Affoué Lucie Bédé¹, Amon Benjamine Assoma¹, El Hadji Sawaliho Bamba^1,, Maftei Dan², Ionel Humelnicu²

This study is part of the search for solutions to the resistance of the parasite to antimalarials. The aim of this work is to analyze the relative stability and reactivity of adducts in order to understand the resistance of the parasite to artemisinin. The DFT/B3LYP/GenECPs method associated with bases 6-31G, 6-31G ** and LANL2DZ is used to perform these calculations. On one hand analysis of the thermodynamic quantities of formation and reaction revealed that β adduct is the most stable among the studied adducts. In other words, the latter is the majority product of the interaction between heme and artemisinin. On the other hand, the adduct γ is the least stable. The values of the pameters such as dipole moments, intramolecular hydrogen bond lengths and thermodynamic parameters (formation and reaction quantities) have shown that it can exist a correlation between the following three parameters those are the relative stability of adducts (α, β, δ), their dipole moment and the binding intramolecular hydrogen. The analysis of the Frontier Molecular Orbitals also showed that the β adduct is susceptible to electrophilic attack, unlike the γ adduct, which is rather favorable to nucleophilic attack and can be the most excited component. Moreover, the determination of the alkylation rate will be considered in order to specify the order of complexation of the meso positions α, β and δ of the heme.

malaria, adducts, heme, artemisinin, DFT/B3LYP/genECPs