A topological study of the decomposition of 6,7,8-trioxabicyclo[3.2.2]nonane induced by Fe(II): modeling the artemisinin reaction with heme.

We report a theoretical study on the electronic and topological aspects of the reaction of dihydrated Fe(OH)(2) with 6,7,8-trioxabicyclo[3.2.2]nonane, as a model for the reaction of heme with artemisinin. A comparison is made with the reaction of dihydrated ferrous hydroxide with O(2), as a model for the heme interaction with oxygen. We found that dihydrated Fe(OH)(2) reacts more efficiently with the artemisinin model than with O(2). This result suggests that artemisinin instead of molecular oxygen would interact with heme, disrupting its detoxification process by avoiding the initial heme to hemin oxidation, and killing in this way the malaria parasite. The ELF and AIM theories provide support for such a conclusion, which further clarifies our understanding on how artemisinin acts as an antimalarial agent.