Tapan Kanti Paine

Oxygen activation at mononuclear nonheme iron centers: a superoxo perspective.

Dioxygen (O(2)) activation by iron enzymes is responsible for many metabolically important transformations in biology. Often a high-valent iron oxo oxidant is proposed to form upon O(2) activation at a mononuclear nonheme iron center, presumably via intervening iron superoxo and iron peroxo species. While iron(IV) oxo intermediates have been trapped and characterized in enzymes and models, less is known of the putative iron(III) superoxo species. Utilizing a synthetic model for the 2-oxoglutarate-dependent monoiron enzymes, [(Tp(iPr2))Fe(II)(O(2)CC(O)CH(3))], we have obtained indirect evidence for the formation of the putative iron(III) superoxo species, which can undergo one-electron reduction, hydrogen-atom transfer, or conversion to an iron(IV) oxo species, depending on the reaction conditions. These results demonstrate the various roles that the iron(III) superoxo species can play in the course of O(2) activation at a nonheme iron center.

Biomimetic metal-radical reactivity: aerial oxidation of alcohols, amines, aminophenols and catechols catalyzed by transition metal complexes.

Abstract The contributions of the authors to the research program ‘Radicals in Enzymatic Catalysis’ over the last ca. 5 years are summarized. Significant efforts were directed towards the design and testing of phenol-containing ligands for synthesizing radical-containing transition metal complexes as potential candidates for catalysis of organic substrates like alcohols, amines, aminophenols and catechols. Functional models for different copper oxidases, such as galactose oxidase, amine oxidases, phenoxazinone synthase and catechol oxidase, are reported. The copper complexes synthesized can mimic the function of the metalloenzymes galactose oxidase and amine oxidases by catalyzing the aerial oxidation of alcohols and amines. Even methanol could be oxidized, albeit with a low conversion, by a biradical-copper(II) compound. The presence of a primary kinetic isotope effect, similar to that for galactose oxidase, provides compelling evidence that H-atom abstraction from the α-C-atom of the substrates is the rate-limiting step. Although catechol oxidase and phenoxazinone synthase contain copper, manganese(IV) complexes containing radicals have been found to be useful to study synthetic systems and to understand the naturally occurring processes. An ‘on-off’ mechanism of the radicals without redox participation from the metal centers seems to be operative in the catalysis involving such metal-radical complexes.

Oxidative Decarboxylation of Benzilic Acid by a Biomimetic Iron(II) Complex: Evidence for an Iron(IV)–Oxo–Hydroxo Oxidant from O2

The existence of dioxygen-activating nonheme iron enzymes that carry out four-electron substrate oxidations requires a mechanism where the initially formed iron(III)–superoxide species must be involved as an oxidant to initiate the reaction. Such a step has been proposed for many aromatic and aliphatic C C bond cleaving dioxygenases. Recently discovered examples include 2-hydroxyethylphosphonate (HEP) dioxygenase (HEPD) which catalyzes the cleavage of the HEP C1 C2 bond to form hydroxymethylphosphonate and formate, and CloR, which is involved in the conversion of a mandelate moiety to benzoate in the biosynthesis of chlorobiocin, an aminocoumarin antibiotic. For the above examples, the substrate provides all four electrons needed for the reduction of O2 to water. In contrast, the Rieske dioxygenases require two electrons from NADH to carry out the cis-dihydroxylation of aromatic C=C bonds. 7] A high-valent iron–oxo–hydroxo intermediate has been proposed to carry out this transformation. Recently, a synthetic iron(II)–mandelate complex supported by a tripodal N4 donor ligand was reported by us [8] to undergo nearly quantitative oxidative decarboxylation in the presence of dioxygen, thereby mimicking the C C bond cleavage reaction of CloR. An iron(III)–superoxo species has been implicated in the reaction pathway. In exploring the O2 reactivity of related iron(II)–a-hydroxy acid complexes, specifically those of benzilic acid (2,2-diphenyl-2-hydroxyacetic acid), we discovered a new mode of O2 activation that leads to the formation of an iron(IV)–oxo–hydroxo oxidant. These intriguing results are reported here. The iron(II) model complex [ðTp2ÞFe(benzilate)] (1), where Tp2 = hydrotris(3,5-diphenylpyrazolyl)borate, was synthesized by reacting equimolar amounts of the polydentate ligand, iron(II) perchlorate, benzilic acid, and triethylamine in methanol. The H NMR spectrum of 1 shows broad and paramagnetically shifted peaks indicative of the high-spin nature of the iron(II) complex (Figure S1 in the Supporting Information). The X-ray crystal structure of 1 shows a distorted square-pyramidal iron(II) center (t = 0.46) that is coordinated by the facial tridentate Tp2 ligand and the carboxylate of the benzilate monoanion (Figure 1). The

A functional model of extradiol-cleaving catechol dioxygenases: mimicking the 2-his-1-carboxylate facial triad.

