Metabolite assignment of ultrafiltered synovial fluid extracted from knee joints of reactive arthritis patients using high resolution NMR spectroscopy

Currently, there are no reliable biomarkers available that can aid early differential diagnosis of reactive arthritis (ReA) from other inflammatory joint diseases. Metabolic profiling of synovial fluid (SF)—obtained from joints affected in ReA—holds great promise in this regard and will further aid monitoring treatment and improving our understanding about disease mechanism. As a first step in this direction, we report here the metabolite specific assignment of ¹H and ¹³C resonances detected in the NMR spectra of SF samples extracted from human patients with established ReA. The metabolite characterization has been carried out on both normal and ultrafiltered (deproteinized) SF samples of eight ReA patients (n = 8) using high-resolution (800 MHz) ¹H and ¹H─¹³C NMR spectroscopy methods such as one-dimensional ¹H CPMG and two-dimensional J-resolved¹H NMR and homonuclear ¹H─¹H TOCSY and heteronuclear¹H─¹³C HSQC correlation spectra. Compared with normal SF samples, several distinctive ¹H NMR signals were identified and assigned to metabolites in the ¹H NMR spectra of ultrafiltered SF samples. Overall, we assigned 53 metabolites in normal filtered SF and 64 metabolites in filtered pooled SF sample compared with nonfiltered SF samples for which only 48 metabolites (including lipid/membrane metabolites as well) have been identified. The established NMR characterization of SF metabolites will serve to guide future metabolomics studies aiming to identify/evaluate the SF-based metabolic biomarkers of diagnostic/prognostic potential or seeking biochemical insights into disease mechanisms in a clinical perspective.     

Reversal Diastereoselectivity Between the Organomagnesium and Organolithium Reagents on Chiral N-Tert-Butylsulfinylaldimines for the Preparation of Chiral Amines

The asymmetric synthesis of both the enantiomer of chiral amines from the single chiral source of N-tert-butylsulfinylaldimines (3) by simply changing the organometallic reagents through diastereoselective addition. An efficient enantioselective synthesis of chiral amines including (S)-3-methyl-1-(2-piperidin-1-yl-phenyl)butyl amine (6a), a key intermediate to prepare antidiabetic drug repaglinide (1), is reported.     

In vitro anti-cataract evaluation of standardised Abies pindrow leaf extract using isolated goat lenses

Oxidative stress is known to spark off the pathogenesis of cataract. Antioxidant potential of Abies pindrow Royle leaf extract (APE) is well established in the literature. In this context, standard aqueous leaf extract of this plant was evaluated for its role in hydrogen peroxide-induced cataract in isolated goat lenses using varying concentrations (5, 10, 15 and 20 mg/mL). Total phenol and flavonoidal content was evaluated and found to be high in concentration. Biochemical parameters, namely superoxide dismutase (SOD), glutathione (GSH), total protein content (TPC) and malondialdehyde (MDA), were evaluated. SOD, GSH and TPC formation was found to increase proportionally with increasing concentration. However, MDA level decreased significantly as the concentration of the extract increased. The results suggest that the extract under investigation can delay the onset and/or prevent the progression of cataract. Its anti-cataract potential may be attributed to the presence of high phenolics and flavonoids in APE. Photographic evaluation, further, confirmed the observation.     

Development and validation of a sensitive LC-MS/MS method with electrospray ionization using multiple ions for quantitation of torcetrapib in hamster and dog plasma

A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of torcetrapib (TTB) with 100 microL hamster/dog plasma using DRL-16126 as an internal standard (IS). The API-4000 Q Trap LC-MS/MS was operated under multiple-reaction monitoring mode using the electrospray ionization technique. The assay procedure involved extraction of TTB and IS from plasma with acetonitrile, which yielded consistent recoveries of 65.73 and 94.01% for TTB and 79.68 and 90.70% for IS in hamster and dog plasma, respectively. The total chromatographic run time was 3.0 min and the elution of TTB and IS occurred at approximately 2.25 and 2.20 min, respectively. The resolution of peaks was achieved with 0.01 m ammonium acetate:acetonitrile (15:85, v/v) at a flow rate of 0.40 mL/min on an Inertsil ODS-3 column. The method was proved to be accurate and precise at linearity range of 1.00-200 ng/mL with a correlation coefficient (r) of > or = 0.993. The method was rugged with 1.00 ng/mL as the lower limit of quantitation. TTB was stable in the battery of stability studies. The application of the assay to preclinical pharmacokinetic studies confirmed the utility of the assay to derive hamster/dog pharmacokinetic parameters.     

