Highly Efficient,Tripodal Ion-Pair Receptors for Switching Selectivity between Acetates and Sulfates Using Solid–Liquid and Liquid–Liquid Extractions

A tripodal, squaramide-based ion-pair receptor 1 was synthesized in a modular fashion, and ¹H NMR and UV-vis studies revealed its ability to interact more efficiently with anions with the assistance of cations. The reference tripodal anion receptor 2, lacking a crown ether unit, was found to lose the enhancement in anion binding induced by presence of cations. Besides the ability to bind anions in enhanced manner by the “single armed” ion-pair receptor 3, the lack of multiple and prearranged binding sites resulted in its much lower affinity towards anions than in the case of tripodal receptors. Unlike with receptors 2 or 3, the high affinity of 1 towards salts opens up the possibility of extracting extremely hydrophilic sulfate anions from aqueous to organic phase. The disparity in receptor 1 binding modes towards monovalent anions and divalent sulfates assures its selectivity towards sulfates over other lipophilic salts upon liquid–liquid extraction (LLE) and enables the Hofmeister bias to be overcome. By changing the extraction conditions from LLE to SLE (solid–liquid extraction), a switch of selectivity from sulfates to acetates was achieved. X-ray measurements support the ability of anion binding by cooperation of the arms of receptor 1 together with simultaneous binding of cations.     

对羟基偶氮苯磺酸钠应用于水相中的阴离子识别研究

合成主体对羟基偶氮苯磺酸钠,并通过紫外-可见吸收光谱及最色反应研究了水作为溶剂时主体对无机盐阴离子的识别作用.结果表明,对羟基偶氮苯磺酸钠可在水中对磷酸根离子进行选择性识别,并产生显著光谱效应和颜色变化,而对其他阴离子则无明显响应,从而实现水相中对磷酸根的裸眼检测.因此该化合物可作为检测水中磷酸根的化学敏感器.     

Utilizing an Amino Acid Scaffold to Construct Heteroditopic Receptors Capable of Interacting with Salts under Interfacial Conditions

A 4-nitro-L-phenylalanine scaffold was used to construct effective ion pair receptors capable of binding anions in an enhanced manner with the assistance of alkali metal cations. A benzocrown ether was linked to a receptor platform via the amide function so as to support the squaramide function in anion binding and to allow all three NHs to act simultaneously. The binding properties of the receptors were determined using UV-vis, ¹H NMR, 2D NMR, and DOSY spectroscopy in MeCN and in the solid state by X-ray measurements. Ion pair receptor 2 was found to interact with the most strongly with salts, and the removal of its key structural elements was shown to hinder the receptor action. The amide proton was recognized to switch from having involvement in an intramolecular hydrogen bond to interacting with anions upon complexation. Apart from carboxylates, which promote deprotonation, and other monovalent salts creating 1:1 complexes with the receptor, more complex equilibria were established upon the complexation of 2 with sulfates. Receptor 2 was shown to be capable of the extraction of ion pairs from the aqueous to organic phase and of the cation-enhanced transport chloride and sulfate anions across a bulk chloroform membrane. These features may open the door for its use in regulating ion concertation under interfacial conditions and acting as a potential drug to treat channelopathies.     

光学活性1,1'-联-2-萘酚类合成受体的应用研究新进展

具有光学活性的1,1'-联-2-萘酚及其衍生物由于其本身具有C2对称轴而具有独特的化学性质和手性诱导功能,且在适合结构基团修饰下能产生很强的荧光,在不对称催化和手性客体的荧光识别等方面得到了广泛的应用.在与手性胺、手性醇、糖类、手性阴离子、手性氨基醇和手性氨基酸等手性化合物作用时,该类受体在不同位点接受客体分子,通过光...     

