Pt(II) Rollover Cyclometalated Complexes Supported by 2,2’-Bipyridine N-Oxide: Synthesis, Characterization, and Biological Evaluation

Four platinum(II) rollover cyclometalated complexes derived from 2,2’-bipyridine N-oxide (bpyNO), [Pt(bpyNO-H)(DMSO)Me] (1a), [Pt(bpyNO-H)(PPh3)Me] (2a), [Pt(bpyNO-H)(DMSO)Cl] (3a), and [Pt(bpyNO-H)(PPh3)Cl] (4a), were synthesized, characterized, and evaluated for their antimicrobial and cytotoxic activities. The electron-poor nature of bpyNO enables rollover C–H bond activation at room temperature. NMR and X-ray analysis (4a) revealed distinctive features, including an intramolecular interaction between the H3′ hydrogen and the N-oxide oxygen. A correlation between the direct 195Pt–31P coupling constant and the donating properties of cyclometalated ligands has been found, allowing a useful scale of donor properties. A preliminary screening of antimicrobial activity against E. coli, K. pneumoniae, S. aureusmultidrug resistant (MDR), S. pyogenes, P. aeruginosa, and C. albicans demonstrated selective activity. Complex 3a showed the most promising results against E. coli and multidrug-resistant S. aureus. Significantly, the complexes also exhibited biofilm inhibitory behavior; notably, complex 1a showed activity against K. pneumoniae. Additionally, preliminary cytotoxicity tests on human tumor (HT29) cells and normal (CCD 841 CoN) cells were performed. Among the investigated compounds, 1a, 2a, and 3a exhibited a significant reduction in tumor cell viability, whereas complex 4a displayed moderate activity. These results establish 2,2’-bipyridine N-oxide as a promising ligand scaffold for developing platinum complexes.