Photoactivatable Ru^II Complex Bearing 2,9‐Diphenyl‐1,10‐phenanthroline: Unusual Photochemistry and Significant Potency on Cisplatin‐Resistant Cell Lines

Abstract

The current study investigates [Ru(bipy) 2 (dpphen)]-Cl 2 [where bipy = 2,2′-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline] (complex 1) for photoactivatable chemotherapy (PACT) application on five cancer cell lines.[Ru(bipy) 2 (phen)]Cl 2 [where phen = 1,10-phenanthroline] (complex 2) was included as an unstrained control. Upon excitation with visible light, complex 2 proved to be photostable while complex 1 underwent a quantitative dissociation of the bipy ligand and formation of a Ru II polypyridyl aqua complex in water. Complex 1 demonstrated only marginal activity in the dark; its cytotoxicity increased significantly upon photoactivation with a high phototoxicity index (PI = [IC 50 dark]/[IC 50 light]) [a]

Enhanced cellular uptake and photochemotherapeutic potential of a lipophilic strained Ru(ii) polypyridyl complex

“…The instrumental parameters used for 1 H NMR, 13 C NMR, MALDI-TOF MS, LC-MS/MS and irradiation were previously reported. 13 Elemental analysis and HR-ESI MS were performed at Atlantic Microlab and Michigan State University respectively.…”

“…The instrumental parameters used for 1 H NMR, 13 C NMR, MALDI-TOF MS, LC-MS/MS and irradiation were previously reported. 13 Elemental analysis and HR-ESI MS were performed at Atlantic Microlab and Michigan State University respectively. Cell death was assessed by Annexin V/PI staining, using a C6 ow cytometer (BD Accuri, Ann Arbor, MI) and data were analyzed on FL1-H versus FL2-H scatter plot.…”

“…Conversion of the complex to chloride salt was performed as previously reported, using dowex beads. 13 Synthesis of [Ru(bipy) 2 (phen)]Cl 2 (complex 2)…”

“…Cell survival assays were performed on human alveolar adenocarcinoma A549, murine melanoma B16-F10, human colon adenocarcinoma Caco-2, human colorectal adenocarcinoma HT-29 and triple negative human breast adenocarcinoma MDA-MB-231 cell lines treated with complexes 1 and 2, cisplatin, bipy, and BC, as previously described. 13 Briey, DMEM containing 10% FBS and 1.5% pen-strep at 37 C with 5% CO 2 was used to maintain cells. The latter were seeded and allowed to adhere at a concentration of 10 4 cells per well in a 96 well-plate.…”

“…8 We have recently reported the quantitative ejection of the non-straining ligand bipy in [Ru(bipy) 2 dpphen] 2+ [where bipy ¼ 2,2 0 -bipyridine and dpphen ¼ 2,9-diphenyl-1,10-phenanthroline] and the formation of aquated photoproduct. 13 Other groups evaluated the photochemistry and photobiology of similar Ru(II) bipyridine complexes in water where aqua complexes like [Ru(bipy) 2 (H 2 O) 2 ] 2+ and [Ru(bipy) 2 (H 2 -O)(OH)] + were produced upon dissociation of the straining ligand. Photoproducts were proved to damage DNA by variable mechanisms including DNA binding, intercalation, or cleavage.…”