Intermolecular complexation thermodynamics between water-soluble calix[4]arenes and diazacycloalkanes

Calorimetric titration experiments have been performed in pH 2.0 and 7.2 phosphate buffer solutions at 298.15 K to calculate the complex stability constants (K_S) and thermodynamic parameters (ΔG°, ΔH°, and TΔS°) for the stoichiometric 1:1 inclusion complexation of water-soluble calix[4]arene tetrasulfonate (CAS) and thiacalix[4]arene tetrasulfonate (TCAS) with some diazacycloalkane guests, i.e. piperazine (1), homopiperazine (2) and 1,5-diazacyclooctane (3). The results indicated that complexes of CAS and TCAS with diazacycloalkane guests were enthalpy-stabilized, and an acidic environment was more favorable to host-guest complexation than a neutral one. CAS forms more stable complexes with guest molecules than TCAS due to the more favorable enthalpic gain.     

Solvent effect on the complex formation of distally dialkylated calix[4]arenes with 1-chloro-4-(trifluoromethyl)benzene

The complexation behavior of the distally dialkylated calix[4]arenes and 4-tert-butylcalix[4]arenes (hosts) with 1-chloro-4-(trifluoromethyl)benzene (guest) was examined in four different alcohols (MeOH, EtOH, n-PrOH, n-BuOH) as solvents. The complex stability constants (K_s) and the complexation energy of the host-guest complexes were determined. Fair ‘by group’ linear correlations between each log K series determined in the same solvent and the complex stabilization energies were found. As a consequence, the solvents having high permittivities result in less stability of the host-guest complex in these particular cases examined.     

Synthesis and host-guest properties of pillar[6]arenes

A facile method for the synthesis of pillar[6]arenes was developed.A series of pillar[6]arenes were prepared with FeCl 3 as catalyst and chloroform as solvent at room temperature in moderate yields(30%-40%).Their host-guest properties with n-cetyltrimethyl ammonium bromide were investigated by 1 HNMR.The results showed that high selectivity in the host-guest relationship became apparent between pillar[6]arenes and pillar[5]arenes based on the different size of the inner cavity.     

Complexation thermodynamics of water-soluble calix[4]arene derivatives with lanthanoid(III) nitrates in acidic aqueous solution

Microcalorimetric titrations have been performed in acidic aqueous solution at 25 °C to calculate the complex stability constants (K_S) and thermodynamic parameters (ΔG°, ΔH°, and TΔS°) for the stoichiometric 1:1 complexation of lanthanoid(III) nitrates (La-Gd, Tb) with 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis(hydroxycarbonylmethoxy)calix[4]arene (2) and 5,11,17,23-tetrasulfonato-thiacalix[4]arene (3). Using the present and previous reported data on water-soluble calix[4]arenesulfonates (1) and structurally related analogues 2 and 3, the complexation behavior is discussed comparatively from the thermodynamic point of view. Possessing four carboxyls at the lower rim of parent calix[4]arenesulfonate (1), the derivative 2 displays the enhanced binding abilities for Sm³⁺. As compared with 1 and 2, p-sulfonatothiacalix[4]arene (3) gives not only the lower binding constants for all of lanthanoid(III) ions but also lower cations selectivity. Thermodynamically, the resulting complexes of lanthanoid(III) ions with 1 and its derivatives 2 and 3 is absolutely entropy-driven in aqueous solution, typically showing larger positive entropy changes. These larger positive entropy changes (TΔS°) and somewhat smaller positive enthalpy changes (ΔH°) are directly contributed to the complexes stability as a compensative consequence.     

