RESUMEN
A series of surface-confined ionic liquid (SCIL) stationary phases for high-performance liquid chromatography were synthesized in-house. The synthesized phases were characterized by the linear solvation energy relationship (LSER) method to determine the effect of residual linking ligands and the role of the cation and the anion on retention. Statistical analysis was utilized to determine whether the system coefficients returned from multiple linear regression analysis of chromatographic retention data for a set of 28 neutral aromatic probe solutes were significantly different. Examination of the energetics of retention via kappa-kappa plots agrees with the results obtained from the LSER analysis. Residual linking ligands were determined to contribute reversed-phase-type retention character to the chromatographic system. Furthermore, retention on the SCIL phases was observed to be more profoundly affected by the identity of the anion than by that of the cation.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Líquidos Iónicos/química , Aniones/química , Cationes/química , Cromatografía Líquida de Alta Presión/instrumentación , Imidazoles/química , Líquidos Iónicos/síntesis química , Ligandos , Modelos Lineales , Estructura Molecular , Silanos/química , Solventes/química , Propiedades de Superficie , Factores de TiempoRESUMEN
Long wavelength solar UVA radiation stimulates formation of reactive oxygen species (ROS) and prostaglandin E(2) (PGE(2)), which are involved in skin photosensitivity and tumor promotion. High levels of 7-dehydrocholesterol (7-DHC), the precursor to cholesterol, cause exaggerated photosensitivity to UVA in patients with Smith-Lemli-Opitz syndrome (SLOS). Partially replacing cholesterol with 7-DHC in keratinocytes rapidly (<5 min) increased UVA-induced ROS, intracellular calcium, phospholipase A(2) activity, PGE(2), and NADPH oxidase activity. UVA-induced ROS and PGE(2) production were inhibited in these cells by depleting the Nox1 subunit of NADPH oxidase using siRNA or using a mitochondrial radical quencher, MitoQ. Partial replacement of cholesterol with 7-DHC also disrupted membrane lipid raft domains, although depletion of cholesterol, which also disrupts lipid rafts, did not affect UVA-induced increases in ROS and PGE(2). Phospholipid liposomes containing 7-DHC were more rapidly oxidized by a free radical mechanism than those containing cholesterol. These results indicate that 7-DHC enhances rapid UVA-induced ROS and PGE(2) formation by enhancing free radical-mediated membrane lipid oxidation and suggests that this mechanism might underlie the UVA photosensitivity in SLOS.
Asunto(s)
Deshidrocolesteroles/farmacología , Queratinocitos/efectos de la radiación , Lípidos/química , Mitocondrias/metabolismo , NADPH Oxidasas/metabolismo , Estrés Oxidativo , Síndrome de Smith-Lemli-Opitz , Rayos Ultravioleta/efectos adversos , Calcio/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Células Cultivadas , Colesterol/metabolismo , Dinoprostona/metabolismo , Técnica del Anticuerpo Fluorescente , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Liposomas , Microdominios de Membrana , Mitocondrias/efectos de los fármacos , Mitocondrias/efectos de la radiación , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/genética , Fosfolípidos/metabolismo , ARN Interferente Pequeño/farmacología , Especies Reactivas de Oxígeno/metabolismo , Síndrome de Smith-Lemli-Opitz/metabolismo , Síndrome de Smith-Lemli-Opitz/patologíaRESUMEN
Pyrene dihydrodioxins (1 and 2) have been synthesized and shown to be effective photochemical blocking groups for pyrene-4,5-dione (3). The mechanism of quinone release proceeds through the formation of a remarkably stable radical cation. Direct evidence is provided that this radical cation is not only thermally labile but also photochemically labile, and that both pathways lead to quinone extrusion. Once initiated with UV light, the pyrene quinone product serves as an electron-transfer photosensitizer for the further release of quinone with visible light.