Mononuclear Copper(II) Phosphinates Bearing Mono‐, Bi‐, and Tridentate <i>N</i> ‐Donor Ligands: DNA Binding and Cleavage, Cytotoxicity, and Nanoencapsulation

Mononuclear Cu(II) phosphinate-based compounds, [Cu(H₂L₁)₂(Py)₂] (1), [Cu(OAc)(H₂L₁)(Cl-tpy)] (2), and [Cu(H₂L₁)(Phen)₂]H₂L₁ (3) (Py = pyridine, Cl-tpy = 4'-chloro-2,2':6',2''-terpyridine, Phen = 1,10-phenanthroline monohydrate) were synthesized by reacting Cu(OAc)₂·2H₂O with N-donor ligands in the presence of bis(2-hydroxy-5-methylphenyl) phosphinic acid (H₃L₁). The compounds were isolated as single crystals and characterized by spectroscopic and microanalytical techniques. Owing to the bioavailability and biocompatibility of copper, the oxidative DNA cleavage ability of 1-3 was studied by incubating supercoiled (SC) pUC19 DNA (40 µM). The highest cleavage efficiency of complex 3 is attributed to the strong partial intercalation of 1, 10-phenanthroline rings, which enhances reactive oxygen species (ROS) generation. Encapsulation of 3 in a polydiacetylene-supported liposome nanocarrier (Lip-(3)) improves biocompatibility and anticancer activity while addressing solubility and toxicity concerns. The spherical nanoparticles (∼93 nm), characterized by UV-vis, TEM, DLS, and EDX studies exhibit stability, efficient encapsulation, and suitability for targeted drug delivery.