Nanoencapsulation of calix[4]arene inclusion complexes

A hexameric resorcinarene nanocapsule in wet CDCl3 forms inclusion complexes of calix[4]arene with tetramethylammonium and trimethylsulfoxonium cations to give highly stable Russian-doll-type multicomponent assemblies. The 2D NOESY experiments revealed the size of the assembly, the close proximity of the encapsulated calix[4]arene molecule to the resorcinarene molecules of the capsule, and the inclusion of the tetramethylammonium cation in the calix[4]arene cavity.     

Preparation and physicochemical characterization of carbamazepine (CBMZ): para-sulfonated calix[n]arene inclusion complexes

The formation of inclusion complexes with para-sulfonated calix[n]arene (PSC[n]A) was studied for carbamazepine (CBMZ), a poorly water soluble anticonvulsant drug. The effect of PSC[4]A and PSC[6]A on aqueous solubility of carbamazepine was studied extensively. The complete complexation of the drug was achieved after 48 h of shaking with PSC[n]A in water and evaporation of water to get solid complex. The interaction between PSC[n]A and CBMZ in solid state inclusion complexes was accomplished by aqueous phase solubility studies, HPLC, DSC, PXRD, FTIR, UV–Vis, and FT-Raman spectroscopy. The solubility of CBMZ increases as a function of PSC[n]A concentration. The results of the two phase solubility experiments are in good conformity to signify the formation of 1:1 (PSC[6]A:CBMZ) and 2:1 PSC[4]A:CBMZ complexes. The order of dissolution rate of CBMZ is inclusion complex > physical mixture > drug alone. The purpose of this study was to enhance solubility resulting in high dissolution rate and bioavailability of this essentially water insoluble drug.     

Heterocalix[8]arene inclusion complexes: Crystal structure and mobility of the host shape

A supramolecular host-guest system based on heterocalix[8]arene 1, incorporating benzimidazol-2-one and 2-methoxy-5-tert-butyl-1,3-phenylene subunits in an alternate cyclic arrangement, has been studied. The crystal structures of two solvent endo/exo inclusion complexes formed from the host molecule 1 and 3-methylpyridine in hydrated and unhydrated forms demonstrate the influence of crystal packing on the shape of the host molecule.     

Synthesis and metal complexation studies of [2n]thiacalix[m]arene[m]pyrazine

Novel [2_n]thiacalixarenepyrazine and [2_n]thiacalixarenetriazine systems were synthesised by one-pot S_NAr reactions. A screening of the metal-complexing ability of [2₆]hexathiacalix[3]arene[3]pyrazine revealed its affinity for Cu^I, Cu^II and Ag^I metal salts.     

Molecular inclusion of organometallic sandwich complexes within hybrid cavitand-resorcin[4]arene receptors

Two different hybrid cavitand-resorcin[4]arenes are shown to be effective and selective receptors for the molecular inclusion of positively charged organometallic sandwich complexes of appropriate size. The binding constants of the 1 : 1 complexes formed with a series of neutral and positively charged metallocenes have been calculated using different titration techniques. The motion of the included metallocene and the kinetics of the complexation process are investigated. The voltammetric behaviour of the inclusion complexes formed with cobaltocenium is also studied.     

Spectroscopic studies on inclusion properties of fullerenocalix[4]arene conjugates with metal ions

Metal-chelating properties-in the ground and excited states-of fullerenocalix[4]arenes containing two malonamide substituents at the upper rim and four alkyl ester chains at the lower rim have been studied by means of steady-state absorption, fluorescence spectroscopy, and time-resolved transient absorption spectra. In particular, the influence that Ag+ enforces on the fullerene electronic spectra is due to direct interactions between Ag+ and the surface of C60. The effects stemming from Na+, Mg2+, and Ba2+, on the other hand, are indirect and are introduced through chelating the metal ions to the calix[4]arene moiety. They strongly depend on the molecular structure of the fullerenocalix[4]arenes. No spectroscopic evidence was obtained for any influence caused by Mn2+, although the malonamide groups provide good chelating ability even for this transition metal ion.     

杯芳烃的研究 II: 四羟基杯[4]芳烃包合性能的研究

本文利用X射线衍射法研究了四羟基杯[4]芳烃与水、氯仿的包合物的晶体结构,它们属六方晶系, 为分子间包合物。通过这些研究发现: 在晶体中, 四羟基杯[4]芳烃是通过六重螺旋轴的作用形成一种管道型的空间来包合客体分子, 这种管道具有对客体分子选择性等特点。     

Spectroscopic studies on the inclusion interaction of p-sulfonatocalix[6]arene with vitamin B6

The formation of the inclusion complex of p-sulfonatocalix[6]arene (SCX6) with different forms of vitamin B₆ (VB₆) was studied by using fluorescence spectroscopy. VB₆ can exist in one of three forms (the acidic form, neutral zwitterionic form and basic form) depending on pH. The fluorescence intensities of acidic and basic forms of VB₆ remarkably decreased in presence of SCX6. SCX6 preferred to form 1:1 inclusion complexes with acidic and basic forms of VB₆ but hardly form inclusion complex with neutral zwitterionic form. According to the nonlinear curve fitting method, the inclusion constant (K) for the formation of inclusion complexes of acidic and basic forms of VB₆ with SCX6 were evaluated to be 1.4?×?10⁴ and 9?×?10³ L/mol, respectively. The binding affinity of SCX6 towards acidic form is attributed to hydrogen bonds and hydrophobic interaction, furthermore, additional electrostatic interaction also plays a crucial role. The possible inclusion mode was given by ¹H NMR technique.     

