Conformation, electronic structure, and biological activity of antitumour triazenes

Abstract

The MNDO molecular orbital method has been used to calculate the preferred conformation and values of electronic indices for some antitumour triazenes. The computed rotation barrier about the N(2)–N(3) bond shows a good correlation with the Hammett σ substituent constant, and increases as the ability of the substituent to withdraw electrons increases. Analysis of the stretching force constant for the N(3)–Me bond indicates that the demethylation of triazenes observed in vitro should occur more readily in the planar conformation, which is the most stable. On the other hand, the antitumour activity shows a high correlation with the LUMO orbital energy, suggesting a charge-transfer mechanism with electron-acceptor triazenes. Finally, with respect to toxicity, no important correlation was found with the electronic indices considered.