2D-quantitative structure–activity relationships model using PLS method for anti-malarial activities of anti-haemozoin compounds

Background Emergence of cross-resistance to current anti-malarial drugs has led to an urgent need for identification of potential compounds with novel modes of action and anti-malarial activity against the resistant strains. One of the most promising therapeutic targets of anti-malarial agents related to food vacuole of malaria parasite is haemozoin, a product formed by the parasite through haemoglobin degradation. Methods With this in mind, this study developed two-dimensional-quantitative structure–activity relationships (QSAR) models of a series of 21 haemozoin inhibitors to explore the useful physicochemical parameters of the active compounds for estimation of anti-malarial activities. The 2D-QSAR model with good statistical quality using partial least square method was generated after removing the outliers. Results Five two-dimensional descriptors of the training set were selected: atom count (a_ICM); adjacency and distance matrix descriptor (GCUT_SLOGP_2: the third GCUT descriptor using atomic contribution to logP); average total charge sum (h_pavgQ) in pKa prediction (pH = 7); a very low negative partial charge, including aromatic carbons which have a heteroatom-substitution in “ortho” position (PEOE_VSA-0) and molecular descriptor (rsynth: estimating the synthesizability of molecules as the fraction of heavy atoms that can be traced back to starting material fragments resulting from retrosynthetic rules), respectively. The model suggests that the anti-malarial activity of haemozoin inhibitors increases with molecules that have higher average total charge sum in pKa prediction (pH = 7). QSAR model also highlights that the descriptor using atomic contribution to logP or the distance matrix descriptor (GCUT_SLOGP_2), and structural component of the molecules, including topological descriptors does make for better anti-malarial activity. Conclusions The model is capable of predicting the anti-malarial activities of anti-haemozoin compounds. In addition, the selected molecular descriptors in this QSAR model are helpful in designing more efficient compounds against the P. falciparum 3D7A strain.

Group contribution and atomic contribution models for the prediction of various physical properties of deep eutectic solvents

The urgency of advancing green chemistry from labs and computers into the industries is well-known. The Deep Eutectic Solvents (DESs) are a promising category of novel green solvents which simultaneously have the best advantages of liquids and solids. Furthermore, they can be designed or engineered to have the characteristics desired for a given application. However, since they are rather new, there are no general models available to predict the properties of DESs without requiring other properties as input. This is particularly a setback when screening is required for feasibility studies, since a vast number of DESs are envisioned. For the first time, this study presents five group contribution (GC) and five atomic contribution (AC) models for densities, refractive indices, heat capacities, speeds of sound, and surface tensions of DESs. The models, developed using the most up-to-date databank of various types of DESs, simply decompose the molecular structure into a number of predefined groups or atoms. The resulting AARD% of densities, refractive indices, heat capacities, speeds of sound and surface tensions were, respectively, 1.44, 0.37, 3.26, 1.62, and 7.59% for the GC models, and 2.49, 1.03, 9.93, 4.52 and 7.80% for the AC models. Perhaps, even more importantly for designer solvents, is the predictive capability of the models, which was also shown to be highly reliable. Accordingly, very simple, yet highly accurate models are provided that are global for DESs and needless of any physical property information, making them useful predictive tools for a category of green solvents, which is only starting to show its potentials in green technology.

Wilson statistics

In a very traditional village game, popular over the period of Lent (usually on the pigñata day, the first Sunday of Lent), a young player, suitably blindfolded and armed with a long cudgel, tries to hit a pot (the pigñata) located some distance away, in order to win the sweetmeats contained inside. To break the pot they take random steps, and at each step they try to hit the pot with the cudgel. Is it possible to guess the distance of the player from their starting position after n random steps? Is it possible to guess the direction of the vectorial resultant of the n steps? A very simple analysis of the problem suggests that the distance after n steps may be estimated but the direction of the resultant step cannot, because a preferred privileged orientation does not exist. The situation is very similar to structure factor statistics. Each of the N atoms in the unit cell provides the vectorial contribution . . . fj = fj exp(2πih · rj) = fj exp(i θj). . . to the structure factor; this is equivalent to a vectorial step of the pigñata player. The modulus of the atomic contribution, like the amplitude of the step in the pigñata game, is known (because the chemical composition of the molecules in the unit cell is supposed to be known), but the phase θj (corresponding to the direction of the step) remains unknown; indeed we do not know the position rj of the j th atom. The analogy with the pigñata game suggests that some information on the moduli of the structure factors can be obtained via a suitable statistical approach, while no phase information can be obtained using this approach. This chapter deals just with this statistical approach and owing to the relevant contributions of A. J. C. Wilson, we call this chapter Wilson statistics.

Atomic Contribution to Valence Band Density of States in Gallium Oxide and Silicon Oxide Nano Layered Films

High resolution X-ray photoelectron spectroscopy (XPS) is used to investigate the spectra of nanolayered films. Amorphous gallium oxide (Ga2O3)-silicon dioxide (SiO2) nanolayered thin films are grown using ultrahigh vacuum radio frequency (rf) magnetron sputtering on sapphire substrates at room temperature. Films are layered with 15-angstrom Ga2O3 oxide and 75-angstrom SiO2 for a total of 10 layers. Referring to atomic core levels, atomic contribution to valence band density of states is experimentally nominated. This analytical technique has particular applicability to the evaluation of the density of states with atomic contributions.

Structure determination of quasicrystals and neutron scattering

We review the use of neutron scattering in the structure determination of quasicrystals. The contrast between X-ray and neutron cross-section gives a useful complementary information. When feasible, contrast variation techniques allow to disentangle the different atomic contribution. Diffuse scattering studies are also simplified, thanks to the possibility of an energy analysis. We discuss results obtained in the case of the i-AlPdMn phase.