Solvent‐mediated pseudo‐quadruple hydrogen‐bond motifs in three lamotrigine–carboxylic acid complexes

Lamotrigine, an antiepileptic drug, has been complexed with three aromatic carboxylic acids. All three compounds crystallize with the inclusion of N,N‐dimethylformamide (DMF) solvent, viz. lamotriginium [3,5‐diamino‐6‐(2,3‐dichlorophenyl)‐1,2,4‐triazin‐2‐ium] 4‐iodobenzoate N,N‐dimethylformamide monosolvate, C₉H₈Cl₂N₅⁺·C₇H₄IO₂⁻·C₃H₇NO, (I), lamotriginium 4‐methylbenzoate N,N‐dimethylformamide monosolvate, C₉H₇Cl₂N₅⁺·C₈H₈O₂⁻·C₃H₇NO, (II), and lamotriginium 3,5‐dinitro‐2‐hydroxybenzoate N,N‐dimethylformamide monosolvate, C₉H₈Cl₂N₅⁺·C₇H₃N₂O₇⁻·C₃H₇NO, (III). In all three structures, proton transfer takes place from the acid to the lamotrigine molecule. However, in (I) and (II), the acidic H atom is disordered over two sites and there is only partial transfer of the H atom from O to N. In (III), the corresponding H atom is ordered and complete proton transfer has occurred. Lamotrigine–lamotrigine, lamotrigine–acid and lamotrigine–solvent interactions are observed in all three structures and they thereby exhibit isostructurality. The DMF solvent extends the lamotrigine–lamotrigine dimers into a pseudo‐quadruple hydrogen‐bonding motif.     

Large amplitude free vibration analysis of thermally post-buckled composite doubly curved panel embedded with SMA fibers

Thermal post-buckled vibration of laminated composite doubly curved panel embedded with shape memory alloy (SMA) fiber is investigated and presented in this article. The geometry matrix and the nonlinear stiffness matrices are derived using Green–Lagrange type nonlinear kinematics in the framework of higher order shear deformation theory. In addition to that, material nonlinearity in shape memory alloy due to thermal load is incorporated by the marching technique. The developed mathematical model is discretized using a nonlinear finite element model and the sets of nonlinear governing equations are obtained using Hamilton’s principle. The equations are solved using the direct iterative method. The effect of nonlinearity both in geometric and material have been studied using the developed model and compared with those published literature. Effect of various geometric parameters such as thickness ratio, amplitude ratio, lamination scheme, support condition, prestrains of SMA, and volume fractions of SMA on the nonlinear free vibration behavior of thermally post-buckled composite flat/curved panel been studied in detail and reported.     

Study of variation in slab thickness of ionospheric F-region during earthquake by wavelet analysis

The present work deals with the anomalies in ionospheric slab thickness of F-region associated with strong seismic activity. In this regard we have considered ionosonde data of Critical frequency of F2 layer (foF2) and Ionospheric Total Electron Content (ITEC) observed for Athens [38°N, 24°E] and Rome [42°N, 13°E] stations. We have considered three cases of earthquake occurring on December 20, 2007, June 08, 2008 and April 06, 2009 and analyzed the ionosonde data of foF2 and ITEC for slab thickness of F-region of the ionosphere in one-hour interval time series record by filtering the geomagnetic disturbances. The result of the study shows that some unusual perturbations were observed in slab thickness of F-region for some days before the main seismic event. It may be due to the generation of seismogenic electric field above the surface of the earth well before the seismic event. This anomalous behavior of perturbations may be used as earthquake precursor.     

A new methodology for crisp equivalent of fuzzy chance constrained programming problem

This paper deals with a chance constrained programming model, where both fuzziness and randomness are present in the objective function and constraints. The concept of fuzzy random variable, mean and variance of fuzzy random variable, minimum of fuzzy numbers are used in the model. The methodology is verified through a numerical example.     

Synthesis of cell wall-active lipopeptide diastereomers

The first synthesis of cell wall-active lipopeptide diastereomers from easily accessible starting materials has been reported. The synthetic strategy involves Jacobsen resolution, TEMPO/BAIB & 2C-Wittig (one pot reaction), and peptide couplings.     

Three structures of dispirooxindole derivatives generated in situ through a three‐component one‐pot strategy with complete regio‐ and stereoselectivity

The challenging molecular architecture of spirooxindoles is appealing to chemists because it evokes novel synthetic strategies that address configurational demands and provides platforms for further reaction development. The [3+2] cycloaddition of the carbonyl ylide with arylideneoxindole via a five‐membered cyclic transition state gave a novel class of dispirooxindole derivatives, namely tert‐butyl 4′‐(4‐bromophenyl)‐1′′‐methyl‐2,2′′‐dioxo‐5′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐1‐carboxylate, C₃₆H₃₁BrN₂O, (Ia), 5′‐(4‐bromophenyl)‐1,1′′‐dimethyl‐4′‐phenyl‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐2,2′′‐dione, C₃₂H₂₅BrN₂O₃, (Ib), and tert‐butyl 1′′‐methyl‐2,2′′‐dioxo‐4′‐phenyl‐5′‐(p‐tolyl)‐4′,5′‐dihydrodispiro[indoline‐3,2′‐furan‐3′,3′′‐indoline]‐1‐carboxylate, C₃₇H₃₄N₂O₅, (Ic). Crystal structure analyses of these dispirooxindoles revealed the formation of two diastereoisomers selectively and confirmed their relative stereochemistry (SSSR and RRRS). In all three structures, intramolecular C—H...O and π–π interactions between oxindole and dihydrofuran rings are the key factors governing the regio‐ and stereoselectivity, and in the absence of conventional hydrogen bonds, their crystal packings are strengthened by intermolecular C—H...π interactions.     

Validation of capillary electrophoresis method for determination of N-methylpyrrolidine in cefepime for injection

The present study relates to a new capillary electrophoresis method for the determination of N-methylpyrrolidine, an impurity considered to be toxic and also potential degradation impurity in cefepime hydrochloride drug substance. The newly developed capillary electrophoresis method for determining the content of N-methylpyrrolidine in cefepime for injection has been validated as per International Conference on Harmonization (ICH) guidelines to prove the selectivity, sensitivity, suitability, robustness, and ruggedness of the method. This simple, efficient, and rapid methodology may be used by pharmaceutical industry for routine analysis as well as during stability studies. The newly developed capillary electrophoresis method to determine the content of N-methylpyrrolidine in cefepime for injection requires 10 min for data acquisition, and uses an indirect UV photometry method to detect the analyte signal at 240 nm against the reference signal at 210 nm. The electrophoretic system is optimized to get stable base line, higher signal to noise ratio and peaks with narrow peak width. The method employs bare fused silica capillary with extended light path, effective length of capillary is 56 cm and inner diameter of capillary is 50 μm, 5 mmole of imidazole buffer adjusted to pH 5.1 with 3 molar acetic acid solution is used as background electrolyte. The sample is introduced in hydrodynamic mode employing pressure of 50 mbar for 5 s, and the desired separation is achieved with constant applied voltage of 25 kV at ambient temperature (~25°C).