Half-sandwich d⁶ metal complexes comprising of 2-substituted-1,8-napthyridine ligands with unexpected bonding modes: Synthesis, structural and anti-cancer studies

The Friedländer condensation reaction between 2-aminonicotinealdehyde and acetophenone derivatives in presence of potassium hydroxide yielded 2-substituted-1,8-napthyridine derivatives viz. 2-(1,8-napthyridin-2-yl)phenol (PHNp), 2-(1,8-napthyridin-2-yl)aniline (AnNp) and 2-(pyridine-4-yl)-1,8-napthyridine (PyNp). Treatment of the chloro-bridged dimers [(arene)MCl₂]₂ [arene = p-cymene, Cp*; M = Ru, Rh and Ir] with two equivalents of napthyridine ligands (PHNp, AnNp and PyNp) allowed the formation of mononuclear napthyridine complexes having formula [(arene)M(PHNp)Cl₂] (1–3), [(arene)M(AnNp)Cl]PF₆ (4–6) and [(arene)M(PyNp)Cl₂] (7–9). These napthyridine compounds were isolated as neutral and cationic complexes which were further characterized by analytical and spectroscopic techniques. The molecular structures of some of the respective napthyridine complexes were established by carrying out the single crystal X-ray analysis. Single crystal X-ray studies revealed the coordination of the napthyridine ligands to the metal center wherein AnNp ligand coordinated metal in a bidentate chelating NN′ manner and PHNp and PyNp ligand coordinated metal in a monodentate fashion. In case of PHNp complexes the coordination occurs through napthyridine nitrogen N(1) whereas in case of PyNp complexes the coordination takes place through pyridine nitrogen N(1). These napthyridine complexes possessed cytotoxicity against HCT-116 (human colorectal cancer) and MIA-PaCa-2 (pancreatic carcinoma) cancer cell lines as compared to non-cancer cell line ARPE-19.