新型Schiff碱分子钳对中性分子的识别性能研究

采用差紫外光谱法考察了3种新型Schiff碱分子钳对一系列二苯甲酮、芳香二胺的识别性能.测定了主客体间的结合常数(Ka)和自由能变化(ΔG0).结果表明,分子钳对所考察的客体显示良好的识别作用,主客体间形成1:1型超分子配合物.讨论了识别作用的推动力与形状、大小匹配和几何互补等因素对形成主客体配合物的影响,并利用核磁氢谱与计算机模拟作为辅助手段对主要的实验结果与现象进行了解释.     

Nucleotide recognition by protonated aminoglycosides

Interactions of protonated forms of kanamycin A with nucleotides and several simple phosphate anions have been studied by potentiometric and NMR titrations. The affinity of kanamycin A to anions is comparable to that observed with other aliphatic polyammonium receptors of similar charge, but it discriminates triphosphate nucleotides with different nucleobases with binding constants following the order GTP?CTP ≈ ATP. Kanamycin A also binds the respective uncharged nucleosides with the same selectivity. Binding of ATP is exothermic with a negative entropic contribution in contrast to what is expected for simple ion pairing. Other tested aminoglycosides, amikacin and streptomycin, bind ATP less efficiently than kanamycin A. Models of structures of kanamycin A complexes with ATP and GTP obtained by molecular mechanics (OPLS-2005) calculations based on ¹H and ³¹P NMR data confirm the possibility of nucleotide discrimination by simultaneous ion pairing of terminal nucleotide phosphate groups with ammonium sites of rings B and C and hydrogen bonding of the nucleobase at the ring A of the aminoglycoside.     

Langmuir and Langmuir-Blodgett monolayers of molecular tweezers and clips

Molecular clips and tweezers are able to selectively bind electron-deficient aromatic and aliphatic substrates. By means of pressure-area isotherms and Brewster angle microscopy (BAM), the self-association process and phase behavior of dimethylene-bridged molecular clips and tetramethylene-bridged molecular tweezers each substituted with two acetoxy groups as polar head groups were investigated. In a series of experiments, we observed that the molecular surface area of the clips and tweezers only depended on the skeletal structure and not on the polar groups. The measured areas agreed with the effective molecular diameters of the molecules if the aromatic side walls of the clips or tweezers were assumed to be aligned perpendicularly to the water surface. We compared the phase behavior of the pure molecular clips and tweezers with that of the host-guest complexes of these molecules, which were formed with 1,2,4,5-tetracyanobenzene (TCNB) as the guest molecule. For the clips with a central benzene (I) and naphthalene spacer unit (II), the complex formation with TCNB had no measurable influence on the phase diagrams of the films. We observed, however, a dramatic difference in the BAM images and pi-A isotherms between the pure molecular tweezers III and its complex with TCNB (TCNB@III). In addition to the pi-A isotherms, we used the surface potential (V)-area (A) isotherms to compare the pure tweezers III with the corresponding complex (TCNB@III). There was a strong difference in the maximum surface potential value for the pure tweezers (450 mV) and that for the complex (300 mV). In additional experiments, we prepared LB layers of such molecules, which were investigated by fluorescence spectroscopy. In comparison to the pure tweezers III, a luminescence emission of charge-transfer (CT) origin was observed for the host-guest complex (TCNB@III) fixed on the solid substrate. It turned out that the spectra were in good agreement with the results observed in chloroform solution.     

Synthesis and supramolecular properties of trimethylene-bridged clips

The novel trimethylene-bridged clips 3 and 4 have been synthesized by using repetitive stereoselective Diels-Alder reactions of the benzo- and naphthobismethylenenorbornenes 8 and 19 as dienes and norbornadiene 9 as bisdienophile, and subsequent dehydrogenation of the primary cyclobisadducts 10 and 20 by using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Clips 3 and 4 serve as receptors for a variety of electron-deficient neutral and cationic aromatic substrates, comparable to the molecular tweezers 1 and 2. The thermodynamic parameters of the complex formation, K(a) and DeltaG, were determined by (1)H NMR titration experiments and, in the case of the highly stable complex TCNB 32@4, by the use of isothermal titration microcalorimetry. The finding that clip 4 forms more stable complexes than 3 can be explained by the larger van der Waals contact surfaces of the naphthalene sidewalls in 4 compared to the corresponding benzene systems in 3. In the complexes with 4 as receptor, the plane of each aromatic substrate molecule is calculated to be oriented almost parallel to the naphthalene sidewalls. However, in the complexes of tweezers 2, the substrate is usually oriented parallel to the central naphthalene spacer unit. Due to the more open topology of 4, most complexes were calculated to consist of two or more equilibrating noncovalent conformers.     

