Recognition of guests bearing donor and acceptor hydrogen bonding groups by heteroditopic calix[4]arene receptors

The synthesis of new hosts specifically designed for the recognition of neutral guests bearing donor-acceptor hydrogen bonding groups is described. These hosts are characterized by the presence of two distinct binding region in close proximity: the rigid π-donor cavity and the H-bond donor N-methylene-N′-phenylureido group inserted onto the upper rim of the calix[4]arene skeleton. The binding abilities of these receptors were investigated toward a series of neutral ditopic organic molecules in CDCl₃ solution by ¹H NMR spectroscopy. The results obtained show that rigidity of the calix[4]arene apolar cavity is the control element in determining efficiency. In fact, compared with the more rigid 2, host 10, where the rigidity of the cone structure is maintained by hydrogen bonding of the OH of the lower rim, a decrease of efficiency of almost one order of magnitude was observed. The cooperative effect of the two binding region of host 2 was verified with different classes of ditopic guests. Good efficiency in the recognition of urea derivatives and dimethylsulfoxide was achieved.     

Inclusion of naturally occurring amino acids in water soluble calix[4]arenes: a microcalorimetric and 1H NMR investigation supported by molecular modeling

The thermodynamic parameters for the inclusion of some naturally occurring amino acids into a series of p-sulfonated calix[4]arenes, were determined via both 1H NMR and calorimetric titrations in buffered aqueous solution at 25 degrees C. The calorimetric data show that inclusion is enthalpically driven in all cases, regardless of flexibility of the host and the nature of the guest. The most efficient receptor is the calix[4]arene tetrasulfonate 1, which exists in solution at pH 7 in a cone conformation, stiffened by H-bonding at the lower rim.Molecular mechanics data help in the understanding of why some hosts do not form inclusion complexes at all. The comparison of our data with literature reports shows that there are dramatic buffer-dependent changes in the binding affinities.     

Recognition of N‐Alkyl and N‐Aryl Acetamides by N‐Alkyl Ammonium Resorcinarene Chlorides

N‐Alkyl ammonium resorcinarene chlorides are stabilized by an intricate array of intra‐ and intermolecular hydrogen bonds that leads to cavitand‐like structures. Depending on the upper‐rim substituents, self‐inclusion was observed in solution and in the solid state. The self‐inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self‐included dimers spontaneously reorganize to 1:1 host–guest complexes. These host compounds show an interesting ability to bind a series of N‐alkyl acetamide guests through intermolecular hydrogen bonds involving the carbonyl oxygen (C?O) atoms and the amide (NH) groups of the guests, the chloride anions (Cl^?) and ammonium (NH₂⁺) cations of the hosts, and also through CH ??? π interactions between the hosts and guests. The self‐included and host–guest complexes were studied by single‐crystal X‐ray diffraction, NMR titration, and mass spectrometry.     

Calix[4]arenequinazolinones. Synthesis and structure

The synthesis of calix[4]arenes bearing two quinazolin-4-ones group at the upper rim is decribed. ¹H NMR spectra and quantum chemical calculations make it possible to suggest that calix[4]arenequinazolinones form three rotamers in solutions at room temperature, due to the restricted rotation of the quinazolinone fragments. The X-ray structure investigation indicates that quinazolin-4-onecalix[4]arene exists in the crystal state as the methanol 1:1 inclusion complex.     

1H NMR and Calorimetric Studies of the Inclusion of Trimethylammonium Cations into Water Soluble Calixresorcinarenes

Abstract

The complexation of tetramethylammonium (TEMA), benzyltrimethylammonium (BTMA), p-nitrobenzyltrimethylammonium (BTMAN) and N, N, N-trimethylanilinium (TMA) by the tetrasulphonate derivative of the resorcinol cyclic tetramer (1), was studied in aqueous solution by ¹H NMR and calorimetry. Host 1 specifically recognizes the—N⁺ (CH₃)₃ group of TEMA, BTMA and BTMAN, whereas it binds TMA unselectively; TMA is included both via the charged group and the aromatic moiety. The binding constants of all four guests with 1, as determined by both ¹H NMR and calorimetric titrations, show that all inclusion processes are almost equally stabilised.

ΔHΔ and ΔSΔ values, determined by direct calorimetry, reveal specific interactions that are not expressed in the ΔGΔ terms and indicate that we are dealing with “non-classical hydrophobic effects”. The effects of the structural, conformational and electronic properties of the guests on the forces driving the inclusion processes are discussed.     

