Conformational Behavior and Influence of Organic Solvents on a Strong Polar Group Nematogen at Room Temperature—A Computational Model

The conformational behavior and influence of organic solvents on a nematogen, 4’-n-alkyl-4-cyanobiphenyl, with strong polar group propyl (3CB) that is of commercial and application interest has been studied with respect to the translational and orientational motions. The atomic net charge and dipole moment components at each atomic center have been evaluated using the complete neglect differential overlap (CNDO/2) method. The modified Rayleigh-Schrodinger Perturbation theory with the multicentered-multipole expansion method has been employed to evaluate the long-range interactions, and a “6-exp.” potential function has been assumed for the short-range interactions. The minimum energy configurations obtained during the different modes of interactions have been taken as input to calculate the configurational probability using the Maxwell–Boltzmann formula in nonpolar organic solvents, i.e., carbon tetrachloride (CCl₄), and chloroform (CHCl₃) at room temperature 300 K. It has been observed that the molecules show the interesting property in the organic solvents. The interaction energies of dimer complexes have been taken into consideration in order to investigate the most energetically stable configuration. An attempt has been made to develop an interesting computational model for nematogen at molecular level.     

Analysis of duloxetine hydrochloride and its related compounds in pharmaceutical dosage forms and in vitro dissolution studies by stability indicating UPLC

A reproducible gradient reversed-phase ultra-performance liquid chromatographic method is developed for quantitative determination of duloxetine hydrochloride in pharmaceutical dosage forms. The method is also applicable for analysis of related substances and for study of in vitro dissolution profiles. Chromatographic separation is achieved on a 50 mm × 4.6 mm, 1.8 μm C-18 column. Mobile phase A contains a mixture of 0.01 M KH(2)PO(4) (pH 4.0) buffer, tetrahydro furan, and methanol in the ratio 67:23:10 (v/v/v), respectively, and mobile phase B contains a mixture of 0.01 M KH(2)PO(4), (pH 4.0) buffer, and acetonitrile in the ratio 60:40 (v/v), respectively. The flow rate is 0.6 mL/min, and the detection wavelength is monitored at 236 nm. Resolution of duloxetine hydrochloride and three potential impurities is greater than 2.0 for all pairs of components. The drug was subjected to ICH prescribed hydrolytic, oxidative, photolytic, and thermal stress conditions. Method is validated for linearity, specificity, accuracy, precision, ruggedness, and robustness.     

Phase behavior of diglycerol fatty acid esters-nonpolar oil systems

Phase behavior of diglycerol fatty acid esters (Qn-D, where n represents the carbon number in the alkyl chain length of amphiphile, n = 10-16) were investigated in different nonpolar oils, liquid paraffin (LP70), squalane, and squalene. There is surfactant solid at lower temperature, and the surfactant solid does not swell in oil, and the melting temperature is almost constant in a wide range of compositions. In all of the systems, a lamellar liquid crystal (L(alpha)) is formed in a concentrated region at a temperature between the solid melting temperature and the isotropic two- or single-phase regions. In the dilute regions, reverse vesicles are formed in L(alpha) + O regions. There are two liquid-phase regions above the L(alpha) present region. This two-phase boundary corresponds to the cloud-point curve of nonionic surfactant aqueous solutions. However, instead of being less soluble in water at high temperature for the cloud point, the surfactant becomes more soluble in the organic solvents at high temperature. Namely, the effect of temperature on the solubility is opposite to the clouding phenomenon. When the hydrocarbon chain of the diglycerol surfactant decreases, the two-phase region becomes wider. In the case of a fixed surfactant, the surfactant is most miscible with squalene (narrowest two-phase regions) and the order of dissolutions tendency is squalene > LP70 > squalane. These results show that the hydrophilic moiety (diglycerol group) is more insoluble in oil compared with that of a conventional poly(oxyethylene)-type nonionic surfactant. Formation of reversed rodlike micelles was confirmed by SAXS scattering curve. When the hydrocarbon chain of surfactant is short, the micellar size becomes larger. In a fixed surfactant system, the reverse micellar size increases by changing oil from squalene to LP70. A small amount of water induces a dramatic elongation of reverse micelles.     

