Copper dioxygen (bio)inorganic chemistry

Abstract

Cu/O 2 intermediates in biological, homogeneous, and heterogeneous catalysts exhibit unique spectral features that reflect novel geometric and electronic structures that make significant contributions to reactivity. This review considers how the respective intermediate electronic structures overcome the spin forbidden nature of O 2 binding, activate O 2 for electrophillic aromatic attack and H-atom abstraction, catalyze the 4 e-reduction of O 2 to H 2 O, and discusses the role of exchange coupling between Cu ions in determining reactivity.Our focus has been on the use of spectroscopic methods to elucidate active sites in catalysis. In the area of Cu/O 2 chemistry, this has mostly involved studies on metalloenzymes, however these have led to parallel studies in Cu coordination chemistry and now to studies on Cu sites in zeolites. There are five main topics in Cu/O 2 biological, homogeneous and heterogeneous reactivity that will be the scope of this overview. First is the spin-forbidden, reversible binding of dioxygen by the coupled binuclear Cu site in hemocyanin. Next, we will consider O 2 activation by coupled binuclear copper sites for electrophilic attack on phenolic substrates in tyrosinase and related model complexes. We will then consider Hatom abstraction from relatively weak C-H bonds (~85 kcal/mol) by the "non-coupled" binuclear Cu enzymes and how the difference in magnetic "exchange" coupling can control reactivity. We will then move to the four e-reduction of O 2 to H 2 O by the multi-copper oxidases at a trinuclear Cu cluster, a structural motif originally defined to be present by MCD spectroscopy. 1, 2 Finally, we will focus on O 2 activation for H-atom abstraction from the strong C-H bond of methane (~105 kcal/mol) which in biology is accomplished by methane monooxygenases (MMO) but can now be achieved in the active sites of zeolites . The copper-oxygen intermediates in these systems have unique spectroscopic features that we have shown to reflect novel geometric and electronic structures that make key contributions to reactivity. I. Reversible O 2 Binding: Coupled binuclear Cu SitesHemocyanin (Hc) functions as an extracellular oxygen transport protein in arthropods and mollusks. 3 Deoxy-Hc contains 2 Cu(I) ions that reversibly bind O 2 to form the binuclear cupric site in oxy-Hc. Thus, 2e − are transferred to O 2 reducing it to the peroxide level. As will be discussed below, oxy-Hc has unique spectral features, and to understand these we first consider "normal" peroxide-Cu(II) bonding. 4 O 2 is a triplet that has two unpaired electrons in the doubly degenerate π * orbitals. Reduction of O 2 to peroxide leads to a fully occupied π * HOMO. As shown in Fig. 1A, upon binding O 2 2− end-on to a Cu(II), one π * orbital is stabilized due to σ bonding with the d 9 Cu(II) half occupied d orbital, which is in turn destabilized. This leads to the characteristic EPR Correspondence to: Edward I. Solomon. NIH Public Access Author ManuscriptFaraday Discuss. Author manuscript; available in PMC 2012 Januar...

Spectroscopic and computational insight into the activation of O 2 by the mononuclear Cu center in polysaccharide monooxygenases

“…Cu-superoxide species have been proposed as reactive intermediates in H-atom abstraction in the noncoupled binuclear Cu enzymes (1,29,30), although a Cu(II)-superoxide enzyme species has yet to be spectroscopically characterized. Alternatively, a variety of inorganic Cu(II)-superoxide model complexes have been trapped at low temperature (31)(32)(33)(34)(35).…”

“…Several classes with either binuclear or trinuclear copper active sites have been identified and their different strategies for O 2 activation have been elucidated (1). These include the multicopper oxidases that use three Cu ions to reduce O 2 to water with very little overpotential (2,3), the coupled binuclear Cu enzymes that are involved in dioxygen transport and monooxygenase reactivity (4), and the noncoupled binuclear Cu monooxygenases that activate O 2 for hydroxylation of peptides and hormones (5).…”

Mechanism of O2activation and substrate hydroxylation in noncoupled binuclear copper monooxygenases

“…A large intrinsic substrate H/D isotope effect (10.6) on the C-H cleavage step in PHM is consistent with homolytic C-H cleavage [i.e., via H-atom abstraction (HAA)] (8); however, the small isotope effect on k cat (∼1.5) (9) leads to a triplet ground state because the small d=π σ * splitting is insufficient to overcome the spin pairing energy (Fig. 2) (3,19).…”

“…C opper is an essential cofactor for many cellular processes requisite for life (1). In particular, one or multiple coppers are found in active sites of enzymes that bind, activate, and reduce O 2 using the biologically accessible Cu II /Cu I redox couple (2,3). One important class of Cu-dependent O 2 -activating enzymes is responsible for the stereospecific C-H α-hydroxylation of hormones and glycine-extended neuropeptides for proper neurotransmitter regulation and hormone biosynthesis.…”

Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

“…The MCOs have been extensively studied by both experimental 1,3,6-11 and theoretical [10][11][12][13] methods. Crystal structures are available from ~20 different organisms.…”