柱芳烃的合成与应用

综述了近四年来新型超分子主体化合物柱芳烃的合成、发展和应用.其中,柱芳烃及其衍生物的合成主要有两种有机化学合成策略,即"先成环后修饰"和"先修饰后成环".由于这类新型主体化合物具有非常特殊的空间结构和理化性质,目前,它主要应用在主客体包合与分子识别、自组装体系的构筑和智能材料等领域.     

Solution NMR studies of supramolecular complexes of [60]- and [70]fullerenes with mono O-substituted calix[6]arene

Supramolecular complexation of [60]- and [70]fullerenes with 37-allyl-38,39,40,41,42-pentahydroxy-5,11,17,23,29,35-hexa(4-tert butyl)calix[6]arene (I) has been studied in CCl(4) medium by NMR spectrometric method. All of the complexes are found to be stable with 1:1 stoichiometry. Formation constants (K) of the above supramolecular complexes have been determined from systematic variation of NMR chemical shifts of specific protons of I in the presence of [60]- and [70]fullerenes. Trends in the K value suggest that [70]fullerene binds more strongly with I relative to [60]fullerene. Both PM3 and ab initio calculations reveal that the intermolecular interaction in the [70]fullerene/I complex proceeds through quite deep energy minima.     

Laser spectroscopic and theoretical studies of encapsulation complexes of calix[4]arene

The complexes between the host calix[4]arene (C4A) and various guest molecules such as NH(3), N(2), CH(4), and C(2)H(2) have been investigated via experimental and theoretical methods. The S(1)-S(0) electronic spectra of these guest-host complexes are observed by mass-selected resonant two-photon ionization (R2PI) and laser-induced fluorescence (LIF) spectroscopy. The IR spectra of the complexes formed in molecular beams are obtained by IR-UV double resonance (IR-UV DR) and IR photodissociation (IRPD) spectroscopy. The supramolecular structures of the complexes are investigated by electronic structure methods (density functional and second order perturbation theory). The current results for the various molecular guests are put in perspective with the previously reported ones for the C4A-rare gas (Rg) (Phys. Chem. Chem. Phys. 2007, 126, 141101) and C4A-H(2)O complexes (J. Phys. Chem. A, 2010, 114, 2967). The electronic spectra of the complexes of C4A with N(2), CH(4), and C(2)H(2) exhibit red-shifts of similar magnitudes with the ones observed for the C4A-Rg complexes, whereas the complexes of C4A with H(2)O and NH(3) show much larger red-shifts. Most of the IR-UV DR spectra of the complexes, except for C4A-C(2)H(2), show a broad hydrogen-bonded OH stretching band with a peak at ~3160 cm(-1). The analysis of the experimental results, in agreement with the ones resulting from the electronic structure calculations, suggest that C4A preferentially forms endo-complexes (guests inside the host calizarene cavity) with all the guest species reported in this study. We discuss the similarities and differences of the structures, binding energies, and the nature of the interaction between the C4A host and the various guest species.     

Thermodynamic study of functionalized calix[n]arene and resorcinol[n]arene monolayers spreaded at an aqueous pendant drop

The behavior of insoluble calix[n]arene and resorcinol[n]arene derivatives monolayers were studied through the use of a constant surface Langmuir balance based on Axisymmetric Drop Shape Analysis (ADSA). In each case, a stable monolayer was obtained and different transitions (induced for lateral compression) could be identified. Thermodynamic parameters were computed through two dimensional Clausius–Clayperon equations and used to valuate the monolayer stability. A noticeable reduction of thermodynamic parameters occurred at highly tested temperatures (328 and 338 K) for those compounds that had hydrocarbon tails or benzene rings attached to one side of macrocyclic rim. Such fact was related to a monolayer rearrangement where the macrocyclic ring changed from a parallel to a perpendicular orientation. In this orientation the hydrophobic interactions between hydrocarbon chains and benzene rings were maximized. At highly temperature, where vigorous molecular motion existed, those interactions were superior to the stabilization effect through hydrogen bond.     

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.     

