Study on the inclusion interaction of p-sulfonatocalix[n]arenes with norfloxacin

The inclusion complexes of norfloxacin (NFX) with p-sulfonatocalix[n]arenes (SCXn) were studied. The characteristics of host–guest (HG) complexation between p-sulfonatocalix[n]arenes with NFX were investigated by fluorescence spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Stoichiometry and association constants (K) of the inclusion complexes were determined by the non-linear fitting method. An interesting 1:1 stochiometric of HG complexes were formed at different pH values (pH = 3.00, 6.00, 8.00) The inclusion mode of NFX with p-sulfonatocalix[n]arenes was confirmed by NMR spectroscopy.     

Controlled self-assembly by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes

The complexation-induced critical aggregation concentrations of 1-pyrenemethylaminium by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes (n=4, 5) were systemically measured by fluorescence spectroscopy. In all cases, the complexation-induced critical aggregation concentration decreases by about 3 times upon addition of p-sulfonatocalix[n]arenes. However, the optimal molar ratios for the aggregation of 1-pyrenemethylaminium by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes are distinctly different: For mono-p-sulfonatocalix[n]arenes, the optimum mixing ratio for the aggregation of 1-pyrenemethylaminium is 1:4 mono-p-sulfonatocalix[n]arenes/1-pyrenemethylaminium, whereas only 2.5 molecules of 1-pyrenemethylaminium can be bound by one cavity of bis-p-sulfonatocalix[n]arenes. The intermolecular complexation of mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes with 1-pyrenemethylaminium led to the formation of two distinctly different nanoarchitectures, which were shown to be nanoscale vesicle and rod aggregates, respectively, by using dynamic laser scattering, TEM, and SEM. This behavior is also different from the fiber-like aggregates with lengths of several micrometers that were formed by 1-pyrenemethylaminium itself above its critical aggregation concentration. Furthermore, the obtained nanoaggregates exhibit benign water solubility, self-labeled fluorescence, and, more importantly, temperature responsiveness.     

杯芳烃和柱芳烃桥梁部位的衍生及其功能化

随着大环化学的快速发展,对杯芳烃、柱芳烃及其他类似化合物的桥梁亚甲基部位进行高效修饰的方法日益引起人们的关注.桥梁部位修饰后的大环衍生物,在不改变其原有属性的基础上增加了新的功能,不仅可以引入更多的功能基团,而且可以通过主客体的自组装行为,进一步拓展杯芳烃和柱芳烃等超分子大环在药物递送、化学传感、荧光体系构建等诸多领域...     

Biochemistry of the para-sulfonato-calix[n]arenes

The biochemistry of the para-sulfonato-calix[n]arenes has shown rapid development during the past ten years, the highly diverse biomedical applications of these molecules now include anti-viral, anti-thrombotic activities, enzyme blocking and protein complexation. The future is even more promising as para-sulfonato-calix[n]arenes have, now, been shown to have potential in the diagnosis of prion-based diseases. Their innocuous nature, as far as is known at present, may open up their future use in medications.     

Inclusion of Organic Cations by Calix[n]arenes

Calix[n]arenes represent an interestingclass of preorganized aromatic hostsexhibiting an enhanced ability forcation- interaction. Recent resultsobtained with the complexation of variouscalix[n]arenes and five structural typesof organic cations, namely ammonium ions,quaternary ammonium ions, phosphonium ions,iminium ions and tropylium ions are reviewed.The influence of both the guest structure and theshape and flexibility of the hosts on the complexstability in the gas phase and (mainly) in solutionis considered.     

Thermodynamic origins of selective binding affinity between p-sulfonatocalix[4,5]arenes with biguanidiniums

The binding geometries, abilities and thermodynamic parameters for the intermolecular complexation of two water-soluble calixarenes, p-sulfonatocalix[4]arene (SC4A) and p-sulfonatocalix[5]arene (SC5A), with biguanidinium guests, metformin (MFM) and phenformin (PFM), were investigated by (1)H and 2D NMR spectroscopy, X-ray crystallography, and isothermal titration calorimetry (ITC). The obtained results show that biguanidinium guests are captured by calixarenes with the alkyl or aromatic portion immersed into the cavities and the guanidinium portion fixed at the upper-rims. At both acidic and neutral conditions, SC4A always presents stronger binding affinities to biguanidinium guests than SC5A. Moreover, SC4A prefers to include MFM rather than PFM. As a result, the binding selectivity of MFM is up to 44.7 times for the SC4A/SC5A hosts. The intrinsic relationship between binding structures and selectivities were comprehensively analyzed and discussed from the viewpoint of thermodynamics. Finally, the ITC measurements were further performed in phosphate buffer instead of aqueous solution, to examine the buffer effects, counterion effect, and the differences between thermodynamic and apparent association constants.     

