Hydrolysis of l-phenylalanine mustard (melphalan). II. Further observations on the effects of pH,chloride ions and buffers on the rate of reaction |
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| Institution: | 1. Department of Neurology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA;2. Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany, NY, USA;3. Department of Biostatistics, Population Health Observatory, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, USA;4. The Program for the Study of Neurodevelopment in Rare Disorders, Children’s Hospital Pittsburgh of UPMC, Pittsburgh, PA, USA.;1. Departments of Chemistry, University of Washington, Seattle, WA 98195, USA;2. Departments of Biochemistry, University of Washington, Seattle, WA 98195, USA;1. Centre of Medical Genetics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110060, India;2. Preventive Medicine Foundation, Taipei, Taiwan;3. Erasmus MC, University Medical Center, Rotterdam, The Netherlands |
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| Abstract: | The effects of pH (3.7—13), ionic strength, buffer composition (acetate, phosphate and borate) and buffer concentration (15–200 mM) on the rate of degradation of melphalan in the presence 0.3 M chloride at 50 ± 0.1 °C were investigated using high-performance liquid chromatography. In addition, the data published in the literature for the degradation of phosphoramide mustard have been compared with those of melphalan, placing emphasis on mechanisms of hydrolysis and the effects of pH and chloride. In the presence of chloride, the degradation rate of melphalan was influenced by pH and buffer composition but not by ionic strength. These effects were not seen in the absence of added chloride and have been explained in terms of competition between chloride and other nucleophiles such as the hydroxide ion, water and buffer components for the active intermediate of the alkylating agent. These results help to explain differences in reported values for the rates of hydrolysis of various alkylating agents in the presence of chloride. |
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