Molecular Modeling Studies Of Bromopyrrole Alkaloids As Potential Antimalarial Compounds: A DFT Approach

The World Health Organization has reported about 214 million new cases of malaria with about 438,000 deaths worldwide in 2015. An example of antimalarial compounds isolated from plants, and is currently in use, may be mentioned quinine and artemisinin. However, one of the major problems that have arisen in recent years is the resistance of parasites against existing antimalarial drugs. Thus, there is a strong need to find new agents to control and to eradicate the disease. In this regard, marine organisms constitute a universally recognized source of potentially bioactive molecules, which have been enzymatically engineered and biologically validated. In this study, a quantitative structure–activity relationship (QSAR) analysis has been performed on data set of 14 bromopyrrole alkaloids (sponge metabolites) for antimalarial activity. Using density functional theory (DFT) several types of descriptors, including thermodynamics and electronic, have been calculated, in order to derive a quantitative relationship between antimalarial activity and structural properties. Simple and multiple regressions were used to generate the model. The best model (r2 = 0.97, Q2 = 0.86, F = 41.85) was obtained with descriptors as entropy, dipole momentum, molecular polarizability, HOMO energy softness, and electrophilic Index. The robustness of the QSAR models was verified by the leave-one-out cross-validation and external validation methods. The model obtained in this study should aid further study and could suggest some characteristics of novel potent bromopyrrole alkaloids against malaria

Molecular Interactions Between Polymer Matrices Of LLDPE/Chitosan/PELBD-G-Acrylamide: Computational Study

En este estudio, usando la Teoría del Funcional de la Densidad (DFT), las cargas NBO y la aproximación de la supermolécula, se han podido determinar las interacciones moleculares entre el polietileno lineal de baja densidad (PELBD) y el quitosano (Q), usando la modificación química del PELBD con acrilamida (AAm) como agente compatibilizante (PELBD-g-AAm). Los resultados obtenidos indican que en las moléculas de la mezcla de PELBD/Q están actuando fuerzas intermoleculares muy débiles del tipo Debye, mientras que entre las moléculas de Q/PELBD-gAAm se puede formar un complejo "estable" debido a la presencia de enlaces de hidrógenoBy using the Density Functional Theory (DFT), NBO charges and the “supermolecule”approach we have been able to determine the molecular interactions between low density linear polyethylene (LLDPE) and chitosan (Q), employing the chemical modification of PELBD with acrylamide (AAm) as a compatibilizing agent LLDPE-g-AAm). The obtained results indicate that in the molecules of the LLDPE/Ch blend are acting very weak intermolecular forces of Debye type, while among molecules of Q/ LLDPE-g-AAm blend may be forming a "stable" complex due to the presence of hydrogen bonds

Characterization and stabilization of the metastable phase of Calcium carbonate obtained by application of a layer of Bi2O2CO3:Al at room temperature

La cristalización de CaCO3 fue realizada por el método de difusión de gas en solución acuosa usando una capa insoluble de Bi2O2CO3 dopado con Al como agente director de la cristalización y con CaCl2 y (NH4)2CO3 como fuentes de iones Ca2+ y CO3 2- , respectivamente. La caracterización por difracción de rayos X de los polimorfos de CaCO3 permitió identificar la formación de las fases polimórficas calcita, aragonita y vaterita. La fase metaestable aragonita fue obtenida en bajas concentraciones, mientras que la fase metaestable vaterita fue favorecida con el aumento de partículas de Bi2O2CO3:Al en la reacción.The crystallization of CaCO3 was done by gas diffusion method in aqueous solution using an insoluble layered of Al doped Bi2O2CO3 as crystallization director agent and CaCl2 and (NH4)2CO3 as source of Ca2+ and CO3 2- ions, respectively. The characterization by X-ray diffraction of polymorphs CaCO3 allowed identifying the formation of the calcite, aragonite and vaterite polymorphic phases. The aragonite metastable phase was obtained in low concentrations, while the vaterite metastable phase was obtained with the rising of Bi2O2CO3:Al particles in the reactio

Computational study of [1,3] sigmatropic rearrangement of the (Z)-3-(4-(dimethylamino)benzyliden)thiocroman-4- one

This research is based on a computational study of a [1,3] sigmatropic intramolecular hydrogen rearrangement for (Z)-3-(4-(dimethylamino)benzylidene)thiochroman-4-one, applying the Density Functional Theory with the exchangecorrelation functional B3LYP and 6-31G(d,p) set basis using software package Gaussian 09W. Two possible suprafacials and anatarafacials migrations of the hydrogen atom bonded to ring thiopyran-4-one of the (Z)-3-(4-(Dimethylamino)- benzylidene)thiochroman-4-one were evaluated, results show an activation energy of 4 Kcal/mol which is more favorable for a transition state featuring characteristics related to a [1,2] suprafacial shift, in comparison with the amount of activation energy of a [1,3] antarafacial shift transition state

The mechanism of the gas-phase elimination kinetics of the β,γ-unsaturated aldehyde 2,2–dimethyl-3-butenal: a theoretical study

The study on the mechanism of the gas-phase elimination or thermal decomposition kinetics of 2, 2-dimethyl-3-butenal has been carried out by using theoretical calculation at MP2, combined ab initio CBSQB3 and DFT (B3LYP, B3PW91, MPW1PW91, PBEPBE, PBE1PBE, CAMB3LYP, M06, B97d) levels of theory. A good reasonable agreement between experimental and calculated parameters was obtained by using CAMB3LYP/6-311G(d,pd) calculations. The contrasted calculated parameters against experimental values suggested decarbonylation reaction to proceed through a concerted five-membered cyclic transition state type of mechanism, involving the hydrogen transfer from the carbonyl carbon to the gamma carbon, consistent with observed kinetic isotope effect. The breaking of alpha carbon–carbonyl carbon bond to produce carbon monoxide is 50% advanced in the transition state. The reaction mechanism may be described as a concerted moderately non-synchronous process. Examination of the Atoms in Molecules (AIM) analysis of electron density supports the suggested mechanism

Predicting new potential antimalarial compounds by using Zagreb topological indices

Molecular topology allows describing molecular structures following a two-dimensional approach by taking into account how the atoms are arranged internally through a connection matrix between the atoms that are part of a structure. Various molecular indices (unique for each molecule) can be determined, such as Zagreb, Balaban, and topological indices. These indices have been correlated with physical chemistry properties such as molecular weight, boiling point, and electron density. Furthermore, their relationship with a specific biological activity has been found in other reports. Therefore, its knowledge and interpretation could be critical in the rational design of new compounds, saving time and money in their development process. In this research, the molecular graph of antimalarials already in the pharmaceutical market, such as chloroquine, primaquine, quinine, and artemisinin, was calculated and used to compute the Zagreb indices; a relationship between these indices and the antimalarial activities was found. According to the results reported in this work, the smaller the Zagreb indices, the higher the antimalarial activity. This relationship works very well for other compounds series. Therefore, it seems to be a fundamental structural requirement for this activity. Three triazole-modified structures are proposed as possible potential antimalarials based on this hypothesis. Finally, this work shows that the Za