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)] + ( 1 a ) and [(L N3‐OH )Cu I ‐Fe II (TMP)] + ( 2 a )—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 1 a in MeCN and in other solvents produces a low‐temperature‐stable dioxygen‐bridged peroxide [(L N4‐OH )Cu II ‐O 2 ‐Fe III (TMP)] + { ν OO =799 ( 16 O 2 )/752 cm −1 ( 18 O 2 )}, while a heme superoxide species [(TMP)Fe III (O 2 − )⋅⋅⋅Cu II L N3‐OH ] { ν   FeO   2: 576 ( 16 O 2 )/551 cm −1 ( 18 O 2 )} 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 II L N3‐OH ] and a bridged peroxide [(L N3‐OH )Cu II ‐O 2 ‐Fe III (TMP)] + species in equal amounts is observed when the oxygenation reaction of 2 a is performed in CH 2 Cl 2 /7 % EtCN, while the percentage of the peroxide (≈70 %) in relation to superoxide (≈30 %) increases further when the crosslinked phenol moiety in 2 a is deprotonated to produce the bridged peroxide [(L N3‐OH )Cu II ‐O 2 ‐Fe III (TMP)] + { ν OO : 812 ( 16 O 2 )/765 cm −1 ( 18 O 2 )} as the main dioxygen intermediate. The weak reducibility and decreased O 2 reactivity of the tricoordinated Cu I 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 2 a is suggested and the deprotonated crosslinked His‐Tyr moiety might contribute to enhancement of the O 2 affinity of the Cu I site at an early stage of the dioxygen‐binding process.