O₂ and N₂O Activation by Bi-, Tri-, and Tetranuclear Cu Clusters in Biology

Abstract

Copper cluster sites in biology exhibit unique spectroscopic features reflecting exchange coupling between oxidized Cu's and e − delocalization in mixed valent sites. These novel electronic structures play critical roles in O 2 binding and activation for electrophilic aromatic attack and H atom abstraction, the 4e − /4H + reduction of O 2 to H 2 O, and in the 2e − /2H + reduction of N 2 O. These electronic structure/reactivity correlations are summarized below.Cu proteins play central roles in Fe, Cu, and O 2 metabolism, are related to a range of genetic diseases and are important in biotechnology, detoxification, and the elimination of greenhouse gases. Understanding Cu biochemistry on a molecular level provides mechanisms to improve or inhibit these processes and enhance drug design. The Cu proteins involved in O 2 binding, activation, reduction to H 2 O and the reduction of N 2 O to water and dinitrogen are summarized in Figure 1. The term "coupled" is used here to refer to the antiferromagnetic (AF) "coupling" between paramagnetic metal centers that can lead to a diamagnetic S tot =0 ground state. If two Cu(II)'s, S=1/2, directly overlap they will spin pair. If, however, they are far enough apart so that their d orbitals do not directly overlap but have a bridging ligand this can provide a superexchange pathway (i.e. a delocalized molecular orbital) between the two paramagnetic Cu(II)'s that results in their spin pairing, indirectly through overlap with the bridge. This is described by the exchange Hamiltonian H =−2JS A ·S B which spin couples the two S=1/2's on Cu A and Cu B to form total spins S tot =1 and 0 where for AF coupling the S tot =0 is lower in energy by 2J (J<0).In this paper we will: 1) consider the unique spectral features of the coupled binuclear Cu proteins, hemocyanin (Hc), catechol oxidase, and tyrosinase (Ty), that reflect a novel electronic structure that allows their reversible binding of O 2 (a spin forbidden process) and its activation for electrophilic attack on an aromatic substrate by Ty; 2) contrast this electronic structure to that of the non-coupled binuclear Cu enzymes (i.e. no magnetic interaction between the two Cu(II)'s S=1/2) to evaluate the contribution of these differences in AF exchange coupling to the reaction mechanisms, where the non-coupled binuclear Cu sites in dopamine α-monooxygenase (DβM) and peptidylglycine α-hydroxylating monooxygenase (PHM) activate O 2 for H-atom abstraction; 3) Extend these studies to the trinuclear Cu cluster site in the multicopper oxidases, where the exchange coupling among the three coppers plays a central role in the 4e − /4H + reduction of O 2 to H 2 O; and 4) Consider how the interactions among the coppers in the μ 4 sulfide bridged tetranuclear Cu z cluster promote the 2e − /2H + cleavage of the N-O bond by N 2 O reductase. for trigonal bipyramidal geometries. Peroxide has a doubly degenerate highest occupied molecular orbital (HOMO) set which will split in energy upon binding to Cu(II), the π* σ being stabilized to deeper bi...

Reversibility and efficiency in electrocatalytic energy conversion and lessons from enzymes

“…For example, pausing at H 2 O 2 relaxes the four-electron problem but introduces an overpotential requirement of up to 0.54 V in both directions (nevertheless, a lower cost than pausing at either radical state). Specific binding of the intermediate helps further: Indeed, spectroscopic studies of blue Cu oxidases have detected a peroxy-intermediate (37), and X-ray diffraction has revealed an O-O species coordinated between three Cu atoms (38) (see Scheme 1,5).…”

Structural and spectroscopic studies of a model for catechol oxidase

“…Dimeric copper sites play an important role in the activation of biological oxygen [2][3][4], and the study of structural and functional aspects of copper metalloenzymes via model systems is a subject of intense research [5][6][7][8][9][10]. A member of the family of dicopper proteins is catechol oxidase, which features a type 3 copper center with two proximate copper ions coordinated primarily by histidine donors [11][12][13].…”

Enzymatic activity mastered by altering metal coordination spheres

“…Therefore, two electrons must enter the enzyme and two protonation steps have to occur in order for the enzyme to return to its initial state. This is accomplished through efficient electron pathways [69][70][71].…”