Host-Guest Complexation of Oxaliplatin and Para-Sulfonatocalix[n]Arenes for Potential Use in Cancer Therapy

P-sulfonatocalix[n]arenes have demonstrated a great potential for encapsulation of therapeutic drugs via host-guest complexation to improve solubility, stability, and bioavailability of encapsulated drugs. In this work, guest-host complexes of a third-generation anticancer drug (oxaliplatin) and p-4-sulfocalix[n]arenes (n = 4 and 6; p-SC4 and p-SC6, respectively) were prepared and investigated, using ¹H NMR, UV, Job’s plot analysis, and DFT calculations, for use as cancer therapeutics. The peak amplitude of the prepared host-guest complexes was linearly proportional to the concentration of oxaliplatin in the range of 1.0 × 10⁻⁵ M⁻¹ to 2.1 × 10⁻⁴ M⁻¹. The reaction stoichiometry between either p-SC4 or p-SC6 and oxaliplatin in the formed complexes was 1:1. The stability constants for the complexes were 5.07 × 10⁴ M⁻¹ and 6.3 × 10⁴ M⁻¹. These correspond to complexation free energy of −6.39 and −6.52 kcal/mol for p-SC4 and p-SC6, respectively. Complexation between oxaliplatin and p-SC4 or p-SC6 was found to involve hydrogen bonds. Both complexes exhibited enhanced biological and high cytotoxic activities against HT-29 colorectal cells and MCF-7 breast adenocarcinoma compared to free oxaliplatin, which warrants further investigation for cancer therapy.     

p-tert-Butyl thiacalix[4]arenes functionalized at the lower rim by o-, m-, p-amido and o-, m-, p-(amidomethyl)pyridine fragments as receptors for α-hydroxy- and dicarboxylic acids

A series of new p-tert-butyl thiacalix[4]arenes with o-, m-, p-amido and o-, m-, p-(amidomethyl)pyridine substituents at the lower rim in cone, partial cone, and 1,3-alternate conformations were synthesized. The ability of the obtained compounds to recognize the α-hydroxy (glycolic, tartaric) and dicarboxylic (oxalic, malonic, succinic, fumaric, and maleic) acids was investigated by UV-vis spectroscopy. Also, the efficiency and selectivity of binding, the association constants log K_a (10² to 10⁷ M⁻¹) and the stoichiometry were determined for the complexes of p-tert-butyl thiacalix[4]arenes with the acids. The receptors based on p-tert-butyl thiacalix[4]arenes with (amidomethyl)pyridine substitutes are most efficient in complexation in many cases.     

Correlation between Thermodynamic Behavior and Structure in the Complexation of Modified β-Cyclodextrins and Bile Salts

Complex stability constants (K _S), standard molar enthalpy changes (ΔH ⁰) and entropy changes (ΔS ⁰) for the inclusion complexation of two cyclodextrin dimers, 6,6′-{2,2′-diselenobis[2-(benzoylamino)ethylamino]}-bridged bis(β-cyclodextrin) (1) and o-phenylenediseleno bridged bis(β-cyclodextrin)s (3), and their monomer analogs, 6-deoxy-6-{[2-(2,3-dihydro-3-oxo-1,2-benzisoselenazol-2-yl)ethyl]amino}-β-cyclodextrin (2) and mono[6-(phenylseleno)-6-deoxy]-β-cyclodextrin (4), with two bile salt guests, sodium cholate (CA) and sodium deoxycholate (DCA), were determined at 25°C in Tris buffer solutions (pH 7.4) at 298.15?K by means of isothermal titration microcalorimetry (ITC). The interactions and binding modes between the host cyclodextrins and the guest bile salts were further studied by ROESY spectroscopy. The thermodynamic parameters obtained, together with the ROESY spectra, were used to examine the correlations between thermodynamic behavior and binding modes of the host–guest complexation. The results indicate that the length, structure and conformation of the tethers linked to the cyclodextrins determine the binding modes and the binding abilities between hosts and guests to a great extent, leading to a reversion in binding ability when comparing the corresponding dimer and its monomer analog.     

