Experimental and theoretical investigations of cyclometalated ruthenium(ii) complex containing CCC-pincer and anti-inflammatory drugs as ligands: synthesis, characterization, inhibition of cyclooxygenase and in vitro cytotoxicity activities in various cancer cell linesElectronic supplementary information (ESI) available: A detailed description of the experimental and computational methods can be found: 1H, 13C, and 31P NMR spectra of ligands 1, 2, and complex 3; mass spectra of ligands 1, 2, and

The new cyclometalated ruthenium( ii ) complex, [Ru(CCC-Nap)(Ibu)(PTA)] was designed and synthesized using ibuprofen (Ibu), 1,3,5-triaza-7-phosphaadamantane (PTA) and CCC-pincer containing naproxen moiety (CCC-Nap) as ligands. The compounds were fully characterized by elemental analysis, FT-IR, multinuclear ( 1 H, 13 C, and 31 P) NMR spectroscopy, and electrospray ionization mass spectrometry. The cytotoxicity of the newly synthesized Ru( ii ) complex was found to be low, and the complex was about twice as active as cisplatin with IC 50 values in the range of 0.9-1.32 μM for both MCF-7 and MDA-MB-231 cell lines. Cyclooxygenase (COX) inhibition studies revealed that the Ru( ii ) complex displayed strong interactions with COX-2, about 16 and 5 times more than free Ibu and CCC-Nap ligands, respectively. The Ru( ii ) complex improved the production of reactive oxygen species (ROS) by 10.7 fold compared to the control (H 2 O 2 as a positive control) in MCF-7 cells. Quantum chemical calculations gave more insights into the geometry and electronic properties of the novel Ru( ii ) complex, while molecular docking provided theoretical information on the interactions of Ru( ii ) complex with human cyclooxygenase-2 (COX-2) and the results were compared with those of the interactions of the free ligands with COX-2. The cyclometalated ruthenium( ii ) complex was synthesized and studied for cytotoxicity. The interaction of Ru( ii ) complex with COX-2 was studied by experimental and molecular docking.