title: Mechanistic insights from reactions between copper(II)-phenoxyl complexes and substrates with activated C-H bonds.
abstract: The reactivities of two copper(II)-phenoxyl analogues of the oxidized, active form of the metalloenzyme galactose oxidase, [1tBu2]+ and [2tBu2]+, have been studied using the substrates benzyl alcohol and 9,10-dihydroanthracene, for a total of four reactions. The reaction stoichiometries in all cases show a 2:1 ratio of oxidant to benzaldehyde or anthracene product, indicating that [1tBu2]+ and [2tBu2]+ behave ultimately as only one-electron oxidants, but the reaction kinetics each indicate that only a single copper(II)-phenoxyl complex is involved in the rate-determining step. For each substrate, rate laws indicate that [1tBu2]+ and [2tBu2]+ react by different mechanisms: one proceeds by a simple bimolecular reaction, while the other first enters into a substrate-binding equilibrium before subsequently reacting by an intramolecular reaction. The reactions proceeding by the latter mechanism have faster overall rates, which correlates to a lower entropic barrier for the substrate-binding mechanism. Correlation of the reaction rates with the C-H bond dissociation energies of substrates as well as significant deuterium kinetic isotope effects indicates that the rate-determining steps involve hydrogen atom abstraction from the activated C-H bonds. A variable-temperature study (268-308 K) of the nonclassical KIE of the [1tBu2]+/benzyl alcohol reaction (kH/kD = 15 at 298 K) failed to show evidence for quantum tunneling. The rapid sequence by which a second 1 equiv of copper(II)-phenoxyl oxidant completes the reaction after the rate- and product-determining hydrogen atom abstraction step cannot be probed kinetically. Comparisons are made to the reactivities of other copper(II)-phenoxyl complexes reported in the literature and to galactose oxidase itself.
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305, USA.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Pratt
authors.forename: T Daniel P
authors.initials: TD
authors.lastname: Stack
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D005692:Galactose Oxidase / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D010636:Phenols; D003300:Copper; D005692:Galactose Oxidase