Chiral Schiff base derivatives of calix[4]arene: synthesis and complexation studies with chiral and achiral amines

Novel chiral Schiff base derivatives of calix[4]arenes 1–3 have been prepared from the reaction of 5,17-diformyl-25,27-dipropoxy-26,28-dihydroxycalix[4]arene 4 with (S)-(−)-1-phenylethylamine, (R)-(−)-1-cyclohexylethylamine, and (R)-(−)-2-heptylamine, respectively, by a convenient method in 69–80% yields. Spectrophotometric titrations have been performed in CHCl₃ at 20–30 °C in order to obtain the binding constants (K) and thermodynamic quantities (ΔH and ΔS) for the stoichiometric 1:1 inclusion complexation of various amines with these new host compounds. The molecular recognition abilities and enantioselectivity for guests (R)- and (S)-α-phenylethylamine, 3-morpholinopropylamine and n-butylamine are discussed from a thermodynamic point of view.     

Synthesis of novel p-tert-butyl-calix[4]arene derivatives and their cation binding ability: chromogenic effect upon side arms binding

A series of novel double-armed calix[4]arene derivatives, i.e. 5,11,17,23-tetra-tert-butyl -25,27-bis[2-[(2-hydroxy-5-(4-nitroazo)benzylidene)amino]ethoxy]-26,28-dihydroxy-calix[4]-arene (4), 5,11,17,23-tetra-tert-butyl-25,27-bis[2-[(2-hydroxy-5-(2-nitroazo)benzylidene) amino]ethoxy]-26,28-dihydroxycalix[4]arene (5), 5,11,17,23-tetra-tert-butyl-25,27-bis[2-[(2-hydroxy-5-(4-chloroazo)benzylidene)amino]ethoxy]-26,28-dihydroxycalix[4]arene (6), have been synthesized as an selective chromoionophore for Na⁺. The complexation behavior of ligands 4-6 with alkali metal ions Na⁺, K⁺, Rb⁺and Cs⁺ has been evaluated by using UV-Vis spectrometry in CH₃CN-H₂O (99:1/V:V) solution at 25°C. The UV-Vis spectra show that the complexation of 4-6 with Na⁺exhibits obvious bathochromic shifts (λ_max 379→480 nm) and there is a unique color change in the solution from yellow to red upon complexation. The binding constants for Na⁺ are higher than that of other alkali metal ions, giving the highest cation selectivity up to 7 for Na⁺/K⁺. The binding ability and photophysical behavior of alkali cations by calix[4]arene derivatives 4-6 are discussed from the point of view of substituted effects at the lower rim of parent calix[4]arene and size-fit concept between host calix[4]arenes and guest cations.     

Synthesis and conformational behaviour of lower-rim tetraacetylated thiacalix[4]arenes

The acylation of thiacalix[4]arenes with AcCl or Ac₂O gave the corresponding lower-rim tetraacetoxy derivatives. In contrast to classical calix[4]arenes, tetraacetylated thiacalix[4]arenes are conformationally mobile in solution and represent a thermodynamic equilibrium of three different conformers at room temperature. As proven by a dynamic ¹H NMR study, conformational preferences of acetylated thiacalix[4]arenes considerably depend on the upper-rim substitution. Hence, t-Bu thiacalixarene prefers 1,3-alternate and 1,2-alternate conformations (43% and 38%, respectively), while the upper-rim unsubstituted compound adopts preferably the partial cone conformation (70%).     

Efficient synthesis of copillar[5]arenes and their host-guest properties with dibromoalkanes

An efficient method for the synthesis of copillar[5]arenes was developed with FeCl(3) as catalyst and different 1,4-dialkoxybenzenes and paraformaldehyde as reactants (yields: 50-85%). The host-guest property of (co)pillar[5]arenes and terminal dibromoalkanes was investigated by (1)H NMR measurements and an X-ray study. The complexation behavior of the copillar[5]arenes can be tuned by changing the substituents on the host. A complete complexation selectivity was found between pillar[5]- and pillar[6]arenes, which is an interesting aspect for sensor techniques.     

