The pKa and pH dependence of the formation of nitroxide radicals from some drug substances with an aliphatic secondary amino group by oxidation with hydrogen peroxide. An Electron Spin Resonance (ESR) Study.
The pKa and pH dependence of the formation of nitroxide radicals from the following drugs that contain an aliphatic secondary amino group, by oxidation with hydrogen peroxide, have been studied by ESR spectroscopy: Ephedrine, (1R,2S)-1-phenyl-2-methyl-aminopropanol, timolol, (S)-1-(tert-butyl-amino)-3-[(4-morpholino-1,2,3-thiadiazol-3-yl)ox y]-2- propanol, metoprolol, 1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]-2-propanol and terodiline, N-tert-butyl-3,3-diphenyl-1-methylpropylamine. Radicals were formed from the non-ionized base only. Therefore, the pKa value of the amine and the pH of the reaction mixture is of crucial importance for the yield of nitroxide radical. At 37 degrees C the pKa values of 1-3 are about 9.2, and of 4 about 9.6, which means that 1.5% of 1-3, and 0.6% of 4, are present in the reactive base form at the physiological pH of 7.4. Horse-radish peroxidase was found both to enhance radical production and to decrease the life-time of the radicals formed in the reaction with hydrogen peroxide.
Lagercrantz
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Department of Medical Physics, University of Göteborg, Sweden.
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006735:Horseradish Peroxidase; D006861:Hydrogen Peroxide; D006863:Hydrogen-Ion Concentration; D009589:Nitrogen Oxides / Q000032:analysis*; D009590:Nitrogen Radioisotopes; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000032:analysis*
D005609:Free Radicals; D009589:Nitrogen Oxides; D009590:Nitrogen Radioisotopes; D004364:Pharmaceutical Preparations; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase