title: Mechanistic investigation of the degradation of sulfamic acid 1,7-heptanediyl ester, an experimental cytotoxic agent, in water and 18oxygen-enriched water.
abstract: The hydrolytic degradation of sulfamic acid 1,7-heptanediyl ester was carried out in water and 18O-enriched water at 47 degrees C. The degradation of 1 was also studied at various pH values in the range of 2.5 to 8.0 at constant ionic strength (0.15 M) and temperature (25 degrees C). The hydrolysis was first order and independent of pH with a mean (+/- SD) observed rate constant (kobs) of 2.38 +/- 0.6 X 10(-3) h-1. No significant buffer catalysis was observed. From TLC, HPLC, and mass spectral studies, 1 initially degraded to sulfamic acid 1,7-heptanemonoyl ester and subsequently to 1,7-heptanediol. The site of bond cleavage was assessed by mass spectrometry of the 18O-enriched water reaction mixtures. Exclusive C--O bond fission was observed. Several mechanistic pathways for the degradation of 1 could be postulated. The results from 18O-labeling studies, the pH-rate profile and buffer studies, and kinetic solvent isotope effect (KSIE) studies were consistent with an SN2 mechanism with an early transition state (reactant-like transition state) where no appreciable bond had developed between the incoming nucleophile, water, and the carbon atom of 1. Although an SN1 mechanism was unlikely, based on the need to postulate the formation of a primary carbocation, this mechanism could not be totally ruled out.
mesh_terms: D000970:Antineoplastic Agents; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D013058:Mass Spectrometry; D010103:Oxygen Isotopes; D013451:Sulfonic Acids; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D010103:Oxygen Isotopes; D013451:Sulfonic Acids; D014867:Water; C052475:hepsulfam