The rebound mechanism for alkane hydroxylation was invoked over 40 years ago to help explain reactivity patterns in cytochrome P450, and subsequently has been used to provide insight into a range of biological and synthetic systems. Efforts to model the rebound reaction in a synthetic system have been unsuccessful, in part because of the challenge in preparing a suitable metal-hydroxide complex at the correct oxidation level. Herein we report the synthesis of such a complex. The reaction of this species with a series of substituted radicals allows for the direct interrogation of the rebound process, providing insight into this uniformly invoked, but previously unobserved process.

One-electron reduction of [Fe(NO)-(N3PyS)]BF4 (1) leads to the production of the metastable nonheme {FeNO}8 complex, [Fe(NO)(N3PyS)] (3). Complex 3 is a rare example of a high-spin (S = 1) {FeNO}8 and is the first example, to our knowledge, of a mononuclear nonheme {FeNO}8 species that generates N2O. A second, novel route to 3 involves addition of Piloty’s acid, an HNO donor, to an FeII precursor. This work provides possible new insights regarding the mechanism of nitric oxide reductases.

The selective alkylation of a single meso-N atom of a corrolazine macrocycle is reported. Alkylation has a dramatic impact on the physicochemical properties of ReV(O)(TBP8Cz). New electron-transfer and hydrogen-atom-transfer reactivity is also seen for this complex, including one-electron reduction, which gives an air-stable 19π-electron aromatic radical complex.

The rational design of well-defined, first-row transition metal complexes that can activate dioxygen has been a challenging goal for the synthetic inorganic chemist. The activation of O2 is important in part because of its central role in the functioning of metalloenzymes, which utilize O2 to perform a number of challenging reactions including the highly selective oxidation of various substrates. There is also great interest in utilizing O2, an abundant and environmentally benign oxidant, in synthetic catalytic oxidation systems. This Perspective brings together recent examples of biomimetic Fe and Mn complexes that can activate O2 in heme or nonheme-type ligand environments. The use of oxidants such as hypervalent iodine (e.g., ArIO), peracids (e.g., m-CPBA), peroxides (e.g., H2O2) or even superoxide is a popular choice for accessing well-characterized metal–superoxo, metal–peroxo, or metal–oxo species, but the instances of biomimetic Fe/Mn complexes that react with dioxygen to yield such observable metal–oxygen species are surprisingly few. This Perspective focuses on mononuclear Fe and Mn complexes that exhibit reactivity with O2 and lead to spectroscopically observable metal–oxygen species, and/or oxidize biologically relevant substrates. Analysis of these examples reveals that solvent, spin state, redox potential, external co-reductants, and ligand architecture can all play important roles in the O2 activation process.

The synthesis and reactivity of a series of mononuclear nonheme iron complexes that carry out intramolecular aromatic C–F hydroxylation reactions is reported. The key intermediate prior to C–F hydroxylation, [FeIV(O)(N4Py2Ar1)](BF4)2 (1-O, Ar1 = −2,6-difluorophenyl), was characterized by single-crystal X-ray diffraction. The crystal structure revealed a nonbonding C–H···O═Fe interaction with a CH3CN molecule. Variable-field Mössbauer spectroscopy of 1-O indicates an intermediate-spin (S = 1) ground state. The Mössbauer parameters for 1-O include an unusually small quadrupole splitting for a triplet FeIV(O) and are reproduced well by density functional theory calculations. With the aim of investigating the initial step for C–F hydroxylation, two new ligands were synthesized, N4Py2Ar2 (L2, Ar2 = −2,6-difluoro-4-methoxyphenyl) and N4Py2Ar3 (L3, Ar3 = −2,6-difluoro-3-methoxyphenyl), with −OMe substituents in the meta or ortho/para positions with respect to the C–F bonds. FeII complexes [Fe(N4Py2Ar2)(CH3CN)](ClO4)2 (2) and [Fe(N4Py2Ar3)(CH3CN)](ClO4)2 (3) reacted with isopropyl 2-iodoxybenzoate to give the C–F hydroxylated FeIII–OAr products. The FeIV(O) intermediates 2-O and 3-O were trapped at low temperature and characterized. Complex 2-O displayed a C–F hydroxylation rate similar to that of 1-O. In contrast, the kinetics (via stopped-flow UV–vis) for complex 3-O displayed a significant rate enhancement for C–F hydroxylation. Eyring analysis revealed the activation barriers for the C–F hydroxylation reaction for the three complexes, consistent with the observed difference in reactivity. A terminal FeII(OH) complex (4) was prepared independently to investigate the possibility of a nucleophilic aromatic substitution pathway, but the stability of 4 rules out this mechanism. Taken together the data fully support an electrophilic C–F hydroxylation mechanism.

Discerning the factors that control the reactivity of high-valent metal–oxo species is critical to both an understanding of metalloenzyme reactivity and related transition metal catalysts. Computational studies have suggested that an excited higher spin state in a number of metal–oxo species can provide a lower energy barrier for oxidation reactions, leading to the conclusion that this unobserved higher spin state complex should be considered as the active oxidant. However, testing these computational predictions by experiment is difficult and has rarely been accomplished. Herein, we describe a detailed computational study on the role of spin state in the reactivity of a high-valent manganese(V)–oxo complex with para-Z-substituted thioanisoles and utilize experimental evidence to distinguish between the theoretical results. The calculations show an unusual change in mechanism occurs for the dominant singlet spin state that correlates with the electron-donating property of the para-Z substituent, while this change is not observed on the triplet spin state. Minimum energy crossing point calculations predict small spin–orbit coupling constants making the spin state change from low spin to high spin unlikely. The trends in reactivity for the para-Z-substituted thioanisole derivatives provide an experimental measure for the spin state reactivity in manganese–oxo corrolazine complexes. Hence, the calculations show that the V-shaped Hammett plot is reproduced by the singlet surface but not by the triplet state trend. The substituent effect is explained with valence bond models, which confirm a change from an electrophilic to a nucleophilic mechanism through a change of substituent.

The nonheme iron complex, [Fe(NO)(N3PyS)]BF4, is a rare example of an {FeNO}7 species that exhibits spin-crossover behavior. The comparison of X-ray crystallographic studies at low and high temperatures and variable-temperature magnetic susceptibility measurements show that a low-spin S = 1/2 ground state is populated at 0–150 K, while both low-spin S = 1/2 and high-spin S = 3/2 states are populated at T > 150 K. These results explain the observation of two N–O vibrational modes at 1737 and 1649 cm–1 in CD3CN for [Fe(NO)(N3PyS)]BF4 at room temperature. This {FeNO}7 complex reacts with dioxygen upon photoirradiation with visible light in acetonitrile to generate a thiolate-ligated, nonheme iron(III)-nitro complex, [FeIII(NO2)(N3PyS)]+, which was characterized by EPR, FTIR, UV–vis, and CSI-MS. Isotope labeling studies, coupled with FTIR and CSI-MS, show that one O atom from O2 is incorporated in the FeIII–NO2 product. The O2 reactivity of [Fe(NO)(N3PyS)]BF4 in methanol is dramatically different from CH3CN, leading exclusively to sulfur-based oxidation, as opposed to NO· oxidation. A mechanism is proposed for the NO· oxidation reaction that involves formation of both FeIII-superoxo and FeIII-peroxynitrite intermediates and takes into account the experimental observations. The stability of the FeIII-nitrite complex is limited, and decay of [FeIII(NO2)(N3PyS)]+ leads to {FeNO}7 species and sulfur oxygenated products. This work demonstrates that a single mononuclear, thiolate-ligated nonheme {FeNO}7 complex can exhibit reactivity related to both nitric oxide dioxygenase (NOD) and nitrite reductase (NiR) activity. The presence of the thiolate donor is critical to both pathways, and mechanistic insights into these biologically relevant processes are presented.

