para‐Sulfonated Calixarenes Used as Synthetic Receptors for Complexing Photolabile Cholinergic Ligand

The water‐soluble tetra‐, hexa‐ and octasulfonated calix[4]arenes, calix[6]arenes, and calix[8]arenes 1 – 3 , respectively, were investigated as potential synthetic receptors for photolabile cholinergic ligand A , a photolytic precursor of choline. Ligand A is a bifunctional molecule carrying a photolabile 2‐nitrobenzyl group at one end and a choline moiety at the other end. Results from NMR studies have shown that calixarenes 1 – 3 form stable 1 : 1 complexes with A , having similar binding potential to that observed with the cholinergic enzymes acetylcholinesterase and butyrylcholinesterase. Further studies have suggested that calix[8]arene forms a ditopic complex by binding concomitantly to both the cationic choline moiety and the aromatic photolabile group of A , whereas calix[4]arene and calix[6]arene form monotopic complexes with A . The ditopic complex between calix[8]arene and A results from mutually induced fitting process, while the monotopic complexes between calix[4]arene and A can be regulated by pH: at neutral pH, calix[4]arene specifically binds the cationic choline moiety, while, at acidic pH, it complexes unselectively both the cationic choline moiety and the aromatic group of A . Our results show that para‐sulfonated calixarenes are versatile artificial receptors which bind in various ways to the bifunctional photolabile cholinergic ligand A , depending on their size, geometry, and state of protonation.     

Directed molecular recognition: furfurylamine appended ditopic receptor for succinic acid

A furfurylamine appended ditopic receptor (R1) for dicarboxylic acids has been designed and synthesised. The association constants (K_a) between receptors and dicarboxylic acids have been determined using UV–vis and NMR titration techniques. The binding constant (K_a) of succinic acid with R1 was observed maximum, which implies the optimum chain length selectivity for succinic acid. Theoretical calculation and molecular modelling using Gaussian 03 program also support the optimised receptor's cavity for succinic acid.     

Molecular Tweezers for Dicarboxylic Acids Based on a Saddle-Shaped Metallomacrocyclic Platform

A new metal containing molecular receptor was prepared from a 15-membered nickel(II) macrocyclic cyclidene platform and two cyclic tetramine (cyclen) recognition cites. In the saddle shaped conformation of the platform, the cyclen receptors are positioned for ditopic binding of difunctional substrates. NMR titration experiments demostrate that the molecule binds dicarboxylic acids in DMSO with apparent equilibrium constants ranging from 10 to 10⁴ M^-1. Incusion of dicarboxylates into the protonated macrocyclic host is shape-selective, with cis-1,2-dicarboxylates (succinate, maleate, and o-phthalate) being the best guests.     

Ion pair recognition by Zn-porphyrin/crown ether conjugates: visible sensing of sodium cyanide

Synthesis and complexation behavior of ditopic neutral receptors composed of both a Lewis-acidic binding site (zinc porphyrin moiety) and a Lewis-basic binding site (crown ether moiety) are reported; the receptors bound only NaCN in a ditopic fashion with a color change, and in contrast other sodium salts bound to the receptors in a monotopic fashion without a color change.     

Insights into the Dynamics and Molecular Recognition Features of Glycopeptides by Protein Receptors: The 3D Solution Structure of Hevein Bound to the Trisaccharide Core of N‐Glycoproteins

Protein‐carbohydrate interactions are at the heart of a variety of essential molecular recognition events. Hevein, a model lectin related to the superantigen family, recognizes the trisaccharide core of N‐glycoproteins ( 1 ). A combined approach of NMR spectroscopy and molecular modeling has permitted us to demonstrate that an Asn‐linked Man(GlcNAc)₂ ( 2 ) is bound with even higher affinity than (GlcNAc)₃. The molecular recognition process entails conformational selection of only one of the possibilities existing for chitooligosaccharides. The deduced 3D structure of the hevein/ 2 complex permits the extension of polypeptide chains from the Asn moiety of 2 , as well as glycosylation at Man O‐3 and Man O‐6 of the terminal sugar. Given the ubiquity of the Man(GlcNAc)₂ core in all mammalian N‐glycoproteins, the basic recognition mode presented herein might be extended to a variety of systems with biomedical importance.     

