MECHANISMS OF CITRAL PHOTOTOXICITY

Citral, a monoterpene aldehyde synthesized by several plant genera, has been reported to exhibit antimicrobial activity. For the first time, we report that critral exhibits UV-A (315-400 nm) light enhanced oxygen-dependent toxicity against a series of Escherichia coli strains differing in DNA repair and catalase proficiency. Those E. coli strains carrying a gene leading to catalase deficiency (katF) are particularly sensitized to inactivation by citral and UV-A treatment when compared to catalase proficient strains (katF+). Consistent with these in vivo observations, citral when treated with UV-A in vitro produces H2O2. When tested against Fusarium oxysporum and F. solani, fungal root pathogens of Citrus, enhanced toxicity by citral in the presence of UV-A was demonstrated, while dark toxicity was negligible. When the plasmid pBR322 was treated with citral in the presence of UV-A, a change in conformation from the covalently closed circular to the open circular and, ultimately, the linear form was observed. The change in plasmid conformation corresponded to a reduction in transforming activity. Holding plasmid DNA which had been treated with UV-A light in the presence of citral at 4 degrees C for 22 h in the dark resulted in continued degradation of the DNA and loss of transforming activity. Holding plasmid DNA treated with UV-A or citral alone under identical conditions had no detectable effect on either plasmid conformation or transforming activity.     

5-Nitroisocoumarins from tandem Castro-Stephens coupling—6-endo-dig cyclisation of 2-iodo-3-nitrobenzoic acid and arylethynes and ring-closure of methyl 2-alkynyl-3-nitrobenzoates with electrophiles

Reaction of 2-iodo-3-nitrobenzoic acid with arylalkynyl copper(I) reagent gave 3-aryl-5-nitroisocoumarins. Castro-Stephens coupling was followed by in situ Cu-catalysed ring-closure. ¹H NMR and X-ray crystallography showed the cyclisations to be 6-endo, contrasting with reports of 5-exo cyclisation of analogous 2-iodobenzoate esters with alkynes. Sonogashira couplings of methyl 2-iodo-3-nitrobenzoate with phenylacetylene and with trimethylsilylacetylene gave the corresponding 2-alkynyl-3-nitrobenzoate esters. With HgSO₄, the phenylalkyne underwent 6-endo cyclisation to give 5-nitro-3-phenylisocoumarin. The disubstituted alkyne esters gave 4-phenylselenylisocoumarins with PhSeCl. 5-Nitro-3-phenyl-4-phenylselenylisocoumarin shows significant sterically-driven distortion of the isocoumarin ring. Reaction of methyl 3-nitro-2-phenylethynylbenzoate with ICl gave the 4-iodoisocoumarin. Thus the nitro group tends to direct these electrophile-driven cyclisations towards the 6-endo mode.     

Development and Validation of Highly Sensitive LC–ESI-MS/MS Method for Bortezomib and Its Applications for Plasma Levels and Drug Content of Branded and Generic Formulations in India

In the present study, a highly sensitive and reproducible bio-analytical method was developed using LC–ESI-MS/MS to assess the lower plasma levels of bortezomib in multiple myeloma patients. The gradient elution was optimized using reverse-phase C18 column with mobile phases consisting of water and acetonitrile in 0.1% formic acid. Multiple reaction monitoring mode was used for quantification using precursor-to-product ion transition for bortezomib and sulfadiamethoxine was used as internal standard. This method was validated with a linearity range of 0.195–25 ng mL^?1. Intra-day and inter-day accuracy was 99.17–101.89% and 95.01–102.92% with precision of?<?9.87% and?<?8.77%, respectively. Bortezomib was stable in plasma samples stored at ? 80 °C for up to 10 months. The lower limit of quantification was found to be 0.195 ng mL^?1. This method was also found to be capable of quantifying bortezomib trough levels (ranging 0.19–0.7 ng mL^?1) in plasma of multiple myeloma patients post-cycle 1–6. Bortezomib content in the commonly prescribed generic formulations was also studied. The concentration in all formulations was within the 90–110% of the innovator, as prescribed by the USFDA, ruling out their role blood level variation. The study supports the use of this method for trough level estimation and therapeutic drug monitoring of bortezomib in multiple myeloma patients.

     

Numerical investigations of response surface methodology for organic dye adsorption onto Mg-Al LDH -GO Nano Hybrid: An optimization,kinetics and isothermal studies

We developed Mg-Al LDH intercalated with NO₃^- decorated Graphene Oxide nanohybrid with positive cationic textile dye adsorption, such as methylene blue. Contact time, initial dye concentration, and pH were among the independent variables used in the study. The Response Surface Model (RSM) was used to optimise and describe the interdependencies of the different variables. The method was evaluated using the Box-Behnken design (BBD). A second-order polynomial model was used to understand the experimental results, and the effectiveness of the chosen model was verified by its strong agreement in determination coefficient values. The adsorption results suited the best for the Langmuir isotherm than the D-R and Freundlich isotherms, resulting in efficient adsorption of 187.62 ?mg/g, proving LDH-GO is an effective dye adsorbent. Simultaneously, the kinetics were based on the pseudo-second-order model, and additional kinetic factors such as Elovich, pseudo-first-order, and intra-particular diffusion were examined. According to Thermodynamic studies, the adsorption process is spontaneous, which is exothermic and characterised by increased randomness. According to a regeneration test, even after four cycles, 37% of the removal efficiency for MB can be achieved. Based on this report, these materials can be used as an adsorbent to remove the dye.     

