexes [Cu₂(R-XYL)(OH)]³⁺ (5) are obtained. A stopped-flow kinetics study of O₂ reactions of 1 in CH₂Cl₂ demonstrates that [Cu₂(R-XYL)(O₂)]²⁺ (2a,c-f) complexes form reversibly, proceeding via the reaction 1 + O₂ ? 2 (K₁ = k₁/k_-1); this is followed by the irreversible reaction 2 → 3 (k₂). Analysis of temperature-dependent data which is accompanied by spectrophotometric monitoring yields both kinetic and thermodynamic parameters for R = H, t-Bu, F, and NO₂. Dioxygen binding to 1 occurs in a single observable step with low activation enthalpies (6-29 kJ mol^-1) and large, negative activation entropies (-66 to -167 J K^-1 mol^-1). The remote R-substituent has a significant effect on the dioxygen-binding process and this is explained in terms of its multistep nature. Strong binding (K₁) occurs at low temperature (e.g. -80 °C), and thermodynamic parameters indicate a large enthalpic contribution (ΔH° = -52 to -74 kJ mol^-1), but room-temperature stabilities of the dioxygen adducts are precluded by very large unfavorable entropies (ΔS° = -156 to -250 J K^-1 mol^-1). Electron-releasing R-substituents cause a small but significant enhancement of k₂, the hydroxylation step, consistent with a mechanism involving electrophilic attack of the Cu₂O₂ intermediate 2 upon the xylyl aromatic ring. The influence of substituent upon the various rates of reaction allows for stabilization (～minutes), allowing the bench-top observation of 2d,e,f using UV-visible spectroscopy at -80 °C. "Vacuum-cycling" experiments can be carried out on 1f/2f, i.e., the repetitive oxygenation of 1f at -80 °C, followed by removal of O₂ from 2f by application of a vacuum. Dicopper(I) complexes I have been characterized by ¹H and ¹³C NMR spectroscopy, along with analogs in which an ethyl group has been placed in the 5-position of the pyridyl ring donor groups, i.e., [Cu^I₂(R-XYL-(5-Et-PY))]²⁺ (1g, R = H; 1h, R = NO₂). Variable-temperature ¹H NMR spectroscopic studies provide clues as to why [Cu₂(MeO-XYL)]²⁺ (1b) does not oxygenate (i.e., bind O₂ and/or hydroxylate) at low temperature, the conclusion being that significant interactions of the coordinately unsaturated copper(I) ion(s) with the chelated methoxybenzene group result in conformations unsuitable for O₂-reactivity. The biological implications of the biomimetic chemistry described here are discussed, as a system effecting oxidative C-H functionalization using O₂ under mild conditions and as a monooxygenase model system for tyrosinase (phenol o-monooxygenase), with its dinuclear active site.