Reactions of copper(II), nickel(II), and zinc(II) acetates with a new water-soluble 4-phenylthiosemicarbazone Schiff base ligand: Synthesis, characterization, unexpected cyclization, antimicrobial, antioxidant, and anticancer activities

Abstract

A new Schiff base thiosemicarbazone ligand with aqueous solubility, namely, sodium 3-([(anilinocarbonothioyl)hydrazono]methyl}-4-hydroxy benzene sulfonate (NaH2L) was synthesized by condensation of 4-phenylthiosemicarbazide and sodium salicylaldehyde-5-sulfonate (NaSalO()) and characterized by elemental analysis, spectroscopic methods (UV-Vis, H-1 NMR, FTIR) and electrospray ionization mass spectrometry. A co-crystal (Na(H2L)center dot Na(SalS03)) of NaH2L and NaSalSO was prepared which confirmed the expected structure of the ligand. Reactions of NaH2L-0.5H(2)O with copper(II), nickel(II), and zinc(II) acetates were investigated under reflux conditions in methanol to produce following complexes ECu2(Lcycl)(2)(H2O)(2)]center dot 2H(2)O (CuLcycl), Ni(HL)(H2O)(3) (NiL), and Zn(HL)(H2O)(3) (ZnL). In the copper case, dinuclear copper complex [Cu-2(Lcyd)(2)(H2O)(2)]center dot 2H(2)O (where HLcycl- esents incorporating of 1,3-benzothiazole ligand, formed by in situ cyclization of H2L-) was isolated. In the dimer structure copper atoms adopt a five-coordinate near square pyramidal geometry. Two oxygens derived from two sulfonate groups occupy the apical positions on both the metal centers and bridge them. The compounds have remarkable solubility in water at 25 degrees C: 50, 10, 50, and 50 g/L for NaH2L-0.5H(2)O, CuLcycl, N, and ZnL, respectively. The stability of the compounds was checked in acidic, neutral, and basic aqueous solutions. Antimicrobial activity results indicated CuLcyd and NiL possess activity against gram-positive bacteria and fungus while the free ligand and ZnL are inactive. Antioxidant activity of the compounds was evaluated and the ligand indicated the strongest radical scavenging relative to the complexes and L-ascorbic acid as a water-soluble standard. It was observed that copper and nickel complexes decreased the viability of the human chronic myeloid leukemia K562 cells in a dose-and time-dependent manner and the ligand and zinc complex were not active. The IC50 values were 31 2.5 and 6 1.0 pz/mL (72 h) for copper and nickel complexes, respectively. Morphological and DNA fragmentation assay studies clearly indicated that the nickel complex as the strongest compound induce apoptosis in the K562 cell line. (C) 2016 Elsevier Ltd. All rights reserved.