Synthesis, Crystal Design and Anticancer Potential of Novel Cu(II), Ni(II), and Pd(II) Complexes with Carbazate Ligand

The current study reports the synthesis and characterization of the ligand 2-acetylpyridine-methylcarbazate (Hapmc), and its metal complexes [Cu-(apmc)-Cl]₂ (1), [Cu-(Hapmc)-Br₂] (2), [Ni-(apmc)₂] (3) and [Pd-(apmc)-Cl]₂ (4). All compounds were characterized by single-crystal X-ray diffraction and spectroscopic analyses. The free carbazate ligand is in the keto tautomer and coordinates in this way to form complexes (2) and (4) and is converted to its enolic tautomer to form complexes (1) and (3). The crystal structures of complexes (1) and (2) revealed a dimer and a monomer compound, respectively, with a distorted square pyramid geometry with each metal center coordinated to a ligand molecule by the <i>NNO</i> system and two halide ions (Cl^- or Br^-). Complex (3) presents an octahedral geometry with the Ni-(II) atom coordinated to two deprotonated ligand molecules. In contrast, the dimer (4) presents an unusual coordination mode by <i>NNN</i>-donor atoms of the ligand and each Pd-(II) has a square planar geometry. Noncovalent interactions were evaluated in qualitative and quantitative studies by computational calculations of the Hirshfeld surfaces and showed the most contribution to the formation of the crystal lattice are H···H interactions. The synthesized compounds were investigated in vitro against human cancer cells of A549 lung cancer, MCF-7 breast cancer, A2780cis cisplatin-resistant ovarian cancer, and noncancerous human lung cell MRC-5. All metal complexes exhibit better anticancer activity when compared to the free ligand and, in some cases, outperform the widely used reference drugs, showing strong potential in cancer treatment.