RESUMO
Although the interactions of sulfur mustard (HD) with nucleic acids and proteins have been well studied, the toxic interactions with the membrane matrix and specially the phospholipid bilayer have so far been poorly investigated. We have used several NMR techniques to study these interactions: 1H NMR to observe the localization of HD in membranes of small unilamellar vesicles (SUV) of lecithin; 31P NMR to verify the hypothesis of pore formation in membranes of large unilamellar vesicles (LUV); and pseudo solid state 31P and 2H NMR to analyze the dynamic consequences of the presence of HD in multilayer dispersions of dimyristoylphosphatidylcholine (DMPC). Immediate and late modifications of the DMPC-HD complexes have been observed at the macroscopic and microscopic levels. After intoxication, HD is spontaneously incorporated into the membrane and locates at the level of the chain methylene groups. This incorporation occurs without formation of pores in the membrane. The presence of HD in the phospholipid dispersion differentially increases the membrane fluidity depending upon the level involved. Weak at the superficial level (phosphate group), this increase is dose-dependent on progression into the membrane. This increase is related to a lowering of transition temperature when measured at the chain level. Macroscopically, HD induces dose- and time-dependent modifications of the DMPC-HD complexes, leading to the formation of an optically transparent gel. This gel formation is confirmed at a microscopic level, where all structures disappear after intoxication.
Assuntos
Bicamadas Lipídicas/química , Fluidez de Membrana/efeitos dos fármacos , Gás de Mostarda/química , Fosfolipídeos/química , Dimiristoilfosfatidilcolina/química , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância Magnética , Modelos Químicos , Ácidos Fosfatídicos/química , Fosfatidilcolinas/químicaRESUMO
Hexakis(3,6-anhydro)tetrakis(2A,B,D,E-O-octyl) cyclomatohexaose (OCT) has been recently shown as a powerful cryptant for lead, mercury, and especially for uranyl. As previous results have been obtained in an organic solvent (methanol), a similar evaluation of OCT complex formation was achieved in aqueous medium and in the presence of membrane-mimicking systems such as phospholipid vesicles, liposomes and micelles. It was found that OCT, while completely insoluble in water, forms solid gel structures when in equimolar mixtures of water and methanol. Moreover, OCT exhibits detergent properties. Finally, OCT was successfully introduced in detergent solutions while keeping. Uranyl complexing properties. Possible applications of such models were also discussed.
Assuntos
Quelantes/química , Ciclodextrinas/química , Urânio/química , gama-Ciclodextrinas , Espectroscopia de Ressonância Magnética , Micelas , Soluções , SolventesRESUMO
The selection of the cations bound by hexakis (3,6-anhydro) tetrakis (2A,B,D,E-O-octyl) cyclomatohexaose (OCT) was performed by thin layer chromatography. The three cations selected, UO(2)2+, Pb2+ and Hg2+ were then studied by 1H-NMR. A 2:1 OCT/cation stoichiometry was identified in the cases of UO(2)2+ and Pb2+. While UO(2)2+ binding (logK around 6) followed a fast exchange kinetics, a slow or intermediate complexation was found with Pb2+ (logK = 5.6) and Pb2+, respectively. In the latter case, the poor solubility of Hg2+ precluded to propose neither a stoichiometry nor an estimation of the affinity constant.
