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.     

Size complementarity in anion recognition by neutral macrocyclic tetraamides

Comparison of the anion binding properties of a series of uncharged macrocyclic tetraamides reveal significant effects of the receptor's size on the strength of its anion complexes. This study allowed for estimation of the optimal size of a macroring for complexation of common anions.     

发光性受体的分子设计与分子识别

介绍了发光受体的几种典型分子识别模型。从分子识别与超分子化学的角度综述了它们在分子离子识别中的应用。对近几年发展较快的分子印迹技术及其应用进行了综述。引用文献71篇。     

Molecular recognition of biotin, barbital and tolbutamide with new synthetic receptors

We have measured, by means of NMR titrations, the binding constants for the complexes between hosts N,N′-bis(6-methylpyridin-2-yl)-1,3-benzenedicarboxamide (7) and 4-chloro-N,N′-bis(6-methylpyridin-2-yl)-2,6-pyridinedicarboxamide (8, hydrated) with biotin methyl ester (1), N,N′-dimethylurea (2), 2-imidazolidone (3), N,N′-trimethylenurea (4), barbital (5) and tolbutamide (6) as guests. Molecular Mechanics calculations (Monte Carlo Conformational Search, AMBER and OPLS force fields, MacroModel v.8.1) on the complexes formed between the foregoing guests and hosts 7 and 8, comparatively with 4-oxo-N,N′-bis(6-methylpyridin-2-yl)-1,4-dihydro-2,6-pyridinedicarboxamide (9a) have been carried out in order to determine the correlation between experimental and theoretical results and to understand the behaviour of the designed new hosts. Finally we have performed single point DFT [B3LYP/6-31G(d,p)] calculations on the optimised Molecular Mechanics geometries for the complexes between hosts 7-9 and water.     

采用X射线衍射解析人鸟嘌呤核苷酸解离刺激因子(RaIGDS)Ras结合结构域的空间结构

Ras结合结构域(RBD)是鸟嘌呤核苷酸解离刺激因子(RalGDS)家族成员C-端的高保守区,通过它连接Ras和Ras相关蛋白.利用Red Wings和SGC-1 screens相关的悬滴法设盘结晶,按体积比1∶1加蛋白液到含1∶100胞内蛋白酶Glu-C(w/w)的结晶溶液(2 mol/L(NH4)2 SO4,0.2 mol/L NaAc,0.1 mol/L HEPES,5％ MPD,pH 7.5)中,晶体3天长成可组装大小.利用X-射线晶体衍射技术解析了人RalGDS的Ras结合域(RalGDS-RBD)的晶体结构,对比鼠和人RalGDS-RBD,主要是Ras结合区的C-端不同.人RalGDS-RBD通过Glu838和Glu840在RalGDS和Ras蛋白间形成氢键,而在同一位点,鼠RalGDS-RBD通过Asp820和Asp822形成氢键.人RalGDS-RBD结构中含ββαββαβ-型三维结构的泛素样构象,一个单体的C-端残基与相邻单体的β折叠形成平行βββββ结构.     

Anion recognition with porphyrin-bottomed tetraurea receptors

Three tetraurea-appended porphyrin-derived anion receptors were synthesized and were found to efficiently encapsulate various anions with high association constants of up to 1.1×10⁸ L/mol.     

Chiral recognition by molecularly imprinted polymers in aqueous media

Summary Molecularly imprinted polymers were prepared using 2-vinylpyridine and/or methacrylic acid as functional monomers in a self-assembly imprinting protocol. The resulting polymers were analyzed in aqueous media, and the effects from the pH of the mobile phase and the degree of added organic solvent were investigated. The results are indicative of the importance of ionic bonds in conjunction with hydrophobic interactions in the formation of the complexes between the analyte and the polymers.     

Tripodal pyrrolotetrathiafulvalene receptors for recognition of electron-deficient molecular guests

We report the synthesis of tripodal receptors with monopyrrolo-tetrathiafulvalene arms 1a,b, based on 1,3,5-substituted 2,4,6-triethylbenzene scaffold. The three converging pyrrolotetrathiafulvalene groups form an electron rich cone-shaped binding site. Molecular hosts 1a,b are capable of binding neutral electron deficient guests in solution, as well as positively charged pyridinium species in the gas phase.     

Hydrogen bonding in molecular recognition by HIV-1 protease

Molecular recognition of the cleavage sites of the substrates by HIV-1 protease is analyzed in terms of hydrogen bonding. Crystal structures of an inactive enzyme complexed with six different substrates were used as reference structures. Applying molecular mechanics calculations it can be shown that the interaction energies between the real substrate and the enzyme are larger than with other peptides. From the analysis, it can be concluded that water molecules are essential in the recognition process. Moreover, the hydrogen bonds between the protease and various substrates are characterized in detail.     

