Mechanism of hydrolysis of halogenated nitrosoureas.
The hydrolysis kinetics of halogenated nitrosoureas were investigated using chlorozotocin as a model. Evidence is presented to show that the hydrolytic reaction of halogenated nitrosoureas between pH 3 and 8 is a summation of spontaneous water and hydroxide-ion-catalyzed reactions; the later reaction is the sum of two parallel reactions. The relative contribuiton of each reaction changes with pH and results in different product distributions. Dianionic phosphate (HPO42-) increased the amount of free chloride-ion production without significantly altering the hydrolysis rate. A mechanism is proposed to explain this behavior. The role of hydrolytic decomposition products produced at physiological pH on the biological activity of nitrosoureas is discussed.
Mechanism of hydrolysis of halogenated nitrosoureas. The hydrolysis kinetics of halogenated nitrosoureas were investigated using chlorozotocin as a model. Evidence is presented to show that the hydrolytic reaction of halogenated nitrosoureas between pH 3 and 8 is a summation of spontaneous water and hydroxide-ion-catalyzed reactions; the later reaction is the sum of two parallel reactions. The relative contribuiton of each reaction changes with pH and results in different product distributions. Dianionic phosphate (HPO42-) increased the amount of free chloride-ion production without significantly altering the hydrolysis rate. A mechanism is proposed to explain this behavior. The role of hydrolytic decomposition products produced at physiological pH on the biological activity of nitrosoureas is discussed.