Analysis of the Electron Density of a Water Molecule Encapsulated by Two Cholic Acid Residues.

Cholic acid is a trihydroxy bile acid with a nice peculiarity: the average distance between the oxygen atoms (O7 and O12) of the hydroxy groups located at C7 and C12 carbon atoms is 4.5 Å, a value which perfectly matches with the O/O tetrahedral edge distance in Ih ice. In the solid phase, they are involved in the formation of hydrogen bonds with other cholic acid units and solvents. This fact was satisfactorily used for designing a cholic dimer which encapsulates one single water molecule between two cholic residues, its oxygen atom (Ow) being exactly located at the centroid of a distorted tetrahedron formed by the four steroid hydroxy groups. The water molecule participates in four hydrogen bonds, with the water simultaneously being an acceptor from the 2 O12 (hydrogen lengths are 2.177 Å and 2.114 Å) and a donor towards the 2 O7 (hydrogen bond lengths are 1.866 Å and 1.920 Å). These facts suggest that this system can be a nice model for the theoretical study of the formation of ice-like structures. These are frequently proposed to describe the water structure found in a plethora of systems (water interfaces, metal complexes, solubilized hydrophobic species, proteins, and confined carbon nanotubes). The above tetrahedral structure is proposed as a reference model for those systems, and the results obtained from the application of the atoms in molecules theory are presented here. Furthermore, the structure of the whole system allows a division into two interesting subsystems in which water is the acceptor of one hydrogen bond and the donor of another. The analysis of the calculated electron density is performed through its gradient vector and the Laplacian. The calculation of the complexation energy used correction of the basis set superposition error (BSSE) with the counterpoise method. As expected, four critical points located in the H…O bond paths were identified. All calculated parameters obey the proposed criteria for hydrogen bonds. The total energy for the interaction in the tetrahedral structure is 54.29 kJ/mol, while the summation obtained of the two independent subsystems and the one between the alkyl rings without water is only 2.5 kJ/mol higher. This concordance, together with the calculated values for the electron density, the Laplacian of the electron density, and the lengths of the oxygen atom and the hydrogen atom (involved in the formation of each hydrogen bond) to the hydrogen bond critical point, suggests that each pair of hydrogen bonds can be considered independent of each other.

Effect of Gold Nanoparticles on the Physical Properties of an Epoxy Resin.

The effect of doping the bisphenol A diglycidyl ether (DGEBA)/m-xylylenediamine (mXDA) system with gold nanoparticles (AuNP) has been studied with differential scanning calorimetry (DSC), thermogravimetric analysis, dynamic mechanical analysis (DMA), and dielectric analysis (DEA). The evolved heat (ΔHt), the glass transition temperature (Tg), and the associated activation energies of this relaxation process have been determined. Below a certain concentration of AuNPs (=8.5%, in mg AuNP/g epoxy matrix), Tg decreases linearly with the concentration of AuNPs, but above it, Tg is not affected. The degree of conversion α of this epoxy system was analyzed by the semiempirical Kamal's model, evidencing that diffusion correction is required at high values of α. Activation energy values suggest that AuNPs can cause some impediments at the beginning of the crosslinking process (n-order mechanism). The slight difference between the initial decomposition temperature, as well as the temperature for which the degradation rate is at a maximum, for both systems can be accepted to be within experimental error. Mechanical properties (tension, compression, and bending tests) are not affected by the presence of AuNPs. Dielectric measurements show the existence of a second Tg at high temperatures, which was analyzed using the Tsagarapoulos and Eisenberg model of the mobility restrictions of network chains bound to the filler.

Efficient Synthesis of 2-Aminopyridine Derivatives: Antibacterial Activity Assessment and Molecular Docking Studies.

A new and suitable multicomponent one-pot reaction was developed for the synthesis of 2-amino-3-cyanopyridine derivatives. BACKGROUND: This synthesis was demonstrated by the efficient and easy access to a variety of substituted 2-aminopyridines using enaminones as key precursors under solvent-free conditions. METHODS: A range of spectroscopic techniques was used to determine and confirm the chemical structures (FTIR, 1H NMR, 13C NMR). The antimicrobial potency of synthesized compounds (2a-d) was tested using disk diffusion assays, and the Minimum Inhibitory Concentration (MIC) for the active compounds was determined against a panel of microorganisms, including Gram-positive and Gram-negative bacteria and yeasts. Moreover, a docking analysis was conducted by Molecular Operating Environment (MOE) software to provide supplementary information about the potential, as well as an ADME-T prediction to describe the pharmacokinetic properties of the best compound and its toxicity. RESULTS: The results of the antimicrobial activity indicated that compound 2c showed the highest activity against Gram-positive bacteria, particularly S. aureus and B. subtilis whose MIC values were 0.039 ± 0.000 µg·mL-1. The results of the theoretical study of compound 2c were in line with the experimental data and exhibited excellent antibacterial potential. CONCLUSIONS: On the basis of the obtained results, compound 2c can be used as an antibacterial agent model with high antibacterial potency.

Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study.

Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et3NH][HSO4])-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 4(a-f) and 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a-f). All the synthesized derivatives 4(a-f) and 6(a-f) were evaluated for their in vitro antifungal and antibacterial activity, by method recommended by National Committee for Clinical Laboratory Standards (NCCLS). The compound 6c bearing a fluoro group on the chromone ring and oxygen and a hydrazino group (-NHNH2) on the pyrimidine ring, was found to be the most potent antibacterial compound amongst the synthesized derivatives. The compound 6f bearing a methoxy group (-OCH3) on the chromone ring and sulphur group on the pyrimidine ring, was found to exhibit equipotent antifungal activity when compared with the standard drug miconazole. A D-alanine-D-alanine ligase (DdlB) enzyme assay study and an ergosterol extraction and quantitation assay study were performed to predict the mode of action of the synthesized compounds. A molecular docking study was performed to predict the binding interactions with receptors and mode of action of the synthesized derivatives. Further, analysis of the ADMET parameters for the synthesized compounds has shown that these compounds have good oral drug-like properties and can be developed as oral drug candidates. To establish the antimicrobial selectivity and safety, the most active compounds 6c and 6f were further tested for cytotoxicity against the human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 6c and 6f and the results indicated that the compounds are non-toxic in nature.

Ionic Liquid-Catalyzed Green Protocol for Multi-Component Synthesis of Dihydropyrano[2,3-c]pyrazoles as Potential Anticancer Scaffolds.

A series of 6-amino-4-substituted-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles 5a-j were synthesized via one-pot, four-component condensation reactions of aryl aldehydes 1a-j, propanedinitrile (2), hydrazine hydrate (3) and ethyl acetoacetate (4) under solvent-free conditions. We report herein the use of the Brønsted acid ionic liquid (BAIL) triethylammonium hydrogen sulphate [Et3NH][HSO4] as catalyst for this multi-component synthesis. Compared with the available reaction methodology, this new method has consistent advantages, including excellent yields, a short reaction time, mild reaction conditions and catalyst reusability. Selected synthesized derivatives were evaluated for in vitro anticancer activity against four human cancer cell lines viz. melanoma cancer cell line (SK-MEL-2), breast cancer cell line(MDA-MB-231), leukemia cancer cell line (K-562) and cervical cancer cell line (HeLa). Compounds 5b, 5d, 5g, 5h and 5j exhibited promising anticancer activity against all selected human cancer cell lines, except HeLa. Molecular docking studies also confirmed 5b and 5d as good lead molecules. An in silico ADMET study of the synthesized anticancer agents indicated good oral drug-like behavior and non-toxic nature.

Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study.

The work reports the synthesis under solvent-free condition using the ionic liquid [Et3NH][HSO4] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2-onederivatives 4a-o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, ¹H-NMR, 13C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their in vitro antifungal and antibacterial activity. The compound 4k bearing 4-hydroxy-3-ethoxy group on the phenyl ring was found to be the most active antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring was found to be the most active antibacterial agent. The mode of action of the most promising antifungal compound 4k was established by an ergosterol extraction and quantitation assay. From the assay it was found that 4k acts by inhibition of ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which suggests that the tested compounds inhibit the synthesis of this enzyme. The synthesized compounds were analyzed for in silico ADMET properties to establish oral drug like behavior and showed satisfactory results. To establish the antimicrobial selectivity and safety, the most active compounds 4e and 4k were further tested for cytotoxicity against human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 4e and 4k and results indicated that the compounds are non-toxic.

Triacylglyceride, antioxidant and antimicrobial features of virgin Camellia oleifera, C. reticulata and C. sasanqua Oils.

Virgin oils obtained from seeds of Camellia oleifera (CO), Camellia reticulata (CR) and Camellia sasanqua (CS) were studied for their triacylglyceride composition, antioxidant and antimicrobial activities. Levels of fatty acids determined by ¹H-nuclear magnetic resonance analysis were similar to those reported for olive oils (82.30%-84.47%; 5.69%-7.78%; 0.26%-0.41% and 8.04%-11.2%, for oleic, linoleic, linolenic and saturated acids, respectively). The CR oil showed the best antioxidant potential in the three in vitro models tested. With regard to EC50 values (µg/mL), the order in DPPH radical-scavenging was CR (33.48) < CO (35.20) < CS (54.87). Effectiveness in reducing power was CR (2.81) < CO (3.09) < CS (5.32). IC50 for LPO inhibition were 0.37, 0.52 and 0.75 µg/mL for CR, CO and CS, respectively. All the oils showed antimicrobial activity, and exhibited different selectivity and MICs for each microorganism tested (E. coli, B. cereus and C. albicans). B. cereus was the less sensitive species (MIC: 52.083 ± 18.042 for CO; 41.667 ± 18.042 for CR; 104.167 ± 36.084 for CS mg/mL) and the E. coli was the most sensitive to camellia oil's effect. The standard gentamicin presented higher MIC for E. coli (4.2) than the CR (MIC= 2.6) and CO (MIC = 3.9) oils.