Artemisinin and some derivatives with activity against D-6 strains of Plasmodium falciparum were studied. Molecular electrostatic potential (MEP) maps were used in an attempt to identify key features of the compounds that are necessary for their activities, and then use those to propose new artemisinin derivatives. The partial least squares (PLS) method was then used to generate a predictive model. The PLS model with three latent variables explaining 88.9% of total variance, with Q((2)) = 0.839 and R(2) = 0.935, was obtained for 15/6 compounds in the training/external validation set. For construction of the model, the most important descriptors were the highest occupied molecular orbital (HOMO) energy, atomic charges on the atoms O1 (Q(1)) and C3 (Q(3)), molecular volume (VOL), and hydrophilic index (HYF). From a set of 20 proposed artemisinin derivatives, one new compound (39) with higher antimalarial activity than the molecules initially studied was predicted. Synthesis of these new derivatives may follow the results of the MEP maps studied and the PLS modeling.

This work employed computational chemistry to study dispiro-1,2,4-trioxolanes with antimalarial activities against K-1 strains of Plasmodium falciparum. Molecules were optimized with B3LYP/6-31G* method. Maps of molecular electrostatic potential helped to identify features related to their activities. Molecular docking was performed to study the complex formed. A predictive model was generated by PLS method, with three latent variables explaining 99.8% of the total variance, Q 2 = 0 87, R 2 = 0 85, obtained for 16/4 molecules in the training/external validation set. The descriptors selected for the model were the binding free energy, logarithm of octanol-water partition coefficient (logP ) and molecular volume. As an application, we tested our PLS model to predict the pIC 50 of 20 dispiro-1,2,4-trioxolanes whose biological tests were not performed with them yet. Three compounds showed higher antimalarial activity than artemether and artesunate.

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In previous articles we reported through theoretical studies the piezoelectric effect in BaTiO3, SmTiO3, and YFeO3. In this paper, we used the Douglas-Kroll-Hess (DKH) second-order scalar relativistic method to investigate the piezoelectricity in YTiO3. In the calculations we used the [6s4p] and [10s5p4d] Gaussian basis sets for the O (3P) and Ti (5S) atoms, respectively, from the literature in combination with the (30s21p16d)/[15s9p6d] basis set for the Y (3D) atom, obtained by generator coordinate Hartree-Fock (GCHF) method, and they had their quality evaluated using calculations of total energy and orbital energies (HOMO and HOMO-1) of the 2TiO+1 and 1YO+1 fragments. The dipole moment, the total energy, and the total atomic charges in YTiO3 in Cs space group were calculated. When we analyze those properties we verify that it is reasonable to believe that YTiO3 does not present piezoelectric properties.