KINETICS AND MECHANISM OF CHLORAMBUCIL HYDROLYSIS

The kinetics and mechanism of hydrolysis of the cytotoxic drug chlorambucil were investigated. A study of the reaction order and of the pH, dielectric constant, and ionic strength effects on the reaction rate revealed that the hydrolysis was a limiting unimolecular nucleophilic substitution, the rate‐determining step being the ionization of the first 2‐chloroethylaniine chlorine. The hydrolysis rate was markedly dependent on the protonation degree of the chlorambucil basic group, indicating that a cyclic ethyleneimmonium ion may be involved in the rate‐determining step. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company