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

DAIER, VERÓNICA; SIGNORELLA, SANDRA

Los Cocos

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 disproportionate 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 by 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 with 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 made the disproportion of hydrogen peroxide and superoxide simultaneously and with therapeutic applications. We propose the synthesis, characterization and the 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 as a  potential SOD and CAT mimic. The complexes obtained were:   (C1) [Mn(salbutO)]SCN. 2H2O    and     (C2): [Mn2(salbutO)2]BPh4 Structural characterization in solid state and solution  of complexes:  by  elementary analysis , IR and electronic spectra,  EPR spectra, termogravimetric analysis (TGA), Electro spray ionisation (MS-ESI)-mass spectra, electrochemical experiments, 1H and 13C NMR, Variable-temperature magnetic susceptibility, 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, with 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, using the reduction of riboflavine by methionine to generate superoxide. The reactions use the conversion of Nitro-Blue Tetrazolium into formazan, spectrophotometrically measured at 560nm (Beauchamp & Fridovich, 1971).