Biochemistry of anionic calix[n]arenes

This review treats the biological properties of the various anionic calix[n]arenes, both as soluble forms and in the colloidal state. The complexation of these molecules with amino-acids, peptides and proteins is discussed, as is their interaction with model membranes. The complexations with various Active Pharmaceutical Ingredients as complexes, for tamoxifen as solid state and colloidal structures, are treated in depth. Two sections deal with the direct biological action of the calix[n]arenes and their use as biosensors. A final section deals with the toxicity, in reality the lack of toxicity of the calix[n]arenes.     

Highly effective binding of methyl viologen dication and its radical cation by p-sulfonatocalix[4,5]arenes

The binding behaviors and thermodynamic origins of p-sulfonatocalix[4]arene (C4AS) and p-sulfonatocalix[5]arene (C5AS) with methyl viologen (MV2+) have been investigated by the methods of isothermal titration calorimetry, NMR, and cyclic voltammetry, showing that the binding abilities of C4AS and C5AS and their host selectivity are dramatically pH-controlled, which is closely discussed from the viewpoint of thermodynamics. Moreover, the radical form of MV+* can also be effectively included by C4AS and C5AS.     

Synthetic protocols towards homodithiacalix[n]arenes

Synthetic procedures towards homodithiacalix[n]arenes are developed, starting from simple and readily available bifunctional aryl building blocks, by a dynamic covalent chemistry approach. Reaction of 1,3-bis(mercaptomethyl)-5-tert-butyl-2-methoxybenzene under basic conditions leads to a mixture of trimeric, tetrameric and pentameric dimethylenedithia-bridged cyclooligomers, whereas reaction of 5-tert-butyl-2-methoxy-1,3-bis(thiocyanatomethyl) benzene under reducing conditions (and subsequent oxidation) affords the homodithiacalix[4]arene macrocycle in a very selective fashion through efficient disulphide exchange chemistry.     

Adsorption Mechanism of Benzene Derivatives by Pagoda[n]arenes

Despite the widespread use in industrial production, benzene derivatives are harmful to both human beings and the environment. The control of these substances has become an important subject of scientific research. This study introduces a new approach for adsorption and separation of benzene derivatives utilizing pagoda[n]arene based supramolecular materials. Density functional theory calculations were employed to investigate the molecular recognition mechanism of benzene derivatives by pagoda[4]arenes and pagoda[5]arenes (Pa[4]As and Pa[5]As). Results indicate that Pa[4]As and Pa[5]As can effectively accommodate benzene derivatives through non-covalent interactions, leading to the formation of stable host-guest complexes. Additionally, molecular dynamics simulations revealed that both crystalline and non-crystalline supramolecular aggregates of Pa[4]As and Pa[5]As possess the ability to adsorb benzene derivatives and maintain the stability of the adsorption. Moreover, increasing the temperature causes benzene derivatives to desorb from the adsorbing aggregates, and thus the material can be reutilized.     

Prospering the biphen[n]arenes family by tailoring reaction modules

Reported here is the comprehensive investigation on the formation of biphen[n]arenes by tailoring reaction modules. Five new macrocyclic arenes and four oligomers were synthesized by the condensation of monomers possessing different multimethoxyphenyl reaction modules and paraformaldehyde. We proved that the number and sites of methoxy on reaction modules greatly affected the reaction activity, shape, and connection mode of macrocycles. Moreover, the triangular and saddle-shaped configuration of macrocycles were revealed by single crystal structures. The results provided a typical and fundamental guidance in designing new macrocyclic arenes.     

