An Investigation into Substitution‐Kinetics, Biomolecular Responses and Multimodal Anticancer Potential of a Dihalide Pd(II) Complex

This study addresses a novel palladium dihalide complex, cis-[Pd(PCAH)Cl₂] (C1), as a promising anticancer agent. XRD analysis reveals a deformed square planar geometry stabilized by hydrogen bonds and π•••π interactions. The M-Cl bonds in C1 demonstrate susceptibility to nucleophilic substitution by 2,2'-bipyridine (Bpy), with kinetic parameters evaluated using spectrophotometry. Fluorometric and spectrophotometric investigations demonstrate that C1 binds to CT DNA and protein with an avidity of around 10⁵ M^-1. The interaction with DNA is multifaceted, employing covalent bonding and intercalation, as supported by viscosity measurements. Fluorescence lifetime experiments illustrate that C1 produces static dampening of BSA fluorescence, implying structural adjustments near the tryptophan residue, further corroborated by spectroscopic analyses. The pair's (BSA and C1) FRET distance has also been computed. In vitro cytotoxicity tests suggest that C1 selectively suppresses the growth of breast carcinoma, MDA-MB-231 with IC₅₀=20±2.64 μM, while showing minimal effects on non-cancerous HEK-293 cells. The mechanism of action includes the creation of ROS, leading to mitochondrial apoptosis, as evidenced by various assays, including annexin-V-FITC/PI labeling. Overall, complex C1 exhibits encouraging promise as a selective anticancer drug with a ROS-triggered apoptotic mechanism, particularly effective against breast carcinoma MDA-MB-231 cells.