Low-pressure gas chromatography: Recent trends and developments

In the past few years, low-pressure gas chromatography (LP-GC) has been applied for the fast analysis of various pollutants in different environmental and food matrices. A typical LP-GC set-up involves the use of a short microbore column (typically 0.5–1 m × 0.10 mm internal diameter) at the injector side connected with a zero dead-volume connector to a short megabore column (typically 10 m × 0.53 mm) to be used with higher gas velocities. This set-up maintains atmospheric injection conditions, while the analytical column is operated under low-pressure conditions that are compatible with mass-spectrometer analyzers. Although the use of LP-GC results in a loss of separation efficiency, it offers a 3–5-fold reduction in analysis time for organic compounds and thus increased sample throughput and enhancement of the signal-to-noise ratio leading to improved detection limits. Considering the significance of, and the potential interest in, this topic, this review briefly describes the concept of LP-GC. Furthermore, we explore recent developments and applications of LP-GC, with a focus on the use of various column systems and analyzers. Finally, we critically evaluate the prospects for, and the limitations of, LP-GC.     

Asymmetric Synthesis of Monofluorinated Carbocyclic Alcohols and Vicinal Difluorinated Heterocycles and Carbocycles

A straightforward method to access novel families of enantioenriched cis-monofluorinated carbocyclic alcohols has been developed through ATH/DKR in up to 97 % yield, up to 99 : 1 dr and enantioinductions up to 97 % ee. Trans-difluorinated indans, tetrahydronaphthalenes, tetrahydroquinolines and chromans have been synthesized as well by deoxofluorination of the corresponding cis-fluoro alcohols. The reaction was performed on a series of variously substituted 3-fluorochromanols, 3-fluorotetrahydroquinolinols, 2-fluoro inden-1-ols and 2-fluoro 1,2,3,4-tetrahydronaphthalen-1-ols in up to 86 % yields, with diastereoselectivities up to 97 : 3 and enantioselectivities up to >99 % ee.     

Capturing the Polarization Response of Solvated Proteins under Constant Electric Fields in Molecular Dynamics Simulations

We capture and compare the polarization response of a solvated globular protein ubiquitin to static electric (E-fields) using atomistic molecular dynamics simulations. We collectively follow E-field induced changes, electrical and structural, occurring across multiple trajectories using the magnitude of the protein dipole vector ( P _p ). E-fields antiparallel to P _p induce faster structural changes and more facile protein unfolding relative to parallel fields of the same strength. While weak E-fields (0.1–0.5 V/nm) do not unfold ubiquitin and produce a reversible polarization, strong E-fields (1–2 V/nm) unfold the protein through a pathway wherein the helix:β-strand interactions rupture before those for the β1-β5 clamp. Independent of E-field direction, high E-field induced structural changes are also reversible if the field is switched off before P _p exceeds 2 times its equilibrium value. We critically examine the dependence of water properties, protein rotational diffusion and E-field induced protein unfolding pathways on the thermostat/barostat parameters used in our simulations.     

Conformational flipping of the N(6) substituent in diprotonated N6‐(N‐glycylcarbonyl)adenines: The role of N(6)H in purine‐ring‐protonated ureido adenines

Conformational transitions of the N(6) substituent, in hypermodified nucleic acid base N⁶‐(N‐glycylcarbonyl)adenine, gc⁶Ade, on diprotonation of the adenine ring at any two of N(1), N(3), and N(7) sites, are studied using the quantum chemical perturbative configuration interaction with localized orbitals (PCILO) method. The N(6) substituent retains the usual “distal” orientation (α=0°) in (N(1),N(3)) diprotonated gc⁶Ade, but the “proximal” orientation (α=180°) is preferred instead, for (N(3),N(7)) and (N(7),N(1)) diprotonated gc⁶Ade. The proximal orientation may alter the reading frame during translation. Intramolecular N(6)HO(13b) hydrogen bonding is the key common feature, present in the preferred structure, for each of these variously diprotonated gc⁶Ade. © 2000 John Wiley & Sons, Inc. Int J Quant Chem 78: 398–405, 2000     

Stereoselective total synthesis of the (Z)-isomer of a novel phytotoxic nonenolide from Phomopsis sp. HCCB03520 and its C-6 epimer

The (Z)-isomer of a phytotoxic nonenolide, (6S,7R,9R)-6,7-dihydroxy-9-propylnon-4-eno-9-lactone isolated from Phomopsis sp. HCCB03520 and its C-6 epimer have been synthesized through a common route starting from butyraldehyde. The synthesis involves enantioselective Maruoka allylation, Sharpless asymmetric epoxidation and intramolecular ring closing metathesis as the important steps.     

