The reaction of alkylnitronates with glutathione.
Nitroalkanes are agents of occupational importance, and 2-nitropropane has been shown to be mutagenic and hepatotoxic. Here the reaction of alkylnitronates, such as propyl-2-nitronate, with glutathione and other thiol nucleophiles has been studied by using TLC, HPLC, and spectroscopic methods. Propyl-2-nitronate, but not 2-nitropropane, reacted with glutathione in acidic media. The reaction yielded an inseparable mixture of oxidized glutathione and a product that was identified as S-nitrosoglutathione. S-Nitrosoglutathione is known to be generated by reaction of nitrous acid with glutathione and furnishes a characteristic UV spectrum, but its NMR and mass spectral properties are described here for the first time. The 1H NMR spectrum of S-nitrosoglutathione showed in principle the resonance signals of glutathione except that the cysteine beta-protons gave two broad signals shifted downfield by 1 ppm as compared to the resonance frequencies of the glutathione cysteine beta-protons. The interpretation of the spectrum was aided by investigation of the properties of S-nitroso-N-acetylcysteine, the product of the reaction of N-acetylcysteine with propyl-2-nitronate. The nitronates of primary nitroalkanes, such as nitromethane, nitroethane, or 1-nitropropane, did not react with glutathione. The reaction between propyl-2-nitronate and glutathione did not occur at pH values greater than 5; therefore, the relevance of these findings to the disposition of propyl-2-nitronate in vivo is unclear.
Shaw
A J
AJ
Pharmaceutical Sciences Institute, Aston University, Birmingham, England.
Gescher
A
A
Tooth
D
D
Linhart
I
I
Farmer
P B
PB
D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005978:Glutathione / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D019803:Glutathione Disulfide; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009595:Nitroparaffins / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity
D009595:Nitroparaffins; C069720:propane-2-nitronate; D005978:Glutathione; C016617:2-nitropropane; D011407:Propane; D019803:Glutathione Disulfide