Anti-thrombotic Activity of Water-soluble Calix[n]arenes

The parent p-sulfonato-calix[n]arenes and six O-monosubstituted derivatives were investigated in vitro for anticoagulant activity. Different concentrations of calixarenes were tested, showing that the compound 49-mono-(2-carboxymethoxy)-5,11,17,23,29,35,41,47-octa-sulfonato-calix[8]arene (C8SMA) has a significantly strong prolongation on the activated partial thromboplastin time (APTT) and on the thrombin time (TT) than the other calixarenes. Secondly, investigation of whether the anticoagulant behaviour was via interaction with antithrombin or Heparin Cofactor II was determined. Thrombin inhibition mediated by antithrombin (AT) and Heparin Cofactor II (HCII) activation was investigated in comparison to the biological activators, Heparin (Hep) and Dermatan sulfate (DS). The results show that the 49-mono-(2-carboxymethoxy)-5,11,17,23,29,35,41,47-octa-sulfonato-calix[8]arene (C8SMA) and 5,11,17,23,29,35-hexa-sulfonato-calix[6]arene (C6S) produce activation of HCII at 500 μM comparable to that induced by DS at 100 μM. However, activation of AT by all of the investigated calixarenes is between 10 and 50 times lower than that observed in the presence of heparin. The mechanism of the anticoagulant effect of these calixarenes is as activators of HCII and not as activators of AT.     

Anti-thrombotic Activity of Water-soluble Calix[n]arenes

The parent p-sulfonato-calix[n]arenes and six O-monosubstituted derivatives were investigated in vitro for anticoagulant activity. Different concentrations of calixarenes were tested, showing that the compound 49-mono-(2-carboxymethoxy)-5,11,17,23,29,35,41,47-octa-sulfonato-calix[8]arene (C8SMA) has a significantly strong prolongation on the activated partial thromboplastin time (APTT) and on the thrombin time (TT) than the other calixarenes. Secondly, investigation of whether the anticoagulant behaviour was via interaction with antithrombin or Heparin Cofactor II was determined. Thrombin inhibition mediated by antithrombin (AT) and Heparin Cofactor II (HCII) activation was investigated in comparison to the biological activators, Heparin (Hep) and Dermatan sulfate (DS). The results show that the 49-mono-(2-carboxymethoxy)-5,11,17,23,29,35,41,47-octa-sulfonato-calix[8]arene (C8SMA) and 5,11,17,23,29,35-hexa-sulfonato-calix[6]arene (C6S) produce activation of HCII at 500 μM comparable to that induced by DS at 100 μM. However, activation of AT by all of the investigated calixarenes is between 10 and 50 times lower than that observed in the presence of heparin. The mechanism of the anticoagulant effect of these calixarenes is as activators of HCII and not as activators of AT.in final form: 24 November 2004This revised version was published online in July 2005 with a corrected issue number.     

Synthesis and properties ofN-substituted azacalix[n]arenes

Side arm modifications of hexahomotriazacalix[3]arene (1) were achieved by simple synthetic methods. Compound5 has picolyl side arms and liquid-liquid extraction experiments showed that the alkali cation affinity of5 is much stronger than that of1. A chiral group was also introduced into the azacalixarene structure. Calix[4]arene was converted into dihomoazacalix[4]arene (2) in 8% yield. Clathrate formation of2 with various solvents is described. MM3 calculations were carried out onp-substituted analogs of2. The self-filled structure, in which the benzyl side arm is placed in its cavity, is the most stable structure when thep-positions of the aromatic rings carry small substituents. Strong hydrogen bonds between nitrogen and phenolic hydroxyl groups in dihomoazacalix[4]arene (2) were observed at low temperatures. The¹H-NMR signals of phenolic hydroxyl groups appeared as six singlets in the range of 9.817.1 ppm at –70°C.This paper is dedicated to the commemorative issue on the 50th anniversary of calixarenes.     

Anthocyanin Color Stabilization by Host-Guest Complexation with p-Sulfonatocalix[n]arenes

Flavylium-based compounds in their acidic and cationic form bring color to aqueous solutions, while under slightly acidic or neutral conditions they commonly bring discoloration. Selective host-guest complexation between water-soluble p-sulfonatocalix[n]arenes (SCn) macrocycles and the flavylium cationic species can increase the stability of the colored form, expanding its domain over the pH scale. The association constants between SCn and the cationic (acid) and neutral basic forms of flavylium-based compounds were determined through UV-Vis host-guest titrations at different pH values. The affinity of the hosts for synthetic chromophore was found to be higher than for a natural anthocyanin (Oenin). The higher affinity of SC4 for the synthetic flavylium was confirmed by ¹H NMR showing a preferential interaction of the flavylium phenyl ring with the host cavity. In contrast with its synthetic counterpart, the flavylium substitution pattern in the anthocyanin seems to limit the inclusion of the guest in the host’s binding pocket. In this case, the higher affinity was observed for the octamer (SC8) likely due to its larger cavity and higher number of negatively charged sulfonate groups.     

