Enantioselective LC‐ESI‐MS/MS determination of dropropizine enantiomers in rat plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective and reliable LC–ESI‐MS/MS method for direct quantitation of dropropizine enantiomers namely levodropropizine (LDP) and dextrodropropizine (DDP) in rat plasma without the need for derivatization as per regulatory guidelines. Dropropizine enantiomers and carbamazepine (internal standard) were extracted from 50 μL rat plasma using ethyl acetate. LDP and DDP resolved with good baseline separation (R_s = 4.45) on a Chiralpak IG‐3 column. The mobile phase consisted of methanol with 0.05% diethylamine pumped at a flow rate of 0.5 mL/min. Detection and quantitation were done in multiple reaction monitoring mode following the transitions m/z 237 → 160 and 237 → 194 for dropropizine enantiomers and the internal standard, respectively, in the positive ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 3.23–2022 ng/mL for each enantiomer. The intra‐ and inter‐day precisions were in the ranges of 3.38–13.6 and 5.11–13.8 for LDP and 4.19–11.8 and 8.89–10.1 for DDP. Both LDP and DDP were found to be stable under different stability conditions. The method was successfully used in a stereoselective pharmacokinetic study of dropropizine enantiomers in rats following oral administration of racemate dropropizine at 100 mg/kg. The pharmacokinetic results indicate that the disposition of dropropizine enantiomers is not stereoselective and chiral inversion does not occur in rats.     

Investigation of non-nucleophilic additives for the reduction of morphological anomalies in protein arrays

Uniform spot morphology is of critical importance in the fabrication and successful use of protein arrays, and solution additives are often needed to ensure good spot quality. Whereas hydroxyl-bearing molecules such as glycerol have found wide use, in our experience these reduce the efficiency of probe immobilization (particularly in the context of aldehyde-terminated surfaces). Here, we report a series of non-nucleophilic molecules that can be used as additives to improve spot homogeneity in protein arrays. Arrayed imaging reflectometry, a label-free optical biosensing technique, has been used along with spectroscopic ellipsometry to test the spot homogeneity, antibody immobilization efficiency, and activity of antihuman IgG arrays prepared with these non-nucleophilic additives on glutaraldehyde surfaces. It has been determined that 0.1% v/v 12-crown-4 performs optimally in MPBS buffer.     

Topological and thermodynamic investigations of binary mixtures: Molar excess volumes, molar excess enthalpies and isentropic compressibility changes of mixing

Molar excess volumes, V^E, molar excess enthalpies, H^E, and speeds of sound, u, of o-toluidine (i) + cyclohexane or n-hexane or n-heptane (j) binary mixtures have been determined over entire range of composition at 308.15 K. Speeds of sound data have been utilized to predict isentropic compressibility changes of mixing, of (i + j) mixtures. The observed V^E, H^E and data have been analyzed in terms of Graph theory. The analysis of V^E data by Graph theory reveals that o-toluidine exists as an associated molecular entity and (i + j) mixtures contain 1:1 molecular complex. It has been observed that V^E, H^E and values calculated by Graph theory compare well with their corresponding experimental values. The observed data have also been analyzed in term of Flory theory.     

4-Oxatricyclo[5.2.1.0(2,6)]decan-10-one and 4-oxatricyclo[5.2.1.0(2,6)]dec-8-en-10-one. Experimental and DFT investigations of the pi-selectivities.

Ab initio MO and experimental pi-selectivities of hydride additions to 4-oxatricyclo[5.2.1.0(2,6)]decan-10-one and 4-oxatricyclo[5.2.1.0(2,6)]dec-8-en-10-one are described. The interactions of sigma(C1-C2) and sigma(C6-C7) with pi(C=O), on one hand, and those of sigma(C1-C9) and sigma(C7-C8) with pi(C=O), on the other hand, support anti-selectivities for both. This is in full accordance with the experiments. The arguments that are based on electrostatic interactions and electron donation from the ring oxygen do not apply.     

