The ammonolysis reaction of 3-(formylamino)-4-methyl-2-oxoazetidine-1-sulfonate is investigated by quantum-chemical methods (B3LYP/6-31 G*) as a model system of the aminolysis reaction of monobactam antibiotics involved in the allergic reaction to these drugs. The influence of the N-sulfonate group on the blactam ring, reaction intermediates, and transition states is characterized in terms of the geometries and relative energies of the corresponding critical structures located on the B3LYP/6-31 G* potential-energy surface. It is shown that the N-sulfonate group, which has only a moderate impact on the structure and charge distribution of the b-lactam ring, reduces the rate-determining DG barrier by ca. 20 kcal/mol with respect to a purely uncatalyzed ammonolysis of the unsubstituted system, azetidin-2-one. This intramolecular catalytic effect occurs through a ÀNHÀSO À
3 6 [À NÀSO 3 H] À isomerization process, which is involved in the proton relay from the attacking ammonia molecule to the b-lactam N-atom. Our theoretical results predict that, in aqueous solution, monobactams will show an intrinsic reactivity against amine nucleophiles more important than that of penicillins. a ) Including ZPVE correction from B3LYP/6-31 G* frequencies. b ) Based on B3LYP/6-31 G* electronic energies and thermal corrections. c ) Relative DG solvation with respect to reactants from single-point B3LYP/6-31 G* PCM-UAHF calculations. d ) DG solution DG gas-phase DDG solvation .