Design and catalytic studies of structural and functional models of the catechol oxidase enzyme.
Loading...
Official URL
Full text at PDC
Publication date
2020
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Society for Biological Inorganic Chemistry (SBIC) 2020, Springer
Citations
Exportar
Citation
J Biol Inorg Chem (2020) 25:671-683
Abstract
The catechol oxidase activity of three copper/bicompartmental salen derivatives has been studied. One mononuclear, [CuL](1), one homometallic, [Cu2L(NO3)2] (2), and one heterometallic, [CuMnL(NO3)2] (3) complexes were obtained using the ligand H2L= N,N′-bis(3-methoxysalicylidene)-1,3-propanediamine through different synthetic methods (electrochemical, chemical and solid state reaction). The structural data indicate that the metal ion disposition models the active site of type-3 copper enzymes, such as catechol oxidase. In this way, their ability to act as functional models of the enzyme has been spectrophotometrically determined by monitorization of the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to 3,5-ditert-butyl-o-benzoquinone (3,5-DTBQ). All the complexes show significant catalytic activity with ratio constants (kobs) lying in the range (223–294) × 10–4 min−1. A thorough kinetic study was carried out for complexes 2 and 3, since they show structural similarities with the catechol oxidase enzyme. The greatest catalytic activity was found for the homonuclear dicopper compound (2) with a turnover value (kcat) of (3.89 ± 0.05) × 106 h−1, which it is the higher reported to date, comparable to the enzyme itself (8.25 × 106 h−1).
Description
Catechol oxidase enzyme is present in plants, animals, fungi and bacteria. It takes part in the conversion of a large number of o-catechols into the respective o-benzoquinones, which subsequently auto-polymerize, resulting in the formation of melanin, a dark pigment thought to protect a damaged tissue from pathogens. This enzyme is also relevant in the industry because of its uses as O2 activator or in medical diagnosis of human brain diseases (detection of catecholamines, noradrenaline and dopa in neurological disorders). The type-3 active site of the enzyme consists of a dinuclear copper center where each copper is coordinated by three histidine nitrogen atoms and one hydroxo bridge, in the native met state. Since the discovery of the nature of this active site, a great number of dicopper(II) complexes have been designed to mimic the structure and function of the enzyme. The best catechol oxidase model reported to date with copper complexes exhibit kcat values around 104 h−1, at least two orders of magnitude lower than those of the enzymes isolated from different sources. In that sense, due to the great importance of this enzyme, it is of big interest to develop
new models in order of improving their catecholase activity.
In this work, we report the synthesis and structural characterization of three structural model complexes of catechol oxidase enzyme obtained using one symmetric bicompartmental-salen Schiff base ligand enable to coordinate two 3d metals in the inner and outer cavities, in order to evaluate their catalytic activities.