Polyfunctional recognition of pyridinedicarboxylate anions with macrocyclic polyamine receptors containing heteroaromatic groups

The interaction of the biologically relevant anions deriving from the six pyridinedicarboxylic acids (H2PDC) with two macrocyclic receptors containing a pentamine chain and a bipyridine (1) or a phenanthroline (2) moiety, as well as with the aliphatic analogue [21]aneN7 (3), was studied by means of spectroscopic methods (UV-vis, NMR) and potentiometric titrations affording the stability constants of the adducts formed. All three receptors form stable complexes with the substrates thanks to the formation of several salt bridges and hydrogen bond contacts, as observed in the crystal structure of the H8[3(2,6-PDC)4] x H2O x 0.5 EtOH solid compound. Additional pi-stacking interactions between the aromatic moieties of substrates and receptors enhance the stability of complexes with 1 and 2. Compounds 1 and 2 show a marked selectivity toward 2,6-pyridinedicarboxylate anions. In particular, 1 is able to perform a very efficient recognition of these species in the presence of 2 and 3. Molecular modeling calculations suggested that such recognition ability of 1 can be ascribed to a superior structural and electrostatic complementarity with the substrate compared to 2 and 3.     

微波促进无溶剂条件下酯键型猪去氧胆酸分子钳的快速有效合成

在微波辐射无溶剂条件下, 以固体K2CO3为载体, 猪去氧胆酸甲酯与芳酰氯反应合成了11个猪去氧胆酸分子钳人工受体. 所有化合物的结构均经1H NMR, IR, MS及元素分析所确证. 同传统方法相比, 该法具有简单、快速、 有效、 对环境友好等优点. 同时考察了这类受体对芳胺和手性分子的识别性能. 结果表明, 这类分子钳受体不但对芳胺具有优良的识别性能, 而且对D/L-氨基酸甲酯具有对映选择性识别性能.     

Design and Synthesis of Chiral Molecular Tweezers Based on Deoxycholic Acid

Molecular tweezers is a novel type of artificial receptors, which not only offer the advantage of efficient construction but also their surfaces can be tailored for specific applications. The clefts of molecular tweezers are particularly effective in regard to complementarity with substrates since functional groups attached to the interior of the cleft converge on substrates held inside1. So, in recent years, the molecular tweezers receptors have attracted more and more attention in molecular …     

新型手性不对称脲分子钳受体的设计合成

以芳杂环为隔离基, 手性不对称脲为手臂设计合成了一类新型的分子钳, 其结构经¹H NMR, IR, MS和元素分析所确证, 并且考察了其对卤素阴离子C1^—, Br^—, I^—的识别性能.     

Oxidations of N-(3-indoleethyl) cyclic aliphatic amines by horseradish peroxidase: the indole ring binds to the enzyme and mediates electron-transfer amine oxidation

Although oxidations of aromatic amines by horseradish peroxidase (HRP) are well-known, typical aliphatic amines are not substrates of HRP. In this study, the reactions of N-benzyl and N-methyl cyclic amines with HRP were found to be slow, but reactions of N-(3-indoleethyl) cyclic amines were 2-3 orders of magnitude faster. Analyses of pH-rate profiles revealed a dominant contribution to reaction by the amine-free base forms, the only species found to bind to the enzyme. A metabolic study on a family of congeneric N-(3-indoleethyl) cyclic amines indicated competition between amine and indole oxidation pathways. Amine oxidation dominated for the seven- and eight-membered azacycles, where ring size supports the change in hybridization from sp3 to sp2 that occurs upon one-electron amine nitrogen oxidation, whereas only indole oxidation was observed for the six-membered ring congener. Optical difference spectroscopic binding data and computational docking simulations suggest that all the arylalkylamine substrates bind to the enzyme through their aromatic termini with similar binding modes and binding affinities. Kinetic saturation was observed for a particularly soluble substrate, consistent with an obligatory role of an enzyme-substrate complexation preceding electron transfer. The significant rate enhancements seen for the indoleethylamine substrates suggest the ability of the bound indole ring to mediate what amounts to medium long-range electron-transfer oxidation of the tertiary amine center by the HRP oxidants. This is the first systematic investigation to document aliphatic amine oxidation by HRP at rates consistent with normal metabolic turnover, and the demonstration that this is facilitated by an auxiliary electron-rich aromatic ring.     