Amino acid oxidase‐catalysed resolution and Pictet–Spengler reaction towards chiral and rigid unnatural amino acids

BACKGROUND: The biosynthesis of structurally complex isoquinoline alkaloids and other natural products occurs via aromatic amino acids such as tyrosine, and chiral and rigid amino acids. These structures are also key building blocks of many active pharmaceutical ingredients. The aim of this work was the exploration of a rapid and straightforward route to chiral 6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid. RESULTS: The preparation of (S)‐meta‐tyrosine from racemic meta‐tyro‐ sine with aminoacidoxidase has been developed with ee > 99% and 88% yield. The combination of this resolution with a subsequent Pictet–Spengler reaction enables straightforward and versatile access to chiral (S)‐6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid in 30% yield. CONCLUSIONS: This new short chemoenzymatic route to (S)‐6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid from commercially available DL‐m‐tyrosine is more convenient than other chemical procedures and establishes a new link between the pool of easily accessible racemic aromatic amino acids and the corresponding chiral rigidified amino acids, which are of interest as structural elements of many active pharmaceutical ingredients. These results facilitate synthetic access to a range of active pharmaceutical ingredients and metabolites in chiral form from the oxidation of amino acids. This advances the opportunities to study the molecular interactions with enzymes, receptors and effectors more precisely than with the racemic forms. Copyright © 2007 Society of Chemical Industry     

Specific binding of cholic acid by cross-linked polymers prepared by the hybrid imprinting method

A cholic acid-imprinted polymer has been prepared by a hybrid imprinting method involving the use of a template-containing monomer, 3α-methacryloyl cholic acid methyl ester. The removal of the template can afford the polymer with cavities and carboxylic acid groups well positioned in these cavities for the specific binding of cholic acid via hydrogen bonding. The maximum binding capabilities for the imprinted and non-imprinted polymers were determined to be 344.8 and 43.6 μmol/g, respectively. Scatchard analysis indicates the existence of two kinds of binding sites on the imprinted polymer. The imprinted polymers exhibit high affinity and good recognition selectivity for cholic acid in comparison to other compounds with similar molecular structures. The size-specific binding and hydrogen bonding may be both important for the binding of cholic acid by the imprinted polymers.     

两种结构简单绕丹宁衍生物的合成及其对氟离子的选择性识别研究

设计合成了两个结构简单的绕丹宁衍生物,在CH_2Cl_2-DMSO混合溶剂中利用紫外-可见吸收光谱研究了其与多种阴离子的相互作用,发现它们的吸收光谱对氟离子呈现特异性变化,吸收滴定实验确认它们与氟离子间相互作用的化学计量比为1:1,~1H NMR进一步证实它们与氟离子的作用类型为氢键或脱质子作用。     

Molecular Recognition of Two 2,4‐syn‐Functionalized (S)‐Glutamate Analogues by the Kainate Receptor GluK3 Ligand Binding Domain

The kainate receptors are the least studied subfamily of ionotropic glutamate receptors. These receptors are thought to have a neuromodulatory role and have been associated with a variety of disorders in the central nervous system. This makes kainate receptors interesting potential drug targets. Today, structures of the ligand binding domain (LBD) of the kainate receptor GluK3 are only known in complex with the endogenous agonist glutamate, the natural product kainate, and two synthetic agonists. Herein we report structures of GluK3 LBD in complex with two 2,4‐syn‐functionalized (S)‐glutamate analogues to investigate their structural potential as chemical scaffolds. Similar binding affinities at GluK3 were determined for the 2‐(methylcarbamoyl)ethyl analogue (K_i=4.0 μM ) and the 2‐(methoxycarbonyl)ethyl analogue (K_i=1.7 μM ), in agreement with the similar positioning of the compounds within the binding pocket. As the binding affinity is similar to that of glutamate, this type of Cγ substituent could be used as a scaffold for introduction of even larger substituents reaching into unexplored binding site regions to achieve subtype selectivity.     

