Synthèse, caractérisation et étude des propriétés biologiques des complexes Ni(II), Cu(II) et Zn(II) avec les ligands mixtes dérivés des thiosemicarbazones.

Abstract

Three thiosemicarbazone ligands 2(dimethylamino) benzylidene)hydrazine-1-carbothioamide (H L ), (thiophen-2-ylmethylene) hydrazine-1-carbothioamide (H L ) and 2 (phenyl (pyridin- 11 33 2-yl) methylene) hydrazine-1-carbothioamide (H L ) were synthesised by condensation 22 reaction between p-dimethylaminobenzaldehyde, 2-thiophenecarboxaldehyde, 2- benzoylpyridine and thiosemicarbazide in the ratio 1 : 1 by the reflux method using ethanol as solvent to obtain yields of 86-94%. Cu(II), Ni(II) and Zn(II) thiosemicarbazone complexes, were synthesised under the same operating conditions as the ligands. In addition, mixed ligand complexes of Cu(II), Ni(II) and Zn(II) derived from thiosemicarbazones and L-cysteine were also synthesised by the reflux method in a 1:1:1 ratio in a methanol/water mixture. The ligands and their complexes were characterised by using the analytical methods: IR, H NMR, C NMR, COSY, HSQC, HMBC, UV-Vis spectroscopy, microelemental analysis and TGA. The new ligand 2-(dimethylamino) benzylidene) hydrazine-1 carbothioamide (H L ) was 1 13 11 characterised by single-crystal X-ray diffraction. FTIR spectroscopy showed that thiosemicarbazones behaved as bidentate ligands for H L , 11 H3L3 and tridentate ligands for H L with N and S as donor atoms and the nitrogen of the 22 benzoyl ring. Melting point measurements carried out on the compounds revealed that the ligands melt at temperatures ranging from 143°C to 187°C, while the complexes melt at temperatures ranging from 200°C to over 360°C (limit of the apparatus), reflecting the fact that they are stable at high temperatures. Microelemental analysis of the compound showed good agreement between theoretical and experimental values, confirming the elemental C, H, N and S composition of the proposed complex structures.Solubility studies showed that the ligands are soluble in methanol while the complexes are soluble in DMSO. Determination of the molar conductance revealed that all the complexes synthesised are molecular with relatively low conductance values with the exception of the NiL2 and Zn(L1.L) complexes which have an electrolytic character with high molar conductance values (100 S.mol . Cm ). Visible spectroscopic analyses suggested square planar geometry for all copper (II) thiosemicarbazone complexes, tetrahedral geometry for all zinc (II) complexes and octahedral geometry for nickel (II) complexes. On the basis of the visible spectra obtained, octahedral geometries are proposed for the mixed ligand complexes with the exception of the Zn(L1.L) complex which has a tetrahedral structure. -1 2xix The antimicrobial and antioxidant activity of thiosemicarbazones and their metal complexes were studied in vitro in DMSO. Antimicrobial tests were carried out on six bacterial strains (Staphylococcus aureus(ATCC 43300), Klessiella pneumonae (ATCC 700603), Staphylococcus aureus Méticilline Resistance(ATCC 33591), Shigella flexneri NR 518), Escherishia coli and Pseudomonas aeruginosa and on four fungal strains of the candidase family (Candida albicans NR 29451, Candida albicans NR 29444, Candida albicans NR 29445, Candida krusei ) showed that the ligands exhibit moderate activities on a few strains of bacteria (Staphylococcus aureus Methicillin Resistance (ATCC 33591) and Escherishia coli) with an inhibitory power ranging from 31.25 to 62.5 µg/mL compared to Ciprofloxacin and Gentamycin. The CuL2 complex (3.9 µg/mL) showed greater inhibitory power on the Staphylococcus aureus methicillin-resistant strain (ATCC 33591) than Gentamycin (8 µg/mL), which is used here as the standard. The other CuL1, ZnL1 and ZnL2 complexes were found to be moderately active on bacterial and yeast strains. The mixed ligand complexes were moderately active on the yeast strain, Candida albicans. Only the CuL2L complex showed moderate activity on all bacterial strains. The antioxidant activities revealed that the H L and 11 H3L3 ligands exhibited antioxidant activity similar to that of vitamin C and evolved in almost the same way. In addition, the NiL2 complex (1.52±0.02 µg/mL) showed significant anti- radical activity against the free radical 1,1-diphenyl-2- picryl-hydrazyl (DPPH) compared with ascorbic acid (Vit C) (0.47±0.01 µg/mL), thus plobable its antioxidant capacity to eliminate free radicals. This same complex was able to reduce Fe to Fe by the FRAP method, proving that it is a good antioxidant.