Selective recognition of sodium cyanide and potassium cyanide by diaza-crown ether-capped Zn-porphyrin receptors in polar solvents

Two new ditopic porphyrin receptors Zn1, incorporating a diaza-15-crown-5 unit, and Zn2, incorporating a diaza-18-crown-6 unit, have been prepared and characterized. UV-vis study in polar methanol has revealed that Zn1 is able to selectively recognize sodium cyanide over potassium cyanide (the ratio of their binding constant is ca. 56), whereas Zn2 exhibits a higher binding affinity for potassium cyanide over sodium cyanide (the ratio of their binding constant is ca. 12). In contrast, both receptors display substantially weaker binding affinity for sodium thiocyanate and potassium thiocyanate presumably due to a monotopic binding fashion.     

Synthesis and binding ability of bile acid-based receptors for recognition of flavin analogues

Novel cholaphanes 6a,b, based on lithocholic and deoxycholic acids, were synthesised through 3a,b by a sequence of reactions involving Cs-salt methodology of macrocyclisation. Cholaphanes 6a,b and acyclic steroidal receptors 3a,b bind flavin analogues via three hydrogen bonds in CHCl₃.     

Elucidation of chiral recognition processes of macrocyclic antibiotic vancomycin

A theoretical investigation was carried out on the retention and separation of enantiomeric molecules including nonsteroidal anti-inflammatory drugs, anti-neoplastic compounds and N-derivatized amino acids by capillary electrophoresis using macrocyclic antibiotics, a new class of chiral selectors, as stationary phase. Firstly docking methods were used to study the enantiorecognition in chiral electrophoresis. The molecular dynamics simulations of the two diastereoisomer complexes were then performed in order to understand how these antibiotics recognize the enantiomers. Another approach was applied in this study to establish a quantitative structure-enantioselectivity relationship (QSER) model, able to describe the resolution of a series of chiral compounds in capillary electrophoresis using vancomycin as the resolving agent.     

Design and synthesis of a unique ditopic macrocyclic fluorescent receptor containing furan ring as a spacer for the recognition of dicarboxylic acids

A macrocyclic fluorescent receptor was designed and synthesised and the binding study with three different types of dicarboxylic acids was performed with the receptor being found to have appreciable association constants. Downfield shifts of specific amide protons in 1:1 binding by ¹H NMR and the quenching in the fluorescence spectra reveal strong binding and thus unambiguously support the complexation of the receptor 1 with dicarboxylic acids.     

Nucleotide recognition in water by a guanidinium-based artificial tweezer receptor

The water-soluble tweezer receptor 1 with two symmetric peptidic arms, which are connected by an aromatic scaffold and contain lysine, phenylalanine, and a guanidinium-based anion-binding site as headgroup, has been synthesized. UV/Vis-derived Job plots show that the receptor forms 1:1 complexes with nucleotides and phosphate in buffered water at neutral pH. Binding constants have been determined by fluorescence and UV/Vis spectroscopy. All nucleotides tested were bound very efficiently, even in pure water, with binding constants between 10(4) and 10(5) M(-1) . Interestingly, all mononucleotides were bound much stronger than phosphate by a factor of at least 5 to 10. Furthermore 1 favors the binding of adenosine monophosphate (AMP) over adenosine diphosphate (ADP) and adenosine triphosphate (ATP), which is unprecedented for artificial nucleotide receptors reported so far. According to NMR spectroscopy and molecular modeling studies, the efficient binding is a result of strong electrostatic contacts supported by π-π interactions with the nucleobase within the cavity-shaped receptor.     

Nucleotide Recognition by a Guanidinocalixarene Receptor in Aqueous Solution

Nucleotides participate in various physiological processes through their supramolecular interactions with biomolecules. Therefore, the molecular recognition of nucleotides became an important topic in supramolecular chemistry and exhibited many biomedical applications. Guanidinocalixarenes showed very strong binding affinities towards nucleotides, even reaching the nanomolar level. In this work, we systematically determined the binding constants between a typical guanidinocalixarene(guanidinium-modified calix[5]arene, GC5A) and various nucleotides and revealed the driving forces behind the molecular recognition using theoretical calculations. The electrostatic interactions and hydrogen bonding provided by the phosphate groups of the nucleotides dominated the binding between the nucleotides and GC5A. The lower rim alkyl chains and the skeleton of GC5A provide preorganized cavity and upper guanidinium groups. The difference in the type of nucleobase is also attributed to the different binding affinities. This work provides insight into the molecular recognition of nucleotides and facilitates the development of new supramolecular hosts for nucleotides and related biological applications.     

