NBO Analysis by ONIOM and DFT (B3LYP) Calculations of Intramolecular and Intermolecular Interactions of Artemisinin, Quinine and Thirteen Manzamenones with H<sub>2</sub>O or Alanine

Abstract

This work was undertaken to analyze intramolecular and intermolecular interactions of Manzamenones from natural bond orbitals (NBO method). For their use in the treatment of malaria, the results of these molecules are compared to those of Artemisinin and Quinine. Manzamenones are a class of atypical fatty acids. They are isolated from a marine sponge of the genus Plakortis kenyensis. The analysis of intramolecular interactions compares the results of each molecule (Manzamenones, Artemisinin and Quinine) in the non-complexed state with those of its complex with a water molecule. Thus, for the same electron donors (i) and associated acceptors (j), the electron density (ED), stabilization energy E2 related to the delocalization of i to j, the energies of the NBO orbitals εi and εj of the donor and acceptor, respectively, and element of the Fock matrix Fi,j are determined and compared. The change in E2 is used to deduce whether or not the molecule is stabilized after complex formation. These analyses allowed to match each Manzamenone to one of the two antimalarials. The intermolecular interactions were analyzed, for each molecule (Manzamenones, Artemisinin and Quinine), in two complexes. These complexes are obtained with a water molecule on the one hand and with an alanine molecule on the other hand. For these interactions, the electron donor and its electron density, the electron acceptor and its electron density as well as the donor—acceptor stabilization energy have been calculated. The ONIOM 2 method is used to study Manzamenones. Theoretical calculations were done using density functional theory (B3LYP) by combining one of the two function bases 6-31++G(d,p) and 6-31+G(d,p).