The synthesis and characterization of an iron-catecholate model complex of a tridentate 2-N-1-carboxylate ligand derived from L-proline are reported. The X-ray crystal structure of the complex [(L)(3)Fe(3)(DBC)(3)] (1) (where L is 1-(2-pyridylmethyl)pyrrolidine-2-carboxylate and DBC is the dianion of 3,5-di-tert-butyl catechol) reveals that the tridentate ligand binds to the iron center in a facial manner and mimics the 2-his-1-carboxylate facial triad motif observed in extradiol-cleaving catechol dioxygenases. The iron(III)-catecholate complex (1) reacts with dioxygen in acetonitrile in ambient conditions to cleave the C-C bond of catecholate. In the reaction, an equal amount of extra- and intradiol cleavage products are formed without any auto-oxidation product. The iron-catecholate complex is a potential functional model of extradiol-cleaving catechol dioxygenases.

Copper(II) and Nickel(II) Complexes of β-Aminoketoxime Ligand: Syntheses, Crystal Structures, Magnetism, and Nickel(II) Templated Coupling of Oxime with Nitrile

The syntheses, molecular structures, and magnetic properties of a dicopper(II) complex, [Cu(2)(HL(1))(2)](ClO(4))(2) (1), and its nickel(II) analog, [Ni(2)(HL(1))(2)](ClO(4))(2) (2), of a beta-amino ketoxime ligand (H(2)L(1) = 4,4,9,9-tetramethyl-5,8-diazadodecane-2,11-dione dioxime) are discussed. The metal centers in out-of-plane oximate bridged dinuclear complexes (1 and 2) display distorted trigonal bipyramidal geometry and form a six-membered M(2)(NO)(2) ring oriented in a boat conformation. The two copper(II) centers in 1 interact ferromagnetically giving rise to a triplet-spin ground state whereas the two nickel(II) centers in 2 interact antiferromagnetically to stabilize a singlet-spin state. Variable temperature magnetic susceptibility measurements establish the presence of a weak ferromagnetic coupling (J = 13 cm(-1)) in 1 and a weak anitiferromagnetic coupling (J = -12 cm(-1)) in 2. The exchange coupling constant derived from B3LYP computations in conjunction with broken symmetry spin-projection techniques for the oximate bridged dinuclear copper(II) complex shows excellent agreement with the corresponding experimental value. A square-planar mononuclear nickel(II) complex of the dioxime ligand, [Ni(H(2)L(1))](ClO(4))(2) (3), is reported along with its crystal structure, which reacts with acetonitrile to produce a six-coordinate mononuclear complex, [Ni(L(2))](ClO(4))(2) (4). The ligand (L(2)) in complex 4 is the iminoacyl derivative of oxime, where the coupling of oxime and acetonitrile takes place via a proton-assisted pathway. The iminoacylation of H(2)L(1) works with other nitriles like butyronitrile and benzonitrile. Computational studies support a proton-assisted coupling of oxime with nitrile. The critical transition states have been located for the iminoacylation reaction. Complex 4 can be converted back to complex 3 by reacting with sodium acetate in methanol.

Olefincis-Dihydroxylation and Aliphatic CH Bond Oxygenation by a Dioxygen-Derived Electrophilic Iron-Oxygen Oxidant

Many iron-containing enzymes involve metal-oxygen oxidants to carry out O2-dependent transformation reactions. However, the selective oxidation of C-H and C=C bonds by biomimetic complexes using O2 remains a major challenge in bioinspired catalysis. The reactivity of iron-oxygen oxidants generated from an Fe(II)-benzilate complex of a facial N3 ligand were thus investigated. The complex reacted with O2 to form a nucleophilic oxidant, whereas an electrophilic oxidant, intercepted by external substrates, was generated in the presence of a Lewis acid. Based on the mechanistic studies, a nucleophilic Fe(II)-hydroperoxo species is proposed to form from the benzilate complex, which undergoes heterolytic O-O bond cleavage in the presence of a Lewis acid to generate an Fe(IV)-oxo-hydroxo oxidant. The electrophilic iron-oxygen oxidant selectively oxidizes sulfides to sulfoxides, alkenes to cis-diols, and it hydroxylates the C-H bonds of alkanes, including that of cyclohexane.

Dioxygen Reactivity of Biomimetic Iron–Catecholate and Iron–o-Aminophenolate Complexes of a Tris(2-pyridylthio)methanido Ligand: Aromatic CC Bond Cleavage of Catecholate versus o-Iminobenzosemiquinonate Radical Formation