The synthesis of the first example of a third-row metallocorrolazine characterized by single crystal X-ray diffraction is reported. This ReV(O) porphyrinoid complex shows an exclusively ligand-based reactivity with strong acids and oxidizing agents. The one-electron oxidized π-radical-cation complex is capable of H-atom abstraction.

The addition of Lewis or Brönsted acids (LA = Zn(OTf)2, B(C6F5)3, HBArF, TFA) to the high-valent manganese–oxo complex MnV(O)(TBP8Cz) results in the stabilization of a valence tautomer MnIV(O-LA)(TBP8Cz•+). The ZnII and B(C6F5)3 complexes were characterized by manganese K-edge X-ray absorption spectroscopy (XAS). The position of the edge energies and the intensities of the pre-edge (1s to 3d) peaks confirm that the Mn ion is in the +4 oxidation state. Fitting of the extended X-ray absorption fine structure (EXAFS) region reveals 4 N/O ligands at Mn–Nave = 1.89 Å and a fifth N/O ligand at 1.61 Å, corresponding to the terminal oxo ligand. This Mn–O bond length is elongated compared to the MnV(O) starting material (Mn–O = 1.55 Å). The reactivity of MnIV(O-LA)(TBP8Cz•+) toward C–H substrates was examined, and it was found that H• abstraction from C–H bonds occurs in a 1:1 stoichiometry, giving a MnIV complex and the dehydrogenated organic product. The rates of C–H cleavage are accelerated for the MnIV(O-LA)(TBP8Cz•+) valence tautomer as compared to the MnV(O) valence tautomer when LA = ZnII, B(C6F5)3, and HBArF, whereas for LA = TFA, the C–H cleavage rate is slightly slower than when compared to MnV(O). A large, nonclassical kinetic isotope effect of kH/kD = 25–27 was observed for LA = B(C6F5)3 and HBArF, indicating that H-atom transfer (HAT) is the rate-limiting step in the C–H cleavage reaction and implicating a potential tunneling mechanism for HAT. The reactivity of MnIV(O-LA)(TBP8Cz•+) toward C–H bonds depends on the strength of the Lewis acid. The HAT reactivity is compared with the analogous corrole complex MnIV(O–H)(tpfc•+) recently reported (J. Am. Chem. Soc. 2015, 137, 14481–14487).

UV–vis spectral titrations of a manganese(III) corrolazine complex [MnIII(TBP8Cz)] with HOTf in benzonitrile (PhCN) indicate mono- and diprotonation of MnIII(TBP8Cz) to give MnIII(OTf)(TBP8Cz(H)) and [MnIII(OTf)(H2O)(TBP8Cz(H)2)][OTf] with protonation constants of 9.0 × 106 and 4.7 × 103 M–1, respectively. The protonated sites of MnIII(OTf)(TBP8Cz(H)) and [MnIII(OTf)(H2O)(TBP8Cz(H)2)][OTf] were identified by X-ray crystal structures of the mono- and diprotonated complexes. In the presence of HOTf, the monoprotonated manganese(III) corrolazine complex [MnIII(OTf)(TBP8Cz(H))] acts as an efficient photocatalytic catalyst for the oxidation of hexamethylbenzene and thioanisole by O2 to the corresponding alcohol and sulfoxide with 563 and 902 TON, respectively. Femtosecond laser flash photolysis measurements of MnIII(OTf)(TBP8Cz(H)) and [MnIII(OTf)(H2O)(TBP8Cz(H)2)][OTf] in the presence of O2 revealed the formation of a tripquintet excited state, which was rapidly converted to a tripseptet excited state. The tripseptet excited state of MnIII(OTf)(TBP8Cz(H)) reacted with O2 with a diffusion-limited rate constant to produce the putative MnIV(O2•–)(OTf)(TBP8Cz(H)), whereas the tripseptet excited state of [MnIII(OTf)(H2O)(TBP8Cz(H)2)][OTf] exhibited no reactivity toward O2. In the presence of HOTf, MnV(O)(TBP8Cz) can oxidize not only HMB but also mesitylene to the corresponding alcohols, accompanied by regeneration of MnIII(OTf)(TBP8Cz(H)). This thermal reaction was examined for a kinetic isotope effect, and essentially no KIE (1.1) was observed for the oxidation of mesitylene-d12, suggesting a proton-coupled electron transfer (PCET) mechanism is operative in this case. Thus, the monoprotonated manganese(III) corrolazine complex, MnIII(OTf)(TBP8Cz(H)), acts as an efficient photocatalyst for the oxidation of HMB by O2 to the alcohol.

Zinc plays key structural and catalytic roles in biology. Structural zinc sites are often referred to as zinc finger (ZF) sites, and the classical ZF contains a Cys2His2 motif that is involved in coordinating Zn(II). An optimized Cys2His2 ZF, named consensus peptide 1 (CP-1), was identified more than 20 years ago using a limited set of sequenced proteins. We have reexamined the CP-1 sequence, using our current, much larger database of sequenced proteins that have been identified from high-throughput sequencing methods, and found the sequence to be largely unchanged. The CCHH ligand set of CP-1 was then altered to a CAHH motif to impart hydrolytic activity. This ligand set mimics the His2Cys ligand set of peptide deformylase (PDF), a hydrolytically active M(II)-centered (M = Zn or Fe) protein. The resultant peptide [CP-1(CAHH)] was evaluated for its ability to coordinate Zn(II) and Co(II) ions, adopt secondary structure, and promote hydrolysis. CP-1(CAHH) was found to coordinate Co(II) and Zn(II) and a pentacoordinate geometry for Co(II)–CP-1(CAHH) was implicated from UV-vis data. This suggests a His2Cys(H2O)2 environment at the metal center. The Zn(II)-bound CP-1(CAHH) was shown to adopt partial secondary structure by 1-D 1H NMR spectroscopy. Both Zn(II)–CP-1(CAHH) and Co(II)–CP-1(CAHH) show good hydrolytic activity toward the test substrate 4-nitrophenyl acetate, exhibiting faster rates than most active synthetic Zn(II) complexes.

