Complexation of amino acids derivatives in water by calix[4]arene phosphonic acids

Series of the calix[4]arene phosphonic acids with various substituents at the lower rim was synthesized. Complexing properties of these receptors towards methyl esters of six amino acids strongly depended on the calix[4]arene conformation flexibility. The complex formation processes were monitored using ¹H NMR spectroscopy (deuterated phosphate buffer at pD 7.3, 22 °C) and association constant values were evaluated. Inherently mobile calix[4]arene molecule 3 occurred in cone conformation in aqueous solution turned out to be more effective in complexation of the basic amino acids methyl esters compared to the rigid 2 and flexible 4. Mixed 1:2 and 2:1 (host–guest) complexes were observed for compound 1 with all amino acids methyl esters.     

Dissolution properties of cypermethrin/cyclodextrin complexes

Cypermethrin—a very effective pyrethroid-type insecticide—has been complexed with β-cyclodextrin and peracetylated-β-cyclodextrin with different guest content. Dissolution measurements by reversed phase HPLC method, together with UV-spectrophotometry, differential scanning calorimetry and thermogravimetry were applied to prove the inclusion complex formation and characterize the complexes. With the help of the thermal analysis the really complexed (strongly bound) and surface-bound guests were distinguished. All of the β-cyclodextrin complexes show better dissolution rate than the pure guest. In case of inclusion complexes an oversaturated solution was formed with extremely high concentration of active substance (6–19 mg L^?1) during the first couple of minutes then the concentration decreased gradually until it reached the equilibrium solubility value of the complex (2 mg L^?1). The cypermethrin/peracetylated-β-cyclodextrin complexes prepared with organic solvent method showed slightly retarded dissolution profile compared to the pure guest. The area under the dissolution curves was introduced for quantitative characterization of the dissolution rate. The release was found to depend on the complexed guest content of the samples. The continuous variation plots used first for this parameter gave information on the stoichiometry of the complexes: 1:2 cypermethrin/β-cyclodextrin and 1:1.25 cypermethrin/peracetylated-β-cyclodextrin.     

Characterization of the inclusion complex of β-cyclodextrin with sorbic acid in the solid state and in aqueous solution

Crystal structure of β-cyclodextrin (β-CD) complexes with sorbic acid, usually as food preservative, has been determined by single-crystal X-ray diffraction at 113 K. The space group of β-cyclodextrin-sorbic acid complex is P1 with unit cell dimensions of a = 15.284(3) Å, b = 15.402(3) Å, c = 17.981(4) Å, α = 99.67(3)°, β = 112.83(3)°, γ = 102.48(3)° and Z = 1. The result indicates that the β-CD molecules form head-to-head dimers which pack in the intermediate mode. Each dimer contains two guest molecules whose methyl groups are located at the dimer interface while the carboxyl groups protrude from the β-CD primary faces. Water molecules (25.5) are distributed outside the cyclodextrin cavity over 31 sites. Furthermore, nuclear magnetic resonance spectroscopy (¹H NMR) has been employed to investigate the inclusion behavior between the host β-CD and guest sorbic acid in aqueous solution. The results obtained enabled us to structurally characterize the β-CD inclusion complex with sorbic acid.     

Preparation and properties of inclusion compound of cyclopentadienylmanganese tricarbonyl complex with a ß-cyclodextrin dimer

The host-guest inclusion compound of cyclopentadienylmanganese tricarbonyl (guest) with ß-cyclodextrin dimer (host) bridged with two 1,2-diaminoethane has been prepared as the first example of cyclodextrin dimer inclusion compounds with organotransition metal complexes and characterized by elemental analysis and IR spectra as well as thermogravimetric analysis. The manganese complex included in the dimer is thermally more stable than the free complex. ¹H NMR spectroscopy has established that the cyclopentadienylmanganese complex and the dimer form an inclusion compound in aqueous solution with a stability constant (β₂, 195 mol⁻²l²) at 22°C. The spectroscopic studies and the results of elemental analysis revealed that stoichiometry (1:2, host: guest) of the inclusion compound in water is identical to its stoichiometry in solid state.     

Host–guest complexes of some cucurbit[n]urils with the hydrochloride salts of some imidazole derivatives