Chemoenzymatic synthesis of chiral carboxylic acids via nitriles

BACKGROUND: Enantiomerically pure 1,4‐benzodioxane‐2‐carboxylic acid derivatives are useful building blocks for the synthesis of pharmaceuticals and biologically active compounds whose interaction with their biological target (enzyme, receptor) depends very much on the absolute configuration of the chiral carbon at the 2‐position. The aim of the present work is to investigate the route to racemic nitriles and the subsequent selective enzymatic hydrolysis by nitrilase to optically active 1,4‐benzodioxane‐2‐carboxylic acid and 6‐formyl‐1,4‐benzodioxane‐2‐carboxylic acid. RESULTS: A range of microbial nitrilases from Rhodococcus, Alcaligenes and Pseudomonas strains have been prepared and screened for the desired biotransformations using a chiral high performance liquid chromatography (HPLC) analytical method. The nitrilase from Alcaligenes faecalis ATCC 8750 showed the highest and the nitrilase from Rhodococcus rhodochrous NCIMB 11216 the lowest activity towards 2‐cyano‐6‐formyl‐1,4‐benzodioxane. Lyophilised cells of Rhodococcus R 312 gave the (R)‐1,4‐benzodioxane‐2‐carboxylic acid with high enantioselectivity after 25% conversion. Excellent enantioselectivities for the hydrolysis of both 2‐cyano‐1,4‐benzodioxane as well as 2‐cyano‐6‐formyl‐1,4‐benzodioxane have been achieved and the absolute configuration of 1,4‐benzodioxane‐2‐carboxylic acid was determined to be R by comparison with the specific rotation of commercially available (R)‐1,4‐benzodioxane‐2‐carboxylic acid. CONCLUSIONS: This new nitrilase‐catalysed kinetic resolution of 2‐cyano‐ and 2‐cyano‐6‐formyl‐1,4‐benzodioxane opens a mild route to optically active 1,4‐benzodioxane‐2‐carboxylic acids. As the formyl functional group would be damaged in chemical nitrile hydrolysis, nitrilase‐catalysed hydrolysis solves this synthetic bottleneck and advances nitrilase biocatalytic tools for the preparation of more complex 1,4‐benzodioxane‐2‐carboxylic acids. Copyright © 2007 Society of Chemical Industry     

羧酸类配位聚合物的研究进展

羧酸类金属配位聚合物是一种新型功能性分子材料,近年来得到科学家的普遍关注。本文对羧酸类金属配位聚合物的分类进行了综述,综述了羧酸类金属配位聚合物研究的重要性和国内外羧酸类金属配位聚合物的研究工作,对苯多羧酸类、吡啶羧酸类、草酸类、脂肪族二羧酸类配合物在手性拆分和催化、分子磁体、非线性光学方面的研究进行了详细介绍,列举了近年来这类配位聚合物的研究成果和开发进展,并对其发展趋势进行了展望。     

A supramolecular sensing platform for phosphate anions and an anthrax biomarker in a microfluidic device

A supramolecular platform based on self-assembled monolayers (SAMs) has been implemented in a microfluidic device. The system has been applied for the sensing of two different analyte types: biologically relevant phosphate anions and aromatic carboxylic acids, which are important for anthrax detection. A Eu(III)-EDTA complex was bound to β-cyclodextrin monolayers via orthogonal supramolecular host-guest interactions. The self-assembly of the Eu(III)-EDTA conjugate and naphthalene β-diketone as an antenna resulted in the formation of a highly luminescent lanthanide complex on the microchannel surface. Detection of different phosphate anions and aromatic carboxylic acids was demonstrated by monitoring the decrease in red emission following displacement of the antenna by the analyte. Among these analytes, adenosine triphosphate (ATP) and pyrophosphate, as well as dipicolinic acid (DPA) which is a biomarker for anthrax, showed a strong response. Parallel fabrication of five sensing SAMs in a single multichannel chip was performed, as a first demonstration of phosphate and carboxylic acid screening in a multiplexed format that allows a general detection platform for both analyte systems in a single test run with μM and nM detection sensitivity for ATP and DPA, respectively.     