A large class of heme and non-heme metalloenzymes utilize O2 or its derivatives (e.g., H2O2) to generate high-valent metal–oxo intermediates for performing challenging and selective oxidations. Due to their reactive nature, these intermediates are often short-lived and very difficult to characterize. Synthetic chemists have sought to prepare analogous metal–oxo complexes with ligands that impart enough stability to allow for their characterization and an examination of their inherent reactivity. The challenge in designing these molecules is to achieve a balance between their stability, which should allow for their in situ characterization or isolation, and their reactivity, in which they can still participate in interesting chemical transformations. This Account focuses on our recent efforts to generate and stabilize high-valent manganese–oxo porphyrinoid complexes and tune their reactivity in the oxidation of organic substrates.Dioxygen can be used to generate a high-valent MnV(O) corrolazine (MnV(O)(TBP8Cz)) by irradiation of MnIII(TBP8Cz) with visible light in the presence of a C–H substrate. Quantitative formation of the MnV(O) complex occurs with concomitant selective hydroxylation of the benzylic substrate hexamethylbenzene. Addition of a strong H+ donor converted this light/O2/substrate reaction from a stoichiometric to a catalytic process with modest turnovers. The addition of H+ likely activates a transient MnV(O) complex to achieve turnover, whereas in the absence of H+, the MnV(O) complex is an unreactive “dead-end” complex. Addition of anionic donors to the MnV(O) complex also leads to enhanced reactivity, with a large increase in the rate of two-electron oxygen atom transfer (OAT) to thioether substrates. Spectroscopic characterization (Mn K-edge X-ray absorption and resonance Raman spectroscopies) revealed that the anionic donors (X–) bind to the MnV ion to form six-coordinate [MnV(O)(X)]− complexes. An unusual “V-shaped” Hammett plot for the oxidation of para-substituted thioanisole derivatives suggested that six-coordinate [MnV(O)(X)]− complexes can act as both electrophiles and nucleophiles, depending on the nature of the substrate. Oxidation of the MnV(O) corrolazine resulted in the in situ generation of a MnV(O) π-radical cation complex, [MnV(O)(TBP8Cz•+)]+, which exhibited more than a 100-fold rate increase in the oxidation of thioethers. The addition of Lewis acids (LA; ZnII, B(C6F5)3) to the closed-shell, diamagnetic MnV(O)(TBP8Cz) stabilized a paramagnetic valence tautomer MnIV(O)(TBP8Cz•+)(LA), which was characterized as a second π-radical cation complex by NMR, EPR, UV-vis, and high resolution cold spray ionization MS. The MnIV(O)(TBP8Cz•+)(LA) complexes are able to abstract H• from phenols and exhibit a rate enhancement of up to ∼100-fold over the parent MnV(O) valence tautomer. In contrast, a large decrease in rate is observed for OAT for the MnIV(O)(TBP8Cz•+)(LA) complexes. The rate enhancement for hydrogen atom transfer (HAT) may derive from the higher redox potential for the π-radical cation complex, while the large rate decrease seen for OAT may come from a decrease in electrophilicity for an MnIV(O) versus MnV(O) complex.

The oxygen atom transfer (OAT) reactivity of two valence tautomers of a MnV(O) porphyrinoid complex was compared. The OAT kinetics of MnV(O)(TBP8Cz) (TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3–) reacting with a series of triarylphosphine (PAr3) substrates were monitored by stopped-flow UV–vis spectroscopy, and revealed second-order rate constants ranging from 16(1) to 1.43(6) × 104 M–1 s–1. Characterization of the OAT transition state analogues MnIII(OPPh3)(TBP8Cz) and MnIII(OP(o-tolyl)3)(TBP8Cz) was carried out by single-crystal X-ray diffraction (XRD). A valence tautomer of the closed-shell MnV(O)(TBP8Cz) can be stabilized by the addition of Lewis and Brønsted acids, resulting in the open-shell MnIV(O)(TBP8Cz•+):LA (LA = ZnII, B(C6F5)3, H+) complexes. These MnIV(O)(π-radical-cation) derivatives exhibit dramatically inhibited rates of OAT with the PAr3 substrates (k = 8.5(2) × 10–3 – 8.7 M–1 s–1), contrasting the previously observed rate increase of H-atom transfer (HAT) for MnIV(O)(TBP8Cz•+):LA with phenols. A Hammett analysis showed that the OAT reactivity for MnIV(O)(TBP8Cz•+):LA is influenced by the Lewis acid strength. Spectral redox titration of MnIV(O)(TBP8Cz•+):ZnII gives Ered = 0.69 V vs SCE, which is nearly +700 mV above its valence tautomer MnV(O)(TBP8Cz) (Ered = −0.05 V). These data suggest that the two-electron electrophilicity of the Mn(O) valence tautomers dominate OAT reactivity and do not follow the trend in one-electron redox potentials, which appear to dominate HAT reactivity. This study provides new fundamental insights regarding the relative OAT and HAT reactivity of valence tautomers such as MV(O)(porph) versus MIV(O)(porph•+) (M = Mn or Fe) found in heme enzymes.

Isomorphous crystals of MnV(O) and CrV(O) corrolazines were characterized by single crystal X-ray diffraction. Reactivity studies with H atom donors and separated PCET reagents show a dramatic difference in H atom abstracting abilities for these two complexes. The implied large difference in driving force is opposite the trend in redox potentials, indicating that basicity is a key factor in determining the striking difference in reactivity for two metal-oxo species in identical ligand environments.

The visible light-driven, catalytic aerobic oxidation of benzylic C–H bonds was mediated by a MnIII corrolazine complex. To achieve catalytic turnovers, a strict selective requirement for the addition of protons was established. The resting state of the catalyst was unambiguously characterized by X-ray diffraction as [MnIII(H2O)(TBP8Cz(H))]+, in which a single, remote site on the ligand is protonated. If two remote sites are protonated, however, reactivity with O2 is shut down. Spectroscopic methods revealed that the related MnV(O) complex is also protonated at the same remote site at −60 °C, but undergoes valence tautomerization upon warming.

The synthesis of a pentadentate ligand with strategically designed fluorinated arene groups in the second coordination sphere of a nonheme iron center is reported. The oxidatively resistant fluorine substituents allow for the trapping and characterization of an FeIV(O) complex at −20 °C. Upon warming of the FeIV(O) complex, an unprecedented arene C–F hydroxylation reaction occurs. Computational studies support the finding that substrate orientation is a critical factor in the observed reactivity. This work not only gives rare direct evidence for the participation of an FeIV(O) species in arene hydroxylation but also provides the first example of a high-valent iron–oxo complex that mediates aromatic C–F hydroxylation.

The new ligand N3PyamideSR and its FeII complex [FeII(N3PyamideSR)](BF4)2 (1) are described. Reaction of 1 with PhIO at −40 °C gives metastable [FeIV(O)(N3PyamideSR)]2+ (2), containing a sulfide ligand and a single amide H-bond donor in proximity to the terminal oxo group. Direct evidence for H-bonding is seen in a structural analogue, [FeII(Cl)(N3PyamideSR)](BF4)2 (3). Complex 2 exhibits rapid O-atom transfer (OAT) toward external sulfide substrates, but no intramolecular OAT. However, direct S-oxygenation does occur in the reaction of 1 with mCPBA, yielding sulfoxide-ligated [FeII(N3PyamideS(O)R)](BF4)2 (4). Catalytic OAT with 1 was also observed.

The reaction of a manganese(V)–oxo porphyrinoid complex with the Lewis acid B(C6F5)3 leads to reversible stabilization of the valence tautomer MnIV(O)(π-radical cation). The latter complex, in combination with B(C6F5)3, reacts with ArO–H substrates via formal hydrogen-atom transfer and exhibits dramatically increased reaction rates over the MnV(O) starting material.

The non-heme iron complexes, [FeII(N3PySR)(CH3CN)](BF4)2 (1) and [FeII(N3PyamideSR)](BF4)2 (2), afford rare examples of metastable Fe(III)-OOH and Fe(III)-OOtBu complexes containing equatorial thioether ligands and a single H-bond donor in the second coordination sphere. These peroxo complexes were characterized by a range of spectroscopic methods and density functional theory studies. The influence of a thioether ligand and of one H-bond donor on the stability and spectroscopic properties of these complexes was investigated.

