RESUMEN
The overproduction of reactive oxygen species has been linked to a wide array of health disorders. The ability to noninvasively monitor oxidative stress in vivo could provide substantial insight into the progression of these conditions and, in turn, could facilitate the development of better diagnosis and treatment options. A mononuclear Mn(II) complex with the redox-active ligand N,N'-bis(2,5-dihydroxybenzyl)-N,N'-bis(2-pyridinylmethyl)-1,2-ethanediamine (H4qtp2) was made and characterized. A previously prepared Mn(II) complex with a ligand containing a single quinol subunit was found to display a modest T1-derived relaxivity response to H2O2. The introduction of a second redox-active quinol both substantially improves the relaxivity response of the complex to H2O2 and reduces the cytotoxicity of the sensor but renders the complex more susceptible to transmetalation. The addition of H2O2 partially oxidizes the quinol subunits to para-quinones, concomitantly increasing the r1 from 5.46 mM-1 s-1 to 7.17 mM-1 s-1. The oxidation of the ligand enables more water molecules to coordinate to the metal ion, providing an explanation for the enhanced relaxivity. That the diquinol complex is only partially oxidized by H2O2 is attributed to its activity as an antioxidant; the complex can both catalytically degrade superoxide and serve as a hydrogen atom donor.
Asunto(s)
Antioxidantes/farmacología , Medios de Contraste/química , Peróxido de Hidrógeno/química , Hidroquinonas/química , Manganeso/farmacología , Compuestos Organometálicos/farmacología , Animales , Antioxidantes/síntesis química , Antioxidantes/química , Muerte Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Imagen por Resonancia Magnética , Manganeso/química , Modelos Moleculares , Estructura Molecular , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Oxidación-Reducción , RatasRESUMEN
A manganese(II) complex with a ligand containing an oxidizable quinol group serves as a turn-on sensor for H2O2. Upon oxidation, the relaxivity of the complex in buffered water increases by 0.8 mM(-1) s(-1), providing a signal that can be detected and quantified by magnetic resonance imaging. The complex also serves as a potent antioxidant, suggesting that this and related complexes have the potential to concurrently visualize and alleviate oxidative stress.
