Triazolyl RuII, RhIII, OsII, and IrIII Complexes as Potential Anticancer Agents: Synthesis, Structure Elucidation, Cytotoxicity, and DNA Model Interaction Studies. Organometallics, 2019

Novel conjugated ruthenium(II), rhodium-<br>(III), and iridium(III) organometallic complexes of triazoles<br>1 and 2 synthesized and evaluated for anticancer activity<br>against cervical (HeLa), kidney (HEK293), nonsmall lung<br>cancer (A549), and leukemia (MT4) cancer cell lines are<br>reported herein. The complexes are κ2-N,C coordinated and<br>have the formula [ML(Ar)Cl] (where L is 1-benzyl-4-phenyl-<br>1H-1,2,3-triazole for 1 and 1-benzyl-4-hydroxymethyl-1H-<br>1,2,3-triazole for 2, Ar is p-cymene for RuII and OsII and Cp*<br>for RhIII and IrIII, and M is metal). NMR studies, including<br>HMBC and NOESY, were employed to unambiguously<br>elucidate their structures and provide their conformational information in solution. Single-crystal X-ray diffraction data have<br>been used to establish the solid-state structures of selected complexes, which further confirm the structural elucidation by NMR.<br>Dynamic NMR studies, such as differential transferred NOE, have been employed to distinguish between isomers 1a_I and<br>1a_II of ruthenium(II) complexes of triazole 1. The rhodium(III) (1b) and iridium(III) (1c) complexes exhibited good<br>cytotoxic activities (CC50 = 4−6 μM) comparable to that of the drug auranofin against lung cancer A549 cell lines (CC50 = 4.69<br>μM). While triazole 1 based ruthenium(II) (1a) and osmium(II) (1d) complexes displayed modest anticancer activities against<br>HeLa and HEK293 cell lines, the analogous rhodium(III) and iridium(III) complexes exhibited good potential (CC50 = 9−54<br>μM versus auranofin (3−9 μM)) against these cancer cell lines. Insightful NMR studies on the interaction between the DNA<br>model guanosine 5′-GMP and the complexes 1b,c reveal a possible mode of action of the aquated complexes involving<br>carbenylation with DNA bases or purines through the triazolyl proton H-5. From the findings, these complexes could possibly<br>confer their cytotoxic activities through intercalation with the DNA of pathological cells. Therefore, carbenylation of the<br>triazolylrhodium(III) and iridium(III) complexes by DNA guanosine 5′-GMP is proposed as a novel mode of DNA<br>intercalation of these complexes in cancer cells.<br>