Interaction between the normal cucurbit[n]urils (n = 6,7,8; Q[6], Q[7], Q[8]) and a sym-tetramethyl-substituted cucurbit[6]uril derivative (TMeQ[6]) with the hydrochloride salts of some imidazole derivatives N-(4-hydroxylphenyl)imidazole (g1), N-(4-aminophenyl)imidazole (g2), 2-phenylimidazole (g3) in aqueous solution was investigated by using ¹H NMR spectroscopy, electronic absorption spectroscopy and fluorescence spectroscopy, as well as by using a single crystal X-ray diffraction determination. The ¹H NMR spectra analysis established a basic interaction model in which inclusion complexes with a host:guest ratio of 1:1 forms for the Q[6]s and Q[7] cases, while with a host:guest ratio of 1:2 form for the Q[8] cases. It was common that the hosts selectively bound the phenyl moiety of the guests. Absorption spectrophotometric and fluorescence spectroscopic analysis in aqueous solution defined the stability of the host–guest inclusion complexes at pH 5.8 with a host:guest ratio of 1:1 form quantitatively as logK values between 4 and 5 for the smaller hosts Q[6 or 7]s, while with a host:guest ratio of 1:2 form quantitatively as logK values between 11 and 12 for the host Q[8]. Two single crystal X-ray structures of the inclusion complexes TMeQ[6]-g2 · HCl and TMeQ[6]-g3 · HCl showed the phenyl moiety of these two guests inserted into the host cavity, which supported particularly the ¹H NMR spectroscopic study in solution.     

Spectroscopic studies on the inclusion complex formation between 7-iodo-8-hyroxyquinoline-5-sulfonic acid and β-cyclodextrin

Formation of an inclusion complex between 7-iodo-8-hyroxyquinoline-5-sulfonic acid (IHQS) and β-cyclodextrin is studied by spectrophotometry and ¹H NMR techniques. Spectral changes in the emission spectra upon the addition of β-cyclodextrin to IHQS in aqueous media were too small to allow for the determination of the binding constant. On the other hand; absorption spectra show a pronounced changes upon the addition of β-cyclodextrin that allowed for the determination of the binding constant. Absorption measurements show 1:1 inclusion of IHQS in the β-cyclodextrin cavity with an association constant of 135 ± 25 M^?1. ¹H-NMR studies are used to confirm the inclusion and to provide information about the geometry of IHQS inclusion in the cavity of β-cyclodextrin.     

Binding behaviors of scutellarin with α-, β-, γ-cyclodextrins and their derivatives

A series of cyclodextrin/scutellarin inclusion complexes were prepared from α-cyclodextrin, β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin with scutellarin (SCU), and their inclusion complexation behaviors, such as stoichiometry, complex stability constants and inclusion mode, were investigated by means of UV/Vis spectroscopy, ¹H NMR and 2D NMR. The results showed that the SCU could be efficiently encapsulated in the cyclodextrin cavity in aqueous solution to produce complexes that were more soluble than free SCU. The enhanced binding ability of cyclodextrins towards SCU was discussed from the viewpoint of the size/shape-fit and multiple recognition mechanism between host and guest.     

Host–guest complexes of various cucurbit[n]urils with the hydrochloride salt of 2,4-diaminoazobenzene

The interaction products of normal cucurbit[n]urils (n = 7, 8; Q[7] Q[8]) and a sym- tetramethyl-substituted cucurbit[6]uril derivative (TMeQ[6]) with the hydrochloride salts of 2,4-diaminoazobenzene (g·HCl) were investigated in aqueous solution using ¹H NMR spectroscopy, electronic absorption spectroscopy, as well as single crystal X-ray diffraction. The ¹H NMR spectra analysis established a basic interaction model in which inclusion complexes with a host:guest ratio of 1:1 form for the TMeQ[6] and Q[7] cases, while they form with a host:guest ratio of 1:2 for the Q[8] case. Commonly, the hosts selectively bound to the phenyl moieties of the guests. Absorption spectrophotometric analysis in aqueous solution defined the stability of the host–guest inclusion complexes at pH 3.2. Quantitatively, at this pH, complexes with a host:guest ratio of 1:1—those with smaller hosts TMeQ[6] and Q[7]—formed with logK values between 6 and 7. That with host Q[8] and a host:guest ratio of 1:2 formed with a logK value of 10.8. Single crystal X-ray structures of the inclusion complexes TMeQ[6]–g·HCl and Q[8]–g·HCl showed the phenyl moiety of the guest inserted into the host cavity. This result supports the solution-based ¹H NMR spectroscopic study.     

Complexation studies of pioglitazone hydrochloride and β-cyclodextrin: NMR (1H, ROESY) spectroscopic study in solution

Pioglitazone hydrochloride (PIO) is an agonist of the peroxisome proliferator-activated receptor γ (PPARγ), used to treat diabetes. ¹H-NMR spectroscopic analysis of varying ratios of β-cyclodextrin (β-CyD) and PIO in D₂O confirmed the formation of β-CyD–PIO inclusion complex in aqueous solution. The 1:1 stoichiometry of β-CyD–PIO inclusion complex was determined by Scott’s plot method and binding constant (K _a ) was calculated to be 155 M^?1. 2D ROESY experiments confirmed that the phenyl ring of PIO act as a guest and deeply penetrate in β-CyD cavity from wider as well as narrower rim side and form two 1:1 stable inclusion complexes. Some of the PIO protons exhibited splitting, in the presence of β-CyD, indicating chiral differentiation of PIO by β-CyD.     

