In this study, Cu2+, Co2+, Ni2+, Mn2+, Zn2+, Fe3+, VO2+, and UO22+ complexes derived from a NNO tridentate chelating hydrazone–oxime, namely, N′‐((2E,3Z)‐3‐(hydroxyimino)butan‐2‐ylidene)benzohydrazide (H2L,1) were prepared. The elemental, thermo‐gravimetric, spectral, molar conductivity, and magnetic measurements were applied to elucidate the compositions and structures of these new compounds. In addition to the density functional theory (DFT), studies were employed to acquire optimal structures and quantum chemical parameters. The analyses indicate that the chelator reacted as a neutral or mononegative tridentate ligand bonded to the metal ions via the enolic/ketonic carbonylic oxygen, protonated/deprotonated oximatic nitrogen, and azomethine nitrogen atoms adopting square planar or distorted octahedral geometry. The structural characterization of hydrazone–oxime and its complexes was supported by DFT calculations according to the DFT‐B3LYP procedure and 6‐311+G(d,p) basis set. The theoretical data revealed that the reactivity of the complexes is greater than the free hydrazone–oxime (H2L,1), and there is a good agreement between the practical and theoretical data. The thermogravimetric investigation shows that the complexes break down in two to four decomposing steps in temperature range extended from 50 to 1000°C. In vitro antimicrobial activity data demonstrated an increase in activity of the hydrazone–oxime (H2L,1), upon chelation, and some metal complexes show enhanced antibacterial and antifungal agents.

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.