MNDO/d calculations on the interaction between artemisinin and heme

Abstract The antimalarial activity of artemisinin is supposed to be mediated by its interaction with intraparasitic heme leading to free radicals which would be responsible for killing the parasite. The semi-empirical PM3 method was used to calculate the molecular electrostatic potential of artemisinin. This shows that artemisinin has a wide negative region which extends from the peroxide oxygens O1 and O2 to the carboxyl oxygens O11 and O14. MNDO/d calculations of two complexes between artemisinin and heme, where the Fe (II) ion of heme interacts with either O1 and O2 or with O11 and O14, respectively, indicate that artemisinin interacts with heme preferentially through the peroxide oxygen atoms leading, however, to a complex with low thermodynamic stability.

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