REVERSIBLE DIOXYGEN BINDING AND AROMATIC HYDROXYLATION IN O-2-REACTIONS WITH SUBSTITUTED XYLYL DINUCLEAR COPPER(I) COMPLEXES - SYNTHESES AND LOW-TEMPERATURE KINETIC THERMODYNAMIC AND SPECTROSCOPIC INVESTIGATIONS OF A COPPER MONOOXYGENASE MODEL SYSTEM/

The binding and subsequent reactivity of dioxygen (O-2) upon binding t o copper ion centers is of fundamental interest in chemical and biolog ical processes. We provide here a detailed account of the reaction of O-2 with dicopper(I) complexes, involving O-2-reversible binding, foll owed by the stoichiometric aromatic hydroxylation of the ligand. Thus, tricoordinated dicopper(I) complexes [Cu-2(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 O-2, dioxygen adducts [Cu-2(R-XYL)(O-2)](2+) (2a,c-f) form reversibly, and these sub sequently yield 2-xylylene-hydroxylated products [Cu-2(R-XYL-O-)(OH)]( 2+)(3a-f), which are phenoxo- and hydroxobridged 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-temper ature magnetic properties. Incorporation of the O-atom from dioxygen i nto the phenolic products has been proven by isotopic labeling experim ents, except in the case of 3f; where workup results in an exchange re action causing loss of the oxygen label. In read-ions of O-2 With 1 in dichloromethane at room temperature, 10-25% yields of unhydroxylated complexes [Cu-2(R-XYL)(OH)](3+) (5) are obtained. A stopped-flow kinet ics study of O-2 reactions of 1 in CH2Cl2 demonstrates that [Cu-2(R-XY L)(O-2)](2+) (2a,c-f) complexes form reversibly, proceeding via the re action 1 + O-2 reversible arrow 2 (K-1 = k(1)/k(-1); this is followed by the irreversible reaction 2 - 3 (k(2)). Analysis of temperature-dep endent data which is accompanied by spectrophotometric monitoring yiel ds both kinetic and thermodynamic parameters for R = H, t-Bu, F, and N O2. 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 explain ed in terms of its multistep nature. Strong binding (K-1) occurs at lo w temperature (e.g. -80 degrees C), and thermodynamic parameters indic ate a large enthalpic contribution (Delta H degrees = -52 to -74 kJ me l(-1), but room-temperature stabilities of the dioxygen adducts are pr ecluded by very large unfavorable entropies (Delta S degrees - -156 to -250 J K-1 mol(-1)). Electron-releasing R-substituents cause a small but significant enhancement of k(2), the hydroxylation step, consisten t with a mechanism involving electrophilic attack of the Cu2O2 interme diate 2 upon the xylyl;ylyl aromatic ring. The influence of substituen t upon the various rates of reaction allows for stabilization (similar to minutes), allowing the bench-top observation of 2d,e,f using W-vis ible spectroscopy at -80 degrees C. ''Vacuum-cycling'' experime:nts ca n be carried out on 1f/2f, i.e., the repetitive oxygenation of 1f at-8 0 degrees C, followed by removal of O-2 from 2f by a application of a vacuum. Dicopper(I) complexes I have been characterized by H-1 and C-1 3 NMR spectroscopy, along with analogs in which an ethyl group has bee n placed in the 5-position of the pyridyl ring donor groups, i.e., [Cu -2(I)(R-XYL-(5-Et-PY))](2+) (1g, R = H; 1h, R = NO2). Variable-tempera ture H-1 NMR spectroscopic studies provide clues as to why [Cu-2(MeO-X YL)](2+) (1b) does not oxygenate (i.e., bind O-2 and/or hydroxy)rlate) at low temperature, the conclusion being that significant interaction s of the coordinately unsaturated copper(I) ion(s) with the chelated m ethoxybenzene group result in conformations unsuitable for O-2-reactiv ity. The biological implications of the biomimetic chemistry described here are discussed, as a system effecting oxidative C-H functionaliza tion using O-2 under mild conditions and as a monooxygenase model syst em for tyrosinase (phenol o-monooxygenase), with its dinuclear active site.