Structural, theoretical and biological activity of mono and binuclear nickel(II) complexes with symmetrical and asymmetrical 4,6-diacetylresorcinol-dithiocarbazate ligands.

The present work reports the synthesis and a structural study of two novel dithiocarbazate, the 4,6-diacetylresorcinol-S-benzyldithiocarbazate (HL) and the 4,6-diacetylresorcinol-bis(S-benzyldithiocarbazate) (HL), and their Ni(II) complexes, [Ni(HL)(Py)] (1) and [Ni(L)(PPh)] (2). Single crystal X-ray analyzes reveal mono and binuclear complexes and the metal centers with distorted square planar geometry. The analyses of the Hirshfeld surface and fingerprints plots revealed intermolecular contacts attributed to the H···H and C···H/H···C bonds. The Density Functional Theory (DFT), with the B3LYP functional and 6-311-G(d,p)/LanL2DZ basis sets, was employed to optimize the geometries of synthesized compounds. From the resulting geometries, the highest occupied and lowest unoccupied molecular orbital maps (HOMO-LUMO), orbital energy gap, electron localization function (ELF), electron density, natural bond orbital (NBO) analysis, and complexation of the ligands with Ni(II) were calculated supporting the experimental data. The ESI (+)-MS/MS data indicated the presence in solution of the characteristic fragmentation with the [HL] and [HL] molecular ions for the ligands. The pharmacological potential of the dithiocarbazate ligands and their Ni(II) complexes were evaluated in vitro against MDA-MB-231 human breast cancer cells. A remarkable cytotoxic activity was observed, more evident for free ligands than complexes at low concentrations; however, this latter showed a better dose-response pattern, being more attractive in terms of pharmacokinetics and therapeutic window.