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The polyphenol compound Kaempferol, a relevant member of the class of flavonoids, is a good example where coordination to Zn(II) ion was found to improve the anticancer effects compared to the free ligand. Determination of the metal‐complex molecular structure (and binding sites on Kaempferol) in the liquid phase is fundamental for an understanding of biological activities. Experimental UV‐Vis and EPR data only provide indirect evidence or limited structural information. Therefore, theoretical study of structural and spectroscopic properties of the metal‐polyphenol complex, using computational quantum chemistry methods, is certainly relevant as starting point for the investigation of mechanism of action at a molecular level. In this article, we used the density functional theory (DFT) methodology to predict the molecular structure of [Zn(Kaempferol)(H2O)n]+ and [Zn(Kaempferol)2(H2O)n] complexes (n = 0, 2, or 4) and B‐ring nonplanar conformation of flavonoid using as strategy the best match between theoretical and experimental 1H NMR, IR, and UV‐Vis spectroscopic data in solution. These are valuable information for further studies involving structure‐activity relationship.

Nineteen 10-substitued deoxoartemisinin derivatives and artemisinin with activity against D-6 strains of malarial falciparum designated as Sierra Leone are studied. We use molecular electrostatic potential maps in an attempt to identify key structural features of the artemisinins that are necessary for their activities and molecular docking to investigate the interaction with the molecular receptor (heme). Chemometric modeling: Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), K-Nearest Neighbor (KNN), Soft Independent Modeling of Class Analogy (SIMCA) and Stepwise Discriminant Analysis (SDA) are employed to reduce dimensionality and investigate which subset of descriptors are responsible for the classification between more active (MA) and less active (LA) artemisinins. The PCA, HCA, KNN, SIMCA and SDA studies showed that the descriptors LUMO (Lowest Unoccupied Molecular Orbital) energy, DFeO1 (Distance between the O 1 atom from ligand and iron atom from heme), X1A (Average Connectivity Index Chi-1) and Mor15u (Molecular Representation of Structure Based on Electron Diffraction) code of signal 15, unweighted, are responsible for separating the artemisinins according to their degree of antimalarial activity. The prediction study was done with a new set of eight artemisinins by using the chemometric methods and five of them were predicted as active against D-6 strains of falciparum malaria. In order to verify if the key structural features that are necessary for their antimalarial activities were investigated for the interaction with the heme, we also carried out calculations of the molecular electrostatic potential (MEP) and molecular docking. MEP maps and molecular docking were analyzed for more active compounds of the prediction set.

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