Evaluation interaction of graphene oxide with heparin for antiviral blockade: a study of ab initio simulations, molecular docking, and experimental analysis.

CONTEXT: Heparin, one of the drugs reused in studies with antiviral activity, was chosen to investigate a possible blockade of the SARS-CoV-2 spike protein for viral entry through computational simulations and experimental analysis. Heparin was associated to graphene oxide to increase in the binding affinity in biological system. First, the electronic and chemical interaction between the molecules was analyzed through ab initio simulations. Later, we evaluate the biological compatibility of the nanosystems, in the target of the spike protein, through molecular docking. The results show that graphene oxide interacts with the heparin with an increase in the affinity energy with the spike protein, indicating a possible increment in the antiviral activity. Experimental analysis of synthesis and morphology of the nanostructures were carried out, indicating heparin absorption by graphene oxide, confirming the results of the first principle simulations. Experimental tests were conducted on the structure and surface of the nanomaterial, confirming the heparin aggregation on the synthesis with a size between the GO layers of 7.44 Å, indicating a C-O type bond, and exhibiting a hydrophilic surface characteristic (36.2°). METHODS: Computational simulations of the ab initio with SIESTA code, LDA approximations, and an energy shift of 0.05 eV. Molecular docking simulations were performed in the AutoDock Vina software integrated with the AMDock Tools Software using the AMBER force field. GO, GO@2.5Heparin, and GO@5Heparin were synthesized by Hummers and impregnation methods, respectively, and characterized by X-ray diffraction and surface contact angle.

Ab initio study of water anchored in graphene pristine and vacancy-type defects.

CONTEXT: In this paper, we have addressed two issues that are relevant to the interaction of water in pristine and vacant graphene through first-principles calculations based on the Density Functional Theory (DFT). The results showed that for the interaction of pristine graphene with water, the DOWN configuration (with the hydrogen atoms facing downwards) was the most stable, presenting binding energies in the order of -13.62 kJ/mol at a distance of 2.375 Å in the TOP position. We also evaluated the interaction of water with two vacancy models, removing one carbon atom (Vac-1C) and four atoms (Vac-4C). In the Vac-1C system, the most favourable system was the DOWN configuration, with binding energies ranging from -20.60 kJ/mol to -18.41 kJ/mol in the TOP and UP positions, respectively. A different behaviour was observed for the interaction of water with Vac-4C; regardless of the configuration of the water, it is always more favourable for the interaction to occur through the vacancy centre, with binding energies ​​between -13.28 kJ/mol and -20.49 kJ/mol. Thus, the results presented open perspectives for the technological development of nanomembranes as well as providing a better understanding of the wettability effects of graphene sheets, whether pristine or with defects. METHOD: We evaluated the interaction of pristine and vacant graphene with the water molecule, through calculations based on Density Functional Theory (DFT); implemented by the SIESTA program. The electronic, energetic, and structural properties were analyzed by solving self-consistent Kohn-Sham equations. In all calculations, a double ζ plus a polarized function (DZP) was used for the numerical baise set. Local Density Approximation (LDA) with the Perdew and Zunger (PZ) parameterisation along with a basis set superposition error (BSSE) correction were used to describe the exchange and correlation potential (Vxc). The water and isolated graphene structures were relaxed until the residual forces were less than 0.05 eV/Å-1 in all atomic coordinates.

Graphene oxide and flavonoids as potential inhibitors of the spike protein of SARS-CoV-2 variants and interaction between ligands: a parallel study of molecular docking and DFT.

Nanocarriers allow the connection between biomolecules and other structures to enhance the treatment efficacy, through the biomolecule's properties to an existing drug, or to allow a better and specific delivery. Apigenin and orientin are biomolecules with excellent therapeutic properties that are proposed in the fight against COVID-19. Besides that, graphene oxide is a nanomaterial that exhibits antiviral activity and is used as a nanocarrier of several drugs. We evaluated in this work, through molecular docking, the binding affinity between these structures to the receptor-binding domain of spike protein of two coronavirus variants, Delta and Omicron. The results indicate that all the structures exhibit affinity with the two protein targets, with binding affinity values of -11.88 to -6.65 kcal/mol for the Delta variant and values of -9.58 to -13.20 kcal/mol for the Omicron variant, which is a successful value as found in the literature as a potential inhibitor of SARS-CoV-2 infection. Also, through first-principles calculations based on Density Functional Theory, the interaction of graphene oxide with the biomolecules apigenin and orientin occurred. The results exhibit weak binding energy, which indicates that physical adsorption occurs, with better results when the biomolecule is set in parallel to the nanomaterial due to attractive π-π staking. These results are conducive to the development of a nanocarrier.