An iron(III)-catecholate complex [L(1)Fe(III)(DBC)] (2) and an iron(II)-o-aminophenolate complex [L(1)Fe(II)(HAP)] (3; where L(1) = tris(2-pyridylthio)methanido anion, DBC = dianionic 3,5-di-tert-butylcatecholate, and HAP = monoanionic 4,6-di-tert-butyl-2-aminophenolate) have been synthesised from an iron(II)-acetonitrile complex [L(1)Fe(II)(CH(3)CN)(2)](ClO(4)) (1). Complex 2 reacts with dioxygen to oxidatively cleave the aromatic C-C bond of DBC giving rise to selective extradiol cleavage products. Controlled chemical or electrochemical oxidation of 2, on the other hand, forms an iron(III)-semiquinone radical complex [L(1)Fe(III)(SQ)](PF(6)) (2(ox)-PF(6); SQ = 3,5-di-tert-butylsemiquinonate). The iron(II)-o-aminophenolate complex (3) reacts with dioxygen to afford an iron(III)-o-iminosemiquinonato radical complex [L(1)Fe(III)(ISQ)](ClO(4))(3(ox)-ClO(4); ISQ = 4,6-di-tert-butyl-o-iminobenzosemiquinonato radical) via an iron(III)-o-amidophenolate intermediate species. Structural characterisations of 1, 2, 2(ox) and 3(ox) reveal the presence of a strong iron-carbon bonding interaction in all the complexes. The bond parameters of 2(ox) and 3(ox) clearly establish the radical nature of catecholate- and o-aminophenolate-derived ligand, respectively. The effect of iron-carbon bonding interaction on the dioxygen reactivity of biomimetic iron-catecholate and iron-o-aminophenolate complexes is discussed.

Oxoiron(IV) complexes of the tris(2-pyridylmethyl)amine ligand family: effect of pyridine α-substituents

The oxoiron(IV) complexes of two 6-substituted tris(2-pyridylmethyl)amine ligand derivatives have been generated and characterized with respect to their spectroscopic and reactivity properties. The introduction of an α-substituent maintains the low-spin nature of the oxoiron(IV) unit but weakens the ligand field, as evidenced by red shifts in its characteristic near-IR chromophore. While its hydrogen-atom abstraction ability is only slightly affected, the oxo-transfer reactivity of the oxoiron(IV) center is significantly enhanced relative to that of the parent complex. These results demonstrate that the ligand environment plays a key role in modulating the reactivity of this important biological oxidant.

Reactivity of an Iron–Oxygen Oxidant Generated upon Oxidative Decarboxylation of Biomimetic Iron(II) α-Hydroxy Acid Complexes

Three biomimetic iron(II) α-hydroxy acid complexes, [(Tp(Ph2))Fe(II)(mandelate)(H2O)] (1), [(Tp(Ph2))Fe(II)(benzilate)] (2), and [(Tp(Ph2))Fe(II)(HMP)] (3), together with two iron(II) α-methoxy acid complexes, [(Tp(Ph2))Fe(II)(MPA)] (4) and [(Tp(Ph2))Fe(II)(MMP)] (5) (where HMP = 2-hydroxy-2-methylpropanoate, MPA = 2-methoxy-2-phenylacetate, and MMP = 2-methoxy-2-methylpropanoate), of a facial tridentate ligand Tp(Ph2) [where Tp(Ph2) = hydrotris(3,5-diphenylpyrazole-1-yl)borate] were isolated and characterized to study the mechanism of dioxygen activation at the iron(II) centers. Single-crystal X-ray structural analyses of 1, 2, and 5 were performed to assess the binding mode of an α-hydroxy/methoxy acid anion to the iron(II) center. While the iron(II) α-methoxy acid complexes are unreactive toward dioxygen, the iron(II) α-hydroxy acid complexes undergo oxidative decarboxylation, implying the importance of the hydroxyl group in the activation of dioxygen. In the reaction with dioxygen, the iron(II) α-hydroxy acid complexes form iron(III) phenolate complexes of a modified ligand (Tp(Ph2)*), where the ortho position of one of the phenyl rings of Tp(Ph2) gets hydroxylated. The iron(II) mandelate complex (1), upon decarboxylation of mandelate, affords a mixture of benzaldehyde (67%), benzoic acid (20%), and benzyl alcohol (10%). On the other hand, complexes 2 and 3 react with dioxygen to form benzophenone and acetone, respectively. The intramolecular ligand hydroxylation gets inhibited in the presence of external intercepting agents. Reactions of 1 and 2 with dioxygen in the presence of an excess amount of alkenes result in the formation of the corresponding cis-diols in good yield. The incorporation of both oxygen atoms of dioxygen into the diol products is confirmed by (18)O-labeling studies. On the basis of reactivity and mechanistic studies, the generation of a nucleophilic iron-oxygen intermediate upon decarboxylation of the coordinated α-hydroxy acids is proposed as the active oxidant. The novel iron-oxygen intermediate oxidizes various substrates like sulfide, fluorene, toluene, ethylbenzene, and benzaldehyde. The oxidant oxidizes benzaldehyde to benzoic acid and also participates in the Cannizzaro reaction.

Oxidative decarboxylation of α-hydroxy acids by a functional model of the nonheme iron oxygenase, CloR

Iron(II)-alpha-hydroxy acid complexes of a tripodal N4 ligand undergo oxidative decarboxylation upon exposure to O(2) and mimic the aliphatic C1-C2 cleavage step catalyzed by CloR.