Ab initio evaluation of bond orders and valence numbers in some substituted benzenes

Mayer's definition of bond order and valence number of an atom in a molecule in the ab initio SCF theory have been applied to calculate bond orders and valence numbers using different ab initio methods for some fluorobenzenes. The results have been discussed in the light of Mulliken population analysis. The traditional view that the valency of an atom is directly related to the atomic charge is found to be invalid in the present ab initio calculations.     

Iodo-cyclizations: novel strategy for the total syntheses of polyrhacitide A and epi-cryptocaryolone

Highly stereoselective total syntheses of polyrhacitide A and epi-cryptocaryolone have been achieved in 11 steps with high overall yield of 24% and 28%, respectively, following a recently developed strategy for the construction of trans-2,6-disubstituted-3,4-dihydropyrans. In this report, the versatility of iodo-cyclization for the total syntheses of polyrhacitide A and epi-cryptocaryolone is demonstrated.     

Diastereoselective Mukaiyama aldol reaction of (N-alkyl) isatins with 2-(trimethylsilyloxy)furan by using lanthanum triflate

An efficient vinylogous Mukaiyama aldol reaction (VMAR) of 2-(trimethylsilyloxy)furan with various (N-alkyl)isatins is described in the presence of lanthanum(III) triflates (5 mol %). The reaction proceeds rapidly and affords the corresponding 3-hydroxy-(5-oxo-2,5-dihydrofuran-2-yl)indolin-2-one in high yields with good diastereoselectivities (threo:erythro ratio up to ≤95:5).     

First stereoselective total synthesis of pectinolide A

The enantioselective synthesis of bio-active 5,6-dihydro-α-pyrone, pectinolide A, has been achieved in 10 steps in good overall yield. Of the three stereogenic centres, the C-5/C-6 vic-diol was obtained using diastereo- and enantioselective Brown hydroxyl crotylation, while the C-3′ stereocentre was created by Jacobsen hydrolytic kinetic resolution method.     

Experimental IR and Raman spectra and quantum chemical studies of molecular structures, conformers and vibrational characteristics of L-ascorbic acid and its anion and cation

IR and spectra of the L-ascorbic acid (L-AA) also known as vitamin C have been recorded in the region 4000-50 cm(-1). In order to make vibrational assignments of the observed IR and Raman bands computations were carried out by employing the RHF and DFT methods to calculate the molecular geometries and harmonic vibrational frequencies along with other related parameters for the neutral L-AA and its singly charged anionic (L-AA(-)) and cationic (L-AA(+)) species. Significant changes have been found for different characteristics of a number of vibrational modes. The four ν(O-H) modes of the L-AA molecule are found in the order ν(O(9)-H(10))>ν(O(19)-H(20))>ν(O(7)-H(8))>ν(O(14)-H(15)) which could be due to complexity of hydrogen bonding in the lactone ring and the side chain. The CO stretching wavenumber (ν(46)) decreases by 151 cm(-1) in going from the neutral to the anionic species whereas it increases by 151 cm(-1) in going from the anionic to the cationic species. The anionic radicals have less kinetic stabilities and high chemical reactivity as compared to the neutral molecule. It is found that the cationic radical of L-AA is kinetically least stable and chemically most reactive as compared to its neutral and anionic species.     

Controlled growth of flower-like,rod-like,and snowflake-like ZnO nanostructures using agarose as biotemplate and its photoluminescence property

Different nanostructures such as flower-like, rod-like, and snowflake-like of ZnO have been synthesized by varying the amount of agarose using sonochemical method. It is found that morphology is governed by amount of agarose as well as ultrasonic treatment. Three amounts of agarose 0.01, 0.1, and 1.00 g are used to investigate its effect on ZnO. X-ray diffraction (XRD) confirmed the formation of single phase with hexagonal structure. Scanning electron microscopy (SEM) showed flower-like, rod-like, and snowflake-like morphology for 1.00, 0.1, and 0.01 g agarose, respectively. UV/Visible absorption study showed blue shift at band-edge absorption in comparison to bulk ZnO. Photoluminescence spectra showed band-edge emission at 399 nm for lowest amount of agarose which quenched on increasing the agarose amount. These findings show a better and more environment friendly procedure for production of ZnO of readily adjustable morphology.