Intermolecular interactions and binding mechanism of inclusion complexation between sulfonate calix[<Emphasis Type="Italic">n</Emphasis>]arenes and ethidium bromide

In this work, the interactions between ethidium bromide (ET) and water-soluble sulfonate calix[n]arenes (n: 4, 6, and 8) were investigated by NMR, FT-IR, and fluorescence spectroscopic methods. The aim was to evaluate both the stoichiometry and the mechanism of the possible complex structure between sulfonate calix[n]arenes and ET. The spectroscopic data revealed that a 1:1 binding mode between calixarene and ET was occurred. Furthermore, thermodynamic parameters and fluorescence titration experiments were studied at different temperatures to determine both the quenching mechanism and the type of intermolecular forces in complex formation. Host–guest complexation of sulfonate calix[n]arenes and ET could be used to overcome some adverse effects related to the using of ethidium bromide during biological applications as a DNA marker treatment.     

Fullerene encapsulation with calix[5]arenes

This paper presents the synthesis of the fullerene hosts based on the calix[5]arenes and their binding properties. Calix[5]arenes 1a, 2, 3a bind C₆₀ or C₇₀ in organic solvents. The solvent effect of the fullerene complexation was clearly observed; the association constant decreases in a solvent with high solubility for C₆₀. Covalently linked double-calix[5]arenes 4-6 were also investigated on their binding properties for fullerenes in organic solvents. Their binding abilities for both C₆₀ and C₇₀ are extremely high in toluene solution. Higher binding selectivity toward C₇₀ is observed by all the double-calix[5]arenes. The selectivity of 5a toward C₇₀/C₆₀ is highest in toluene with a value of 10. The structures of the supramolecular complexes of the calix[5]arene hosts and C₆₀ or C₇₀ were investigated by using ¹H and ¹³C NMR studies. The molecular mechanics calculation and X-ray structure reveal that the interior of the calix[5]arene is complementary to the exterior of C₆₀ molecule. In contrast, the host-guest complexes of C₇₀ with the simple calix[5]arenes take many conformational options due to its less symmetric shape. The molecular mechanics calculation and our chemical shift simulation nicely worked to estimate the reliable structures; the calix[5]arene cavity takes up C₇₀ molecule, and the C₇₀ molecule tilts significantly from the C5 axis of the calix[5]arene. In the case of the host-guest complex of C₇₀ with the double-calix[5]arene, the molecular dynamics simulation of the host-guest complex represented the realistic movement of the bound C₇₀ inside the cavity. The combination of the molecular dynamics simulation and the chemical shift simulation of the host-guest complex suggested that the C₇₀ molecule rapidly moves inside the cavity.     

Thermodynamics of Complexation of Tetraalkylammonium and Rare-earth Cations with Two Sulfonatocalix[n]arenes (n=4 and 6) in Aqueous Solution

We report results of a microcalorimetry study of the association of inorganic and organic cations with two p-sulfonatocalix[n]arenes (host 1: n = 4; host 2: n = 6) in aqueous solution at 298.15 K. First, we have determined the thermodynamic parameters for the complexation between the host 2 and a series of quaternary ammonium cations. We have evaluated the influence of the pH on the structure and energetics of these organic complexes. We have also reported the association constant and enthalpy of reaction for the complexation of some rare-earth cations (Sm³⁺, Dy³⁺, Y³⁺ and Sc³⁺ cations) with the two hosts. In all cases we have observed the formation of 1:1 complexes.

Whereas the association is driven by a favourable entropy change for the inorganic cations (ΔH > 0 and TΔS>>0), it is controlled by a favourable enthalpy change for the organic cations (ΔH < < 0 and TΔS < 0 or >0). In acidic solution, the complexes formed between host 2 and tetraalkylammonium cations are weaker than those formed with the cyclic tetramer. In neutral solution this effect is not observed. All the results are in line with a conformational change of host 2 with the pH.     

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.     

Synthesis and structure of lower rim C-linked tetra-N-tosyl peptidocalix[4]arenes

Chiral p-tert-butylcalix[4]arenes perfunctionalised at the lower rim with amino acid residues have been prepared. The ¹H and ¹³C NMR spectra indicate that the macrocycles adopt a cone conformation. Calix[4]arenes bearing amino acid moieties 5a shows strong complexation towards Cl⁻, Br⁻, HSO₄⁻, H₂PO₄⁻ and N-tosyl-(l)-alaninate.     