Spectrophotometric study of the supramolecular complexes of [60]- and [70]Fullerenes with biscalix[6]arene and crown[4]calix[6]arene

[60]- and [70]Fullerenes have been shown to form 1:1 supramolecular complexes with bis[2-(5,11,17,23,29,35-hexa-tert-butyl-37,38,39,40,41-pentahydroxycalix[6]arenyl-oxy ethyl ether) (1) and 5,11,17,23,29,35-hexa-tert-butyl-37,38,40,41-tetra hydroxyl-39,42-(crown-4)calix[6]arene (2) in CHCl3 medium by electronic absorption spectroscopy. Formation constants (K) of the complexes of [60]- and [70]fullerenes with 1 and 2 have been determined at room temperature from which free energy of formation values of the complexes have been estimated. The very high formation constant value of [60]fullerene/1 complex (5900 dm3 mol-1) in indicative of formation of inclusion complex. Moreover, PM3 calculations reveal that intermolecular interaction between [60]fullerene and 1 proceeds through quite deep energy molecular orbital.     

Structural Diversification of Pillar[n]arene Macrocycles

Despite the fact that pillar[n]arenes receive major interest as building blocks for supramolecular chemistry and advanced materials, their functionalization is generally limited to the modification of the hydroxy or alkoxy units present on the rims. This limited structural freedom restricts further developments and has very recently been overcome. In this article, we highlight three very recent studies demonstrating further structural diversification of pillar[n]arenes by partial removal of the alkoxy substituents on the rims, which can be considered as the next generation of pillar[n]arenes.     

NMR studies of inclusion complexation of the pyrrolizidine alkaloid retronecine and p-sulfonic acid calix[6]arene

Accidental or intentional drug toxicity in humans and animals is a major concern and the search for detoxificant agents is a challenge. Pyrrolizidine-producing forages are a threat not only to livestock, but also to humans as a consequence of food contamination. Supramolecular systems are promising as detoxificant agents by decreasing the bioavailability of toxic compounds in biological environment. Cyclodextrin and calix[n]arenes are well known hosts for a variety of molecules and/or ions. Surprisingly, only few studies describe the potential of calix[n]arenes as host for toxic molecules. This study focused on the use of NMR techniques as tools for the investigation of the interactions between p-sulfonic acid calix[6]arene and retronecine, a toxic pyrrolizidine alkaloid.     

Preparation and characterization of inclusion complexes of antitumor camptothecin with cucurbit[n = 7, 8]urils

The slightly water-soluble anticancer drug camptothecin (CPT) and its inclusion complexes with cucurbit[n = 7, 8]uril (Q[n] (n = 7, 8)) were investigated. The formation of 1:2 complexes with Q[n] (n = 7, 8) in aqueous solution was confirmed by fluorescence spectroscopy and the apparent stability constants were determined to be higher than 3.01 × 10¹² L²/mol². The solid inclusion complexes of CPT and Q[n] (n = 7, 8) were also prepared by the co-evaporation method and characterized by Fourier transformation-infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction. Aqueous solubility and dissolution studies indicate that the complexes exhibited significantly increased dissolution rates compared with the pure drug and physical mixtures. The potential of Q[7] or Q[8] for stabilizing lactone modality of CPT was investigated by the High Performance Liquid Chromatography (HPLC) method. The results reveal more than 63% CPT lactone form (active form) in CPT-Q[7] or Q[8] complexes compared to only 36% CPT lactone form in the absence of Q[7] or Q[8] after being incubated in the phosphate buffer solution (pH 7.4 at 37°C) for 5 h.     

去叔丁基杯[8]芳烃乙酸钠对紫杉醇包合作用的研究

采用紫外分光光度法和荧光光谱法研究去叔丁基杯[8]芳烃乙酸钠对紫杉醇的包合和释放过程,考察了二者物质的量之比、温度等因素对包合作用的影响.结果显示去叔丁基杯[8]芳烃乙酸钠在一定条件下与紫杉醇可形成稳定的超分子包合物,包合后水溶性明显提高,且随着去叔丁基杯[8]芳烃乙酸钠/紫杉醇物质的量之比的增加,荧光强度明显增强.去叔丁基杯[8]芳烃乙酸钠今后有望成为紫杉醇类抗肿瘤药物的良好载体.     

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.     

Nonregular structure-property relationships for inclusion parameters of tert-butylcalix[5]arene

The effect of macrocycle size on the structure-property relationships was studied for inclusion compounds of tert-butylcalix[n]arenes (n=4,5) with volatile organic guests having various molecular size and group composition. Vapor-sorption isotherms, guest-inclusion stoichiometry and Gibbs energy, thermostability parameters and decomposition enthalpies were determined for host-guest compounds (clathrates) obtained using saturation of solid calixarene powder with guest vapor. The increase of the host macrocycle in the studied calixarene pair changes the observed structure-property relationship from the guest-binding selectivity mostly seen in inclusion Gibbs energy to the high sensitivity for guest structure in inclusion stoichiometry. The host with the larger macrocycle has more clathrates with stepwise formation and decomposition. Specific types of guest binding with solid hosts are discussed.