Denticity Modulation of a Bioinspired Indole-Based CNP Donor Ligand toward Pd(II): Structural, DFT, Hirshfeld Surface Analysis, and Potent <i>In Vitro</i> Cytotoxicity against Breast Cancer 4T1 Cells

Herein, we report the bioinspired indole-based CNP donor ligand [PhCH2–(NC8H5)–CH=N-(C6H4)-2-P(Ph)2] (L). The reaction of L with Na2PdCl4 in THF under a nitrogen atmosphere in the presence of CH3COONa at 80 °C and without CH3COONa at room temperature revealed palladium complexes [(μ-C-NP-L-H)–Pd-Cl] (C1) and [(μ-NP-L)–Pd-Cl2] (C2), respectively. The molecular compositions of L, C1, and C2 have been determined by spectroscopic and single-crystal X-ray diffraction data. Ligand L crystallized in the monoclinic system with the P21/c space group, whereas both complexes crystallized in the triclinic system with the space group Pi̅. Ligand L coordinated as monoanionic tridentate (μ-C-NP) mode in the case of C1 but neutral bidentate (μ-NP) mode in C2. DFT and Hirshfeld surface analyses also validate the geometrical and noncovalent parameters of L, C1, and C2 with the solid-state structures determined by single-crystal X-ray diffraction data. The cytotoxicities of L, C1, and C2 have been evaluated against 4T1 breast cancer cells. Significant stress-induced morphological changes and cancer cell death have been observed through cellular morphology and cytoskeletal damage assessments. Furthermore, the disruption of cytoskeletal integrity, loss of mitochondrial membrane potential, and significant oxidative stress production highlight the underlying mechanism of cytotoxicity, reinforcing the potential of these compounds for targeted cancer therapy.