Functional models of nonheme diiron enzymes: reactivity of the µ-oxo-µ-1,2-peroxo-diiron(iii) intermediate in electrophilic and nucleophilic reactions.

The reactivity of the previously reported peroxo-adduct [FeIII2(µ-O)(µ-1,2-O2)(IndH)2(solv)2]2+ (1) (IndH = 1,3-bis(2-pyridyl-imino)isoindoline) has been investigated in nucleophilic (e.g., deformylation of alkyl and aryl alkyl aldehydes) and electrophilic (e.g. oxidation of phenols) stoichiometric reactions as biomimics of ribonucleotide reductase (RNR-R2) and aldehyde deformylating oxygenase (ADO) enzymes. Based on detailed kinetic and mechanistic studies, we have found further evidence for the ambiphilic behaviour of the peroxo intermediates proposed for diferric oxidoreductase enzymes.

Stability and Catalase-Like Activity of a Mononuclear Non-Heme Oxoiron(IV) Complex in Aqueous Solution.

Heme-type catalase is a class of oxidoreductase enzymes responsible for the biological defense against oxidative damage of cellular components caused by hydrogen peroxide, where metal-oxo species are proposed as reactive intermediates. To get more insight into the mechanism of this curious reaction a non-heme structural and functional model was carried out by the use of a mononuclear complex [FeII(N4Py*)(CH3CN)](CF3SO3)2 (N4Py* = N,N-bis(2-pyridylmethyl)- 1,2-di(2-pyridyl)ethylamine) as a catalyst, where the possible reactive intermediates, high-valent FeIV=O and FeIII-OOH are known and spectroscopically well characterized. The kinetics of the dismutation of H2O2 into O2 and H2O was investigated in buffered water, where the reactivity of the catalyst was markedly influenced by the pH, and it revealed Michaelis-Menten behavior with KM = 1.39 M, kcat = 33 s-1 and k2(kcat/KM) = 23.9 M-1s-1 at pH 9.5. A mononuclear [(N4Py)FeIV=O]2+ as a possible intermediate was also prepared, and the pH dependence of its stability and reactivity in aqueous solution against H2O2 was also investigated. Based on detailed kinetic, and mechanistic studies (pH dependence, solvent isotope effect (SIE) of 6.2 and the saturation kinetics for the initial rates versus the H2O2 concentration with KM = 18 mM) lead to the conclusion that the rate-determining step in these reactions above involves hydrogen-atom transfer between the iron-bound substrate and the Fe(IV)-oxo species.

Stoichiometric Aldehyde Deformylation Mediated by Nucleophilic Peroxo-diiron(III) Complex as a Functional Model of Aldehyde Deformylating Oxygenase.

The reactivity of the previously reported peroxo adduct [FeIII 2 (µ-O2 )(MeBzim-Py)4 (CH3 CN)2 ]4+ (1) (MeBzim-Py=2-(2'-pyridyl)-N-methylbenzimidazole) towards aldehyde substrates including phenylacetaldehyde (PAA), hydrocinnamaldehyde (HCA), propionaldehyde (PA), 2-phenylpropionaldehyde (PPA), cyclohexanecarboxaldehyde (CCA), and para-substituted benzaldehydes (benzoyl chlorides) has been investigated. Complex 1 proved to be a nucleophilic oxidant in aldehyde deformylation reaction. These models, including detailed kinetic and mechanistic studies, may serve as the first biomimics of aldehyde deformylating oxygenase (ADO) enzymes.

Catalytic and stoichiometric flavanone oxidation mediated by nonheme oxoiron(iv) complexes as flavone synthase mimics: kinetic, mechanistic and computational studies.

The present study describes the first example of the stoichiometric and catalytic oxidation of flavanone by synthetic nonheme oxoiron(iv) complexes and their precursor iron(ii) complexes with m-CPBA as the terminal oxidant. These models, including detailed kinetic, mechanistic and computational studies, may serve as the biomimics of flavone synthase (FS) enzymes.

