Iron and nickel complexes with heterocyclic ligands: Stability, synthesis, spectral characterization, antimicrobial activity, acute and subacute toxicity

Abstract

The synthesis and characterization by elemental analysis, emission atomic spectroscopy, TG measurements, magnetic measurements, FTIR, 1H NMR, UV–visible spectra and conductivity of a series of iron (II) and nickel (II) complexes with two heterocyclic ligands (L1(SMX): sulfamethoxazole and L2(MIZ): metronidazole) used in pharmaceutical field and with a new ligand derived benzoxazole (L3(MPBO): 2-(5-methylpyridine-2-yl)benzoxazole), were reported. The formulae obtained for the complexes are: [M(L1)2 Cl2]·nH2O, [M(L2)2Cl2(H2O)2]·H2O and [M(L3)2(OH)2]·nH2O. Stability constants of these complexes have been determined by potentiometric methods in water–ethanol (90:10, v/v) mixture at a 0.2molL−1 ionic strength (NaCl) and at 25.0±0.1°C. Sirko program was used to determine the protonation constants as well as the binding constants of three species [ML2H2]2+, [ML2] and [ML]2+. The antimicrobial activity of the ligands and complexes was evaluated in vitro against different human bacteria and fungi using agar diffusion method.Iron sulfamethoxazole complex showed a remarkable inhibition of bacteria growth especially on Staphylococcus aureus and P. aeruginosa. The iron metronidazole complex is active against yeasts especially on Candida tropicalis strain. Nickel complexes presented different antibacterial and antifungal behavior's against bacteria and fungal.The acute toxicity study revealed that the iron complexes are not toxic at 2000mg/kg dose orally administrated.LD50 for nickel complexes was determined using graphical method.No significant differences in the body weights between the control and the treated groups of both rat sexes in subacute toxicity study using for iron complexes. Hematological and clinical blood chemistry analysis revealed no toxicity effects of the iron complexes. Pathologically, neither gross abnormalities nor histopathological changes were observed for these complexes.