Photocatalytic oxygenation of 10-methyl-9,10-dihydroacridine (AcrH2) by dioxygen (O2) with a manganese porphyrin [(P)MnIII: 5,10,15,20-tetrakis-(2,4,6-trimethylphenyl)porphinatomanganese(III) hydroxide [(TMP)MnIII(OH)] (1) or 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinatomanganese(III) acetate [(TPFPP)MnIII(CH3COO)] (2)] occurred to yield 10-methyl-(9,10H)-acridone (Acr═O) in an oxygen-saturated benzonitrile (PhCN) solution under visible light irradiation. The photocatalytic reactivity of (P)MnIII in the presence of O2 is in proportion to concentrations of AcrH2 or O2 with the maximum turnover numbers of 17 and 6 for 1 and 2, respectively. The quantum yield with 1 was determined to be 0.14%. Deuterium kinetic isotope effects (KIEs) were observed with KIE = 22 for 1 and KIE = 6 for 2, indicating that hydrogen-atom transfer from AcrH2 is involved in the rate-determining step of the photocatalytic reaction. Femtosecond transient absorption measurements are consistent with photoexcitation of (P)MnIII, resulting in intersystem crossing from a tripquintet excited state to a tripseptet excited state. A mechanism is proposed where the tripseptet excited state reacts with O2 to produce a putative (P)MnIV superoxo complex. Hydrogen-atom transfer from AcrH2 to (P)MnIV(O2•–) generating a hydroperoxo complex (P)MnIV(OOH) and AcrH• is likely the rate-determining step, in competition with back electron transfer to regenerate the ground state (P)MnIII and O2. The subsequent reductive O–O bond cleavage by AcrH• may occur rapidly inside of the reaction cage to produce (P)MnV(O) and AcrH(OH), followed by the oxidation of AcrH(OH) by (P)MnV(O) to yield Acr═O with regeneration of (P)MnIII.

The new biomimetic ligands N4Py2Ph (1) and N4Py2Ph,amide (2) were synthesized and yield the iron(II) complexes [FeII(N4Py2Ph)(NCCH3)](BF4)2 (3) and [FeII(N4Py2Ph,amide)](BF4)2 (5). Controlled orientation of the Ph substituents in 3 leads to facile triplet spin reactivity for a putative FeIV(O) intermediate, resulting in rapid arene hydroxylation. Addition of a peripheral amide substituent within hydrogen-bond distance of the iron first coordination sphere leads to stabilization of a high-spin FeIIIOOR species which decays without arene hydroxylation. These results provide new insights regarding the impact of secondary coordination sphere effects at nonheme iron centers.

We present the synthesis and spectroscopic characterization of [Fe(NO)(N3PyS)]BF4 (3), the first structural and electronic model of NO-bound cysteine dioxygenase. The nearly isostructural all-N-donor analogue [Fe(NO)(N4Py)](BF4)2 (4) was also prepared, and comparisons of 3 and 4 provide insight regarding the influence of S vs N ligation in {FeNO}7 species. One key difference occurs upon photoirradiation, which causes the fully reversible release of NO from 3, but not from 4.

Visible light photoirradiation of an oxygen-saturated benzonitrile solution of a manganese(III) corrolazine complex [(TBP8Cz)MnIII] (1): [TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3–] in the presence of toluene derivatives resulted in formation of the manganese(V)-oxo complex [(TBP8Cz)MnV(O)]. The photochemical oxidation of (TBP8Cz)MnIII with O2 and hexamethylbenzene (HMB) led to the isosbestic conversion of 1 to (TBP8Cz)MnV(O), accompanied by the selective oxidation of HMB to pentamethylbenzyl alcohol (87%). The formation rate of (TBP8Cz)MnV(O) increased with methyl group substitution, from toluene, p-xylene, mesitylene, durene, pentamethylbenzene, up to hexamethylbenzene. Deuterium kinetic isotope effects (KIEs) were observed for toluene (KIE = 5.4) and mesitylene (KIE = 5.3). Femtosecond laser flash photolysis of (TBP8Cz)MnIII revealed the formation of a tripquintet excited state, which was rapidly converted to a tripseptet excited state. The tripseptet excited state was shown to be the key, activated state that reacts with O2 via a diffusion-limited rate constant. The data allow for a mechanism to be proposed in which the tripseptet excited state reacts with O2 to give the putative (TBP8Cz)MnIV(O2•–), which then abstracts a hydrogen atom from the toluene derivatives in the rate-determining step. The mechanism of hydrogen abstraction is discussed by comparison of the reactivity with the hydrogen abstraction from the same toluene derivatives by cumylperoxyl radical. Taken together, the data suggest a new catalytic method is accessible for the selective oxidation of C–H bonds with O2 and light, and the first evidence for catalytic oxidation of C–H bonds was obtained with 10-methyl-9,10-dihydroacridine as a substrate.

The known iron(II) complex [FeII(LN3S)(OTf)] (1) was used as starting material to prepare the new biomimetic (N4S(thiolate)) iron(II) complexes [FeII(LN3S)(py)](OTf) (2) and [FeII(LN3S)(DMAP)](OTf) (3), where LN3S is a tetradentate bis(imino)pyridine (BIP) derivative with a covalently tethered phenylthiolate donor. These complexes were characterized by X-ray crystallography, ultraviolet–visible (UV-vis) spectroscopic analysis, 1H nuclear magnetic resonance (NMR), and Mössbauer spectroscopy, as well as electrochemistry. A nickel(II) analogue, [NiII(LN3S)](BF4) (5), was also synthesized and characterized by structural and spectroscopic methods. Cyclic voltammetric studies showed 1–3 and 5 undergo a single reduction process with E1/2 between −0.9 V to −1.2 V versus Fc+/Fc. Treatment of 3 with 0.5% Na/Hg amalgam gave the monoreduced complex [Fe(LN3S)(DMAP)]0 (4), which was characterized by X-ray crystallography, UV-vis spectroscopic analysis, electron paramagnetic resonance (EPR) spectroscopy (g = [2.155, 2.057, 2.038]), and Mössbauer (δ = 0.33 mm s–1; ΔEQ = 2.04 mm s–1) spectroscopy. Computational methods (DFT) were employed to model complexes 3–5. The combined experimental and computational studies show that 1–3 are 5-coordinate, high-spin (S = 2) FeII complexes, whereas 4 is best described as a 5-coordinate, intermediate-spin (S = 1) FeII complex antiferromagnetically coupled to a ligand radical. This unique electronic configuration leads to an overall doublet spin (Stotal = 1/2) ground state. Complexes 2 and 3 are shown to react with O2 to give S-oxygenated products, as previously reported for 1. In contrast, the monoreduced 4 appears to react with O2 to give a mixture of sulfur oxygenates and iron oxygenates. The nickel(II) complex 5 does not react with O2, and even when the monoreduced nickel complex is produced, it appears to undergo only outer-sphere oxidation with O2.

The generation of a new high-valent iron terminal imido complex prepared with a corrolazine macrocycle is reported. The reaction of [FeIII(TBP8Cz)] (TBP8Cz = octakis(4-tert-butylphenyl)corrolazinato) with the commercially available chloramine-T (Na+TsNCl–) leads to oxidative N-tosyl transfer to afford [FeIV(TBP8Cz+•)(NTs)] in dichloromethane/acetonitrile at room temperature. This complex was characterized by UV–vis, Mössbauer (δ = −0.05 mm s–1, ΔEQ = 2.94 mm s–1), and EPR (X-band (15 K), g = 2.10, 2.00) spectroscopies, and together with reactivity patterns and DFT calculations has been established as an iron(IV) species antiferromagnetically coupled with a Cz-π-cation-radical (Stotal = 1/2 ground state). Reactivity studies with triphenylphosphine as substrate show that [FeIV(TBP8Cz+•)(NTs)] is an efficient NTs transfer agent, affording the phospharane product Ph3P═NTs under both stoichiometric and catalytic conditions. Kinetic analysis of this reaction supports a bimolecular NTs transfer mechanism with rate constant of 70(15) M–1 s–1. These data indicate that [FeIV(TBP8Cz+•)(NTs)] reacts about 100 times faster than analogous Mn terminal arylimido corrole analogues. It was found that two products crystallize from the same reaction mixture of FeIII(TBP8Cz) + chloramine-T + PPh3, [FeIV(TBP8Cz)(NPPh3)] and [FeIII(TBP8Cz)(OPPh3)], which were definitively characterized by X-ray crystallography. The sequential production of Ph3P═NTs, Ph3P═NH, and Ph3P═O was observed by 31P NMR spectroscopy and led to a proposed mechanism that accounts for all of the observed products. The latter FeIII complex was then rationally synthesized and structurally characterized from FeIII(TBP8Cz) and OPPh3, providing an important benchmark compound for spectroscopic studies. A combination of Mössbauer and EPR spectroscopies led to the characterization of both intermediate spin (S = 3/2) and low spin (S = 1/2) FeIII corrolazines, as well as a formally FeIV corrolazine which may also be described by its valence tautomer FeIII(Cz+•).

