Chemistry of Lipid A: At the Heart of Innate Immunity

In many Gram‐negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll‐like receptor 4/myeloid differentiation factor 2 (TLR4/MD‐2) receptor complex. It often causes a wide variety of biological effects ranging from a remarkable enhancement of the resistance to the infection to an uncontrolled and massive immune response resulting in sepsis and septic shock. Since the bioactivity of lipid A is strongly influenced by its primary structure, a broad range of chemical syntheses of lipid A derivatives have made an enormous contribution to the characterization of lipid A bioactivity, providing novel pharmacological targets for the development of new biomedical therapies. Here, we describe and discuss the chemical aspects regarding lipid A and its role in innate immunity, from the (bio)synthesis, isolation and characterization to the molecular recognition at the atomic level.     

Enhanced Catalytic Activity in Liquid‐Exfoliated FeOCl Nanosheets as a Fenton‐Like Catalyst

A facile liquid‐phase exfoliation method to prepare few‐layer FeOCl nanosheets in acetonitrile by ultrasonication is reported. The detailed exfoliation mechanism and generated products were investigated by combining first‐principle calculations and experimental approaches. The similar cleavage energies of FeOCl (340 mJ m^?2) and graphite (320 mJ m^?2) confirm the experimental exfoliation feasibility. As a Fenton reagent, FeOCl nanosheets showed outstanding properties in the catalytic degradation of phenol in water at room temperature, under neutral pH conditions, and with sunlight irradiation. Apart from the increased surface area of the nanosheets, the surface state change of the nanosheets also plays a key role in improving the catalytic performance. The changes of charge density, density of states (DOS), and valence state of Fe atoms in the exfoliated FeOCl nanosheets versus plates illustrated that surface atomistic relationships made the few‐layer nanosheets higher activity, indicating the exfoliation process of the FeOCl nanosheets also brought about surface state changes.     

One-pot,solvent-free and efficient synthesis of 2,4,6-triarylpyridines catalyzed by nano-titania-supported sulfonic acid as a novel heterogeneous nanocatalyst

Nano titania-supported sulfonic acid (n-TSA) has found to be a highly efficient, eco-friendly and recyclable heterogeneous nanocatalyst for the solvent-free synthesis of 2, 4, 6-triarylpyridines through one-pot three-component reaction of acetophenones, aryl aldehydes and ammonium acetate. This reported method illustrates several advantages such as environmental friendliness reaction conditions, simplicity, short reaction time, easy work up, reusability of catalyst and high yields of the products. One new compound is reported too. Furthermore, the catalyst could be recycled after a simple work-up, and reused at least six times without substantial reduction in its catalytic activity.     

Development and validation of a reversed‐phase HPLC method for CYP1A2 phenotyping by use of a caffeine metabolite ratio in saliva

CYP1A2 is important for metabolizing various clinically used drugs. Phenotyping of CYP1A2 may prove helpful for drug individualization therapy. Several HPLC methods have been developed for quantification of caffeine metabolites in plasma and urine. Aim of the present study was to develop a valid and simple HPLC method for evaluating CYP1A2 activity during exposure in xenobiotics by the use of human saliva. Caffeine and paraxanthine were isolated from saliva by liquid‐liquid extraction (chlorophorm/isopropanol 85/15v/v). Extracts were analyzed by reversed‐phase HPLC on a C₁₈ column with mobile phase 0.1% acetic acid/methanol/acetonitrile (80/20/2 v/v) and detected at 273nm. Caffeine and paraxanthine elution times were <13min with no interferences from impurities or caffeine metabolites. Detector response was linear (0.10–8.00µg/ml, R²>0.99), recovery was >93% and bias <4.47%. Intra‐ and inter‐day precision was <5.14% (n=6). The limit of quantitation was 0.10µg/ml and the limit of detection was 0.018±0.002µg/mL for paraxanthine and 0.032±0.002µg/ml for caffeine. Paraxanthine/caffeine ratio of 34 healthy volunteers was significantly higher in smokers (p<0.001). Saliva paraxanthine/caffeine ratios and urine metabolite ratios were highly correlated (r=0.85, p<0.001). The method can be used for the monitoring of CYP1A2 activity in clinical practice and in studies relevant to exposure to environmental and pharmacological xenobiotics. Copyright © 2015 John Wiley & Sons, Ltd.     