手性不对称脲联苯二甲酸分子钳的设计合成

以联苯二甲酸为隔离基,手性不对称脲为手臂,设计合成了一类新型的手性分子钳。4个分子钳均为新化合物,其结构均经1H NMR,IR,MS和元素分析所确证,并且考察了其对卤素阴离子Cl-、Br-、I-的识别性能。初步的实验结果表明,这类分子钳不仅可与所考察的卤素阴离子形成1:1型超分子配合物,而且对卤素阴离子具有良好的识别选择性,识别选择性为I->>C l->B r-。     

Blood group B galactosyltransferase: insights into substrate binding from NMR experiments

The biosynthesis of human blood group B antigens is accomplished by a highly specific galactosyltransferase (GTB). On the basis of NMR experiments, we propose a "molecular tweezers mechanism" that accounts for the exquisite stereoselectivity of donor substrate selection. Transferred NOE experiments for the first time reveal the bioactive conformation of the donor substrate UDP-galactose (UDP-Gal) and of its enzymatically inactive analogue, UDP-glucose (UDP-Glc). Both bind to GTB in a folded conformation that is sparsely populated in solution, whereas acceptor ligands bind in a conformation that predominates in solution. The bound conformations of UDP-Gal and UDP-Glc are identical within experimental error. Therefore, GTB must discriminate between the two activated sugars on the basis of a hitherto unknown transition state that can only be formed in the case of UDP-Gal. A full relaxation and exchange matrix analysis of STD NMR experiments reveals that acceptor substrates dissociate significantly faster (k(off) > 100 Hz) from the binding pocket than donor substrates (k(off) approximately 10 Hz). STD NMR experiments also directly show that proper recognition of the hexopyranose rings of the UDP sugars requires bivalent metal cations. At the same time, this analysis furnishes the complete three-dimensional structure of the enzyme with its bound donor substrate UDP-Gal on the basis of a prior crystal structure analysis. We propose that, upon acceptor binding, GTB uses the Asp 302 and Glu 303 side chains as "molecular tweezers" to promote bound UDP-Gal but not UDP-Glc into a transition state that leads to product formation.     

A new type of calixarene: octahydroxypyridin

A new type of calixarene has been synthesised. Like resorcinol and a number of resorcinol derivatives, 2,6-dihydroxypyridine has been proven to form cyclic tetramers in moderate yields with a number of aliphatic and two aromatic aldehydes in acidic media. The problem of the formation of configurational isomers can be reduced by increasing the reaction temperature and time. With electron-rich aromatic aldehydes, 2,6-dihydroxypyridine unexpectedly yields deep-coloured acyclic quinoid systems. The octahydroxypyridine[4]arenes may have a high potential as receptors for molecular recognition and self organisation.     

A Modular Phosphorylated Glycoluril-Derived Molecular Tweezer for Potent Binding of Aliphatic Diamines

A molecular tweezer based on a glycoluril-derived framework bearing four phosphate groups was synthesized and shown to be capable of binding organic amines in aqueous solution. This work reports the K_a values for 30 complexes of this molecular tweezer and amine guests, determined by means of ¹H NMR titrations. Both the hydrophobic cavity and the phosphate groups contribute to the binding. Bulkier molecules and molecules bearing negatively charged groups like carboxylates in amino acids bind less tightly due to a steric clash and coulombic repulsion. The narrow cavity and the strong ionic interactions of the phosphate groups with ammonium guests favor binding of aliphatic diamines. These binding properties clearly distinguish this system from structurally related molecular clips and tweezers.     

