Tuning the Anticancer Activity of Gold(I) Complexes via Redox-Active Ar-Bian Ligands: Experimental and Theoretical Insights

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Abstract A series of cationic gold(I) complexes of the type [Au(PPh3)(Ar-Bian)](CF3SO3) based on 1,2-bis[(2,4,6-trimethylphenyl)imino]acenaphthene (tmp-Bian), 1,2-bis[(4-chlorophenyl)imino]acenaphthene (4–Cl-C6H4–Bian), 1,2-bis[(4-bromophenyl)imino]acenaphthene (4–Br-C6H4–Bian), and 1,2-bis[(4-iodophenyl)imino]acenaphthene (4–I-C6H4–Bian) were prepared. All complexes were fully characterized by spectrochemical methods, and their crystal structures were established by X-ray diffraction analysis. The electrochemical behavior of all complexes was studied by using cyclic voltammetry. The stability of the complexes in solution was investigated using 1H NMR and UV–vis spectroscopies. The anticancer activity of Au(I) complexes was evaluated against a panel of cell lines in comparison with free 1,2-bis(arylimino)aceaphthenes (Ar-Bian) and initial [Au(PPh3)Cl]. All complexes were cytotoxic in a low micromolar range and showed selectivity toward cancer cells in comparison with MRC-5 human lung fibroblasts. The ability of the complexes to bind DNA and BSA was investigated by spectroscopic methods, molecular docking, and molecular dynamics studies. The DNA-damaging activity of gold(I) complexes was evaluated in MCF-7 cells using the comet assay. Reactive oxygen species production in MCF-7 cells was studied using confocal microscopy. The lipophilicity of complexes was determined using the n-octanol/water shake-flask method. Determination of the cell death pathway was performed using an Annexin-5-FITC/PI double staining test followed by fluorescence-activated cell sorting (FACS) analysis.