Transition metal complexes bearing flexible N3 or N3O donor ligands: reactivity toward superoxide radical anion and hydrogen peroxide.

Mononuclear complexes of N-methylpropanoate-N,N-bis-(2-pyridylmethyl)amine (MPBMPA) and N-propanoate-N,N-bis-(2-pyridylmethyl)amine (HPBMPA) with first row transition metals from Mn to Cu were synthesized and characterized by spectroscopy (infrared, UV-visible), electrochemistry (cyclic voltammetry), microanalysis and in four cases X-ray crystallography. Structure of the complexes revealed high flexibility of these ligands that can adopt facial (Fe) and meridional (Cu) geometry. Activity in the degradation of reactive oxygen species (superoxide radical anion: superoxide dismutase (SOD)-like activity and hydrogen peroxide: catalase-like activity) was tested throughout the complex series in aqueous solutions. In connection with the catalytic dismutation of H(2)O(2), bleaching tests with morin were also conducted in water. Comparison of the two ligands helped in elucidating the possible role of the carboxylate moiety in the different catalytic reactions. Although no general trends could be revealed between reactivity and constitution of the first coordination sphere, plausible explanations for differences are discussed individually for SOD like, catalase-like and bleaching activity.

Bio-inspired flavonol and quinolone dioxygenation by a non-heme iron catalyst modeling the action of flavonol and 3-hydroxy-4(1H)-quinolone 2,4-dioxygenases.

The mononuclear complex, Fe(III)(O-bs)(salen) (salenH(2)=1,6-bis(2-hydroxyphenyl)-2,5-diaza-hexa-1,5-diene; O-bsH=O-benzoylsalicylic acid) was synthesized as synthetic enzyme-depside complex, and characterized by spectroscopic methods and X-ray crystal analysis. The dioxygenation of flavonol (flaH) and 3-hydroxy-4-quinolone (quinH(2)) derivatives in the presence of catalytic amounts of Fe(III)(O-bs)(salen) results in the oxidative cleavage of the heterocyclic ring to give the corresponding O-benzoylsalicylic and anthranilic acid derivatives with concomitant release of carbon monoxide. These reactions can be regarded as biomimetic functional models with relevance to the iron-containing flavonol and the cofactor-independent 3-hydroxy-4(1H)-quinolone 2,4-dioxygenases.

Comparison of the SOD-like activity of hexacoordinate Mn(II), Fe(II) and Ni(II) complexes having isoindoline-based ligands.

Recently, a series of Fe(II) complexes have been published by our group with 3N-donor 1,3-bis(2'-Ar-imino)isoindoline ligands containing various Ar-groups (pyridyl, 4-methylpyridyl, thiazolyl, benzimidazolyl and N-methylbenzimidazolyl). The superoxide scavenging activity of the compounds showed correlation with the Fe(III)/Fe(II) redox potentials. Analogous, electroneutral chelate complexes with Mn(II) and Ni(II) in 2:1 ligand:metal composition are reported here. Each Mn(II) complex exhibits one reversible redox wave that is assigned as the Mn(III)/Mn(II) redox transition. The E(1/2) spans a 180 mV range from -98 (Ar=3-methylpyridyl) to 82 mV (Ar=thiazolyl) vs. the Fc(+)/Fc depending on the Ar-sidearm. The SOD-like (SOD=superoxide dismutase)activity of all complexes was determined according to the McCord-Fridovich method. The Mn(II) isoindolinates have IC(50) values - determined with 50 µM cytochrome c Fe(III) - that range from (3.22±0.39)×10(-6) (Ar=benzimidazolyl) to (10.80±0.54)×10(-6) M (Ar=N-methylbenzimidazolyl). In contrast with the Fe(II) complexes, the IC(50) concentrations show no significant dependence on the E(1/2) values in this narrow potential range emphasizing that the redox potential is not the governing factor in the Mn(II)-containing scavengers. The analogous Ni(II) compounds show no redox transitions in the thermodynamically relevant potential range (-0.40 to 0.65 V vs. SCE) and accordingly, their superoxide scavenging activity (if any) is below the detection level.