Some new protocols for the assignment of absolute configuration by NMR spectroscopy using chiral solvating agents and CDAs

The utility of enantiopure BINOL (1,10-Bi-2-naphthol), in a ternary ion-pair complex, which is obtained using a carboxylic acid and an organic base, as a versatile chiral solvating agent (CSA) has been demonstrated for chiral analysis and the absolute configuration assignment of hydroxy acids. Another protocol where the utility of NOBIN as a CSA has been developed for discrimination and absolute configuration assignment of acids, hydroxy acids and their derivatives with a distinct strategy where a third ingredient, p-toluenesulfonic acid (p-TsOH) serves as a linker. In addition some three component chiral derivatization protocols have been introduced, such as the use of 2-formylphenylboronic acid and enantiopure mandelic acid or a primary amine for the determination of the configuration of primary amines and hydroxy acids, respectively. A simple, rapid and highly efficient three component chiral derivatizing protocol has also been discussed which was developed for assigning the absolute configuration of chiral α-hydroxy acids and their derivatives, which involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and (S)-[1,1-binaphthalene]-2,2-diamine separately. In a few examples, the DFT based theoretical calculations have been carried out to determine the geometry optimized structures of the complexes.     

Ferrocene derivatives of liquid chiral molecules allow assignment of absolute configuration by X-ray crystallography

The present study investigates a synthetically simple ferrocene derivatization of natural products and active pharmaceutical ingredients. Seven new crystal structures are analyzed together with 16 structures of ferrocene derivatives reported previously. In all cases, the unambiguous determination of the absolute structure was established from anomalous dispersion using the methods of Flack and Parsons. A comparison with other derivatization approaches shows the advantage of the described ferrocene derivatization for establishing the absolute configuration of novel compounds.     

Design,synthesis of novel N prenylated indole-3-carbazones and evaluation of in vitro cytotoxicity and 5-LOX inhibition activities

A series of novel N-1 and C-3 substituted indole derivatives (5a–f) were designed, synthesized and evaluated for their cytotoxic properties, viz Brine Shrimp Lethality Bioassay (BSLB) besides 5-Lipoxygenase (5-LOX) inhibitory activities through in vitro assays. Structure Activity Relation (SAR) studies showed that compound 5d with an LC₅₀ of 6.49 μM and 5c with an IC₅₀ of 33.69 μM were found to be interesting for cytotoxicity and 5-LOX inhibitory activity respectively.     

Synthesis of novel rhodanine based functionalized furans from the reaction of tert-butyl isocyanide with acetylenic esters in the presence of rhodanine acetic acid derivatives

The reactive 1:1 intermediate produced from the reaction of tert-butyl isocyanide and dialkyl acetylenedicarboxylates was trapped by rhodanine-N-acetic acid derivatives to generate polyfunctionalized furan rings in fairly good yields.     

Development and validation of stability indicating RP-HPLC and HPTLC for determination of Niclosamide in bulk and in synthetic mixture

Two simple, specific, sensitive, accurate and precise stability indicating methods were described for quantitative determination of the anthelmintics drug Niclosamide. The first method was high performance liquid chromatographic with the use of a reversed phase hibar^R C-18 column (250 mm × 4.66 mm, 5 μm) and mobile phase of methanol: 1 mM ammonium phosphate buffer (85:15 v/v) at a flow rate of 1.2 mL/min. The retention time of drug was found to be 6.45 ± 0.02 min. Quantification of drug was achieved with diode array detection (DAD) at 332 nm. Linear calibration curve was obtained in concentration range 0.01–100 μg/mL with r² value of 0.999. The limit of detection and limit of quantification were found to be 0.048 μg/mL and 0.01 μg/ml respectively. The second method involved a high performance thin layer liquid chromatographic. Chromatographic separation was carried out with precoated silica gel G60 F254 aluminum sheets using toluene:ethyl acetate (7:3% v/v) as a mobile phase. Linearity of proposed method was found to be 200–700 ng/band at 332 nm with retention factor of 0.59 and r² value of 0.998. The limit of detection and limit of quantification were found to be 36.21 ng/band and 109.7 ng/band respectively. Both the developed methods were successfully validated as per International Conference on Harmonization guideline (ICH). Niclosamide was subjected to different stress conditions. The degraded product peaks were well resolved from the pure drug peak with significant difference in their retention time. Stress samples were successfully assayed by developed high performance liquid chromatographic and high performance thin layer liquid chromatographic method. Statistically analysis proves that there were no statistical significant differences between two developed methods.     