偶氮苯水杨醛的合成及阴离子识别研究

将显色性良好的偶氮苯与水杨醛反应合成得到3种阴离子受体分子偶氮苯水杨醛衍生物,利用紫外光谱仪考察了受体分子与客体阴离子相互作用;通过改变偶氮苯环伞代基来调控或改善受体分子对阴离子的亲合力和选择性.实验表明:乙腈中F~-、CH_3CO_2~-等阴离子加入,受体分子b吸收光谱显著红移,溶液的颜色由无色转变为红色,可以实现F~-、CH_3CO_2~-裸眼识别的检测.Job-Plot测定受体分子b与F~-、CH_3CO_2~-结合比均为1∶1.~1HNMR滴定为受体分子b与阴离子间的氢键作用本质提供了直接证据.     

Regulatory effects of Zn(II) on the recognition properties of metal coordination imprinted polymers

Using a Zn(II)–quercetin complex as a template (quercetin is a kind of flavonoid; flavonoids are important active ingredients of Chinese herbs), we prepared a new kind of metal coordination imprinted polymer (MCIP) in methanol by a molecular imprinting technique. The coordination mode and coordination ratio between quercetin and Zn(II) were studied in differential ultraviolet absorption spectrometry, and the ternary coordination of quercetin, Zn(II), and 4‐vinylpyridine was verified by similar methods. The effect of the crosslinking agent dosage on the morphology and network structure of MCIP and its binding capacity were studied by transmission electron microscopy and equilibrium binding experiments. The regulation of different anions and cations on the identification system of MCIP was studied in detail. In addition, the binding characteristics of MCIP were evaluated by Scatchard analysis. The experimental results show that the Zn(II)–quercetin imprinted polymer had selective binding to its template complex, including selectivities to the anions and cations, and a class of homogeneous recognition sites was formed in the polymer within the range of studied concentration. The dissociation constant and most apparent specific adsorption amount of the Zn(II)–quercetin imprinted polymer was calculated to be 0.6983 mmol/L and 78.72 μmol/g, respectively. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Chemosensors for pyrophosphate

The selective detection of the anion pyrophosphate (PPi) is a major research focus. PPi is a biologically important target because it is the product of ATP hydrolysis under cellular conditions, and because it is involved in DNA replication catalyzed by DNA polymerase, its detection is being investigated as a real-time DNA sequencing method. In addition, within the past decade, the ability to detect PPi has become important in cancer research. In general, the sensing of anions in aqueous solution requires a strong affinity for anions in water as well as the ability to convert anion recognition into a fluorescent or colorimetric signal. Among the variety of methods for detecting PPi, fluorescent chemosensors and colorimetric sensors for PPi have attracted considerable attention during the past 10 years. Compared with the recognition of metal ions, it is much more challenging to selectively recognize anions in an aqueous system due to the strong hydration effects of anions. Consequently, the design of PPi sensors requires the following: an understanding of the molecular recognition between PPi and the binding sites, the desired solubility in aqueous solutions, the communicating and signaling mechanism, and most importantly, selectivity for PPi over other anions such as AMP and ADP, and particularly phosphate and ATP. This Account classifies chemosensors for PPi according to topological and structural characteristics. Types of chemosensors investigated and reported in this study include those that contain metal ion complexes, metal complexes combined with excimers, those that function with a displacement approach, and those based on hydrogen-bonding interaction. Thus far, the utilization of a metal ion complex as a binding site for PPi has been the most successful strategy. The strong binding affinity between metal ions and PPi allows the detection of PPi in a 100% aqueous solution. We have demonstrated that carefully designed receptors can distinguish between PPi and ATP based on their different total anionic charge densities. We have also demonstrated that a PPi metal ion complex sensor has a bioanalytical application. This sensor can be used in a simple and quick, one-step, homogeneous phase detection method in order to confirm DNA amplification after polymerase chain reaction (PCR).     

