New functional models for catechol oxidases

Gentschev, Pavel; Möller, Niclas; Krebs, Bernt

doi:10.1016/s0020-1693(99)00553-8

Cited by 132 publications

(65 citation statements)

References 48 publications

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“…The catalytic oxidation of H 2 dtbc was already widely studied with regards of catechol oxidase activity of copper(II) complexes, [52][53][54][55][56][57][58][59][60][61][62] since the bulky substituents hinder further oxidation of the product 3,5-di-tert-butyl-1,2-benzoquinone (dtbq). Catechol oxidases are type 3 copper enzymes, 62 therefore mostly dinuclear complexes [52][53][54][55][56][57][58][59] were used for the biomimetic studies.…”

Section: Kinetic Studiesmentioning

confidence: 99%

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A novel 1,3,5-triaminocyclohexane-based tripodal ligand forms a unique tetra(pyrazolate)-bridged tricopper(ii) core: solution equilibrium, structure and catecholase activity

et al. 2016

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Section: Kinetic Studiesmentioning

confidence: 99%

“…Catechol oxidases are type 3 copper enzymes, 62 therefore mostly dinuclear complexes [52][53][54][55][56][57][58][59] were used for the biomimetic studies.…”

Section: Kinetic Studiesmentioning

confidence: 99%

A novel 1,3,5-triaminocyclohexane-based tripodal ligand forms a unique tetra(pyrazolate)-bridged tricopper(ii) core: solution equilibrium, structure and catecholase activity

et al. 2016

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“…By comparison with other mononuclear or dinuclear copper catecholase model complexes [13][14][15]50 the copper(II) fenoprofenate shows moderate catecholase activity. It is necessary to take into account that comparisons are not always straightforward because of the use of different solvents, temperatures and degrees of solvent oxygenation.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

“…A number of researchers have found that some complexes show similar but not significantly greater anti-inflammatory activity. 10,11 It is also known that dinuclear copper active centres play an important role in biological metalloproteins [12][13][14] as tyrosinase, hemocyanin or catechol oxidase. Catechol oxidase (EC 1.10.3.1) is a type III copper enzyme containing a dinuclear copper centre and belongs to the polyphenol oxidases group, 15 which catalyses exclusively the oxidation of catechols to the corresponding o-quinones in the presence of oxygen.…”

Section: Introductionmentioning

confidence: 99%

“…15 The catecholase activity has been determined in vitro for many mononuclear and dinuclear copper(II) complexes. Specialized research groups have developed μ-hidroxo, μ-carboxylato or μ-imidazole dinuclear copper(II) compounds with the aim of mimicking the active site of the catechol oxidase enzyme, [12][13][14][15][18][19][20][21][22][23][24][25][26][27][28][29] and the mechanism of the catalytic cycle has been proposed for some complexes. Catecholase activity has been also determined for a few mononuclear and dinuclear copper(II)-NSAIDs complexes, [30][31][32] but the mechanism of the catalytic oxidation remains unclear.…”

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confidence: 99%

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Significant anti-inflammatory properties of a copper(II) fenoprofenate complex compared with its parent drug: Physical and chemical characterization of the complex

