Here we describe a new approach for the generation of heme-peroxo-Cu compounds, using a “naked” complex synthon, [(F8)FeIII-(O22–)-CuII(MeTHF)3]+ (MeTHF = 2-methyltetrahydrofuran; F8 = tetrakis(2,6-difluorophenyl)porphyrinate). Addition of varying ligands (L) for Cu allows the generation and spectroscopic characterization of a family of high- and low-spin FeIII-(O22–)-CuII(L) complexes. These possess markedly varying CuII coordination geometries, leading to tunable Fe-O, O-O, and Cu-O bond strengths. DFT calculations accompanied by vibrational data correlations give detailed structural insights.

The 4H+/4e− reduction of O2 to water, a key fuel-cell reaction also carried out in biology by oxidase enzymes, includes the critical O–O bond reductive cleavage step. Mechanistic investigations on active-site model compounds, which are synthesized by rational design to incorporate systematic variations, can focus on and resolve answers to fundamental questions, including protonation and/or H-bonding aspects, which accompany electron transfer. Here, we describe the nature and comparative reactivity of two low-spin heme–peroxo–Cu complexes, LS-4DCHIm, [(DCHIm)F8FeIII-(O22−)-CuII(DCHIm)4]+, and LS-3DCHIm, [(DCHIm)F8FeIII-(O22−)-CuII(DCHIm)3]+ (F8 = tetrakis(2,6-difluorophenyl)-porphyrinate; DCHIm = 1,5-dicyclohexylimidazole), toward different proton (4-nitrophenol and [DMF·H+](CF3SO3−)) (DMF = dimethylformamide) or electron (decamethylferrocene (Fc*)) sources. Spectroscopic reactivity studies show that differences in structure and electronic properties of LS-3DCHIm and LS-4DCHIm lead to significant differences in behavior. LS-3DCHIm is resistant to reduction, is unreactive toward weakly acidic 4-NO2–phenol, and stronger acids cleave the metal–O bonds, releasing H2O2. By contrast, LS-4DCHIm forms an adduct with 4-NO2–phenol, which includes an H-bond to the peroxo O-atom distal to Fe (resonance Raman (rR) spectroscopy and DFT). With addition of Fc* (2 equiv overall required), O–O reductive cleavage occurs, giving water, Fe(III), and Cu(II) products; however, a kinetic study reveals a one-electron rate-determining process, ket = 1.6 M−1 s−1 (−90 °C). The intermediacy of a high-valent [(DCHIm)F8FeIV = O] species is thus implied, and separate experiments show that one-electron reduction-protonation of [(DCHIm)F8FeIV=O] occurs faster (ket2 = 5.0 M−1 s−1), consistent with the overall postulated mechanism. The importance of the H-bonding interaction as a prerequisite for reductive cleavage is highlighted.

Bimetallic (Et4N)2[Co2(L)2], (Et4N)2[1] (where (L)(3-) = (N(o-PhNC(O)(i)Pr)2)(3-)) reacts with 2 equiv of O2 to form the monometallic species (Et4N)[Co(L)O2], (Et4N)[3]. A crystallographically characterized analog (Et4N)2[Co(L)CN], (Et4N)2[2], gives insight into the structure of [3](1-). Magnetic measurements indicate [2](2-) to be an unusual high-spin Co(II)-cyano species (S = 3/2), while IR, EXAFS, and EPR spectroscopies indicate [3](1-) to be an end-on superoxide complex with an S = 1/2 ground state. By X-ray spectroscopy and calculations, [3](1-) features a high-spin Co(II) center; the net S = 1/2 spin state arises after the Co electrons couple to both the O2(•-) and the aminyl radical on redox non-innocent (L(•))(2-). Dianion [1](2-) shows both nucleophilic and electrophilic catalytic reactivity upon activation of O2 due to the presence of both a high-energy, filled O2(-) π* orbital and an empty low-lying O2(-) π* orbital in [3](1-).

