A green and efficient multicomponent route afforded a 3-hydroxy-2-pyrrolidone ligand and its Zn(II), Cu(II), Pd(II), and Fe(III) complexes, enabling evaluation of how metal coordination modulates structural, electronic, and biological properties. Elemental analysis and FAB+ mass spectrometry allow to propose an ML2 stoichiometry for Zn(II), Pd(II), and Cu(II), and an ML3 complex for Fe(III). FTIR, UV–Vis, and EPR spectroscopy were employed to elucidate the coordination modes of the metal complexes. Density functional theory calculations yielded optimized geometries for the proposed coordination models of the Zn(II), Cu(II), Pd(II), and Fe(III) complexes. The models displayed distorted-tetrahedral coordination for Zn(II), distorted square-planar coordination for Cu(II), approximately square-planar coordination for Pd(II), and distorted-octahedral coordination for Fe(III). These optimized structures describe the proposed coordination models and should not be interpreted as crystallographically determined molecular structures.Pro-oxidant activity was assessed using TBARS assays in rat brain homogenates. All complexes induced higher lipid peroxidation than the free ligand, with Fe(III) and Zn(II) producing the strongest effects (4.4-fold and 1.3-fold increases, respectively). Cytotoxicity assays against a panel of human cancer cell lines showed that metal coordination enhanced antiproliferative activity, following the order Fe(III) ≈ Cu(II) > Zn(II) > Pd(II) ≫ free ligand. At 25 μM, the Fe(III), Cu(II), and Zn(II) complexes produced growth inhibition greater than 60% in U251, HCT-15, and MCF-7 cells. Growth inhibition in the non-tumoral COS-7 cell line was generally lower than that observed in several cancer cell lines; however, the Cu(II) complex reached 51% inhibition, indicating that additional concentration–response studies are required to establish selectivity. Overall, the combined theoretical, pro-oxidant, and cytotoxicity results establish an structure–activity relationship linking metal identity, electronic structure, redox behavior, and biological response, highlighting the potential of 3-hydroxy-2-pyrrolidone -based metal complexes as tunable redox-modulating agents.
The ionic platinum(II) complex [PtCl(HL)]2[PtCl4] (HL = 4-{[2-(pyridin-2-ylmethylamino)ethylamino]methyl}benzoic acid) was synthesized and characterized by elemental analysis, IR, 1H and 13C NMR, ESI-MS, single-crystal X-ray diffraction, Hirshfeld surface analysis, and DFT calculations. Spectroscopic data confirm N,N,N-coordination of HL to platinum(II). The crystal structure reveals two square-planar [PtCl(HL)]+ cations and one [PtCl4]2− counterion. Coordination makes two nitrogen atoms stereogenic; however, a racemic mixture of R,S and S,R enantiomers is observed in the centrosymmetric unit cell. Hirshfeld and QTAIM analyses highlight the role of weak N–H···Pt and H···Cl interactions in stabilizing the ionic assembly and confirm the partially covalent character of PtN and PtCl bonds.