Ruthenium(II), rhodium(III) and iridium(III) based effective catalysts for hydrogenation under aerobic conditions

The new cationic mononuclear complexes [(η⁶-arene)Ru(Ph-BIAN)Cl]BF₄ [η⁶-arene = benzene (1), p-cymene (2)], [(η⁵-C₅H₅)Ru(Ph-BIAN)PPh₃]BF₄ (3) and [(η⁵-C₅Me₅)M(Ph-BIAN)Cl]BF₄ [M = Rh (4), Ir (5)] incorporating 1,2-bis(phenylimino)acenaphthene (Ph-BIAN) are reported. The complexes have been fully characterized by analytical and spectral (IR, NMR, FAB-MS, electronic and emission) studies. The molecular structure of the representative iridium complex [(η⁵-C₅Me₅)Ir(Ph-BIAN)Cl]BF₄ has been determined crystallographically. Complexes 1–5 effectively catalyze the reduction of terephthaldehyde in the presence of HCOOH/CH₃COONa in water under aerobic conditions and, among these complexes the rhodium complex [(η⁵-C₅Me₅)Rh(Ph-BIAN)Cl]BF₄ (4) displays the most effective catalytic activity.     

Asymmetric synthesis of (–)-leiocarpin A via (–)-(S)-goniothalamin employing Julia–Kocienski olefination

A concise and enantioselective syntheses of antileukemic natural products such as (–)-(S)-goniothalamin and (–)-leiocarpin A has been accomplished in excellent yields. By employing reported conditions on suitable substrates via Julia–Kocienski olefination, intramolecular lactonization, and subsequently dehydroxylative olefination, (–)-(S)-goniothalamin was synthesized. Then Sharpless asymmetric dihydroxylation–intramolecular Michael addition on (–)-(S)-goniothalamin provided (–)-leiocarpin A.     

The Neumann Problem for the Kohn-Laplacian on the Heisenberg Group ℍn$\mathbb H_{n}$

The existence and uniqueness of the solution of the Neumann problem for the Kohn-Laplacian relative to the Korányi ball on the Heisenberg group \(\mathbb {H}_{n}\) are discussed. Explicit representation for a Green’s type function (Neumann function) for the Korányi ball in \(\mathbb {H}_{n}\) for circular functions has been obtained. This function is then used on the above region in \(\mathbb {H}_{n}\) to solve the inhomogeneous Neumann boundary value problem for certain circular data.     

Application of Doehlert design in optimizing the determination of degraded products of nerve agents by ion-pair liquid chromatography electrospray ionization tandem mass spectrometry

A qualitative method was developed for the determination of degraded products of nerve agents by using ion-pair liquid chromatography electrospray ionization tandem mass spectrometry (IP-LC-ESI-MS(n)). Generally, alkylphosphonic acids (APAs) and O-alkyl alkylphosphonic acids (AAPAs) give deprotonated molecular ion [M-H](-) in negative mode. Interestingly, first time we obtained the molecular radical anion [M](.-) of phosphonic acids in negative mode by using tri-n-butyl amine as an ion-pairing agent. We interpreted this observation as an indication of electrochemical reduction of phosphonic acids in electrospray needle. Three variables such as sheath gas flow, electrospray needle voltage and pH of the mobile phase were investigated to enhance the molecular radical anion [M](.-) signal of each analyte. The Doehlert design was used to obtain the region in which the optimum value of such variables is simultaneously achieved. Limit of detection achieved was 0.5 microg mL(-1) for AAPAs and 10 microg mL(-1) for APAs. Excellent precision was observed with less than 8.61% RSD. Finally, the method was applied for the detection of ethyl methylphosphonic in aqueous extract of soil sample.