Comparison of three cyclodextrins to optimize bisphenol A extraction from source water: Computational, spectroscopic, and analytical studies.

Computationally and spectroscopically assisted analytical comparative investigation into the extraction of bisphenol A using three cyclodextrins, that is, α, ß, and γ respectively, were performed. A simple, self-tailored µ-solid-phase extraction podium was used to extract bisphenol A from water samples, and high-performance liquid chromatography-ultraviolet was used for the qualitative and quantitative analysis of bisphenol A. Density functional theory first principle calculations, attenuated total reflectance Fourier-transform infrared spectroscopy and Fourier-transform Raman spectroscopy data supports the analytical selection of ß-cyclodextrin as the adsorbent for bisphenol A extraction. Analytical optimization of various parameters including sample volume, sample pH, eluting solvent and its volume was performed to discover the most proper conditions for maximum extraction. Under the optimized conditions, a limit of detection value of 0.70 ng/ml and a limit of quantification value of 2.31 ng/ml was achieved with ß-cyclodextrin, with recovery (%) values over 98.40-102.50 in real source water samples. Overall, well assisted by comprehensive computational and spectroscopic studies, a novel, simple, sensitive and economic analytical method was developed for the extraction of bisphenol A from source water using cyclodextrin.

Influence of magnetite incorporation into chitosan on the adsorption of the methotrexate and in vitro cytotoxicity.

Emerging pollutants are a group of substances involved in environmental contamination resulting mostly from incomplete drug metabolism, associated with inadequate disposal and ineffective effluent treatment techniques. Methotrexate (MTX), for instance, is excreted at high concentrations in unchanged form through the urine. Although the MTX is still effective in cancer and autoimmune disease treatment, this drug shows the ability of bioaccumulation and toxicity to the organism. Thus, the present work aimed to evaluate the adsorption of the MTX drug onto magnetic nanocomposites containing different amounts of incorporated magnetite (1:1, 1:5, and 1:10 wt%), combining the theoretical-experimental study as well as the in vitro cytotoxicity. Moreover, equilibrium studies (Langmuir, Freundlich, Temkin, Dubinin-Radushkevich, Hill, Redlich-Peterson, and Sips), kinetic (PFO, PSO, and IPD), and thermodynamic (ΔG°, ΔH°, and ΔS°) were used to describe the experimental data, and ab initio simulations were employed in the theoretical study. Magnetic nanocomposites were synthesized by the co-precipitation method using only FeCl2 as the iron precursor. Adsorbents were characterized by FTIR, XRD, Raman, SEM-EDS, BET, and VSM analysis. Meanwhile, cytotoxic effects on L929 and A375 cell lines were evaluated through MTT, NR, and LDH assays. The adsorption of the MTX was carried out in a typical batch system, exploring the different experimental conditions. The theoretical study suggests the occurrence of chemisorption between CS·Fe3O4-MTX. The maximum adsorption capacity of MTX was 285.92 mg g-1, using 0.125 g L-1 of CS·Fe3O4 1:1, with an initial concentration of the MTX (50 mg L-1), pH 4.0 at 293 ± 1.00 K. The best adjustment of equilibrium and kinetic data were the Sips (low values for statistical errors) and PSO (qe = 96.73 mg g-1) models, respectively. Thermodynamic study shows that the adsorption occurred spontaneously (ΔG° < 0), with exothermic (ΔH° = - 4698.89 kJ mol-1) and random at the solid-solution interface (ΔS° = 1,476,022.00 kJ mol-1 k-1) behavior. Finally, the in vitro study shows that magnetic nanomaterials exhibit higher cytotoxicity in melanoma cells. Therefore, the magnetic nanocomposite reveals to be not only an excellent tool for water remediation studies but also a promising platform for drug delivery.