Calix[4]arene-Based Triple-Stranded Metallohelicate in Water

The title complex is a triple-stranded metallohelicate organized by the self-assembly of 5,17-difunctionalized calix[4]arenes and metal cations with octahedral coordination geometry. Due to hydrophilic triethylene glycol chains on the lower rim of the calix[4]arene, the metallohelicate can encapsulate cationic guests in water. NMR and UV-vis titration experiments reveal that the metallohelicate captures a pyridinium guest with an alanine derivative to form a host-guest complex with a host-guest ratio of 1 : 1. CD spectroscopy confirms the bias of the P- and M-helical sense of the metallohelicate by the captured guest. The metallohelicate captures two molecules of dicationic N,N’-dimethyl-DABCO and monocationic N-methyl quinuclidine, exhibiting a positive allosteric effect. ¹H NMR titration experiments indicate that the bound guests are in close proximately to the aromatic rings of the ligands. Molecular mechanics calculations based on the UV-vis and NMR observations suggest that the first guest preorganizes the conformation of the metallohelicate to facilitate access of the second guest to the cavity.     

Synthesis of nucleobase-calix[4]arenes via click chemistry and evaluation of their complexation with alkali metal ions and molecular assembly

In this study, calix[4]arene derivatives (11–14) bearing a single nucleobase (adenine, thymine, cytosine or guanine) were synthesised via click chemistry. The complexation ability of the synthesised derivatives with alkali metal ions was measured using MALDI-TOF mass spectrometry, and their molecular assembly in CDCl₃ was determined using ¹H NMR. Calix[4]arene derivatives (11–14) formed 1:1 complexes with all alkali metal ions and the rank order for the complexation selectivity was Rb⁺ > Cs⁺ > K⁺ ? Na⁺ > Li⁺. The attachment of nucleobase at the upper rim of calix[4]arene had little effect on its complexation selectivity for alkali metal ions. Thymine-, adenine- and guanine-calix[4]arenes formed self-assembled structures in CDCl₃ via base–base interactions. In addition, adenine-calix[4]arene (11) bound to thymine-calix[4]arene (12) to form a discrete species via Hoogsteen hydrogen bonding.     

Synthesis and spectroscopic studies of isosteviol-calix[4]arene and -calix[6]arene conjugates

Novel calix[4]arene derivatives functionalized with two or four isosteviol units at the upper rim and a new calix[6]arene having six isosteviol moieties at the lower rim have been synthesized. The structures of these compounds have been confirmed by NMR and mass spectrometry data. All ¹H and ¹³C NMR chemical shifts of isosteviol were fully assigned by extensive NMR spectroscopic methods, and used to clarify the structures and conformations of isosteviol-calixarene conjugates.     

Water-soluble calixarenes—self-aggregation and complexation of noncharged aromatic guests in buffered aqueous solution

Water-soluble calix[4]arenes are useful receptors for hydrophobic substrates in aqueous buffered solution. The inclusion of 22 aromatic guests as well as the self-aggregation behavior of amphiphilic hosts was studied by ¹H NMR spectroscopy. The association constants obtained range from 10 to 1000 L mol⁻¹. In all cases, the aromatic moiety is included into the hydrophobic pocket of the calixarenes maximizing hydrophobic contacts. Additionally, substituents such as methyl or chlorine exhibit a preference for inclusion in the pocket of the macrocycles owing to CH/π or Cl/π interactions. In case self-aggregation is observed, millimolar CMC values are to be found.     

Synthesis, NMR, X-ray structural analyses and complexation studies of new Ag selective calix[4]arene based dipodal hosts—a co-complexation of neutral and charged species

New podands based on the p-tert-butylcalix[4]arene unit with substitution at the lower rim incorporating imine units, have been synthesized in high yield by simple condensation method. These podands have been shown to extract and transport Ag⁺ selectively over alkali, alkaline earth metal cations, Zn²⁺, Pb²⁺ and Hg²⁺ ions, from neutral aqueous phase to organic phase. In all the ligands the calix unit has been found to be present in a cone conformation except for the one having pyridine as end group, at the ortho position. It has been isolated in two conformations; cone and 1,2-alternate. To the best of our knowledge, this may be the first 1,3-lower rim substituted calix[4]arene to exist in a 1,2-alternate conformation and is among a few known compounds with this conformation in the general class of calix[4]arenes. A complex of this ligand, which happens to be the highest extractant of Ag⁺ has been isolated and characterized using mass, ¹H and ¹³C NMR spectroscopy's and elemental analysis. The spectroscopic evidence and molecular modelling studies performed on the complex suggest a participation of the imine and pyridine nitrogens and two of the ether oxygens in coordination to the metal ion. The X-ray crystal structures of three of the ligands establish the formation of inclusion complexes with polar acetonitrile solvent molecules. The ¹H and ¹³C NMR spectra of all the compounds, taken in CDCl₃, show the presence of acetonitrile molecules in the cavity of the calix[4]arene, indicating inclusion of the neutral guest molecules in the solution phase as well. For one of the podands X-ray crystal structure has shown a formation of clatharate complex of chloroform with the ligand which has rarely been found in the case of calix[4]arenes.     