Synthesis of 3,5-Bis(trifluoromethyl)phenyl-Substituted Pyrazole Derivatives as Potent Growth Inhibitors of Drug-Resistant Bacteria

Enterococci and methicillin-resistant S. aureus (MRSA) are among the menacing bacterial pathogens. Novel antibiotics are urgently needed to tackle these antibiotic-resistant bacterial infections. This article reports the design, synthesis, and antimicrobial studies of 30 novel pyrazole derivatives. Most of the synthesized compounds are potent growth inhibitors of planktonic Gram-positive bacteria with minimum inhibitory concertation (MIC) values as low as 0.25 µg/mL. Further studies led to the discovery of several lead compounds, which are bactericidal and potent against MRSA persisters. Compounds 11, 28, and 29 are potent against S. aureus biofilms with minimum biofilm eradication concentration (MBEC) values as low as 1 µg/mL.     

Molecular Ordering of a Nematogen at Phase Transition Temperature - A Theoretical Study

Molecular ordering in 4-cyano-4'- n -propylbiphenyl ( CB3 ), a nematic liquid crystal, has been studied with the help of intermolecular interaction energy calculations. The CNDO / 2 method has been employed to compute the net atomic charge and atomic dipole moment at each atomic centre. Modified Rayleigh-Schrodinger perturbation theory along with multicentered-multipole expansion method has been employed to evaluate long-range intermolecular interactions, while a ' 6-exp ' potential function has been assumed for short-range interactions. The interaction energy values obtained through these computations were used to calculate the probability of each configuration at the phase transition temperature using Maxwell-Boltzmann formula. All possible geometrical arrangements between molecular pair have been considered during stacking, in-plane and terminal interactions. An attempt has been made to identify the most probable configuration at the phase transition temperature during stacking, in-plane and terminal interactions. Results obtained have been discussed in the light of experimental as well as other theoretical observations.     

Brain-derived neurotrophic factor modulation of Kv1.3 channel is disregulated by adaptor proteins Grb10 and nShc

Background

Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel), because of large variances in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'typical' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique.

Results

The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N = 38) falling outside of the control group (N = 39) 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subgroups was observed between subjects with lower cerebellar declive (LCD) grey matter volumes than controls and subjects with higher cerebellar declive (HCD) grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and higher lentiform grey matter volumes compared to controls differently modulated the phonological and lexical performances. Best performances (observed in controls) corresponded to an optimal value of grey matter and they dropped for higher or lower volumes.

Conclusion

These results provide evidence for the existence of various subtypes of dyslexia characterized by different brain phenotypes. In addition, behavioural analyses suggest that these brain phenotypes relate to different deficits of automatization of language-based processes such as grapheme/phoneme correspondence and/or rapid access to lexicon entries.     

An LC Method for Quantification of 2,3-Dichlorobenzoyl Cyanide and Its Related Regio Isomers

A simple, sensitive and selective gradient reversed phase LC method has been developed for separation and determination of 2,3-dichlorobenzoyl cyanide and its regio isomers which is an intermediate of lamotrigine pure form. The separation was achieved on a reversed phase C-18 column using 0.01 M ammonium acetate buffer at pH 5.5 and methanol (50:50 v/v) mixture as solution A and methanol, water mixture (90:10 v/v) as solution B in a gradient elution at a flow rate of 1.5 mL min^?1 with UV detection at 215 nm. The method is found to be selective, precise, linear, accurate and also robust. It was not only used for quality assurance, but also monitoring the synthetic reactions involved in the process development of Lamotrigine. The LC method is found to be simple, rapid, specific and reliable for the determination of unreacted levels of raw materials and isomers in reaction mixtures and finished product Lamotrigine. The method was fully validated as per ICH guidelines and results from validation confirm that the method is highly suitable for its intended purpose.     

Multicomponent Approach Towards the Synthesis of Substituted Pyrroles under Supramolecular Catalysis Using β‐Cyclodextrin as a Catalyst in Water Under Neutral Conditions

Synthesis of substituted pyrroles in H₂O by using β‐cyclodextrin as a supramolecular catalyst is described. This reaction has several advantages over existing methods and provides substituted pyrroles in good‐to‐excellent yields (79–89%). The supramolecular catalysis of the reaction was studied using ¹H‐NMR spectroscopy. β‐Cyclodextrin can be recovered and reused several times without loss of activity.     

Resistance of a circular cylinder due to a pair of vortices moving symmetrically

Zusammenfassung Es wird versucht, den veränderlichen Widerstand, welchen ein unter Bildung zweier Wirbel in eine gleichförmige Strömung gelegter, runder Zylinder erfährt, einer Berechnung zu unterziehen.