A calorimetric study of β-sultams and β-lactams

The hydrolytic degradation of a series of β-sultams and β-lactams was investigated using isothermal microcalorimetry (IMC), to determine kinetic and enthalpic data. The importance of these studies was to model the process of hydrolysis as this was a simplification of the mechanism by which β-lactams and β-sultams function as serine protease inhibitors.

Calorimetric studies were conducted using a Thermal Activity Monitor (TAM 2277). Three categories of experiments were conducted: in the solid state, varying relative humidity (R/H) and in aqueous solution. Hydrolytic rate constants and enthalpies were determined for the solid state studies and these were related to substituent effects. However, for the experiments relating to the R/H studies no conclusive results were obtained. As expected, for solution state studies the hydrolytic rate constant in all cases changed with temperature (298K, 310K and 323K).

Theoretical predictions were then made for a novel β-sultam based on these results with an excellent correlation observed between theoretical calculations and experimental results.

Finally, calorimetric experiments were conducted on a series of β-lactams. This was for two reasons firstly; to determine if calorimetry can monitor low reaction rates and secondly; to compare rates of hydrolysis with the β-sultams. For a series of β-lactams, solution state hydrolytic rate constants and enthalpies were determined. An overall comparison of β-lactams and β-sultams appeared to indicate that in all cases β-lactams reacted slower than β-sultams.