title: DFT study of the reductive decomposition of artemisinin.
abstract: Artemisinin is a sesquiterpene lactone with an endoperoxide function that is essential for its antimalarial activity. The DFT B3LYP method, together with the 6-31G(d) and 6-31+G(d,p) basis set, is employed to calculate a set of radical anions and neutral species supposed to be formed during the rearrangement of artemisinin from the two radicals (C-centered and O-centered) that are supposed to play a relevant role in the mechanism of action. The B3LYP results show that the primary and the secondary radicals centered on C(4), generated by homolytic break of the C(3)-C(4) bond and by 1,5 hydrogen shift, respectively, are more stable than radicals centered on oxygen. The calculations show that the activation barriers for rearrangements are low, leading to a thermodynamically favorable process. These results reinforce our previous conclusions based on semi-empirical calculations but also give additional information on the reductive decomposition of artemisinin.
authors.affiliation: Departamento de Saúde, Universidade Estadual de Feira de Santana, BA, Brazil.
authors.forename: Alex Gutterres
authors.initials: AG
authors.lastname: Taranto
authors.forename: José Walkimar
authors.initials: JW
authors.lastname: de Mesquita Carneiro
authors.forename: Martha Teixeira
authors.initials: MT
authors.lastname: de Araujo
mesh_terms: D000962:Antimalarials / Q000378:metabolism* / Q000494:pharmacology; D037621:Artemisinins / Q000378:metabolism* / Q000494:pharmacology; D003198:Computer Simulation; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D008433:Mathematics; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D012717:Sesquiterpenes / Q000378:metabolism* / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D006859:Hydrogen; C031327:artemisinin; D010100:Oxygen