间苯二甲酰腙分子钳的合成及阴离子识别研究

设计合成了3种新型间苯二甲酰腙类化合物,利用UV-Vis及¹H NMR考察了其与F^-、Cl^-、Br^-、I^-、CH₃COO^-、HSO₄^-、H₂PO4-、ClO4-阴离子的相互作用。结果表明,主体分子4a(双对硝基苯并呋喃甲醛间苯二甲酰腙)在DMSO溶液中对F-和CH₃COO-有显著识别效果,溶液颜色由黄色变为深黄色和棕红色。通过¹H NMR滴定及质子溶剂效应进一步证明,主体分子与阴离子之间是以氢键作用方式相结合。Job曲线表明,主客体间形成1：1型氢键络合物。基于实验结果,探讨了主客体间形状和大小匹配对识别能力的影响以及主客体之间的识别模式。     

Highly efficient recognition of native TpT by artificial ditopic hydrogen-bonding receptors possessing a conformationally well-defined linkage

Synthesis and binding affinity of rationally designed artificial ditopic nucleobase receptors are reported. The ditopic receptors were designed to recognize thymine-thymine dinucleotides by their two hydrogen-bonding moieties, which are connected to conformationally well-defined linkages such as ferrocene and biphenylene. The ditopic receptors exhibited a remarkably strong binding affinity for lipophilic TpT analogue in CDCl(3)/DMSO-d(6) (85:15, v/v). The binding affinity of the ditopic receptors for the dinucleotide was so high that even native TpT was extracted by them into CDCl(3). Detailed comparisons for the recognition abilities of the ditopic receptors were also conducted.     

Transport of alkali halides through a liquid organic membrane containing a ditopic salt-binding receptor

A ditopic receptor is shown to have an impressive ability to recognize and extract the ion pairs of various alkali halides into organic solution. X-ray diffraction analysis indicates that the salts are bound in the solid state as contact ion pairs. Transport experiments, using a supported liquid membrane and high salt concentration in the source phase, show that the ditopic receptor can transport alkali halide salts up to 10-fold faster than a monotopic cation or anion receptor and 2-fold faster than a binary mixture of cation and anion receptors. All transport systems exhibit the same qualitative order of ion selectivity; that is, for a constant anion, the cation selectivity order is K+ > Na+ > Li+, and for a constant cation, the anion transport selectivity order is I- > Br- > Cl-. The data suggest that with a ditopic receptor, the polarity of the receptor-salt complex can be lowered if the salt is bound as an associated ion pair, which leads to a faster diffusion through the membrane and a higher maximal flux.     

Metalloporphyrin receptors for histidine-containing peptides

Two new ditopic metalloporphyrin receptors constructed by combining metalloporphyrin with crown ethers have been prepared and characterized.1H NMR and MS spectra confirmed the complexation of receptor with peptide driven by coordination interaction and hydrogen bonding.UV/vis experiments revealed that the receptors exhibited high binding affinity to histidine-containing peptides.These receptors could differentiate short peptides of C-terminal histidine and N-terminal histidine and formed the most stable complexes with tripeptide.     

Synthesis and Enantioselective Discrimination of Chiral Fluorescence Receptors Bearing Amino Acid Units

Two chiral fluorescence receptors （1, 2） were synthesized, and their structures were characterized by IR, ^1H NMR, ^13C NMR, mass spectra and elemental analysis. The chiral recognition of receptors was studied by ^1H NMR and fluorescence spectra. The results demonstrate that receptors and dibenzoyl tartrate anion formed a 1 ： 1 complex. The receptor 1 exhibited a good enantioselective recognition ability toward the enantiomers of dibenzoyl tartrate anion.     

Highly Effective Recognition of Carbohydrates by Phenanthroline‐Based Receptors: α‐ versus β‐Anomer Binding Preference

¹H NMR spectroscopic titrations in competitive and non‐competitive media, as well as binding studies in two‐phase systems, such as phase transfer of sugars from aqueous into organic solvents and dissolution of solid carbohydrates in apolar media revealed both highly effective recognition of neutral carbohydrates and interesting binding preferences of an acyclic phenanthroline‐based receptor 1 . Compared to the previously described acyclic receptors, compound 1 displays significantly higher binding affinities, the rare capability to extract sugars from water into non‐polar organic solutions and α‐ versus β‐anomer binding preference in the recognition of glycosides, which differs from those observed for other receptor systems. X‐ray crystallographic investigations revealed the presence of water molecules in the binding pocket of 1 that are engaged in the formation of hydrogen‐bonding motifs similar to those suggested by molecular modelling for the sugar OH groups in the receptor–sugar complexes. The molecular modelling calculations, synthesis, crystal structure and binding properties of 1 are described and compared with those of the previously described receptors.     

新型希夫碱型钳形人工受体的微波合成及其对中性分子的识别性能

以对苯二甲酸为起始原料,设计并合成了8个新型的芳环钳形人工受体(3a～3h),其结构经1H NMR,IR,ESI-MS和元素分析表征。利用UV-Vis滴定法初步考察了3a～3h对中性分子(邻苯二胺,间苯二胺,对苯二胺和二苯甲酮)的识别性能,结果表明3a～3h对其具有良好的识别性能。     

Mono- and ditopic models of binding of a photochromic chromene annelated with an 18-crown-6 ether with protonated amino acids

In this work, the interaction of protonated amino acids with a chromene bearing a fused 18-crown-6 ether moiety was studied by UV-vis and NMR spectroscopy. Initial closed forms of the chromene form monotopic 1 : 1 complexes, the ammonium group being localized inside the crown ether cavity. UV-irradiation leads to transformation of the ring-closed species into the ring-opened form. Depending on the amino acid length, either ditopic or monotopic 1 : 1 complexes are formed. Such complexes are stabilized by the additional H-bonding between the carboxylic group of the acid and the carbonyl oxygen atom of the ring-opened form. Cessation of the irradiation results in ring-closure to the chromene with concomitant change of the complexation mode.     

