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.
D002712:Chlorides / Q000032:analysis; D005459:Fluorides / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D009607:Nitrosourea Compounds / Q000032:analysis; D010069:Oxadiazoles; D010710:Phosphates; D013056:Spectrophotometry, Ultraviolet; D014867:Water
D002712:Chlorides; D009607:Nitrosourea Compounds; D010069:Oxadiazoles; D010710:Phosphates; D014867:Water; D005459:Fluorides