一种带疏水长链的水溶性偶氮引发剂的合成及端基疏水聚合物疏水缔合效应研究

以偶氮二异丁腈、十二胺为主要原料,通过Pinner反应制备了一种两端各带有12个碳烷基链的水溶性偶氮引发剂——2,2'-偶氮二异丁基十二脒盐酸盐AIBL.采用核磁氢谱、元素分析及液相色谱对AIBL进行了结构及纯度表征,采用TGA、DSC和紫外分光光度计研究了其热分解现象和热分解动力学,采用表面张力仪对其表面活性进行了测定.结果表明,所合成的引发剂AIBL具有预想的结构和较高的纯度,其热分解反应属于一级反应,热分解活化能为134.80 k J/mol,70℃下水中的半衰期约为4 h;AIBL在水溶液中具有表面活性,其临界胶束浓度为0.13 g/L,对应的表面张力为33.57 m N/m.以丙烯酰胺为单体、AIBL为引发剂制备了水溶性端基疏水聚合物SPAM.采用溴化法研究其转化率,应用乌氏黏度法、零切黏度法以及荧光探针对其缔合作用进行了研究.结果表明,AIBL具有良好的引发丙烯酰胺聚合的能力;相对于不带疏水长链的引发剂所合成的聚合物PAM,SPAM具有明显的疏水缔合效应,这说明AIBL成功地将疏水长链引入到聚合物的端基中,从而形成端基疏水聚合物.     

Nanocrystalline TiO2, via green combustion synthesis,as an efficient and reusable catalyst for the preparation of 1,8‐dioxooctahydroxanthenes and 1,8‐dioxodecahydroacridines

Nanocrystalline TiO₂ is synthesized using a green combustion method and used as a recyclable catalyst for the one‐pot multicomponent synthesis of 1,8‐dioxodecahydroacridines and 1,8‐dioxooctahydroxanthenes, under solvent‐free conditions. This method is mild, environmentally friendly, inexpensive and highly effective for obtaining good to excellent yields of the products. Copyright © 2015 John Wiley & Sons, Ltd.     

不同有机碱对铕-2-羟基喹啉-4-羧酸配合物发光性能的影响

分别在有机碱三乙胺、三丙胺和三丁胺的作用下,使用2-羟基喹啉-4-羧酸(H2hqc)与EuCl3·6H2O反应制备了3种配合物Eu(Hhqc)3(TEL)、Eu(Hhqc)3(TPL)和Eu(Hhqc)3(TBL)。通过元素分析、热重分析、摩尔电导率、紫外光谱、荧光光谱、荧光寿命和量子产率等对配合物进行了表征。所有配合物均在580,592,613,654,702 nm附近产生5条谱带,为Eu3+的特征发射,归属为5D0→7FJ(J=0,1,2,3,4)能级间的跃迁,荧光寿命分别为2.22,3.29,3.31 ms,量子产率分别为0.011,0.019,0.028。随着有机胺碳链长度的增加,配合物的荧光强度依次增大,表明有机碱参与了配合物的分子组成。     

Asymmetric cross-aldol reaction of isatin and ketones catalyzed by crude earthworm extract as efficient biocatalyst

ABSTRACT

The asymmetric cross-aldol reaction of simple ketones (acetone, cyclohexanone) with isatin derivatives in the presence of crude extract from earthworms as green and effective biocatalyst proceeds easily in MeCN/H₂O (1:1) as solvent to afford 3-hydroxy-2-oxindoles derivatives. Ten compounds were synthesized in high yields (62–88%) and moderate ee (29–42%). Structure of the synthesized compounds has been characterized on the basis of NMR spectra and CHN analysis. The ee of the obtained compounds was determined by chiral phase HPLC analysis.