Regioselective Synthesis and Inclusion Properties of distal-Bis[(2-pyridylmethyl) oxy]tetrathiacalix[4]arenes

Regioselective synthesis of bis[(2-pyridylmethyl)oxy]tetrathiacalix[4]arenes was accomplished by a protection–deprotection method using benzyl groups as a protecting group. The conformational studies of distal-bis[(2-pyridylmethyl)oxy]thiacalix[4]arenes in solution and solid state are described. The two-phase solvent extraction data indicated that bis[(2-pyridylmethyl)oxy]tetrathiacalix[4]arenes show strong Ag⁺ (E%, 97%) affinity. In contrast, no significant E% is observed for K⁺. A good Job plots proves 1:1 coordination of 1,3-alternate -3 with Ag⁺ cation. ¹H-NMR Titration of 1,3-alternate- 3 with AgSO₃CF₃ also clearly demonstrates that a 1:1 complex is formed with retention of the original symmetry. The conformational changes of pyridine moiety from the original outward orientation of the ring nitrogen to the inside orientation toward the thiacalixarene cavity were observed in the process of Ag⁺ complexation. The down-field shifts of the benzene protons of the benzyl group were also observed and attributed to the conformational deviation from the original face to face overlapping.     

The influence of isomerism on the self-assembly behavior and complexation property of 1,3-alternate tetraaminopyridyl-thiacalix[4]arene derivatives

A series of 1,3-alternate conformation thiacalix[4]arenes containing different isomeric aminopyridyl pendent arms have been synthesized. It was found that their self-assembly behaviors and complexation properties strongly depended on the structures of aminopyridyl pendent arms. The crystal structures demonstrate that tetra(meta-aminopyridyl)-thiacalix[4]arene motif is capable of forming intramolecular hydrogen bondings between the sp² nitrogen donors in the meta position of the aminopyridyl groups and the facing amide N-H of the adjacent aminopyridyl groups, and self-assembles via C-H?O weak hydrogen bondings and C-H?π interaction to generate a double stranded rectilineal networks. By contrast, in the case of tetra(para-aminopyridyl)-thiacalix[4]arene, the presence of para-aminopyridyl units enables the formation of N-H?N strong hydrogen bondings between the individual molecules leading to the solid-state structure with water-bridged double strands. Their complexation properties had been also studied by measurement of the stability constants for their complexation in a range of metal cations and investigation of their binding models via ¹H NMR titration and ESI-MS experiments. It was found that the three ligands exhibited high and selective extractability toward Ag⁺, and their stoichiometry of ligand to Ag⁺ was 1:1, while the meta-aminopyridyl derivative showed the best extraction capacity and possessed the most efficient binding sites.     

A novel pillar[5]arene-cucurbit[10]uril based host-guest complex: Synthesis,characterization and detection of paraquat

The macrocyclic family comprising pillar[n]arenes and cucurbit[n]urils have received much attention recently. However, studies on the construction of supramolecular complexes formed directly with derivatized pillar[n]arenes and cucurbit[n]urils are scant. Given the interest in such systems, herein we have synthesized a new type of naphthalene-derivatized pillar[n]arene NTP5 and selected Q[10] as the host molecule. The 4-[2-(1-naphthalenyl)ethenyl]pyridine of NTP5 is encapsulated by Q[10] and formed a host-guest complex in water-acetic acid (1:1) solution accompanied by enhanced fluorescence, which changed the morphology of NTP5 from a sphere to a porous form. In addition, the fluorescence of Q[10]-NTP5 can be quenched by the addition of the highly toxic pesticide paraquat (PQ), and the mechanism was shown to be the formation of a new charge transfer ternary system of Q[10]-NTP5-PQ. This work provides new ideas for the contribution of supramolecular assemblies based on derivatized pillar[n]arenes and their combination with cucurbit[n]urils and reveals their potential applications.