The unsymmetrical iron(II) bis(imino)pyridine complexes [FeII(LN3SMe)(H2O)3](OTf)2 (1), and [FeII(LN3SMe)Cl2] (2) were synthesized and their reactivity with O2 was examined. Complexes 1 and 2 were characterized by single crystal X-ray crystallography, LDI-MS, 1H NMR and elemental analysis. The LN3SMe ligand was designed to incorporate a single sulfide donor and relies on the bis(imino)pyridine scaffold. This scaffold was selected for its ease of synthesis and its well-precedented ability to stabilize Fe(II) ions. Complexes 1 and 2 ware prepared via a metal-assisted template reaction from the unsymmetrical pyridyl ketone precursor 2-(OCMe)-6-(2,6-(iPr2-C6H3NCMe)-C5H3N. Reaction of 1 with O2 was shown to afford the S-oxygenated sulfoxide complex [Fe(LN3S(O)Me)(OTf)]2+ (3), whereas compound 2, under the same reaction conditions, afforded the corresponding sulfone complex [Fe(LN3S(O2)Me)Cl]2+ (4).The unsymmetrical sulfide-incorporated bis(imino)pyridine complexes [FeII(LN3SMe)(H2O)3](OTf)2 (1) and [FeII(LN3SMe)Cl2] (2) were synthesized and characterized by X-ray crystallography. Complexes 1 and 2 react with molecular oxygen under identical conditions to afford sulfoxide and sulfone products, respectively.

The direct conversion of a MnIII complex [(TBP8Cz)MnIII (1)] to a MnV–oxo complex [(TBP8Cz)MnV(O) (2)] with O2 and visible light is reported. Complex 1 is also shown to function as an active photocatalyst for the oxidation of PPh3 to OPPh3. Mechanistic studies indicate that the photogeneration of 2 does not involve singlet oxygen but rather likely occurs via a free-radical mechanism upon photoactivation of 1.

The non-heme iron enzyme cysteine dioxygenase (CDO) catalyzes the S-oxygenation of cysteine by O2 to give cysteine sulfinic acid. The synthesis of a new structural and functional model of the cysteine-bound CDO active site, [FeII(N3PyS)(CH3CN)]BF4 (1) is reported. This complex was prepared with a new facially chelating 4N/1S(thiolate) pentadentate ligand. The reaction of 1 with O2 resulted in oxygenation of the thiolate donor to afford the doubly oxygenated sulfinate product [FeII(N3PySO2)(NCS)] (2), which was crystallographically characterized. The thiolate donor provided by the new N3PyS ligand has a dramatic influence on the redox potential and O2 reactivity of this FeII model complex.

Addition of the Lewis acid Zn2+ to (TBP8Cz)MnV(O) induces valence tautomerization, resulting in the formation of [(TBP8Cz+•)MnIV(O)–Zn2+]. This new species was characterized by UV–vis, EPR, the Evans method, and 1H NMR and supported by DFT calculations. Removal of Zn2+ quantitatively restores the starting material. Electron-transfer and hydrogen-atom-transfer reactions are strongly influenced by the presence of Zn2+.

Oxidation of the FeIII complex (TBP8Cz)FeIII [TBP8Cz = octakis(4-tert-butylphenyl)corrolazinate] with O-atom transfer oxidants under a variety of conditions gives the reactive high-valent Fe(O) complex (TBP8Cz+•)FeIV(O) (2). The solution state structure of 2 was characterized by XAS [d(Fe–O) = 1.64 Å]. This complex is competent to oxidize a range of C–H substrates. Product analyses and kinetic data show that these reactions occur via rate-determining hydrogen-atom transfer (HAT), with a linear correlation for log k versus BDE(C–H), and the following activation parameters for xanthene (Xn) substrate: ΔH⧧ = 12.7 ± 0.8 kcal mol–1, ΔS⧧ = −9 ± 3 cal K–1 mol–1, and KIE = 5.7. Rebound hydroxylation versus radical dimerization for Xn is favored by lowering the reaction temperature. These findings provide insights into the factors that control the intrinsic reactivity of Compound I heme analogues.

Density functional theory (DFT) calculations are presented on biomimetic model complexes of cysteine dioxygenase and focus on the effect of axial and equatorial ligand placement. Recent studies by one of us [Y. M. Badiei, M. A. Siegler and D. P. Goldberg, J. Am. Chem. Soc. 2011, 133, 1274] gave evidence of a nonheme iron biomimetic model of cysteine dioxygenase using an i-propyl-bis(imino)pyridine, equatorial tridentate ligand. Addition of thiophenol, an anion – either chloride or triflate – and molecular oxygen, led to several possible stereoisomers of this cysteine dioxygenase biomimetic complex. Moreover, large differences in reactivity using chloride as compared to triflate as the binding anion were observed. Here we present a series of DFT calculations on the origin of these reactivity differences and show that it is caused by the preference of coordination site of anion versus thiophenol binding to the chemical system. Thus, stereochemical interactions of triflate and the bulky iso-propyl substituents of the ligand prevent binding of thiophenol in the trans position using triflate. By contrast, smaller anions, such as chloride, can bind in either cis or trans ligand positions and give isomers with similar stability. Our calculations help to explain the observance of thiophenol dioxygenation by this biomimetic system and gives details of the reactivity differences of ligated chloride versus triflate.

The S-oxygenation of cysteine with dioxygen to give cysteine sulfinic acid occurs at the non-heme iron active site of cysteine dioxygenase. Similar S-oxygenation events occur in other non-heme iron enzymes, including nitrile hydratase and isopenicillin N synthase, and these enzymes have inspired the development of a class of [NxSy]–Fe model complexes. Certain members of this class have provided some intriguing examples of S-oxygenation, and this article summarizes these results, focusing on the non-heme iron(II/III)–thiolate model complexes that are known to react with O2 or other O-atom transfer oxidants to yield sulfur oxygenates. Key aspects of the synthesis, structure, and reactivity of these systems are presented, along with any mechanistic information available on the oxygenation reactions. A number of iron(III)–thiolate complexes react with O2 to give S-oxygenates, and the degree to which the thiolate sulfur donors are oxidized varies among the different complexes, depending upon the nature of the ligand, metal geometry, and spin state. The first examples of iron(II)–thiolate complexes that react with O2 to give selective S-oxygenation are just emerging. Mechanistic information on these transformations is limited, with isotope labeling studies providing much of the current mechanistic data. The many questions that remain unanswered for both models and enzymes provide strong motivation for future work in this area.

