Theoretical study of the interaction between artemisinin and heme

摘要

The purpose of this work is to study theoretically stereoelectronic aspects of the interaction between heme and artemisinin in the transitional heme-artemisinin complex. Through semi-empirical calculations using the PM3 method, the potential energy barrier of artemisinin rotation relative to heme in the heme-artemisinin complex was studied in vacuum and in the partially solvated state. The minimum heat of formation obtained for the complex with and without water molecules is –702.39 and –100.86 kcal mol-1, respectively, which corresponds to the dihedral angle C-Fe-O1-O2 of 43.93?o and 51.90?o around the iron-oxygen O1 bond, respectively. The water molecules bind to heme via 13 hydrogen bonds and O-H•••O and 6 C-H•••O interactions, which accounts for –67.23 kcal mol-1. It is observed that the inclusion of water molecules does not affect significantly the stability of the heme-artemisinin complex.