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-[(L ^N4-OH)Cu^I-Fe^II(TMP)]⁺ (1a) and [(L^N3-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 dioxygen-bridged peroxide [(L^N4-OH)Cu ^II-O₂-Fe^III(TMP)]⁺ (v_O-O = 799 (¹⁶O₂)/752cm ¹ (¹⁸O ²)), while a heme superoxide species [(TMP)Fe^III(O ₂^-)⋯Cu^IIL^N3-OH] {v _Fe-O2: 576 (¹⁶O₂)/551 cm^-1 ( ¹⁸O₂)} is generated when the tridentate model 2 a is oxygenated in EtCN solution under similar experimental conditions. The coexistence of a heme superoxide species [(TMP)Fe^III(O ₂^-)⋯Cu^IIL^N3-OH] and a bridged peroxide [(L^N3-OH)Cu^II-O₂-Fe ^III(TMP)]⁺ species in equal amounts is observed when the oxygenation reaction of 2 a is performed in CH₂Cl₂/7% EtCN, while the percentage of the peroxide (≈70%) in relation to superoxide (≈30%) increases further when the crosslinked phenol moiety in 2a is deprotonated to produce the bridged peroxide [(L^N3-OH)Cu ^II-O₂-Fe^III(TMP)]⁺ {v_O-O: 812 (¹⁶O₂)/765 cm^-1 (¹⁸O ₂)) as the main dioxygen intermediate. The weak reducibility and decreased O₂ reactivity of the tricoordinated Cu^I site in 2a 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-O₂-Cu intermediate by model 2a is suggested and the deprotonated crosslinked His-Tyr moiety might contribute to enhancement of the O₂ affinity of the Cu¹ site at an early stage of the dioxygen-binding process.