Synthetic models of the active site of cytochrome c oxidase: Influence of tridentate or tetradentate copper chelates bearing a His-Tyr linkage mimic on dioxygen adduct formation by Heme/Cu complexes

Two synthetic models of the active site of cytochrome c oxidase-[(LN4-OH)Cu-I-Fe-II(TMP)](+) (1a) and [(LN3-OH) Cu-I-Fe-II(TMP)](+) (2a)-have been designed and synthesized. These models each contain a heme and a covalently attached copper moiety supported either by a tetradentate N4-copper chelate or by a tridentate N3-copper chelate including a moiety that acts as a mimic of the crosslinked His-Tyr component of cytochrome c oxidase. Low-temperature oxygenation reactions of these models have been investigated by spectroscopic methods including UV/Vis, resonance Raman, ESI-MS, and EPR spectroscopy. Oxygenation of the tetradentate model la in MeCN and in other solvents produces a low-temperature-stable dioxygenbridged peroxide [(LN4-OF)Cu-II-O-2-Fe-III-(TMP)](+) {v(o-o)=799 (O-16(2))/752cm(-1) (O-18(2))}, while a heme superoxide species [(TMP)Fe-III(O-2(-))...(CuLN3-OH)-L-II] {v(Fe-O2): 576 (O-16(2))/551 cm(-1) (O-18(2))} is generated when the tridentate model 2a is oxygenated in EtCN solution under similar experimental conditions. The coexistence of a heme superoxide species [(TMP)Fe-III(O-2(-))...(CuLN3-OH)-L-II] and a bridged peroxide [(LN3-OH)CUII- O-2-Fe-III(TMP)](+) species in equal amounts is observed when the oxygenation reaction of 2a is performed in CH2Cl2/7% EtCN, while the percentage of the peroxide (approximate to 70%) in relation to superoxide (approximate to 30%) increases further when the crosslinked phenol moiety in 2a is deprotonated to produce the bridged peroxide [(LN3-OH)Cu-II-O-2-Fe-III(TMP)](+) {v(o-o): 812 (O-16(2))/765 cm(-1) (O-18(2))} as the main dioxygen intermediate. The weak reducibility and decreased O-2 reactivity of the tricoordinated Cut site in 2 a are responsible for the solvent-dependent formation of dioxygen adducts. The initial binding of dioxygen to the copper site en route to the formation of a bridged heme-O-2-Cu intermediate by model 2a is suggested and the deprotonated crosslinked His-Tyr moiety might contribute to enhancement of the O-2 affinity of the Cu-1 site at an early stage of the dioxygen-binding process.