Elucidação estrutural, espectroscópica e perfil farmacológico de novos complexos de ditiocarbamatos derivados de organoestânicos, de outros metais representativos e de alguns cátions de metais de transição

Abstract

In this thesis three new sodium dithiocarbamates (DTC´s) were prepared and characterized: sodium (2,2-dimetoxiethyl)-N-methyldithiocarbamate, Na[S2C6H12NO2](i), sodium (1,3-dioxolane-2-methyl)-N-methyldithiocarbamate, Na[S2C6H10NO2] (ii) and the sodium 2-(hidroximethyl)piperidina -1-dithiocarbamate, Na[S2C7H12NO] (iii). They were used as metal coordinating ligands to prepare complexes with representativeand transition metal cations. Among the representative metal complexes stands out those which were obtained using organotin halides: [SnMe2{S2C6H12NO2}2] (1) [SnMe2{S2C6H12NO2}2] (1), [Sn(n-Bu2){S2C6H12NO2}2] (2), [SnPh2{S2C6H12NO2}2](3), [SnMe2{S2C6H10NO2}2] (4), [Sn(n-Bu)2{S2C6H10NO2}2] (5),[SnPh2{S2C6H10NO2}2] (6), [SnPh3{S2C6H12NO2}] (7), [SnCy3{S2C6H12NO2}] (8), [SnMe3{S2C6H10NO2}] (9), [SnPh3{S2C6H10NO2}] (10) and [SnCy3{S2C6H10NO2}](11). In addition the cations In(III), Ga(III) and Bi(III) were used to obtain the complexes: [In{S2C6H12NO2}3] (12), [Ga{S2C6H12NO2}3] (13), [Bi{S2C6H12NO2}3] (14), [In{S2C6H10NO2)}3] (15), [Ga{S2C6H10NO2)}3] (16), [Bi{S2C6H10NO2}3] (17),[In{S2C7H12NO2}3] (18), [Ga{S2C7H12NO2}3] (19) and [Bi{S2C7H12NO2}3] (20). New Fe(III) and Co(III) containing complexes were as well prepared: [M{S2C6H12NO2}3] (21), (23) and [M{S2C6H10NO2}3] (22), (24). The cations Ni(II),Pd(II), Pt(II), Cu(II), Zn(II), Cd(II) and Hg(II) were furthermore employed in the synthesis of the following complexes: [M{S2C6H12NO2)}2] (25) - (27), (32) and (35) - (37) and [M{S2C6H12NO2)}2] (28) - (30), (33) and (38) - (40), [Ni{S2CN[(CH2)3NCHPhOCH2Ph[CH2CH2OH]]}2] (31),[Cu{S2CN[(CH2)3NCHPhOCH2Ph[CH2CH2OH]]}2] (34) and [Zn{S2C7H12NO2}2] (41). These compounds were characterized by techniques such as melting point, carbon, hydrogen and nitrogen analysis, infrared spectroscopy, 1H, 13C and 119Sn nuclearmagnetic resonance, 119Sn-Mössbauer spectroscopy, electron paramagnetic resonance and electronic spectroscopy. The structure of the sodium salts, (i) and (iii), and of the complexes (1)-(6), (7), (10), (11), (12), (14), (15), (17), (25)-(27), (32), (33), (35) and(36) were authenticated by X-ray crystallography. The in vitro antimicrobial activity of the sodium salts (i) - (iii), as well as those of their metal complexes were evaluated against five species of filamentous fungi:Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Penicillium citrinum, and Curvularia senegalensis, and eight species of bacteria: Gram positive, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereu and Streptococcus sanguinis and Gram negative bacteria, Escherichia coli, Citrobacter freundii, Salmonella typhimurium andPseudomonas aeruginosa. The biological activity of the complexes was represented in terms of the IC90 and IC50 inhibitory concentrations. The complexes derived from triorganotin(IV) were the most active ones against the fungal species which were tested, in comparison with theother complexes prepared and screened in this work. Regarding the biological activities of bacterial strains in the presence of complexes, those derived of diorganotin with R = Me and the complexes of In(III) and Bi(III) were the ones with the best biological activities compared to other metal DTC complexes. The XTT cell viability assay was performed with the triorganotin dithiocarbamates (7) - (11), and with the Cu(II)complexes (32) - (34), indicating a fungistatic activity of them in the presence of A. flavus. The sodium dithiocarbamates salts did not show any significant biological activity against the tested microorganisms. Thus, coordination of the dithiocarbamate ligands to metal centers significantly increases their biological activities. The Chlorella vulgaris alga was quite sensitive to the presence of triorganotin(IV)dithiocarbamate complexes, indicating an ecotoxicity of these complexes.Finally in order to have a better understanding of the structure-activity relationship a theoretical calculations (SAR) of organotin(IV) compounds (1) - (11) were performed to obtain structural and stereo-electronic parameters related to possible mechanisms of action of the complexes (1) - (11) such as transport across cell membranes and possibleinteractions with biological macromolecules, such as enzymes.