Figure 21.

The amidicity scale [MP2(full)/DGDZVP], showing the reactivity of the carbonyl group for the three different forms of penicillin molecule (58, 59 and 60), depending on its protonation degree as well as its conformation. The electron repulsion between the COO− group and the N atom is illustrated by the lone pairs. This strengthening of the amide bond in 59 (larger amidicity) decreases reactivity with respect to 58. In form 60, the internal H-bond withdraws density from the amide bond, weakening it (extremely low amidicity) leading to extremely high reactivity toward nucleophiles.