Scandium(III) coordination polymers containing capsules based on two p-sulfonatocalix[4]arenes

Reactions of sodium p-sulfonatocalix[4]arene and scandium(III) tristriflate in the presence, and absence, of [18]crown-6 give the crystalline complexes [Sc2(mu-OH)2(H2O)10][Na4(H2O)8-[calix[4]arene(SO3)4]2).13 H2O and [[Sc2(mu-OH)2(H2O)8][Sc(H2O)4]2[calix[4]-arene(SO3)4-H+]2([18]crown-6).16H2O. Both complexes involve novel coordination polymers with calixarene units linked through sodium or scandium centers and also feature capsule assemblies through to the head-to-head association of calixarenes. A linear array of capsules associated with an infinite chain of aquo-bridged sodium ions, and an aquated hydroxy-bridged scandium(III) dimer, [Sc2(mu-OH)2(H2O)10]4+, are found in the absence of the crown ether. In the presence of [18]crown-6 both hydrated scandium monomers and dimers bridge between calixarenes in a two-dimensional coordination network. The crown ethers reside in cavities created by two calixarenes from adjacent polymeric sheets via a variety of supramolecular interactions(hydrogen-bonding, shape complementarity), and effectively add a third dimension to the network. The extended structure of both of these polymers is highly porous, and resembles a bilayer.     

Synthesis and inclusion properties of pillar[n]arenes

A detailed study of the reaction conditions revealed that a quantitative cyclocondensation of 1,4-dialkoxy-2,5-bis(alkoxymethyl)-benzenes to pillar[n]arenes can be achieved by catalysis of p-toluenesulfonic acid in CH₂Cl₂. Major product of this new reaction is in each case a cyclopentamer (n = 5), but small amounts of the pillar[n]arenes with n = 6, 7 and 10 can be obtained as well. Different alkoxy groups in 1- and 4-position lead to regioisomers. All cyclooligomers exist in pillar structures as pair of enantiomers, which show a racemisation at room temperature, which is fast in terms of the NMR time scale. The racemisation process occurs by rotation of the 1,4-phenylene segments in the macrocyclic rings. Pillar[n]arenes exhibit novel host–guest behavior.     

Supramolecular interactions of [60]- and [70]fullerenes with calix[n]arenes

[60]- and [70]fullerenes have been shown to form 1:1 supramolecular complexes with (i) 24,26-dimethoxy-25,27-dihydroxy-5,11,17,23-tetra(4-tert-butyl)calix[4]arene (1) and (ii) 37,39,41-trimethoxy-38,40,42-trihydroxy-5,11,17,23,29,35-hexa(4-tert-butyl)calix[6]arene (2) in CCl(4) medium by absorption spectroscopy. Charge transfer absorption bands of the complexes have been located in each of the cases (except [70]fullerene-2 complex) studied from which the vertical ionisation potential of 1 has been obtained. Formation constants of the complexes have been determined at four different temperatures from which the enthalpies and entropies of formation of the complexes have been obtained. Moreover, the formation constant of [70]fullerene-2 complex is higher than that of the [60]fullerene-1 and [60]fullerene-2 complexes at all the four temperatures studied. This has been accounted in terms of greater cavity size of 2 which is a calix[6]arene compared to 1 which is a calix[4]arene and also by the fact that a high degree of preorganisation takes place in case of 2 through intramolecular H-bonding at its lower rim.     

Selective membrane transport of amino acids by functionalised calix[4]arenes

The selective active transport through liquid membrane assisted by the pH gradient of amino acid methylesters by using a series of calix[4]arenes substituted by acid and amido functions, glycolic chains, and hydroxyl groups as carriers has been performed. All these receptors have been found to act as carriers for transport of aromatic amino acid methylesters from the aqueous source phase to the aqueous receiving phase aiming at their separation. The receptors bearing diacid and tetraamido functions have the better ability to transport of amino acids than the other receptors studied. The influence of calixarene and amino acid structures upon transport through liquid membrane is discussed. The obtained results are correlated with those acquired by solvent extraction.