Agotegaray¹,

Boeris²,

Quinzani³

2010

J. Braz. Chem. Soc.

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A síntese, a caracterização físico-química, as propriedades anti-inflamatórias e a atividade mimética de catecolase do complexo de cobre(II) com a droga anti-inflamatória non-esteroidal Fenoprofeno [ácido 2-(3-fenóxifenil)propiônico] com fórmula [Cu 2 (fen) 2 (dmf) 2 ] (fen = ânion do fenoprofenato, dmf = N,N-dimetilformamida) foram investigadas. Os resultados da análise espectroscópica (espectros de FTIR e EPR) e dados de análise termogravimétrica e térmica diferencial obtidos para o complexo sólido estão de acordo com a sua estrutura dinuclear. Os espectros eletrônicos do produto são igualmente apresentados e discutidos neste trabalho. O complexo foi testado para as suas propriedades anti-inflamatórias em comparação com a droga de referência, o sal de cálcio do Fenoprofeno. A administração oral do composto binuclear inibiu o desenvolvimento do edema induzido por carragenana em ratos; esta inibição foi mais significativa do que a obtida com a droga de referência. O estudo cinético da atividade mimética da catecolase foi realizado espectrofotometricamente, monitorando-se a transformação oxidativa do 3,5-di-terc-butilcatecol na o-quinona correspondente. Os parâmetros cinéticos foram determinados pelo emprego do modelo de Michaelis-Menten, que demonstrou que o novo complexo mimetiza a atividade da catecol oxidase.The synthesis, physicochemical characterization, anti-inflammatory properties and catecholase mimetic activity of the dinuclear complex of copper(II) with the non-steroidal anti-inflammatory drug Fenoprofen [2-(3-phenoxyphenyl)propionic acid] with formula [Cu 2 (fen) 4 (dmf) 2 ] (fen = fenoprofenate anion, dmf = N,N-dimethylformamide) have been investigated. Results of spectroscopic analysis (FTIR and EPR) as well as thermogravimetric and differential thermal analysis data obtained for the solid complex are in good agreement with its dinuclear structure. Electronic spectra of the product are also reported and discussed. The complex was tested for anti-inflammatory properties in comparison to the parent drug, Fenoprofen calcium salt. Oral administration of the dinuclear compound inhibited development of carrageenan-induced oedema in mice; this inhibition was higher than that observed for the parent drug. The kinetic study of the catecholase mimetic activity was carried out spectrophotometrically by monitoring the oxidative transformation of 3,5-di-tert-butylcatechol into the corresponding light-absorbing o-quinone. Kinetic parameters were determined employing the Michaelis-Menten model, showing that the new complex presents catechol oxidase mimetic activity.Keywords: copper(II), Fenoprofen, anti-inflammatory properties, catecholase activity IntroductionThe proposed curative properties of copper(II) carboxylate-based non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous mononuclear and dinuclear copper(II) complexes of NSAIDs with enhanced anti-inflammatory activity.1,2 The elevation of total blood copper levels during acute as well as chronic inflammatory states has been re...

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Tuning the Activity of Catechol Oxidase Model Complexes by Geometric Changes of the Dicopper Core

et al. 2002

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Dicopper(II) complexes of a series of different pyrazolate-based dinucleating ligands [L1](-)-[L4](-) have been synthesized and characterized structurally and spectroscopically. A major difference between the four complexes is the individual metal-metal separation that is enforced by the chelating side arms of the pyrazolate ligand scaffold: it varies from 3.45 A in 2 x (BF4)4 to 4.53 A in 4 x (ClO4)2. All complexes have been evaluated as model systems for the catechol oxidase enzyme by using 3,5-di-tert-butylcatechole (DTBC) as the test substrate. They were shown to exhibit very different catecholase activities ranging from very efficient to poor catalysts (k(obs) between 2430+/-202 and 22.8+/-1.2 h(-1)), with an order of decreasing activity 2 x (ClO4)4 > 1 x (ClO4)2 > 3 x (ClO4)2 >> 4 x (ClO4)2. A correlation of the catecholase activities with the variation in Cu...Cu distances, as well as other effects resulting from the distinct redox potentials, neighboring groups, and the individual coordination spheres are discussed. Saturation behavior for the rate dependence on substrate concentration was observed in only two cases, that is, for the most active 2 x (ClO4)4 and for the least active 4 x (ClO4)2, whereas a catalytic rate that is almost independent of substrate concentration (within the range studied) was observed for 1 x (ClO4)2 and 3 x (ClO4)2. H2O2 was detected as the product of O2 reduction in the catecholase reaction of the three most active systems. The structures of the adducts of "L3Cu2" and "L4Cu2" with a substrate analogue (tetrachlorocatecholate, TCC) suggest a bidentate substrate coordination to only one of the copper ions for those catalysts that feature short ligand side arms and correspondingly exhibit larger metal-metal separations; this possibly contributes to the lower activity of these systems. TCC binding is supported by several H-bonding interactions to water molecules at the adjacent copper or to ligand-side-arm N-donors; this emphasizes the importance of functional groups in proximity to the bimetallic active site.

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New functional models for catechol oxidases

Cited by 132 publications

References 48 publications

A novel 1,3,5-triaminocyclohexane-based tripodal ligand forms a unique tetra(pyrazolate)-bridged tricopper(ii) core: solution equilibrium, structure and catecholase activity

A novel 1,3,5-triaminocyclohexane-based tripodal ligand forms a unique tetra(pyrazolate)-bridged tricopper(ii) core: solution equilibrium, structure and catecholase activity

Significant anti-inflammatory properties of a copper(II) fenoprofenate complex compared with its parent drug: Physical and chemical characterization of the complex

Tuning the Activity of Catechol Oxidase Model Complexes by Geometric Changes of the Dicopper Core

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