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-chloroethylamine 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.
D002699:Chlorambucil / Q000378:metabolism*; D000431:Ethanol; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008956:Models, Chemical; D009994:Osmolar Concentration
D002699:Chlorambucil; D000431:Ethanol