Establishing redox and thermodynamic relationships between metal-ion-bound O 2 and its reduced (and protonated) derivatives is critically important for a full understanding of (bio)chemical processes involving dioxygen processing. Here, a ferric heme peroxide complex, [(F 8 )Fe III -(O 2 2− )] − (P) (F 8 = tetrakis(2,6-difluorophenyl)porphyrinate), and a superoxide complex, [(F 8 )Fe III -(O 2•− )] (S), are shown to be redox interconvertible. Using Cr(η-C 6 H 6 ) 2 , an equilibrium state where S and P are present is established in tetrahydrofuran (THF) at −80 °C, allowing determination of the reduction potential of S as −1.17 V vs Fc +/0 . P could be protonated with 2,6-lutidinium triflate, yielding the lowspin ferric hydroperoxide species, [(F 8 )Fe III -(OOH)] (HP). Partial conversion of HP back to P using a derivatized phosphazene base gave a P/HP equilibrium mixture, leading to the determination of pK a = 28.8 for HP (THF, −80 °C). With the measured reduction potential and pK a , the O−H bond dissociation free energy (BDFE) of hydroperoxide species HP was calculated to be 73.5 kcal/mol, employing the thermodynamic square scheme and Bordwell relationship. This calculated O−H BDFE of HP, in fact, lines up with an experimental demonstration of the oxidizing ability of S via hydrogen atom transfer (HAT) from TEMPO-H (2,2,6,6tetramethylpiperdine-N-hydroxide, BDFE = 66.5 kcal/mol in THF), forming the hydroperoxide species HP and TEMPO radical. Kinetic studies carried out with TEMPO-H(D) reveal second-order behavior, k H = 0.5, k D = 0.08 M −1 s −1 (THF, −80 °C); thus, the hydrogen/deuterium kinetic isotope effect (KIE) = 6, consistent with H-atom abstraction by S being the rate-determining step. This appears to be the first case where experimentally derived thermodynamics lead to a ferric heme hydroperoxide OO−H BDFE determination, that Fe III -OOH species being formed via HAT reactivity of the partner ferric heme superoxide complex.

Peroxynitrite (−OON═O, PN) is a reactive nitrogen species (RNS) which can effect deleterious nitrative or oxidative (bio)chemistry. It may derive from reaction of superoxide anion (O2•−) with nitric oxide (·NO) and has been suggested to form an as-yet unobserved bound heme-iron-PN intermediate in the catalytic cycle of nitric oxide dioxygenase (NOD) enzymes, which facilitate a ·NO homeostatic process, i.e., its oxidation to the nitrate anion. Here, a discrete six-coordinate low-spin porphyrinate-FeIII complex [(PIm)-FeIII(−OON═O)] (3) (PIm; a porphyrin moiety with a covalently tethered imidazole axial “base” donor ligand) has been identified and characterized by various spectroscopies (UV–vis, NMR, EPR, XAS, resonance Raman) and DFT calculations, following its formation at −80 °C by addition of ·NO(g) to the heme-superoxo species, [(PIm)FeIII(O2•−)] (2). DFT calculations confirm that 3 is a six-coordinate low-spin species with the PN ligand coordinated to iron via its terminal peroxidic anionic O atom with the overall geometry being in a cis-configuration. Complex 3 thermally transforms to its isomeric low-spin nitrato form [(PIm)FeIII(NO3−)] (4a). While previous (bio)chemical studies show that phenolic substrates undergo nitration in the presence of PN or PN-metal complexes, in the present system, addition of 2,4-di-tert-butylphenol (2,4DTBP) to complex 3 does not lead to nitrated phenol; the nitrate complex 4a still forms. DFT calculations reveal that the phenolic H atom approaches the terminal PN O atom (farthest from the metal center and ring core), effecting O–O cleavage, giving nitrogen dioxide (·NO2) plus a ferryl compound [(PIm)FeIV═O] (7); this rebounds to give [(PIm)FeIII(NO3−)] (4a).The generation and characterization of the long sought after ferriheme peroxynitrite complex has been accomplished.