Mononuclear Copper(II) Phosphinates Bearing Mono-, Bi-, and Tridentate N-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.