Synthesis and Metal Ion Recognition Properties of a Novel Chiral Calix[4](azoxa)crown-7

A novel chiral calix[4](azoxa)crown-7 (9) has been synthesized and its metal ion recognition properties investigated. The starting reagents, chiral diamine 5 and calix[4]arene diacid chloride derivative 8, were prepared according to literature methods. ¹H and ¹³C NMR data show that 9 exists in a cone conformation. In liquid–liquid extraction experiments, 9 exhibits selectivity for Li⁺ among the other alkali metals and a good extraction ability for transition metal cations, suggesting its potential use in different fields, such as a sensor for ions as well as for chiral molecules.     

First Synthesis of 1,3-Alternate 25,27-Dialkyloxy-5,17-diarylcalix[4]arenes-crown-6 as New Cesium Selective Extractants by Suzuki Cross-coupling Reaction

The synthesis of new 25,27-dialkyloxy-5,17-diarylcalix[4]arenes-crown-6 1a–f in 1,3-alternate conformation by Suzuki cross-coupling reaction is reported. Their conformation was determined using ¹H, ¹³C, 2D NMR and ROESY analysis, and X-ray crystallography. Extraction experiments using a two-phase solvent method involving sodium, potassium or cesium picrate showed good extraction of the cesium cation. The X-ray crystal structures of 1,3-alternate 25,27-dipropoxy-5,17-diphenylcalix[4]arene-crown-6 ether 1a and its cesium picrate complex were established. Solid-state data were used to determine the complexation behavior of these new ligands. The efficiency of calixarenes 1a–f for cesium ion extraction could be ascribed to the rigidity and flatness linkages caused by the aryl groups at the lower rim of the aromatic moieties in the calixarene skeleton. In addition, the introduction of these aromatic moieties in positions 5 and 17 enhanced the solubility of the metal complexes in organic media.     

Identification of potential HIV-1 integrase strand transfer inhibitors: In silico virtual screening and QM/MM docking studies

HIV-1 integrase (IN) is a retroviral enzyme that catalyses integration of the reverse-transcribed viral DNA into the host genome, which is necessary for efficient viral replication. In this study, we have performed an in silico virtual screening for the identification of potential HIV-1 IN strand transfer (ST) inhibitors. Pharmacophore modelling and atom-based 3D-QSAR studies were carried out for a series of compounds belonging to 3-Hydroxypyrimidine-2,4-diones. Based on the ligand-based pharmacophore model, we obtained a five-point pharmacophore with two hydrogen bond acceptors (A), one hydrogen bond donor (D), one hydrophobic group (H) and one aromatic ring (R) as pharmacophoric features. The pharmacophore hypothesis AADHR was used as a 3D query in a sequential virtual screening study to filter small molecule databases Maybridge, ChemBridge and Asinex. Hits matching with pharmacophore hypothesis AADHR were retrieved and passed progressively through Lipinski’s rule of five filtering, molecular docking and hierarchical clustering. The five compounds with best hits with novel and diverse chemotypes were subjected to QM/MM docking, which showed improved docking accuracy. We further performed molecular dynamics simulation and found three compounds that form stable interactions with key residues. These compounds could be used as a leads for further drug development and rational design of HIV-1 IN inhibitors.     

QSAR Study on Binding Affinity of PATs (Rodenticides) to the [3H]-Mepyramine-Labelled H1 Receptor In Rat and Guinea Pig Brain

Abstract

The binding of a series of PAT analogues (rodenticides) to the [³H]-mepyramine-labelled H₁ receptor in rat and guinea pig brain was investigated topologically using negentropy (N), molecular redundancy (MRI), first-order molecular connectivity (¹X _v ), Wiener (W), and Szeged (Sz) indices. Multiple regression analyses showed that MRI provided excellent results upon introduction of indicator parameters. Predictive ability of the proposed models was discussed using cross-validation parameters.     

Identification of reducing and nonreducing neutral carbohydrates by laser‐enhanced in‐source decay (LEISD) MALDI MS

In this work, laser‐enhanced in‐source decay (LEISD) technique of matrix‐assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI‐FT‐ICR‐MS) was used to distinguish reducing and nonreducing carbohydrates. Interestingly, easier cleavage of (1 → 2)‐linked glycosidic bonds for nonreducing carbohydrates containing D‐fructofuranosyl units was observed in MALDI‐FT‐ICR‐MS, which was in agreement with the result of theoretical calculation by the software package Gaussian 09. Importantly, no cross‐ring cleavage of fructofuranosyl residues was detected in the LEISD spectra of nonreducing carbohydrates. LEISD method therefore offers an attractive alternative for fast and efficient differentiation of reducing and nonreducing carbohydrates, and the positions of nonreducing monosaccharide residues in a carbohydrate chain could be easily speculated. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis,spectroscopic and crystal structure analysis of 2-(4-fluorobenzyl)-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole and its morpholinomethyl derivative

The preparation of 2-(4-fluorobenzyl)-6-(4-methoxyphenyl)-5-morpholin-1-ylmethyl imidazo[2,1-b][1,3,4]thiadiazole via the intermediate 2-(4-fluorobenzyl)-6-(4-methoxyphenyl)Imidazo[2,1-b][1,3,4] thiadiazole is described. Elemental analysis, IR spectrum, ¹H NMR and X-ray crystal structure analyses were carried out to determine the compositions and molecular structures of the two compounds. The crystal packing exhibits intermolecular C–H?O, C–H?N, C–H?F and π–π stacking interactions leading to the formation of the supramolecular network.