Design, synthesis, characterization and evaluation of the anticancer activity of water-soluble half-sandwich ruthenium() arene halido complexes

• Published in: New journal of chemistry Vol. 44; no. 1; pp. 239 - 257
• Main Authors: Khan, Tanveer A, Bhar, Kishalay, Thirumoorthi, Ramalingam, Roy, Tapta Kanchan, Sharma, Anuj K
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 2020
• Subjects: Anticancer properties; Binding; Bonding strength; Cancer; Chemical analysis; Crystallography; Cytotoxicity; Density functional theory; Deoxyribonucleic acid; DNA; Emission analysis; Empirical analysis; Fluorescence; Graphs; Hydrogen bonding; Infrared analysis; Infrared spectroscopy; Investigations; Mathematical analysis; Optimization; Organic chemistry; Oxazole; Quantum chemistry; Ruthenium; Ruthenium compounds; Serum albumin; Single crystals; Spectra; Spectrum analysis; Synthesis; Toxicity; Voltammetry
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c9nj03663f

The synthesis, detailed characterization, and investigation of the DNA- and BSA-binding affinity and cytotoxicity of three half-sandwich Ru( ii ) arene chlorido complexes ( 1-3 ) are reported. Specifically, organometallic complexes [(η 6 - p -cymene)( L 1 )RuCl]Cl ( 1 ), [(η 6 - p -cymene)( L 2 )RuCl]Cl ( 2 ) and [(η 6 - p -cymene)( L 3 )RuCl]Cl ( 3 ) [ L 1 = 2-(1 H -benzo[ d ]imidazol-2-yl)quinolone, L 2 = 2-(quinolin-2-yl)benzo[ d ]oxazole, and L 3 = 2-(quinolin-2-yl)benzo[ d ]thiazole] were synthesized using [((η 6 - p -cymene)Ru(μ-Cl)Cl) 2 ] and L 1 -L 3 . All the complexes were characterized by various spectroscopic and analytical methods. Complex 1 was also characterized by single crystal X-ray diffraction analysis, the results of which are in-line with the piano-stool structure elucidated from the spectroscopic methods. Cyclic voltammetry of 1-3 showed good stability of the Ru( ii ) state. The interactions of 1-3 with CT-DNA were investigated by UV-Vis studies and competitive binding with ethidium bromide (EthBr) using emission spectroscopy. Steady-state fluorescence quenching and synchronous fluorescence studies were performed to understand the interactions between 1-3 and bovine serum albumin (BSA). The geometry optimization of 1-3 was performed using the density functional theory (DFT). Complexes 1 and 2 were investigated for DNA binding using theoretical calculations. Molecule complexes 1 -DNA and 2 -DNA were huge (482-483 atoms, 2442 electrons) for any level of quantum chemical analysis. The semi-empirical PM6 method, which is more accurate than the force-field methods, was used, and the result suggested that several strong and weak electrostatic and intermolecular hydrogen bonding interactions exist between the outer edge of DNA and complexes 1 and 2 . In addition, the in vitro cytotoxicity of L 1 -L 3 and complexes 1-3 against a breast cancer cell line (MCF-7) was investigated by MTT cytotoxicity analyses. The studies performed here show that these complexes exhibit a good binding behavior with DNA and BSA and show good anticancer potency towards MCF-7 cells. Synthesis, crystal structure determination, DFT studies, experimental and theoretical evaluation of DNA/BSA interactions and cytotoxicity studies of three piano-stool Ru( ii )( p -cymene)chloride complexes ( 1-3 ) are presented herein.