Studies on predicting reactive sites of 3,9-diazatetraasteranes by conceptual density functional theory and experiment

Abstract

Theoretical studies on predicting potential reactive sites of attractive compounds are of significance, which are capable of providing deeper insight into their chemical behaviors as well as foundations for discovering new drug molecules. The 3,9-diazatetraasterane derivatives are a kind of cage compounds equipping with potent biological activities. In this paper, predication of reactive sites of 3,9-diazatetraasteranes bearing phenyl and ester groups (6,12-diphenyl-3,9-diazahexacyclo[6.4.0.02.7.04.11.05.10]-dodecane-1,5,7,11-tetracarboxylate) was carried out by the conceptual density functional theory. Firstly, a conformational search of 3,9-diazatetraasterane was performed by molecular dynamics simulations associating with Quantum Mechanics calculations in order to obtain relative stable conformers. And then the reactive site prediction of 3,9-diazatetraasterane was carried out by the Fukui function and condensed Fukui function. The results exhibited that the potentially chemical reactive site is the N atom of 3,9-diazatetraasterane scaffold, which is readily attacked by electrophilic agent. Meanwhile, the calculated results were validated by experimental outcomes in the derivation of 3,9-diazatetraasteranes.