Synthesis, characterization, DFT and biological studies of Fe(II), Cu(II), and Zn(II) complexes of keto-imine chelators

Abstract

Three naphthoquinone-based chelators, 2-(pyrimidin-2-ylamino)-2,3-dihydronaphthalene-1,4-dione (HLa) 2-((4,6-dihydroxypyrimidin-2-yl)amino-2,3-dihydronaphthalene-1,4-dione (HLb), and 2-((4,6-dimethylpyrimidin-2-yl)amino-2,3-dihydronaphthalene-1,4-dione (HLc), have been synthesized by the reaction of 2-hydroxy-1,4-napthoquinone with 2-aminopyrimidine, 2-amino-4,6-dihydroxypyrimidine, and 2-amino-4,6-dimethypyrimidine respectively. Reaction of the chelators with Fe2+; Cu2+ and Zn2+ sulphate; and acetate salts; plus 2,2′-bipyridine(B) gave the resultant heteroleptic M2+ complexes, which were characterized by analytical, 1H-and 13C NMR, FT-IR, UV–vis, ESI-MS, and TG-DSC analyses. The FT-IR and NMR results showed that the chelators are bidentate and chelated with the M2+ ions via their ketonic oxygen (>CO) and secondary amine nitrogen (HN) atoms. The μeff data and UV–vis spectral evaluations of the complexes provided credence to the 6-coordinate octahedral geometries of the complexes. DFT calculations were performed to understand the mode of complex formation as well as their geometry around the metal centers. Compared to the chelators, the heteroleptic complexes have improved antimicrobial actions attributed to the extra 2-nitrogenous atoms in the 2,2′-bipyridine moiety and the presence of active metal ions. The CuLc complexes displayed the best antibacterial performance with inhibitory effects of 34.0 mm. However, the ZnLb complexes recorded the best antifungal activity (33.0 mm), due to the absorption of Zn2+ ions on the surface of the fungiform cell walls. The antioxidant assays with ferrous ions show that all the keto-imine chelators showed good chelating abilities. HLc showed values of 78.76 plus 74.5 % separately at concentrations of 200 and 100 mg/mL, which are higher than that of the standard ascorbic acid. The DPPH radical scavenging activities of the heteroleptic complexes indicate that they can be used for the synthesis of drugs for the treatment of pathological diseases arising from oxidative stress.