Remarkably selective recognition of iodobenzene derivatives by a macrocyclic bis-Pt(II) metallohost

We designed and synthesized self‐assembled bis‐Pt^II dimer 1? 4 BF₄ with quino[8,7‐b][1,10]phenanthroline as an extended π‐face contact area, which acts as the first artificial receptor with high affinity toward iodinated aromatic compounds significantly based on noncovalent iodine ??? aromatic‐plane interactions in a “side‐on” fashion. Despite their structural similarity to a previously reported metallohost 2 ⁴⁺ that bears 2,2′:6′,2′′‐terpyridine units, a dramatic change in selectivity toward substituted benzene derivatives was observed for 1 ⁴⁺. ¹H NMR spectroscopic titration revealed a high affinity of 1 ⁴⁺ towards haloarenes, with exceptionally large association constants for 2‐iodophenol (K_a=16 000 M ^?1) and 1,2‐diiodobenzene (K_a=21 000 M ^?1), which are 93‐ and 140‐fold higher, respectively, than the values obtained for 2 ⁴⁺. In addition, 1 ⁴⁺ showed a remarkably high affinity and selectivity toward 2,6‐diiodophenol (K_a=35 000 M ^?1), which is an important substructure of the thyroid hormone T₄. X‐ray crystallography and theoretical calculations strongly suggest that “side‐on” iodine ??? aromatic‐plane interactions and π–π stacking contribute to the strong 1,2‐diiodobenzene and 2,6‐diiodophenol binding. The results obtained here give unique and valuable insight into the nature of halogen atom interactions in their “side‐on” region with an electropositive aromatic plane, which may provide useful guidance for designing artificial receptors for iodinated biomolecules.     

Anion recognition by neutral macrocyclic amides

Although amides often serve as anchoring groups in natural and synthetic anion receptors, the structure-affinity relationship studies of amide-based macrocyclic receptors are still very limited. Therefore, we decided to investigate the influence of the size of the macroring on the strength and selectivity of anion binding by uncharged, amide-based receptors. With this aim, we synthesized a series of macrocyclic tetraamides derived from 2,6-pyridinedicarboxylic acid and aliphatic alpha,omega-diamines of different lengths. X-ray analysis shows that all ligands studied adopt expanded conformations in the solid state with the convergent arrangement of all four hydrogen-bond donors. 1H NMR titrations in DMSO solution revealed a significant effect of the ring size on the stability constants of anion complexes; the 20-membered macrocyclic tetraamide 2 is a better anion receptor than its both 18- and 24-membered analogues. This effect cannot be interpreted exclusively in terms of matching between anion diameter and the size of macrocyclic cavity, because 2 forms the most stable complexes with all anions studied, irrespective of their sizes. However, geometric complementarity manifests in extraordinarily high affinity of 2 towards the chloride anion. The results obtained for solutions were interpreted in the light of solid-state structural studies. Taken together, these data suggest that anion binding by this family of macrocycles is governed by competitive interplay between their ability to adjust to a guest, requiring longer aliphatic spacers, and preorganization, calling for shorter spacers. The 20-membered receptor 2 is a good compromise between these factors and, therefore, it was selected as a promising leading structure for further development of anion receptors. Furthermore, the study of an open chain analogue of 2 revealed a substantial macrocyclic effect. X-ray structure of the acyclic model 14 suggests that this may be due to its ill-preorganized conformation, stabilized by two intramolecular hydrogen bonds.     

Synthesis and recognition of amino acids by binaphthyl-crown receptors

Two binaphthyl crown receptors containing phenylboric acid 2 and 2,4-dinitrophenylurea 3 as lariat parts were prepared from the optically active binaphthyl crown alcohol 1 in two and four steps, respectively. Host 2 showed a 30% extraction efficiency for GABA by a solid-liquid extraction method in DMSO. Chromogenic Host 3 discriminated the guest linear amino acid by molecular length and the information was revealed through color changes.     

Molecular recognition of viologen by zinc porphyrinic receptors with diarylurea sidearms. Toward construction of a supramolecular electron transfer system

A series of zinc porphyrinic receptors for a viologen substrate (hexyl viologen, HV²⁺) were synthesized, in which varying numbers of diarylurea moieties, from one to four, were appended at the porphyrin's meso positions. The increase in the number of the diarylurea moiety led to the increase in stability of the receptor-HV²⁺ complex, showing that the convergent dipoles set up on the porphyrin platform played an essential role in the complexation. In this system, formation of the stable electron donor-acceptor complex resulted in the effective electron transfer from the singlet excited state of the zinc porphyrin to HV²⁺.