Treatment of an unsymmetrical bis(imino)pyridyl-thiolate zinc(II) complex [ZnII(LN3S)(OTf)] (1) with LiAlH4 results in the double reduction of the two imino groups in the ligand backbone, and at the same time causes a rare transmetalation reaction to occur. The products formed in this reaction are two novel aluminium(III) bis(amido)pyridyl-thiolate complexes [(R,S/S,R-[AlIII(LH2N3S)(THF)] (2a) and [(R,R/S,S-[AlIII(LH2N3S)(THF)] (2b), which are diastereomers of each other. These complexes have been characterized by single-crystal X-ray diffraction and 1H NMR spectroscopy. Single crystal X-ray structure analysis shows that the AlIII ion is bound in an almost idealized square pyramidal geometry in 2a, while being held in a more distorted square pyramidal geometry in 2b. The major difference between 2a and 2b arises in the orientation of the terminal methyl groups of the ligand backbone in relation to the AlIIIN3S plane. These two complexes are crystallized at different temperatures (room temperature versus −35 °C), allowing for their separate isolation. Structural analysis shows that these complexes are reduced by the formal addition of one hydride ion to each imino group, resulting in a deprotonated bis(amido)pyridyl-thiolate ligand. A detailed analysis of metrical parameters rules out the possibility of pure one- or two-electron reduction of the π-conjugated bis(imino)pyridine framework. 1H NMR spectra reveal a rich pattern in solution indicating that the solution state structures for 2a and 2b match those observed in the solid-state crystal structures, and reveal that both complexes are severely conformationally restricted. Direct organic synthetic methods failed to produce the reduced bis(amino)pyridyl-thiol ligand in pure form, but during the course of these efforts an unusual unsymmetrical aminopyridyl ketone,1-(6-(1-(2,6-diisopropylphenylamino)ethyl)pyridin-2-yl)ethanone was synthesized in good yield and can be used as a possible precursor for further ligand development.Graphical abstractReaction of an unsymmetrical bis(imino)pyridyl-thiolate zinc(II) complex [ZnII(LN3S)(OTf)] (1) with LiAlH4 results in the reduction of the bis(imino) groups and the unexpected transmetalation of ZnII with AlIII. The diastereomeric products [(R,S/S,R-[AlIII(LH2N3S)(THF)] (2a) and [(R,R/S,S-[AlIII(LH2N3S)(THF)] (2b) were characterized by X-ray crystallography and 1H NMR spectroscopy.Highlights► Synthesis and characterization of novel AlIII bis(amido)pyridyl-thiolate complexes. ► Reduction of ZnII(LN3S)(OTf) with LiAlH4 results in a rare transmetallation reaction. ► Complexes characterized by X-ray diffraction and 1H NMR spectroscopy. ► Analysis rules out the possibility of one or two-electron reduction of the ligand. ► Transmetalation reaction may be relevant to olefin polymerization.

In this work, we present the first computational study on a biomimetic cysteine dioxygenase model complex, [FeII(LN3S)]+, in which LN3S is a tetradentate ligand with a bis(imino)pyridyl scaffold and a pendant arylthiolate group. The reaction mechanism of sulfur dioxygenation with O2 was examined by density functional theory (DFT) methods and compared with results obtained for cysteine dioxygenase. The reaction proceeds via multistate reactivity patterns on competing singlet, triplet, and quintet spin state surfaces. The reaction mechanism is analogous to that found for cysteine dioxygenase enzymes (Kumar, D.; Thiel, W.; de Visser, S. P. J. Am. Chem. Soc.2011, 133, 3869–3882); hence, the computations indicate that this complex can closely mimic the enzymatic process. The catalytic mechanism starts from an iron(III)–superoxo complex and the attack of the terminal oxygen atom of the superoxo group on the sulfur atom of the ligand. Subsequently, the dioxygen bond breaks to form an iron(IV)–oxo complex with a bound sulfenato group. After reorganization, the second oxygen atom is transferred to the substrate to give a sulfinic acid product. An alternative mechanism involving the direct attack of dioxygen on the sulfur, without involving any iron–oxygen intermediates, was also examined. Importantly, a significant energetic preference for dioxygen coordinating to the iron center prior to attack at sulfur was discovered and serves to elucidate the function of the metal ion in the reaction process. The computational results are in good agreement with experimental observations, and the differences and similarities of the biomimetic complex and the enzymatic cysteine dioxygenase center are highlighted.

One-electron oxidation of MnV–oxo corrolazine 2 affords 2+, the first example of a MnV(O) π-cation radical porphyrinoid complex, which was characterized by UV–vis, EPR, LDI-MS, and DFT methods. Access to 2 and 2+ allowed for a direct comparison of their reactivities in oxygen-atom transfer (OAT) reactions. Both complexes are capable of OAT to PPh3 and RSR substrates, and 2+ was found to be a more potent oxidant than 2. Analysis of rate constants and activation parameters, together with DFT calculations, points to a concerted OAT mechanism for 2+ and 2 and indicates that the greater electrophilicity of 2+ likely plays a dominant role in enhancing its reactivity. These results are relevant to comparisons between Compound I and Compound II in heme enzymes.

The electron-transfer and hydride-transfer properties of an isolated manganese(V)−oxo complex, (TBP8Cz)MnV(O) (1) (TBP8Cz = octa-tert-butylphenylcorrolazinato) were determined by spectroscopic and kinetic methods. The manganese(V)−oxo complex 1 reacts rapidly with a series of ferrocene derivatives ([Fe(C5H4Me)2], [Fe(C5HMe4)2], and ([Fe(C5Me5)2] = Fc*) to give the direct formation of [(TBP8Cz)MnIII(OH)]− ([2-OH]−), a two-electron-reduced product. The stoichiometry of these electron-transfer reactions was found to be (Fc derivative)/1 = 2:1 by spectral titration. The rate constants of electron transfer from ferrocene derivatives to 1 at room temperature in benzonitrile were obtained, and the successful application of Marcus theory allowed for the determination of the reorganization energies (λ) of electron transfer. The λ values of electron transfer from the ferrocene derivatives to 1 are lower than those reported for a manganese(IV)−oxo porphyrin. The presumed one-electron-reduced intermediate, a MnIV complex, was not observed during the reduction of 1. However, a MnIV complex was successfully generated via one-electron oxidation of the MnIII precursor complex 2 to give [(TBP8Cz)MnIV]+ (3). Complex 3 exhibits a characteristic absorption band at λmax = 722 nm and an EPR spectrum at 15 K with gmax′ = 4.68, gmid′ = 3.28, and gmin′ = 1.94, with well-resolved 55Mn hyperfine coupling, indicative of a d3 MnIVS = 3/2 ground state. Although electron transfer from [Fe(C5H4Me)2] to 1 is endergonic (uphill), two-electron reduction of 1 is made possible in the presence of proton donors (e.g., CH3CO2H, CF3CH2OH, and CH3OH). In the case of CH3CO2H, saturation behavior for the rate constants of electron transfer (ket) versus acid concentration was observed, providing insight into the critical involvement of H+ in the mechanism of electron transfer. Complex 1 was also shown to be competent to oxidize a series of dihydronicotinamide adenine dinucleotide (NADH) analogues via formal hydride transfer to produce the corresponding NAD+ analogues and [2-OH]−. The logarithms of the observed second-order rate constants of hydride transfer (kH) from NADH analogues to 1 are linearly correlated with those of hydride transfer from the same series of NADH analogues to p-chloranil.

The new iron(II)−thiolate complexes [(iPrBIP)FeII(SPh)(Cl)] (1) and [(iPrBIP)FeII(SPh)(OTf)] (2) [BIP = bis(imino)pyridine] were prepared as models for cysteine dioxygenase (CDO), which converts Cys to Cys-SO2H at a (His)3FeII center. Reaction of 1 and 2 with O2 leads to Fe-oxygenation and S-oxygenation, respectively. For 1 + O2, the spectroscopic and reactivity data, including 18O isotope studies, are consistent with an assignment of an iron(IV)−oxo complex, [(iPrBIP)FeIV(O)(Cl)]+ (3), as the product of oxygenation. In contrast, 2 + O2 results in direct S-oxygenation to give a sulfonato product, PhSO3−. The positioning of the thiolate ligand in 1 versus 2 appears to play a critical role in determining the outcome of O2 activation. The thiolate ligands in 1 and 2 are essential for O2 reactivity and exhibit an important influence over the FeIII/FeII redox potential.

