Solubility and preferential solvation of acetaminophen in methanol + water mixtures at 298.15 K

The equilibrium solubility of acetaminophen in methanol + water binary mixtures at 298.15 K was determined and correlated with the Jouyban–Acree model. Preferential solvation parameters by methanol (δx_1,3) were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals method. δx_1,3 values are negative in water-rich mixtures but positive in compositions from 0.32 in mole fraction of methanol to pure methanol. It is conjecturable that in the former case, the hydrophobic hydration around non-polar groups plays a relevant role in the solvation. The higher solvation by methanol in mixtures of similar cosolvent compositions and methanol-rich mixtures could be explained in terms of the higher basic behavior of this cosolvent.     

Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.     

The synergistic co‐operation of N—H…O=P hydrogen bonds and C—H…OX weak intermolecular interactions (X is =P or —C) in the (CH3O)2P(O)(NH–NHC6F5) amidophosphoester: a combined X‐ray crystallographic and theoretical study

The asymmetric unit of O,O′‐dimethyl [(2,3,4,5,6‐pentafluorophenyl)hydrazinyl]phosphonate, C₈H₈F₅N₂O₃P, is composed of two symmetry‐independent molecules with significant differences in the orientations of the C₆F₅ and OMe groups. In the crystal structure, a one‐dimensional assembly is mediated from classical N—H…O hydrogen bonds, which includes R₂²(8), D(2) and some higher‐order graph‐set motifs. By also considering weak C—H…O=P and C—H…O—C intermolecular interactions, a two‐dimensional network extends along the ab plane. The strengths of the hydrogen bonds were evaluated using quantum chemical calculations with the GAUSSIAN09 software package at the B3LYP/6‐311G(d,p) level of theory. The LP(O) to σ*(NH) and σ*(CH) charge‐transfer interactions were examined according to second‐order perturbation theory in natural bond orbital (NBO) methodology. The hydrogen‐bonded clusters of molecules, including N—H…O and C—H…O interactions, were constructed as input files for the calculations and the strengths of the hydrogen bonds are as follows: N—H…O [R₂²(8)] > N—H…O [D(2)] > C—H…O. The decomposed fingerprint plots show that the contribution portions of the F…H/H…F contacts in both molecules are the largest.     

New route to 2-arylthieno[2,3-d]pyrimidin-4(3H)-ones and isolation of the unoxidized intermediates

Abstract  A new route to the synthesis of 2-arylthieno[2,3-d]pyrimidin-4(3H)-ones has been developed through heterocyclization of 2-amino-4,5-dimethylthiophene-3-carboxamide with aromatic aldehydes in boiling glacial acetic acid followed by air oxidation. The unoxidized intermediates, 2-aryl-2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones, are isolated when the reactions are carried out either at room temperature or under a nitrogen atmosphere. Graphical Abstract        

Simultaneous determination of valproic acid and its main metabolite in human plasma using a small scale dispersive liquid–liquid microextraction followed by gas chromatography–flame ionization detection

A simple, sensitive, and rapid analytical method has been developed and validated for the extraction and quantification of valproic acid and its main metabolite (3-heptanone) in human plasma. Initially, the proteins of plasma were precipitated with trifluoroacetic acid. Then a very small volume of a water-immiscible extractant and acetonitrile was mixed and rapidly injected into the pre-treated plasma sample. For further turbidity (dispersion of the extractant into sample solution), the cloudy solution was vortexed. After centrifugation, the settled phase was injected into gas chromatography-flame ionization detection. The effective parameters, such as type and volume of extraction and disperser solvents, vortex time, and pH were studied and optimized. The limits of detection of valproic acid and 3-heptanone were obtained, 0.065 and 0.015 mg L^?1, respectively. An acceptable precision was obtained for a concentration of 2 mg L^?1 of each analyte (relative standard deviation?≤?8%). The average absolute recoveries (n?=?3) of valproic acid and 3-heptanone were 52?±?2 and 42?±?1%, respectively. The validated method has been successfully used in analysis of the analytes in human plasma samples.     

Characterization and Molecular Docking Study of New 4-Acetamidoalkyl Pyrazoles As B-Raf /Cox-2 Inhibitors

Several new 4-acetamidoalkyl pyrazoles are synthesized by an efficient, one-pot three-component reaction of 3,5-dimethyl-1-phenyl-1H-pyrazole or 3-methyl-1-phenyl-1H-pyrazol-5-ol, aromatic aldehydes, and acetonitrile in the presence of chlorosulfonic acid at room temperature. The products are characterized based on IR, ¹H and ¹³C NMR data and evaluated as potential COX-2 and B-Raf inhibitors by molecular docking studies. All the products showed the potency of B-Raf and COX-2 inhibitory effects with a greater binding affinity to B-Raf than COX-2 protein.     

Surface tension calculation of mixed solvents with respect to solvent composition and temperature by using Jouyban-Acree model

Applicability of a solution model, i.e. Jouyban-Acree model (JAM), for calculating surface tension of binary and ternary solvents at various temperatures has been shown employing experimental surface tension data collected from the literature. The accuracy of the model was evaluated by calculating average percentage deviation (APD) between calculated and observed values. The obtained overall APD (+/-S.D.) for JAM using binary solvent data were 4.06 (+/-4.27) and 8.07 (+/-9.78)%, respectively for correlative and predictive analyses. The corresponding values for the best similar model from the literature were 8.86 (+/-6.40) and 37.10 (+/-27.65)% and the mean APD differences between JAM and previously published model were significant (p<0.003). The capability of JAM for correlating surface tension of ternary solvents at various temperatures was also shown and the overall APD was 1.39 (+/-0.37)%.     

Mathematical representation of solubility of electrolytes in binary solvent mixtures using Jouyban-Acree model

Applicability of a solution model for calculating salt's solubility in binary solvent mixtures was shown. The accuracy of the proposed model was evaluated by computing mean percentage deviation (MPD) employing available solubility data of electrolytes in binary solvents at various temperatures from the literature. The overall MPD (+/-S.D.) for correlation of solubility data was 4.7+/-5.1% and for prediction using model trained by a minimum number of experimental data points was 10.5+/-12.5%.     

Lactic acid production from cheese whey by immobilized bacteria

The performance of immobilized Bifidobacterium longum in sodium alginate beads and on a spiral-sheet bioreactor for the production of lactic acid from cheese whey was evaluated. Lactose utilization and lactic acid yield of B. longum were compared with those of Lactobacillus helveticus. B. longum immobilized in sodium alginate beads showed better performance in lactose utilization and lactic acid yield than L. helveticus. In the spiral-sheet bioreactor, a lactose conversion ratio of 79% and lactic acid yield of 0.84 g of lactic acid/g of lactose utilized were obtained during the first run with the immobilized L. helveticus. A lactose conversion ratio of 69% and lactic acid yield of 0.51 g of lactic acid/g of lactose utilized were obtained during the first run with immobilized B. longum in the spiral-sheet bioreactor. In producing lactic acid L. helveticus performed better when using the Spiral Sheet Bioreactor and B. longum showed better performance with gel bead immobilization. Because B. longum is a very promising new bacterium for lactic acid production from cheese whey, its optimum fermentation conditions such as pH and metabolic pathway need to be studied further. The ultrafiltration tests have shown that 94% of the cell and cheese whey proteins were retained by membranes with a mol wt cutoff of 5 and 20 KDa.