Does structural variation in the aziridinium ion facilitate alkylation?

The reactivity and stability of the tricyclic aziridinium ion intermediate of the mustine drug molecule varies with the ∠ NCC bond angle (from 60° to 150°) of the tricyclic ring. As ∠ NCC bond angle increases, the tricyclic ring of the aziridinium ion opens up which leads to variation in its reactivity. We have observed shifting of the reactive center (i.e., the LUMO) of the drug intermediate with variation in the ∠ NCC bond angle in gas phase as well as in aqueous phase. It was also observed that the drug intermediate must undergo some structural changes before alkylating DNA. In addition, the maximum hardness principle and minimum electrophilicity principles were analyzed.