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

• Published in: Organometallics Vol. 38; no. 16; pp. 3197 - 3211
• Main Authors: Rono, Charles K, Chu, William K, Darkwa, James, Meyer, Debra, Makhubela, Banothile C. E
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.08.2019; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Physical Sciences; Science & Technology; CANCER-CELLS; PALLADIUM(II) COMPLEX; IN-VITRO; ARENE COMPLEXES; ABASIC SITES; SINGLE-BASE BULGES; ORGANOMETALLIC CHEMISTRY; AURANOFIN; IRIDIUM CATALYSTS; COORDINATED GOLD COMPOUND
• ISSN: 0276-7333; 1520-6041
• DOI: 10.1021/acs.organomet.9b00440

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