AM1 heats of formation (H_f) for the reaction of MeOH and EtOH with a series of β-lactams and aza-β-lactams are calculated. The ΔH_f values for hemi-acetal and acyl/carbamoyl-enzyme intermediate formation are compared in the two series. These model calculations predict that the reaction of the β-lactamase active site serine hydroxyl with aza-β-lactams will afford carbamate intermediates which should be refractory to hydrolysis, thereby inhibiting the enzyme. Therefore, novel aza-β-lactams are putative β-lactamase inactivators based on semi-empirical computations.

The relative hydrolysis rates of cyclohexanone ethylene ketals having different substituents at theβ- carbon, such as H₂, (OCH₂)₂, (SCH₂)₂, =O, were determined at 20°C in aqueous H₂SO₄-silica gel-CH₂Cl₂ medium. The observed kinetic trend of H₂>(OCH₂)₂>(SCH₂)₂>=O is correlated with calculated ΔH values (AM1, MNDO and PM3) for the ionisation ofβ-substituted cyclohexanes to the corresponding cations.