Theoretical study of small aromatic molecules adsorbed in pristine and functionalised graphene.

Small aromatic molecules are precursors for several biological systems such as DNA, proteins, drugs, and are also present in several pollutants. The understanding of the interaction of these small aromatic molecules with pristine and functionalised graphene (fGr) can generate different applications. We performed ab initio simulations based on the density functional theory to evaluate the interaction between the aromatic compounds, benzene, benzoic acid, aniline and phenol, with pristine and fGr. The results show that the binding energy for all cases is less than 103.24 kJ/mol (1.07 eV) without substantial modification of the electronic properties, indicating that the interaction occurs through a physical adsorption regime. The results are promising because they suggest that pristine graphene and functionalised graphene are suitable for removing these pollutants, or for carrying molecules for biological applications influenced by π-π and H-bonds interaction.

Interactions of graphene derivatives with glutamate-neurotransmitter: A parallel first principles - Docking investigation.

Glutamate plays an important role in excitatory neurotransmission, learning, and memory processes, and under pathological conditions it is directly associated with several chronic neurological disorders, such as depression, epilepsy, schizophrenia, and Parkinson's. Therefore, the detection and quantification of Glutamate is important for the rapid diagnosis of these diseases. Using first principles and molecular docking simulations we have evaluated the energetic, structural, and binding properties of graphene derivatives, such as pristine graphene (pristine-Gr) and oxidized graphene with carboxylic (Gr-COOH), carbonyl (Gr-COH), hydroxyl (Gr-OH), and epoxy (-O-) groups interacting with the glutamate neurotransmitter. The calculated binding affinity free energies from the docking complexes (glutamate-graphene family) suggest higher oxidized graphene-based glutamate molecular recognition than the pristine-Gr, with the following order of oxidized graphene derivatives according to ab initio results: (Gr-O∼Gr-COOH ∼ Gr-COH > Gr-OH)>pristine-Gr. Herein, the ab initio binding energies found for the glutamate-graphene family complexes are in the range of 0.24-0.80 eV. The configurations studied showed a biophysical adsorption regime without significant changes in the physico-chemical properties of the adsorbed glutamate neurotransmitter, in accordance with the general acceptance criteria of the detection systems.

Cytoprotection of lipoic acid against toxicity induced by saxitoxin in hippocampal cell line HT-22 through in silico modeling and in vitro assays.

Saxitoxins (STXs) are potent neurotoxins that block voltage-gated channels in neurons and induce cytotoxicity. These toxins not only can generate reactive oxygen species but also can alter antioxidant levels, promoting oxidative stress. Under this pro-oxidant situation, the use of the antioxidant lipoic acid (LA) can represent a chemoprotective alternative to minimize the deleterious effects induced by neurotoxins as STXs. P-glycoprotein (P-gp) is a well-known ATP-binding cassette (ABC) transporter that plays a crucial role in the extrusion of toxic substances, decreasing their accumulation and potential intracellular effects in virtue of its broad substrate specificity, its expression in many excretory tissues and its large efflux capacity. The interaction of STXs with LA was evaluated by ab initio simulation, molecular docking and bioassays using the cell line HT-22. The interaction of STXs with LA occurs by physisorption. Molecular docking indicated that STXs can be a substrate of P-gp and, estimating the Free Energy of Binding (FEB), LA has lower amino acids residues binding sites, similar to verapamil, while STX and STX+LA_1 have similar amino acids residues and binding sites with similar FEB between this ligands.Cells were exposed to STXs and LA for 30min and 24h. LA treatment minimizes STX cytotoxicity, evaluated by trypan blue and MTT assay and both STX and STX-LA treatments were efficient to induce P-gp activity measured by rhodamine 123 dye extrusion. LA and STX+LA treatments induced low reactive oxygen species levels and low oxygen consumption. Based on our results, it can be concluded that LA was able to induce cytoprotection, including induction of cellular glutathione levels, and that STX+LA interaction reduced toxicity effects induced by STX. Overall, the in vitro results corroborated the semi-empirical evidences found using density functional theory ab initio simulation and molecular docking.