Effect of Ru Substitution in La0.85Sr0.15CoO3 towards Oxygen Evolution Reaction: Activity of Ionic Ru

Nano crystalline La_0.85Sr_0.15CoO₃ and ruthenium doped compounds (La_0.85Sr_0.15Co_0.9975Ru_0.0025O_3, La₀.₈₅Sr_0.15Co_0.995Ru_0.005O_3, La_0.85Sr_0.15Co_0.99Ru_0.01O₃) are synthesized using solution combustion method. Completely characterized samples are studied for electrochemical OER in neutral and basic medium. Significant enhancement in catalytic activity is noticed once Ru is substituted in the cobalt site. With higher doping level of Ru, capacitance also increases as depicted in the CV behavior. Tafel slope measurements indicate that Ru substitution has profound effect as enhancement in the exchange current density is observed in neutral K₂SO₄ medium. Enhancement is anticipated due to substitution of Ru, as the RuO₂ mixed catalyst does not give similar activity.     

Lanthanum(III) and praseodymium(III) complexes of acetylferrocenyl mercaptotriazoles

Schiff base complexes derived from 3-substituted phenyl-4-amino-thiolato-1,2,4-triazoles and acetylferrocene (LH), with lanthanum(III) and praseodymium(III) of the type [M(L)₃] have been prepared and characterised by elemental analysis, electrical conductance, magnetic moments and spectral (electronic, i.r., ¹H-n.m.r. and ¹³C-n.m.r.) data. The thermal behaviour of selected complexes was investigated by t.g. and d.t.g. techniques.     

Simultaneous quantitation of metformin and dapagliflozin in human plasma by LC–MS/MS: Application to a pharmacokinetic study

A single LC–MS/MS assay has been developed and validated for the simultaneous determination of metformin and dapagliflozin in human plasma using ion‐pair solid‐phase extraction. Chromatographic separation of the analytes and their internal standards was carried out on a reversed‐phase ACE 5CN (150 × 4.6 mm, 5 μm) column using acetonitrile–15 mm ammonium acetate, pH 4.5 (70:30, v/v) as the mobile phase. To achieve higher sensitivity and selectivity for the analytes, mass spectrometric analysis was performed using a polarity switching approach. Ion transitions studied using multiple reaction monitoring mode were m/z 130.1 [M + H]⁺/60.1 for metformin and m/z 467.1 [M + CH₃COO]^?/329.1 for dapagliflozin in the positive and negative modes, respectively. The linear calibration range of the assay was established from 1.00 to 2000 ng/mL for metformin and from 0.10 to 200 ng/mL for dapagliflozin to achieve a better assessment of the pharmacokinetics of the drugs. The limit of detection and limit of quantitation for the analytes were 0.39 and 1.0 ng/mL for metformin and 0.03 and 0.1 ng/mL for dapagliflozin, respectively. There was no interference of plasma matrix obtained from different sources, including hemolyzed and lipemic plasma. The method was successfully applied to study the effect of food on the pharmacokinetics of metformin and dapagliflozin in healthy subjects.     

Phonon dispersion and heat capacity of polydichlorobutadiene

Normal modes and their dispersion have been obtained for trans polydichlorobutadiene (PDCB) in the reduced zone scheme using Wilson’s G F matrix method as modified by Higg’s for an infinite polymeric chain. The Urey Bradley potential field is obtained by least square fitting of the observed infrared and Raman bands. The obtained results agree well with the experimental values. Because of the presence of centre of symmetry, the PDCB molecule obeys the mutual exclusion principle. Several new assignments which are missing in the earlier work are reported. The characteristic features of dispersion curves such as repulsion and exchange of character have been discussed and possible explanation has been given. Heat capacity has been calculated via density-of-states using Debye relation in the temperature range 10–450 K.     

Syntheses and crystal structures of gadolinium and europium complexes of AAZTA analogues

Modified 6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid (AAZTA) ligands with a hydroxyl arm have been synthesized and characterized. The crystal structures of its lanthanide complexes, determined by single crystal X-ray crystallography, show centrosymmetric nonacoordinated dimeric M₂L₂ forms where one carboxylate group from each ligand forms a bridge between two metal centers. Each metal center is coordinated with one inner sphere water molecule. The hydroxyl arm does not interfere in the coordination environment of the metal and therefore acts as a good anchor for attaching other functional motifs.     

Thermal, structural and complex impedance analysis of Mn modified BaTiO3 electroceramic

The polycrystalline samples of BaTi_1−xMn_xO₃ (BMT) ferroelectric ceramics with x=0, 0.04, 0.07, 0.10 have been prepared using a solid-state reaction technique. The calcination temperature of the samples was optimized by thermal gravimetric analysis and repeated firing. Preliminary structural study using X-ray diffraction technique at room temperature suggests that structure of Mn modified compounds (BMT) change into orthorhombic crystal system from tetragonal crystal system. The field emission scanning electron micrographs (FE-SEM) show uniform grain distribution throughout the surface of the samples. Complex impedance analysis (CIS) has been carried out to investigate the electrical properties of BMT. The real and imaginary part of complex impedance plots exhibit semicircle(s) in the complex plane. The bulk resistance of the material decreases with rise in temperatures similar to a semiconductor. The variation of bulk ac conductivity with frequency shows that the compounds exhibit dispersive type electrical conductivity.