Kinetics of Phosphoramide Mustard Hydrolysis in Aqueous Solution

摘要: Hydrolysis of phosphoramide mustard was investigated using HPLC, 31P NMR, and GC—MS with specific deuterium labels. The hydrolysis in sodium phosphate buffers found to follow apparent first-order kinetics. rate temperature pH dependent, being slower under acidic conditions. not catalyzed by hydroxyl ion, its dependence appeared be the result a change mechanism at different values. At value approximately above pKa nitrogen, major hydrolytic pathway via formation aziridinium followed nucleophilic attack. values below pKa, cleavage P-N bond predominated. 7.4, an ion rapid yield monohydroxy and, subsequently, dihyroxy products. this adequately described consecutive Seven species mixture have been identified as intact mustard, N-(2-chloroethyl)-N-(2-hydroxyethyl)phosphorodiamidic acid, N,N-bis-(2-hydroxyethyl)phosphorodiamidic phosphoramidic phosphoric N,N-bis-(2-chlorethyl)amine, N-(2-chloroethyl)-N-(2-hydroxyethyl)amine GC–MS aid Phosphoramide stabilized chloride ion. stabilization linearly related concentration, from ions. significantly more stable human plasma 5% serum albumin compared aqueous buffers, observation that may important vivo.