Organometallic Complexes with an Indolo[2,3- c ]Quinoline-Derived Ligand: From Structural Features and Solution Speciation to Nanoformulation for Enhanced Therapeutic Potential

Synthesis and comprehensive solid and solution phase characterization of Ru(II)(η6-p-cymene), Os(II)(η6-p-cymene), and Rh(III)(η5-C5Me5) complexes of an indolo[2,3-c]quinoline-derived Schiff base compound (IQPMA) and its simpler analogue (DIPMA), both bearing a bidentate (N,N) chelating motif, are reported. The complexes exhibit enhanced aqueous solubility compared to the free ligands. The structures of five half-sandwich complexes were determined by single-crystal X-ray diffraction. A correlation analysis revealed that, despite the highly similar coordination geometry, conformational variations are primarily governed by steric and electronic interactions between the aromatic ring systems. Complexation of IQPMA and DIPMA with Rh(III)(η5-C5Me5) promoted ligand hydrolysis, while the corresponding Ru(II) and Os(II) organometallic complexes remained stable at physiological pH (7.4). These latter complexes showed very slow aquation kinetics and strong binding to human serum albumin mediated by intermolecular interactions. IQPMA, its complexes, and the DIPMA complexes exhibited weak-to-moderate cytotoxicity, and the Ru(II)(η6-p-cymene) complex of IQPMA was selectively active toward breast adenocarcinoma MCF-7 cells. Metal coordination significantly enhanced antibacterial efficacy against Gram-positive strains and inhibition of biofilm formation. To improve bioavailability, the Ru(II)(η6-p-cymene) complexes were encapsulated into asolectin-derived liposomes (∼200 nm) with high encapsulation efficiency and colloidal stability. Importantly, cytotoxicity assays confirmed that nanoformulation preserved the biological activity of the metal complexes.