RESUMEN
Ruthenium complexes have been recently reported as potential chemotherapeutic agents that offer tumor selectivity and low tumor resistance. This study investigates the photochemistry and the effect of four strained photoactivatable polypyridyl ruthenium(II) complexes on non-small-cell lung cancer (A549) and triple negative breast cancer (MDA-MB-231) cells. All four ruthenium(II) complexes, [Ru(bpy)2dmbpy]Cl2 (C1) where (bpy = 2,2'-bipyridine and dmbpy = 6,6'-dimethyl-2,2'-bipyridine), [Ru(phen)2dmbpy]Cl2 (C2) where (phen = 1,10-phenanthroline), [Ru(dpphen)2dmbpy]Cl2 (C3) (where dpphen = 4,7-diphenyl-1,10-phenanthroline) and [Ru(BPS)2dmbpy]Na2 (C4) where (BPS = bathophenanthroline disulfonate) eject the dmbpy ligand upon activation by blue light. Determination of the octanol-water partition coefficient (log P) revealed that C3 was the only lipophilic complex (log P = 0.42). LC-MS/MS studies showed that C3 presented the highest cellular uptake. The cytotoxic effect of the complexes was evaluated with and without blue light activation using WST-1 kit. Data indicated that C3 exhibited the highest cytotoxicity after 72 h (MDA-MB-231, IC50 = 0.73 µM; A549, IC50 = 1.26 µM) of treatment. The phototoxicity indices of C3 were 6.56 and 4.64 for MDA-MB-230 and A549, respectively. Upon light activation, C3 caused significant ROS production and induced apoptosis in MDA-MB-231 cells as shown by flow cytometry. It also significantly increased Bax/Bcl2 ratio and PERK levels without affecting caspase-3 expression. C3 exhibited poor dark toxicity (IC50 = 74 µM) on rat mesenchymal stem cells (MSCs). In conclusion, the physical property of the complexes dictated by the variable ancillary ligands influenced cellular uptake and cytotoxicity. C3 may be considered a promising selective photoactivatable chemotherapeutic agent that induces ROS production and apoptosis.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Complejos de Coordinación/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Antineoplásicos/efectos de la radiación , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Complejos de Coordinación/efectos de la radiación , Complejos de Coordinación/toxicidad , Humanos , Luz , Células Madre Mesenquimatosas/efectos de los fármacos , Fármacos Fotosensibilizantes/efectos de la radiación , Fármacos Fotosensibilizantes/toxicidad , Piridinas/farmacología , Piridinas/efectos de la radiación , Piridinas/toxicidad , Ratas , Especies Reactivas de Oxígeno/metabolismo , Rutenio/química , Rutenio/toxicidadRESUMEN
In this study, we report the successful incorporation of the photoactive bis(4'-(4-carboxyphenyl)-terpyridine)ruthenium(II) (Ru(cptpy)2) strut into a robust metal-organic framework (MOF), AUBM-4. The single crystal X-ray analysis revealed the formation of a new one-dimensional structure of Ru(cptpy)2 complexes linked together by Zr atoms that are eight coordinated with O atoms. The chemically stable MOF structure was employed as an efficient photocatalyst for carbon dioxide conversion to formate under visible light irradiation. To the best of our knowledge, the obtained conversion rate is among the highest reported in the literature for similar systems. Our strategy of using the Ru(cptpy)2 complex as a linker to construct the MOF catalyst appears to be very promising in artificial photosynthesis.
RESUMEN
The use of ruthenium complexes as chemotherapeutic agents has been recently explored as one of the alternatives to conventional treatments. In the present study, two Ru(ii) polypyridyl complexes were synthesized and characterized: a strained [Ru(bipy)2(BC)]Cl2 (complex 1) where [bipy = 2,2'-bipyridine and BC = bathocuproine] along with the unstrained control [Ru(bipy)2(phen)]Cl2 (complex 2) where [phen = 1,10-phenanthroline]. The photophysical and photochemical analyses proved that unlike the photostable complex 2, complex 1 ejected both bipy and BC ligands at a ratio of 3 : 1 respectively. Results showed that the activity of complex 1 was significantly enhanced upon photoactivation. The response was however particularly significant in B16-F10 melanoma cells where phototoxicity index (PI = IC50 dark/IC50 light) was >900. When compared to cisplatin, the photoproducts were more potent against all tested cell lines, implying that the complex acquired significant chemotherapeutic potential upon irradiation. Cellular uptake of complex 1 and the free BC ligand were found to be significantly facilitated as evidenced by 400-600 fold increase in concentration of the compounds inside the cells relative to the extracellular culture medium. Complex 2 exhibited 35 times lower cellular concentration relative to complex 1. Flow cytometry and plasmid DNA gel electrophoresis measurements showed that complex 1 interacts with DNA inducing apoptosis in the dark and either late-apoptosis or necrosis upon irradiation. These findings corroborate the importance of lipophilic ligands such as BC to enhance uptake and subsequently improve the photochemotherapy potential of Ru(ii) polypyridyl complexes.
RESUMEN
A photochemically dissociating ligand in Ru(bpy)2(dmphen)Cl2 [bpy = 2,2'-bipyridine; dmphen = 2,9-dimethyl-1,10-phenanthroline] was found to be more cytotoxic on the ML-2 Acute Myeloid Leukemia cell line than Ru(bpy)2(H2O)22+ and prototypical cisplatin. Our findings illustrate the potential potency of diimine ligands in photoactivatable Ru(ii) complexes.
RESUMEN
A green and very efficient synthesis of N-substituted benzoquinonediimines or C-substituted benzo-bis(imidazole) derivatives is described under similar conditions. The different reaction pathway is only controlled by the nature of the primary amines, which tunes the reactivity of the intermediates.
RESUMEN
Stepwise synthesis of linear nickel complex oligomer tapes with no need for solid-phase support has been achieved. The control of the length in flat arrays allows a fine-tuning of the absorption properties from the UV to the NIR region.