Inverting Small Molecule–Protein Recognition by the Fluorine Gauche Effect: Selectivity Regulated by Multiple H→F Bioisosterism

Fluorinated motifs have a venerable history in drug discovery, but as C(sp³)?F‐rich 3D scaffolds appear with increasing frequency, the effect of multiple bioisosteric changes on molecular recognition requires elucidation. Herein we demonstrate that installation of a 1,3,5‐stereotriad, in the substrate for a commonly used lipase from Pseudomonas fluorescens does not inhibit recognition, but inverts stereoselectivity. This provides facile access to optically active, stereochemically well‐defined organofluorine compounds (up to 98 % ee). Whilst orthogonal recognition is observed with fluorine, the trend does not hold for the corresponding chlorinated substrates or mixed halogens. This phenomenon can be placed on a structural basis by considering the stereoelectronic gauche effect inherent to F?C?C?X systems (σ→σ*). Docking reveals that this change in selectivity (H versus F) with a common lipase results from inversion in the orientation of the bound substrate being processed as a consequence of conformation. This contrasts with the stereochemical interpretation of the biogenetic isoprene rule, whereby product divergence from a common starting material is also a consequence of conformation, albeit enforced by two discrete enzymes.     

Chiral separation and thermodynamic investigation of WCK 3023: A novel oxazolidinone antibacterial agent,application to pre‐clinical pharmacokinetic study

A chiral liquid chromatographic method was developed and validated for the quantification of R‐enantiomer impurity (RE) in WCK 3023 (S‐enantiomer), a new drug substance. The separation was achieved on Chiralpak IA (amylose‐based immobilized chiral stationary phase), using a mobile phase consisting of n‐hexane–ethanol–trifluoroacetic acid (70:30:0.2, v/v/v) at a flow rate of 1.0 mL/min. The method was extensively validated for the quantification of RE in WCK 3023 and proved to be robust. For RE the detector response was linear over the concentration range of 0.11–5 μg/mL. The limit of quantitation and limit of detection for RE were 0.11 and 0.04 μg/mL respectively. Average recovery of the RE was in the range of 98.11–99.55%. The developed method was specific, sensitive, precise and accurate for quantitative determination of RE in WCK 3023. The impact of thermodynamic parameters on the chiral separation was evaluated. The method was employed for controlling the enantiomeric impurity in the lots of WCK 3023 used for pre‐clinical studies. The method was successfully applied to evaluate the possible conversion of WCK 3023 to RE in rat serum samples during pre‐clinical pharmacokinetic studies.     

Organic Reactions Using Clay and Clay-Supported Catalysts: A Survey of Recent Literature

Catalysis Surveys from Asia - Clays and modified or supported clays have become some of the widely used catalysts for a variety of organic reactions, due to their easy structural modifications and...     

Interplay of Anion-π+ and π+-π+ Interactions in Novel Pyrido[2,1-a]isoquinolinium-Based AIEgens - Substituent- and Counterion-Dependent Fluorescence Modulation and Applications in Live Cell Mitochondrial Imaging**

Recently, the concept of anion-π⁺ interactions has witnessed unique applications in the field of AIEgen development. In this contribution, we disclose a consolidated study of a library of N-doped ionic AIEgens accessed through silver-mediated cyclization of pyridino-alkynes. A thorough photophysical, computational and crystallographic study has been conducted to rationalize the observed substituent- and counterion-dependent fluorescence properties of these luminogens. We further elucidate the prominent role of anion-π⁺ interactions, π⁺-π⁺ interactions and other non-covalent interactions, in inhibiting the undesired ACQ effect. Finally, we have also demonstrated the application of selected AIEgens for imaging of mitochondria in live cells.