The synthesis of structural and functional models of the active site of the nonheme iron enzyme cysteine dioxygenase (CDO) is reported. A bis(imino)pyridine ligand scaffold was employed to synthesize a mononuclear ferrous complex, FeII(LN3S)(OTf) (1), which contains three neutral nitrogen donors and one anionic thiolato donor. Complex 1 is a good structural model of the Cys-bound active site of CDO. Reaction of 1 with O2 results in oxygenation of the thiolato sulfur, affording the sulfonato complex FeII(LN3SO3)(OTf) (2) under mild conditions. Isotope labeling studies show that O2 is the sole source of O atoms in the product and that the reaction proceeds via a dioxygenase-type mechanism for two out of three O atoms added, analogous to the dioxygenase reaction of CDO. The zinc(II) analog, Zn(LN3S)(OTf) (4), was prepared and found to be completely unreactive toward O2, suggesting a critical role for FeII in the oxygenation chemistry observed for 1. To our knowledge, S-oxygenation mediated by an FeII−SR complex and O2 is unprecedented.

The manganese(V) oxo complex (TBP8Cz)MnV(O) (1) is shown to catalyze the epoxidation of alkenes with a series of iodosylarenes (ArIO) as oxidants. Competition experiments reveal that the identity of ArIO influences the product ratios, implicating an unusual coordinated oxo−metal−ArIO intermediate (1-OIAr) as the active catalytic species. The isoelectronic manganese(V) imido complex (TBP8Cz)MnV(NMes) (2) does not participate in NR transfer but does catalyze epoxidations with ArIO as the O-atom source, suggesting a mechanism similar to that seen for 1. Direct evidence (ESIMS) is obtained for 1-OIMes.

Nanoparticles, each consisting of one of the three molecular corrolazine (Cz) compounds, H3(TBP8Cz), MnIII(TBP8Cz), and FeIII(TBP8Cz) (TBP8Cz = octakis(4-tert-butylphenyl)corrolazinato), were prepared via a facile mixed-solvent technique. The corrolazine nanoparticles (MCz-NPs) were formed in H2O/THF (10:1) in the presence of a small amount of a polyethylene glycol derivative (TEG-ME) added as a stabilizer. This technique allows highly hydrophobic Czs to be “dissolved” in an aqueous environment as nanoparticles, which remain in solution for several months without visible precipitation. The MCz-NPs were characterized by UV−visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging, and shown to be spherical particles from 100−600 nm in diameter with low polydispersity indices (PDI = 0.003−0.261). Particle size is strongly dependent on Cz concentration. The H3Cz-NPs were adsorbed on to a modified self-assembled monolayer (SAM) surface and imaged by atomic force microscopy (AFM). Adsorption resulted in disassembly of the larger H3Cz-NPs to smaller H3Cz-NPs, whereby the resulting particle size can be controlled by the surface energy of the monolayer. The FeIIICz-NPs were shown to be competent catalysts for the oxidation of cyclohexene with either PFIB or H2O2 as external oxidant. The reactivity and product selectivity seen for FeIIICz-NPs differs dramatically from that seen for the molecular species in organic solvents, suggesting that both the nanoparticle structure and the aqueous conditions may contribute to significant changes in the mechanism of action of the FeIIICz catalyst.

The reaction of a series of thiolate-ligated iron(II) complexes [FeII([15]aneN4)(SC6H5)]BF4 (1), [FeII([15]aneN4)(SC6H4-p-Cl)]BF4 (2), and [FeII([15]aneN4)(SC6H4-p-NO2)]BF4 (3) with alkylhydroperoxides at low temperature (−78 °C or −40 °C) leads to the metastable alkylperoxo-iron(III) species [FeIII([15]aneN4)(SC6H5)(OOtBu)]BF4 (1a), [FeIII([15]aneN4)(SC6H4-p-Cl)(OOtBu)]BF4 (2a), and [FeIII([15]aneN4)(SC6H4-p-NO2)(OOtBu)]BF4 (3a), respectively. X-ray absorption spectroscopy (XAS) studies were conducted on the FeIII−OOR complexes and their iron(II) precursors. The edge energy for the iron(II) complexes (∼7118 eV) shifts to higher energy upon oxidation by ROOH, and the resulting edge energies for the FeIII−OOR species range from 7121−7125 eV and correlate with the nature of the thiolate donor. Extended X-ray absorption fine structure (EXAFS) analysis of the iron(II) complexes 1−3 in CH2Cl2 show that their solid state structures remain intact in solution. The EXAFS data on 1a−3a confirm their proposed structures as mononuclear, 6-coordinate FeIII−OOR complexes with 4N and 1S donors completing the coordination sphere. The Fe−O bond distances obtained from EXAFS for 1a−3a are 1.82−1.85 Å, significantly longer than other low-spin FeIII−OOR complexes. The Fe−O distances correlate with the nature of the thiolate donor, in agreement with the previous trends observed for ν(Fe−O) from resonance Raman (RR) spectroscopy, and supported by optimized geometries obtained from density functional theory (DFT) calculations. Reactivity and kinetic studies on 1a− 3a show an important influence of the thiolate donor.

It is shown that an iron(III) meso-N-substituted corrole (TBP8Cz)FeIII (1) (TBP8Cz = octakis(4-tert-butylphenyl)corrolazinato), is a potent catalyst for the oxidation of alkenes in the presence of pentaflouroiodosylbenzene (C6F5IO) as oxidant. In the case of cyclohexene, complex 1 performs on a par with one of the best porphyrin catalysts ((TPPF20)FeCl), exhibiting rapid turnover and a high selectivity for epoxide (CzFeIII/C6F5IO/cyclohexene (1:100:1000) in CH2Cl2/CH3OH (3:1 v:v) gives 33 turnovers of epoxide in <2 min). Reaction rates for 1 are greatly enhanced compared to other Fe or Mn corroles under similar catalytic conditions, consistent with an increase in the electrophilicity of a high-valent iron−oxo intermediate induced by meso-N substitution. Reaction of dark-green 1 (λmax = 440, 611, 747 nm) under single-turnover-like conditions at −78 °C leads to the formation of a new dark-brown species (2) (λmax = 396, 732, 843 nm). The FeIII complex 1 is restored upon the addition of 2 equiv of ferrocene to 2, or by the addition of 1 equiv of PPh3, which concomitantly yields OPPh3. In addition, complex 2 reacts with excess cyclohexene at −42 °C to give 1. Complex 2 was also characterized by EPR spectroscopy, and all of the data are consistent with 2 being an antiferromagnetically coupled iron(IV)-oxo π-cation-radical complex. Rapid-mixing stopped-flow UV−vis studies show that the low-temperature complex 2 is generated as a short-lived intermediate at room temperature.