Molecular Modeling Study of Chiral Separation and Recognition Mechanism of β-Adrenergic Antagonists by Capillary Electrophoresis

Chiral separations of five β-adrenergic antagonists (propranolol, esmolol, atenolol, metoprolol, and bisoprolol) were studied by capillary electrophoresis using six cyclodextrins (CDs) as the chiral selectors. Carboxymethylated-β-cyclodextrin (CM-β-CD) exhibited a higher enantioselectivity power compared to the other tested CDs. The influences of the concentration of CM-β-CD, buffer pH, buffer concentration, temperature, and applied voltage were investigated. The good chiral separation of five β-adrenergic antagonists was achieved using 50 mM Tris buffer at pH 4.0 containing 8 mM CM-β-CD with an applied voltage of 24 kV at 20 °C. In order to understand possible chiral recognition mechanisms of these racemates with CM-β-CD, host-guest binding procedures of CM-β-CD and these racemates were studied using the molecular docking software Autodock. The binding free energy was calculated using the Autodock semi-empirical binding free energy function. The results showed that the phenyl or naphthyl ring inserted in the hydrophobic cavity of CM-β-CD and the side chain was found to point out of the cyclodextrin rim. Hydrogen bonding between CM-β-CD and these racemates played an important role in the process of enantionseparation and a model of the hydrogen bonding interaction positions was constructed. The difference in hydrogen bonding formed with the -OH next to the chiral center of the analytes may help to increase chiral discrimination and gave rise to a bigger separation factor. In addition, the longer side chain in the hydrophobic phenyl ring of the enantiomer was not beneficial for enantioseparation and the chiral selectivity factor was found to correspond to the difference in binding free energy.     

酶催化的动态动力学拆分和去消旋化反应的研究进展

最近,在外消旋化合物的动态动力学拆分以及去消旋化反应方面,新型催化剂的发现以及反应条件的优化都得到了很大的发展。一些特殊功能团使得它们的化合物可以发生动态动力学拆分或是去消旋反应,如仲醇、α-氨基酸、胺及羧酸。在催化反应过程中,一般都是对映体选择性酶与化学试剂的相结合,化学试剂一般常用于催化非活性对映体发生去消旋反应或是回收去消旋化过程中的中间体。在一些动态动力学拆分中,消旋酶还可以催化对映异构体之间发生互变。     

吡啶羧酸类配位聚合物的研究进展

作为潜在的新型功能材料,吡啶羧酸类配位聚合物近年来得到科学家的普遍关注.本文主要对吡啶羧酸类配位聚合物在手性拆分和催化、分子磁体、非线性光学方面的研究进行了综述,列举了近年来这类配位聚合物的研究成果和开发进展,并对其发展前景作出了展望.     

电化学手性识别材料的研究与应用

手性是指物质分子互成镜像但无法重合的性质,手性对映体在生物体内因不同的手性识别而呈现截然不同的作用,所以手性识别在生命科学、医药、食品及材料等领域均具有十分重要的科学意义。手性电化学传感器由于具有制备简单、检测快速和响应灵敏等优点而引起广泛的关注。手性识别材料是构建手性电化学传感器的基础,因此有关手性识别材料的研究在手性电化学检测中尤为重要。综述了近五年手性电化学传感器的研究进展,详细介绍了多种手性识别材料的具体应用,并对该领域的发展前景进行了展望,旨在为今后手性电化学传感器的设计提供参考。     

Formation of Nitrates in Aqueous Solutions Treated with Pulsed Corona Discharge: The Impact of Organic Pollutants

Pulsed corona discharge (PCD) in oxygen-nitrogen mixtures results in formation of nitrogen oxides, transformed to aqueous nitrates in contact with water. The experimental research into the impact of formate and oxalate to nitrate formation in aqueous solutions treated with PCD was undertaken. The impact of paracetamol, ibuprofen, indomethacin and their oxidation products to nitrate formation was also analyzed. Pharmaceuticals obstructed nitrate formation, while carboxylic anions and pharmaceuticals’ oxidation products noticeably improved nitrate formation in treated solutions as compared to water. The nitrate formation enhancement is explained by the aqueous ozone decomposition and hydroxyl radical formation known to be improved by carboxylic anions.