二聚雌二醇受体的设计合成

设计、合成了一类新型的“钳形”二聚雌二醇受体，其结构经MS、IR、^1H NMR及元素分析确证，并进行了识别性能研究。     

Easily‐prepared Hydroxy‐containing Receptors Recognize Anions in Aqueous Media

Despite their ready availability, O?H groups have received relatively little attention as anion recognition motifs. Here, we report two simple hydroxy‐containing anion receptors that are prepared in two facile steps followed by anion exchange, without the need for chromatographic purification at any stage. These receptors contain a pyridinium bis(amide) motif as well as hydroxyphenyl groups, and bind mono‐ and divalent anions in 9:1 CD₃CN:D₂O, showing a selectivity preference for sulfate. Notably, a “model” receptor that does not contain hydroxy groups shows only very weak sulfate binding in this competitive solvent mixture. In the solid state, X‐ray crystallographic studies show that the receptors tend to form extended assemblies with anions; however, ¹H and DOSY NMR studies as well as molecular dynamics simulations show that only 1:1 complexes are present in solution. Molecular dynamics simulations suggest that one of the receptors suffers from competing intramolecular hydrogen bonding, while another binds partially‐hydrated anions, with the receptor's O?H groups forming hydrogen bonds to water molecules within the anion's coordination sphere.     

芳杂环类多重氢键分子钳人工受体对中性分子的识别性能研究

根据多点氢键识别原理,设计合成了新的分子钳受体1～6。研究了其对巴比妥 、尿素、二苯甲酮、戊二酰亚胺等中性分子的识别性能。用差紫外光谱法测定了结 合常数和自由能变化（ΔG）。结果表明,所有分子钳受体与所考察的客体分子均 形成1：1型超分子配合物,识别作用的推动力主要为多重氢键的协同作用。讨论了 主客体间尺寸/形状、几何互补等因素对形成超分子配合物的影响。并利用~1H NMR、计算机模拟作辅助手段对实验结果和现象进行了解释。     

Anion-aromatic bonding: a case for anion recognition by pi-acidic rings

The basis for unprecedented noncovalent bonding between anions and the aryl centroid of electron-deficient aromatic rings has been demonstrated by an ab initio study of the interaction between 1,3,5-triazine and the fluoride, chloride, and azide ion at the MP2 level of theory. Minima are also located corresponding to C[bond]H...X(-) hydrogen bonding, reactive complexes for nucleophilic attack on the triazine ring, and pi-stacking interactions (with azide). Trifluoro-1,3,5-triazine also participates in aryl centroid complexation and forms nucleophilic reactive complexes with anions. This novel mode of bonding suggests the development of new cyclophane-type receptors for the recognition of anions.     

微波干法合成脱氧胆酸分子钳人工受体

在微波辐射无溶剂条件下, 以固体K₂CO₃为载体, 脱氧胆酸甲酯与芳酰氯反应合成了11个脱氧胆酸分子钳人工受体, 其中5个为新化合物, 所有化合物的结构均经¹H NMR, IR, MS及元素分析所确证. 同传统方法相比, 该法具有简单、安全、快速、有效、对环境友好等优点. 同时考察了这类受体对中性和手性分子的识别性能. 结果表明, 这类分子钳受体不但对中性分子具有识别性能, 而且对D/L-氨基酸甲酯具有对映选择性识别性能.     

A water-soluble acyclic phane receptor recognizing 2,3-trans-gallate-type catechins

To recognize gallate-type catechins in aqueous solution, two water-soluble acyclic phane receptors containing three aromatic rings were synthesized. The binding of these receptors to eight catechin analogues was investigated with (1)H NMR spectroscopy. The stoichiometric ratios of the complexes between the receptors and the catechins were 1:1 in every case. The binding abilities were estimated by (1)H NMR titration. The meta-substituted receptor showed excellent binding ability for the 2,3-trans-gallate-type catechins. This study revealed that a simple acyclic phane receptor can distinguish differences in the structures of the catechin analogues.     

Design and Synthesis of Novel Molecular Tweezers Derived from Chenodeoxycholic Acid

A novel type of chiral molecular tweezers has been designed and synthesized by usingchenodeoxy cholic acid as spacer and the aromatic compounds as arm. Their structures werecharacterized by 1HNMR, IR, MS spectra and elemental analysis. These chiral molecular tweezersshowed good enantioselectivity for D-amino acid methyl esters.