Cooperative Binding of Divalent Diamides by N‐Alkyl Ammonium Resorcinarene Chlorides

N‐Alkyl ammonium resorcinarene chlorides, stabilized by an intricate array of hydrogen bonds leading to a cavitand‐like structure, bind amides. The molecular recognition occurs through intermolecular hydrogen bonds between the carbonyl oxygen and the amide hydrogen of the guests and the cation–anion circular hydrogen‐bonded seam of the hosts, as well as through CH ??? π interactions. The N‐alkyl ammonium resorcinarene chlorides cooperatively bind a series of di‐acetamides of varying spacer lengths ranging from three to seven carbons. Titration data fit either a 1:1 or 2:1 binding isotherm depending on the spacer lengths. Considering all the guests possess similar binding motifs, the first binding constants were similar (K₁: 10² M ^?1) for each host. The second binding constant was found to depend on the upper rim substituent of the host and the spacer length of the guests, with the optimum binding observed with the six‐carbon spacer (K₂: 10³ M ^?2). Short spacer lengths increase steric hindrance, whereas longer spacer lengths increase flexibility thus reducing cooperativity. The host with the rigid cyclohexyl upper rim showed stronger binding than the host with flexible benzyl arms. The cooperative binding of these divalent guests was studied in solution through ¹H NMR titration studies and supplemented by diffusion‐ordered spectroscopy (DOSY), X‐ray crystallography, and mass spectrometry.     

Calix[8]arene-based glycoconjugates as multivalent carbohydrate-presenting systems

An efficient approach for the introduction of eight mono- or disaccharide sugar moieties (d-glucose, N-acetyl-d-glucosamine, d-galactose, l-fucose, d-maltose and d-cellobiose) at the upper rim of calix[8]arene 1, using thioureido linkers, is reported. The obtained water-soluble, nanosized glycocalix[8]arenes 5b-10b may act as biomimetic carbohydrate systems and as hosts for highly polar organic molecules. Preliminary ¹H NMR complexation experiments of octaglycosyl derivative 7b and 10b with ionic guests are also reported.     

Head-to-tail Aggregates of Sulfonatomethylated Calix[4]resorcinarene in Aqueous Solutions

Two amphiphilic water-soluble sulfonatomethylated calix[4]resorcinarene derivatives were studied by various ¹H NMR techniques (¹H NMR titration, 2D NOESY, NMR diffusion measurements). The derivative with methyl moieties at the lower rim (1) was found to be non-aggregated in the range 0–10 mM in aqueous solutions. Lengthening of the lower rim substituent to pentyl (2) results in self-aggregation of 2 in aqueous solutions with the aggregation number varying from 3 at 1 mM to 20 at 10 mM. The 2D NOESY ¹H NMR spectroscopy data reveal an unusual head-to-tail packing mode in aqueous solutions, resulting from the cooperative effect of weak hydrophobic interactions. Binding of guests (tetramethylammonium and N-methylpyridinium) results in additional stabilization of the aggregates whilst the head-to-tail packing mode of the aggregate is retained.     

杯[4]芳烃二肟酸-Cu(Ⅰ)配合物的设计与自组装合成

Cu是许多酶中的必须元素[1],Cu与有机配体形成的配合物不仅具有氧化、还原、催化、超分子化合物结构控制等重要作用,而且具有抗菌、抗癌、抗病毒等生物活性.     

氨基甲酸酯型脱氧胆酸分子钳对中性分子的识别性能研究

利用差紫外光谱法考察了新型分子钳1～6对苯胺、对硝基苯胺、对甲氧基苯胺等中性分子的识别性能, 测定了25 ℃下, 在CHCl₃中主客体间的结合常数(K_a)和自由能变化(ΔG⁰). 结果表明, 所有分子钳主体对所考察的客体分子显示良好的识别作用, 主客体间形成1∶1型主客体络合物. 识别作用的主要推动力为多重氢键和π-π重叠等的作用. 讨论了主客体间形状、大小匹配和几何互补及识别模式等因素对识别能力的影响, 并利用核磁共振氢谱与计算机模拟作为辅助手段对实验结果进行了解释.     