Self-assembly via ionic interactions of calix[6]arene-based receptors displaying remarkable host-guest properties toward neutral guests

The association of a C_3v-symmetrical calix[6]tris-amine with different concave tris-carboxylic acids of various degrees of flexibility has been explored by ¹H NMR spectroscopy. In all cases, self-assembled structures directed by the selective inclusion of a neutral guest molecule were obtained, the more preorganized being stable in protic solvents. With a rigid C₃-symmetrical cap, chiral guest recognition in the calixarene cavity resulted. A large tris-acidic partner gave a unique molecular ditopic receptor that is able to simultaneously accommodate two neutral molecules in two distinct hydrophobic cavities with different binding processes.     

Selective recognition and electrochemical sensing of dopamine using a ferrocene-based heteroditopic receptor

A redox-active ferrocene-based heteroditopic receptor bearing a boronic acid (as a catechol recognition site) and a benzo-18-crown-6-ether unit (as an ammonium ion recognition site) was synthesized. A 1:1 ditopic complex with dopamine was evidenced by mass spectrometry and NMR spectroscopy. Cyclic voltammetry measurements on the receptor in the presence of a series of organic guest species demonstrated the successful electrochemical sensing of dopamine through a distinct change in the ferrocene-centred redox-couple upon complex formation.     

Synthetic Receptors for the High‐Affinity Recognition of O‐GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water‐soluble carbohydrate receptors (“synthetic lectins”). Both systems show outstanding affinities for derivatives of N‐acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc‐β‐OMe with K_a≈20 000 m ^?1, whereas the other one binds an O‐GlcNAcylated peptide with K_a≈70 000 m ^?1. These values substantially exceed those usually measured for GlcNAc‐binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl–peptide complex can be explained by extra‐cavity interactions, raising the possibility of a family of complementary receptors for O‐GlcNAc in different contexts.     

三足苯甲酰基硫脲类离子受体的合成及识别性能

本文设计并合成了两种新型含酰基硫脲结构单元的三足受体1和2,并对其结构进行了表征确证。研究表明该类受体化合物对F^-、Ac^-和CN-表现出良好的紫外识别能力,由于受体1分子内电荷转移作用较强,故对阴离子表现出裸眼识别性能。紫外滴定表明,该类化合物对F^-和CN^-具有更好的结合能力;核磁滴定表明,阴离子通过分子间氢键与受体化合物结合形成主客体配合物,在高浓度F^-时受体化合物发生脱质子行为。此外,该类化合物对Hg^2+具有一定的荧光选择性识别能力。     

Dynamic Interactions in Synthetic Receptors: A Guest Exchange Saturation Transfer Study

The accumulated knowledge regarding molecular architectures is based on established, reliable, and accessible analytical tools that provide robust structural and functional information on assemblies. However, both the dynamicity and low population of noncovalently interacting moieties within studied molecular systems limit the efficiency and accuracy of traditional methods. Herein, the use of a saturation transfer-based NMR approach to study the dynamic binding characteristics of an anion to a series of synthetic receptors derived from bambusuril macrocycles is demonstrated. The exchange rates of BF₄⁻ are mediated by the side chains on the receptor (100 s⁻¹<k_ex<5000 s⁻¹), which play a critical role in receptor-anion binding dynamics. The signal amplification obtained with this approach allows for the identification of different types of intermolecular interactions between the receptor and the anion, something that could not have been detected by techniques hitherto used to study molecular assemblies. These findings, which are supported by a computational molecular dynamic study, demonstrate the uniqueness and added value of this NMR method.     

含脲苯并咪唑类离子液体的合成及阴离子识别性能

设计并合成了含脲苯并咪唑离子液体受体分子1~3, 利用紫外-可见光谱、 荧光光谱和 ¹H NMR滴定研究了其对F^-, Cl^-, Br^-, I^-, CH₃COO^-, HSO₄^-, H₂PO₄^-等阴离子的识别性能. 紫外-可见光谱研究发现, 受体分子1~3可选择性地识别F^-, 并形成1: 1型主客体配合物; 荧光光谱研究发现, 受体分子1~3对碱性阴离子有较好的识别作用, 主客体结合常数的顺序为H₂PO₄^->CH₃COO^-≈ F^->HSO₄^- ≈ Cl^->Br^- ≈ I^-; ¹H NMR滴定研究发现, 该类受体分子以咪唑2位CH和脲基NH与阴离子通过氢键结合, 但高浓度的F^-会导致受体分子发生脱质子作用.