Ferrocene-functionalized dithiocarbamate complexes bearing thiophene arms: synthesis, crystal structure, electrochemical characterization, in silico interaction profiling, and apoptosis induction in HeLa cells

Abstract

A new series of ferrocene-based transition-metal dithiocarbamate complexes with pendant thiophenyl groups, formulated as [M{κ²S,S-S₂CN(R)CH₂Fc}₂] (R = 2-thiophenemethyl; M = Ni^II 1, Cu^II 2, and Zn^II 3; R = 2-thiopheneethyl; and M = Ni^II 4, Cu^II 5, and Zn^II 6), is presented herein. These complexes were synthesized utilizing the ligands N-thiophenemethyl-N-methylferrocenylamine (L¹) and N-thiopheneethyl-N-methylferrocenylamine (L²). The complexes were studied using a variety of spectroscopic techniques, including FT-IR, UV-visible absorption, ¹H and ¹³C{¹H} NMR spectroscopy also accompanied by elemental analysis. The molecular structure of complex 3 was determined by single-crystal X-ray diffraction (SCXRD). Magnetic moment measurements and UV-visible spectra indicate a square-planar coordination around the Ni^II/Cu^II centers and a tetrahedral geometry around the Zn^II centers, as further supported by DFT calculations. The complexes showed thermal stability up to ∼200 °C, with their HOMO–LUMO band gaps ranging from 3.345 eV to 4.235 eV, suggesting their non-conducting behavior. Cyclic voltammetry reveals a quasi-reversible redox process for the synthesized complexes. In vitro antiproliferative studies demonstrated that Zn^II complexes 3 and 6 exhibit significant antiproliferative activity compared to that of the standard drug 5-fluorouracil (5-FU) against the HeLa cell line and notable activity against the SW1573 cell line. Moreover, continuous live-cell imaging reveals that the most active complexes, 3 and 6, induce apoptosis in HeLa cells after 15 h of exposure. Additionally, in silico investigations were conducted to support the experimental results.