A new five-coordinate, (N4S(thiolate))FeII complex, containing tertiary amine donors, [FeII(Me4[15]aneN4)(SPh)]BPh4 (2), was synthesized and structurally characterized as a model of the reduced active site of superoxide reductase (SOR). Reaction of 2 with tert-butyl hydroperoxide (tBuOOH) at −78 °C led to the generation of the alkylperoxo-iron(III) complex [FeIII(Me4[15]aneN4)(SPh)(OOtBu)]+ (2a). The nonthiolate-ligated complex, [FeII(Me4[15]aneN4)(OTf)2] (3), was also reacted with tBuOOH and yielded the corresponding alkylperoxo complex [FeIII(Me4[15]aneN4)(OTf)(OOtBu)]+ (3a) at an elevated temperature of −23 °C. These species were characterized by low-temperature UV−vis, EPR, and resonance Raman spectroscopies. Complexes 2a and 3a exhibit distinctly different spectroscopic signatures than the analogous alkylperoxo complexes [FeIII([15]aneN4)(SAr)(OOR)]+, which contain secondary amine donors. Importantly, alkylation at nitrogen leads to a change from low-spin (S = 1/2) to high-spin (S = 5/2) of the iron(III) center. The resonance Raman data reveal that this change in spin state has a large effect on the ν(Fe−O) and ν(O−O) vibrations, and a comparison between 2a and the nonthiolate-ligated complex 3a shows that axial ligation has an additional significant impact on these vibrations. To our knowledge this study is the first in which the influence of a ligand trans to a peroxo moiety has been evaluated for a structurally equivalent pair of high-spin/low-spin peroxo-iron(III) complexes. The implications of spin state and thiolate ligation are discussed with regard to the functioning of SOR.

Addition of O2(g) at low-temperature to a mononuclear, nonheme iron(II) complex comprising a tetraazamacrocyclic N4 donor and an arylthiolate S donor leads to the generation of a deep red complex assigned as a low-spin FeIII–OOH complex, formed via metal- and ligand-assisted oxidation.

Screening of a “one-bead-one-compound” peptide library containing biomimetic His/Cys ligands has led to the discovery of sequences that hydrolyze ester substrates in combination with Zn2+.

The new sterically encumbered, tripodal N2S(alkylthiolate) ligand, LIm2SH, has been synthesized and used to prepare [(LIm2S)ZnCH3], which upon protonolysis under acidic conditions leads to the synthesis of a novel dinucleating ligand and a zinc dimer with an unusual structure.

The synthesis and crystallographic characterization of a new (N2S)zinc–alkyl complex and (N2S)zinc–formate complex is described; the bonding mode of the formate complex has implications for the mechanism of action of the enzyme peptide deformylase.

Addition of anionic donors to the manganese(V)–oxo corrolazine complex MnV(O)(TBP8Cz) has a dramatic influence on oxygen-atom transfer (OAT) reactivity with thioether substrates. The six-coordinate anionic [MnV(O)(TBP8Cz)(X)]− complexes (X = F–, N3–, OCN–) exhibit a ∼5 cm–1 downshift of the Mn–O vibrational mode relative to the parent MnV(O)(TBP8Cz) complex as seen by resonance Raman spectroscopy. Product analysis shows that the oxidation of thioether substrates gives sulfoxide product, consistent with single OAT. A wide range of OAT reactivity is seen for the different axial ligands, with the following trend determined from a comparison of their second-order rate constants for sulfoxidation: five-coordinate ≈ thiocyanate ≈ nitrate < cyanate < azide < fluoride ≪ cyanide. This trend correlates with DFT calculations on the binding of the axial donors to the parent MnV(O)(TBP8Cz) complex. A Hammett study was performed with p-X-C6H4SCH3 derivatives and [MnV(O)(TBP8Cz)(X)]− (X = CN– or F–) as the oxidant, and unusual “V-shaped” Hammett plots were obtained. These results are rationalized based upon a change in mechanism that hinges on the ability of the [MnV(O)(TBP8Cz)(X)]− complexes to function as either an electrophilic or weak nucleophilic oxidant depending upon the nature of the para-X substituents. For comparison, the one-electron-oxidized cationic MnV(O)(TBP8Cz•+) complex yielded a linear Hammett relationship for all substrates (ρ = −1.40), consistent with a straightforward electrophilic mechanism. This study provides new, fundamental insights regarding the influence of axial donors on high-valent MnV(O) porphyrinoid complexes.

The selective alkylation of a single meso-N atom of a corrolazine macrocycle is reported. Alkylation has a dramatic impact on the physicochemical properties of ReV(O)(TBP8Cz). New electron-transfer and hydrogen-atom-transfer reactivity is also seen for this complex, including one-electron reduction, which gives an air-stable 19π-electron aromatic radical complex.

The synthesis of the first example of a third-row metallocorrolazine characterized by single crystal X-ray diffraction is reported. This ReV(O) porphyrinoid complex shows an exclusively ligand-based reactivity with strong acids and oxidizing agents. The one-electron oxidized π-radical-cation complex is capable of H-atom abstraction.

Addition of O2(g) at low-temperature to a mononuclear, nonheme iron(II) complex comprising a tetraazamacrocyclic N4 donor and an arylthiolate S donor leads to the generation of a deep red complex assigned as a low-spin FeIII–OOH complex, formed via metal- and ligand-assisted oxidation.

The non-heme iron complexes, [FeII(N3PySR)(CH3CN)](BF4)2 (1) and [FeII(N3PyamideSR)](BF4)2 (2), afford rare examples of metastable Fe(III)-OOH and Fe(III)-OOtBu complexes containing equatorial thioether ligands and a single H-bond donor in the second coordination sphere. These peroxo complexes were characterized by a range of spectroscopic methods and density functional theory studies. The influence of a thioether ligand and of one H-bond donor on the stability and spectroscopic properties of these complexes was investigated.

Density functional theory (DFT) calculations are presented on biomimetic model complexes of cysteine dioxygenase and focus on the effect of axial and equatorial ligand placement. Recent studies by one of us [Y. M. Badiei, M. A. Siegler and D. P. Goldberg, J. Am. Chem. Soc. 2011, 133, 1274] gave evidence of a nonheme iron biomimetic model of cysteine dioxygenase using an i-propyl-bis(imino)pyridine, equatorial tridentate ligand. Addition of thiophenol, an anion – either chloride or triflate – and molecular oxygen, led to several possible stereoisomers of this cysteine dioxygenase biomimetic complex. Moreover, large differences in reactivity using chloride as compared to triflate as the binding anion were observed. Here we present a series of DFT calculations on the origin of these reactivity differences and show that it is caused by the preference of coordination site of anion versus thiophenol binding to the chemical system. Thus, stereochemical interactions of triflate and the bulky iso-propyl substituents of the ligand prevent binding of thiophenol in the trans position using triflate. By contrast, smaller anions, such as chloride, can bind in either cis or trans ligand positions and give isomers with similar stability. Our calculations help to explain the observance of thiophenol dioxygenation by this biomimetic system and gives details of the reactivity differences of ligated chloride versus triflate.

The S-oxygenation of cysteine with dioxygen to give cysteine sulfinic acid occurs at the non-heme iron active site of cysteine dioxygenase. Similar S-oxygenation events occur in other non-heme iron enzymes, including nitrile hydratase and isopenicillin N synthase, and these enzymes have inspired the development of a class of [NxSy]–Fe model complexes. Certain members of this class have provided some intriguing examples of S-oxygenation, and this article summarizes these results, focusing on the non-heme iron(II/III)–thiolate model complexes that are known to react with O2 or other O-atom transfer oxidants to yield sulfur oxygenates. Key aspects of the synthesis, structure, and reactivity of these systems are presented, along with any mechanistic information available on the oxygenation reactions. A number of iron(III)–thiolate complexes react with O2 to give S-oxygenates, and the degree to which the thiolate sulfur donors are oxidized varies among the different complexes, depending upon the nature of the ligand, metal geometry, and spin state. The first examples of iron(II)–thiolate complexes that react with O2 to give selective S-oxygenation are just emerging. Mechanistic information on these transformations is limited, with isotope labeling studies providing much of the current mechanistic data. The many questions that remain unanswered for both models and enzymes provide strong motivation for future work in this area.