Biomimetics complexes of Mn-superoxide dismutase and Mn- catalase enzymes. Structural characterization and catalytic activity

DAIER VERÓNICA; SIGNORELLA SANDRA

Los Cocos- Argentina

Congreso; 9th Latin American Conference on Physical Organic Chemistry.; 2007

UNC

Superoxide dismutases (SOD) are metalloenzymes that efficiently catalyze the dismutation of superoxide anion (O2-) to hydrogen peroxide and dioxygen which is subsequently disproportionated into water and oxygen by catalase (CAT). They constitute an important defence system in living organisms against several diseases in which (O2-) appears to play an important role, such us: tissue inflammation, symptoms of aging, some cancers, and cellular degenerating process promoted by AIDS. This work is aimed at modelling de active sites of  these enzymes through the synthesis of manganese mimics complexes with comparables structural and spectroscopy properties and the same function  as the natural sites. The rational design and synthesis of low molecular weight catalysts that mimic natural enzyme function has potential for use as a human pharmaceutical in the treatment or prevention of cellular diseases. Until now, different classes of synthetics models of Mn-SOD and Mn-CAT are being studied to be used pharmacologically, but only a few compounds of Mn have both activities. The actual challenge is to obtain efficient compounds which disproportionate hydrogen peroxide and superoxide simultaneously. In this work, we describe the synthesis, characterization and determination of the SOD and CAT activity of new complexes of manganese with the ligand 1, 4-bis(salicylidenamino)butan-2-ol (salbutOH) and different counter anions: The complexes obtained were:    (C1) [Mn(salbutO)]SCN. 2H2O     (C2) [Mn(salbutO)]N3     and     (C3): [Mn2(salbutO)2]BPh4 The complexes were characterized in solid state and solution  by  elementary analysis , IR and electronic spectra,  EPR spectra, termogravimetric analysis (TGA), Electrospray ionisation (MS-ESI)-mass spectra, electrochemistry, 1H and 13C NMR, variable-temperature magnetic susceptibility and  X- Ray crystal structure determination. The Catalase activity was measured in anaerobic conditions by the Oxygen released in the H2O2 disproportionation with an YSI oxygen monitoring system, using a Clark type electrode which measures dissolved oxygen, in presence of catalytic quantities of complexes.  The SOD-like activity was measured by its ability to inhibit O2- dependent reactions. We used the fotorreduction of Nitro-Blue Tetrazolium in the presence of complexes C1- C3, using the reduction of riboflavine by methionine to generate superoxide. The method measures the conversion of Nitro-Blue Tetrazolium into formazan, that is followed spectrophotometrically at 560nm (Beauchamp & Fridovich, 1971). These complexes are efficient SOD-mimics and possess CAT activity higher than others SOD/ CAT mimics reported in the literature.