Preliminary cytotoxic and antioxidant studies of POCOP-Ni(II) pincer complexes functionalized with different chlorinated linkers. In silico assays and DNA interaction

Six new POCOP-type Ni(II) pincer complexes were synthesized using two new linkers derived from chloroacetyl chloride ( 1Ni 3Ni ) and 1,2-dichloroethane ( 4Ni 6Ni ). All complexes were characterized by various analytical techniques. In addition, the six complexes were unequivocally characterized by single-crystal X-ray diffraction, revealing a square-planar geometry around the metal center in all cases. The cytotoxic activity of the six complexes was also evaluated through a primary screening against different cancer cell lines, as well as against a healthy cell line (COS7). The results showed that complexes 2Ni and 5Ni exhibited the lowest cytotoxicity toward COS7 cells (45.59 μM and 63.83 μM, respectively). However, the remaining complexes displayed high cytotoxicity across all evaluated cell lines, without evidencing any selectivity toward cancer cells. Furthermore, the antioxidant activity of these complexes was assessed, with 5Ni being the most effective antioxidant (IC 50 = 2.24). In addition, to understand their DNA-binding modes, circular dichroism (CD) studies indicated that complexes 3Ni and 6Ni interact with DNA through groove binding. The experimental findings were supported by in silico studies, which also suggested the possibility that this class of complexes may interact with other molecular targets such as topoisomerases I and II, CDK1 and CDK2, as well as HSA.