Monometallic complexes of novel dihydrazone‐oxime ligand: Synthesis, structure, spectral, DFT, and in vitro bioactivity investigation against fungal, bacterial, and tumor cells

Abstract

In the current study, uni‐metallic Cu2+, Ni2+, Mn2+, Co2+, and Zn2+ complexes of ONN‐tridentate dihydrazone‐oxime incorporating indolin‐2‐one moiety (HL,1) were synthesized and structurally characterized employing elemental, spectral, thermo‐gravimetric, magnetic, and molar conductivity measurements, to investigate the structure and composition of these new uni‐metallic complexes. According to the results of several analyses, the dihydrazone‐oxime behaved as a mono‐negative or neutral tridentate ONN chelator bound the metal cations in molar ratio (1M:1L) through the isatinic carbonylic oxygen, azomethine nitrogen, and nitrogen atom of deprotonated/protonated oximatic moiety forming uni‐metallic complexes with formulae [M(L)XYZ(H2O)].nH2O (where M = Cu2+ (2–4), Ni2+, Mn2+, Co2+, or Zn2+, X = Cl, CH3COO, or NO3, Y = H2O or 0, Z = H2O or 0, n = 2, 0) and [Cu (HL)(SO4)(H2O)]. The Cu2+ complexes were found to have a tetragonally distorted octahedral or square pyramidal geometry, whereas those of Mn2+, and Ni2+, exhibited a tetrahedral geometry but Co2+ complex demonstrated a distorted octahedral geometry. Based on DFT‐B3LYP technique and 6‐311G++(d,p) basis set, The DFT data confirmed the structural investigation of dihydrazone‐oxime and its complexes, revealing that the complexes reactivity is more than un‐complexed dihydrazone‐oxime. Moreover, quantum chemical parameters of dihydrazone‐oxime and its uni‐metallic complexes like the energies of both lowest unoccupied molecular orbital (ELUMO) and highest occupied molecular orbital (EHOMO), separation energy (ΔE = ELUMO − EHOMO), chemical potential, absolute electronegativity, absolute hardness, and absolute softness were obtained. According to the thermogravimetric analysis, the complexes breakdown in two to four disintegrating phases in range of temperature 25°C to 575°C leaving the oxide of metal or metal oxide contaminated with carbon. In vitro microbicide effect of the un‐complexed dihydrazone‐oxime and its uni‐metallic complexes toward various bacterial and fungal strains was tested by agar‐well diffusion method. It is demonstrated that the complexes are more effective than free dihydrazone‐oxime. The antitumor activity has been also analyzed against three cell lines including prostate adenocarcinoma (PC‐3), ovarian adenocarcinoma (SKOV3), and cervical cancer (HeLa) cell lines. Studies showed that all complexes have greater inhibition activity against the above three cell lines than the free dihydrazone oxime and the most effective compound was the Zn2+ complex (9) with IC50, 27.42, 35.16, and 46.77 μg/ml, respectively.