Chemoimmunotherapy of cancer. 3. Analytical measurement of chemical half-lives of monofunctional alkylators

J Med Chem. 1977 Dec;20(12):1700-2. doi: 10.1021/jm00222a037.

Abstract

The objective of this study is the measurement of the rates of hydrolysis of a series of chloroethyl sulfide derivatives, under stimulated physiological conditions. Interferences encountered with the conventional spectrophotometric method prompted the use of a rapid-response, chloride selective electrode. This probe was readily capable of monitoring the hydrolytic rate, which is identical with the rate of chloride ion formation. Since the desired subsecond half-lives were not achieved by any of the compounds, factors influencing the rates were investigated. The results suggest that the rate-controlling cyclization step may be inhibited, due to coordination of undissociated protonic functional groups on the aromatic portions of the structures with the lone-pair electrons on sulfur.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chemical Phenomena
  • Chemistry
  • Electrochemistry
  • Half-Life
  • Hydrolysis
  • Kinetics
  • Nitrogen Mustard Compounds / metabolism*
  • Thermodynamics

Substances

  • Nitrogen Mustard Compounds