RESUMO
Experimental and density functional theory (DFT) studies are described that are focused on outlining the reactivity of the known photochemical nitric oxide precursor trans-Cr(cyclam)(ONO)(2)(+) ("CrONO", cyclam = 1,4,8,11-tetrazacycltetradecane). Studies in both aerated and deaerated aqueous media are described as are the roles of both the oxidant O(2) and a reductant such as glutathione in trapping the apparent Cr(IV) photoreaction intermediate trans-Cr(cyclam)(O)(ONO)(+). Also reported and characterized structurally is the Cr(V) product of long-term photolysis in the absence of reducing agents, the trans-dioxo species [trans-Cr(cyclam)(O)(2)](ClO(4)). Photosensitization experiments indicate that at least a significant fraction of the reaction occurs from the lowest energy doublet excited state(s). Lastly, cell culture experiments demonstrate that CrONO has little or no acute toxicity either before or after photolysis.
Assuntos
Cromo/química , Compostos Heterocíclicos/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/efeitos da radiação , Óxido Nítrico , Fotólise , Fármacos Fotossensibilizantes/metabolismo , Pró-Fármacos/metabolismo , Linhagem Celular Tumoral , Cromo/metabolismo , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Glutationa/química , Glutationa/metabolismo , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/farmacologia , Humanos , Cinética , L-Lactato Desidrogenase/análise , Luz , Estrutura Molecular , Terapia de Alvo Molecular/métodos , Monócitos/patologia , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Oxirredução/efeitos da radiação , Fotoquímica/métodos , Fotólise/efeitos dos fármacos , Fotólise/efeitos da radiação , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Fototerapia/métodos , Pró-Fármacos/síntese química , Pró-Fármacos/farmacologia , Estereoisomerismo , TermodinâmicaRESUMO
Several dienes of varying steric bulk containing an enol carbonate have been synthesized and reacted selectively with ozone at the isolated double bonds. Rate measurements have been made for ozonolysis in a series of substituted cyclohexenes to demonstrate the unusually slow reactivity of the enol carbonate. Proton and carbon NMR chemical shifts have been presented to show that the enol carbonate is not particularly electron deficient in its double bond. Calculation of partial charges from the Mulliken population analysis shows good correlation with the NMR data. The results suggest a carbonate association with ozone that slows the rate of carbon-carbon bond cleavage.
RESUMO
Hydroxy fatty acids from Euglena gracilis were identified by reverse-phase high performance liquid chromatography coupled to a mass spectrometer run in atmospheric pressure chemical ionization positive ion mode. These metabolites were converted to methyl esters to improve stability and chromatographic properties. A detection limit of 20 pg/microl per injection was determined for 5-HETE methyl ester based on the signal to noise ratio of the m/z 317 ion which corresponds to the loss of a hydroxyl group (M-17) and the major fragment in all HETE methyl esters studied. This is the first report for these metabolites in E. gracilis.