Thermodynamics of sublimation of calix[4]arene complexes with solvent molecules

The inclusion of small neutral organic guests (C₆H₁₄, CH₂Cl₂, CH₃OH) by calix[4]arene receptors was found by ¹H NMR spectroscopy and microanalysis. The studied calix[4]arenes can form stable intramolecular complexes with solvent molecules which keep the stoichiometric composition without changing under conditions of the sublimation experiment. The saturated vapour pressures of calix[4]arenes and complexes of calix[4]arenes with solvent molecules were determinated for the first time by the Knudsen’s effusion method in the wide temperature range. The changing of standard thermodynamic parameters of complexation by transfer process from condensed state to vapour phase was estimated. It was shown that the large flexibility of the calixarene ligand structure corresponds to a strongly negative entropic contribution as well as negative enthalpy term to the Gibbs energy of formation of host–guest complexes in the gas phase.     

Aggregation of amphiphilic aminomethylated calix[4]resorcinarenes and the nonionic surfactant Triton-X-100 in organic solvents

Aggregation and intermolecular interactions of amphiphilic calix[4]resorcinarene (1), aminomethylated calix[4]resorcinarenes (AMC 2—7) with different structures of the upper rim (including the oxazine structure in 6 and 7) and hydrophobic substituents on the lower (2—5), upper (6), or both rims (7) in the absence and in the presence of the nonionic surfactant Triton-X-100 (8) and p-nitrophenol (9) in chloroform and 1,4-dioxane were studied by permittivity measurements and 2D ROESY ¹H NMR technique. The tendency of amphiphilic derivatives 1—7 toward self-aggregation and mixed aggregation with surfactant 8 primarily depends on the nature of both the solvent and the polar groups on the upper rim of calixarenes. In chloroform, AMC—8 aggregates show interactions of the methyl and methylene groups of the hydrophobic substituents of AMC with the ethyleneoxy fragments of surfactant 8, while in stable intermolecular complexes of 5 and 6 with compound 9, the methylene groups of the long-chain radicals of the AMC strongly interact with the aromatic protons ortho to the hydroxy group of 9. In 1,4-dioxane, calix[4]resorcinarenes 1 and 5 are bound in stable solvates, which prevents them from forming aggregates and mixed micelles.     

Selectively formylated and bridged calix[6]arene derivatives at the upper rim

The strategy of bridging the anisole units at the upper rim of calix[6]arene has been applied to strain the conformations of calix[6]arene. Based on the selective formylation of the 1,3,5-tri-p-tert-butylcalix[6]arene, several new calix[6]arene derivatives with different 1,3-bridged chains or a 1,3,5-tripod bridge at the upper rim have been prepared with moderate yields. The ¹H NMR spectra indicate that these calix[6]arene derivatives adopt a cone conformation, which has also been confirmed by the theoretical calculation at AM1 level. X-ray crystal structure of 1,3,5-tripod bridged compound 5 discloses that the calix[6]arene host stands in a cone conformation with approximate C_3v symmetry, and that a methanol molecule is enclosed in its hydrophobic cavity and stabilized by multi hydrogen bonds.     

New artificial receptors from selectively functionalized calix[4]arenes

Abstract

The development of new synthetic methods for the monoalkylation of calix[4]arenes at the lower rim allows the synthesis of a new class of trihydroxamate siderophores. Three chelating hydroxamic acid units are introduced through a sequence of reactions which blocks the macrocycle in the cone conformation. The new ligands obtained form neutral 1:1 complexes (FeL) with iron (III), which are stable in EtOH/H₂O 9:1 at pH 2–7. Calix[4]arene bis-crown ethers are prepared by exploiting the selective 1,2-(proximal) functionalization of calix[4]arenes at the lower rim. These ligands are, however, less effective in complexing alkali metal cations compared with the 1,3-calix[4]arene crown-ethers which, in their partial cone structure, offer a better shielding for the complexed cations. Rigid upper rim-bridged calix[4]arenes potentially useful for the inclusion of neutral molecules are prepared by exploiting the selective 1,3-diformylation of calix[4]arene at the upper rim. Finally a new chloromethylation method for calix[4]arenes blocked in the cone conformation is described together with the synthesis of new cavitands.     

Upper Rim Diester—bridged Calix[4] arenes and Oligocalix [4]—arenes：the Effects of the Length of Bridged Reagents on Their Distribution

A series of monobridged calix [4] arenes 3a-f,cyclic biscalix-[4] arenes 4a-f ,diametrically bridged at the upper rim with saturated aliphatic diester chians,have been synthesized,The results at diluted conditions show that the percentage of yields of mono-,bis- and oligo-calix[4] arenes are related to the legth of the chains ,With the shortening of the chains ,the percent-age of monocalix[4] arenes decreased ,All the calix [4] arene moieties are in a cone conformaiton according to the AB quar-tet pattern of the methylene protons between the phenolic rings in the ^1H NMR spectra.