UHPLC-MS/MS assay using environment friendly organic solvents: A green approach for fast determination of quetiapine in rat plasma

Reduction or elimination of traditional hazardous chemicals in chromatographic separation and sample preparation is comparatively safer and can be considered as a greener approach for the determination of analytes in biological matrices. A rapid and sensitive UHPLC-MS/MS assay for determination of quetiapine in rat plasma was developed and validated using environment friendly and low toxic organic solvents as organic modifier in mobile phase and sample preparation. Quetiapine and risperidone (internal standard) were separated on Acquity BEH? C₁₈ column (50 × 2.1 mm, i.d. 1.7 μm) using ethanol–water-formic acid (80:20:0.1, v/v/v) as mobile phase at a flow rate of 0.3 mL/min. Detection was performed on tandem mass spectrometer using positive electrospray ionization source by multiple reaction monitoring mode. The precursor to product ion transitions of m/z 384.13 > 253.00 for quetiapine and m/z 411.18 > 191.07 for IS was used to quantify them respectively. The method was found to be linear in the concentration range of 0.45–500 ng/mL. All validation parameters were within acceptable range, as defined by guidelines of bio-analytical method validation. In conclusion, bioanalytical assay using UHPLC-MS/MS together with environment friendly and low toxic organic solvents in mobile phase and sample preparation may be considered as greener approach for quantification of analytes in plasma samples.     

Synthesis of 3-aminoindan-1-one derivatives from 2-acetylbenzaldehydes and secondary amines by Mannich annulation

An acid-promoted 2-component Mannich annulation reaction of readily available acetylbenzaldehydes and secondary amines has been reported. The approach provides a simple and efficient method under mild conditions to synthesize 3-aminoindan-1-one derivatives in moderate to good yields.     

Synthesis,characterization, and in vitro toxicity evaluation of upconversion luminescence NaLuF4:Yb3+/Tm3+ nanoparticles suitable for medical applications

Synthesis, characterization, and in vitro toxicity evaluation of upconversion luminescence NaLuF₄:Yb³⁺/Tm³⁺ nanoparticles (UCLNPs) are reported in the current study. Initially, the synthesized lanthanide trifluoroacetate (Ln(OOCCF₃)₃) precursor was used to fabricate NaLuF₄ nanoparticles doped with Yb³⁺ and Tm³⁺ metal ions. The nanoparticles were coated with calcium carbonate (CaCO₃) after removing the hydrophobic species on them to enhance their biocompatibility. The in vitro methylthiazolyldiphenyl-tetrazoliumbromide (MTT) test was used to evaluate the toxicity of synthesized NaLuF₄:Yb³⁺/Tm³⁺ nanoparticles (NLF-5) on L929 mouse fibroblast cell lines. The transmission electron microscopy image showed that the particle size of NaLuF₄:Yb³⁺/Tm³⁺ was 32 nm. The synthesized NLF-5 nanoparticles have both α-cubic and β-hexagonal crystalline structures that provided a superb near-infrared-to-near-infrared upconversion luminescence signal when excited at 980 nm. MTT test results show that the death of L929 fibroblast cells was observed only at concentrations above 250 μg/mL of NaLuF₄:Yb³⁺/Tm³⁺ nanoparticles. In addition, with an increase in patrol time of 24, 48, and 72 hr, cell toxicity increased significantly, while the coated nanoparticles did not have any toxic effects. The synthesized nanoparticles could be used as a suitable material for medical applications due to their small particle size, high photoluminescence emission intensity, and low toxicity.     

Single drop microextraction or solid phase microextraction-gas chromatography-mass spectrometry for the determination of iodine in pharmaceuticals, iodized salt, milk powder and vegetables involving conversion into 4-iodo-N,N-dimethylaniline

A rapid sequence of oxidation and iodination using 2-iodosobenzoate as an oxidizing agent and N,N-dimethylaniline as an iodine scavenger at pH 6.4, when 4-iodo-N,N-dimethylaniline is formed, has been used for the determination of iodide by GC-MS. Solid phase microextraction (SPME) and single drop microextraction (SDME) have been used for the extraction of the iodo-derivative and their relative efficiencies compared. Pharmaceutical samples were subjected to solid phase extraction (SPE) for cleanup and the eluate analyzed for iodide. Iodate in salt samples was reduced to iodide with ascorbic acid. Milk powder and dried vegetables were wet combusted with peroxydisulfate to liberate covalently bound iodine as iodate which was reduced before derivatization. A rectilinear calibration graph was obtained for 0.1 microg-10 mg l(-1) iodide by both extraction methods, the correlation coefficient and limit of detection (LOD) were 0.9995 and 25 ng l(-1) iodide by SPME method, and 0.9998 and 10 ng l(-1) iodide by SDME method, respectively. SDME appeared to be more efficient technique than SPME for the present system. From the pooled data, the average recovery of spiked iodide to real samples was 100.7% (range 96.5-107.0%) with an average R.S.D. of 3.1% (range 2.6-4.5%).