Inclusion behavior of water-soluble thiacalix- and calix[4]arenes towards substituted benzenes in aqueous solution

Inclusion abilities of thiacalix- and calix[4]arenetetrasulfonate (3 and 4) towards mono-substituted benzenes were investigated in neutral aqueous solution. In general, the hosts regioselectively encapsulated the guests from the aromatic moiety except the complexation of toluene by 4, in which the guest penetrated from either the aromatic or the methyl group. Stabilities of the inclusion complexes increased with the electron-withdrawing ability of the substituent on the guest, suggesting pi-pi electronic interaction between the host and guest. In spite of the lower electron density of the aromatic ring, thiacalix[4]arene 3 showed higher inclusion ability than calix[4]arene 4, suggesting that the size rather than the electron density of the calix framework is a more important factor in determining the inclusion ability.     

Determination of Tryptophan using a p-Sulfonated Calix [4,6,8]arene Modified Gold Electrode

The ability of p-sulfonated calix[n]arenes (n = 4, 6, 8) to form complexes with tryptophan was studied. The electrochemical properties of these complexes immobilized on gold surfaces were examined by cyclic voltammetry. Parameters affecting the performance of the modified electrodes including the arene concentration, scan rate, applied potential, and pH were optimized. Under the optimal conditions, the method had a linear response to tryptophan between 1 × 10^?7 M and 1 × 10^?5 M with a detection limit of 3 × 10^?8 M. The interaction of the tryptophan–p-sulfonated calix[4]arene complex was more stable than the tryptophan–p-sulfonated calix[6]arene and p-sulfonated calix[8]arene complexes. Molecular modeling calculations indicated that electrostatic interactions and structural matching effects were predominant stabilizing factors. The modified electrodes demonstrated good reproducibility and high selectivity, illustrating their effectiveness for analytical measurements.     

Host–guest Complex of a Water-soluble Cucurbit[6]uril Derivative with the Hydrochloride Salt of 3-amino-5-phenylpyrazole

Interaction between tetramethylcucurbit[6]uril and 3-amino-5-phenylpyrazole hydrochloride in aqueous solution has been investigated by using ¹H NMR spectroscopy, electronic absorption spectroscopy and fluorescence spectroscopy, as well as by a single crystal X-ray diffraction determination. The ¹H NMR spectra analysis established a basic interaction model in which an inclusion complex with a host:guest ratio of 1:1 forms, in which the host selectively binds the phenyl moiety of the guest. Absorption spectrophotometric and fluorescence spectroscopic analysis in aqueous solution defined the stability of the host–guest inclusion complexes quantitatively as 6.8 × 10⁵ mol^? 1 L at pH 2.6; the interaction is pH dependent, decreasing as pH rises. The single crystal X-ray structure of the isolated inclusion complex shows the phenyl moiety of the guest inserted into the host cavity, which supports particularly the ¹H NMR spectroscopic study in solution. In the crystal structure of the inclusion complex, the host–guest interaction involves both inter- and intra-complex hydrogen bonding, forming 2:2 dimers that stack in one dimension as supramolecular tubes.     

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.     

Spectroscopic (fluorescence, 1D-ROESY) and theoretical studies of the thiabendazole and β-cyclodextrin inclusion complex

The inclusion complex between the anti-helminthic drug thiabendazole (TBZ) and the β-cyclodextrin (βCD) was characterized in solution using fluorescence and ¹H-Nuclear Magnetic Resonance spectroscopy and studied theoretically by semi empirical PM3 and density functional theory (DFT) quantum mechanical calculations. Thermodynamic stability associated with the formation of the TBZ:βCD inclusion complex in aqueous solution was determined treating the drug’s fluorescence enhancement in the presence of cyclodextrin by a non-linear model, which indicated a moderate host–guest affinity at equilibrium (K 150 ± 31 at 25 °C). Its supramolecular structure in solution was studied through the 1D-ROESY NMR experiment, which produced evidence that the guest molecular encapsulation occurs preferably via the drug’s benzimidazole group. Theoretical study employing molecular optimization with the semi empirical PM3 method provided two energetic-equivalent complex structures that are in accordance with the NMR experimental evidences. Single point energy calculations with DFT at the B3LYP/6-31G (d,p) level suggest the most stable structure of the inclusion complex and further comprehension on the interactions and conformational strains involved in its formation.     

An inclusion complex of β-cyclodextrin with mnt anion (mnt = maleonitriledithiolate) studied by induced circular dichroism

A new inclusion complex of β-cyclodextrin with sodium maleonitriledithiolate (Na₂mnt) was investigated by electronic spectra, induced circular dichroism (ICD), and quantum mechanics (QM) methods. The orientation of the guest anion inside the host cavity was studied by ICD spectra and analyzed by structural optimization using PM3 quantum chemical method. Finally, the inclusion constant was determined by both a linear and a non-linear fitting methods, which were based on the variation of ICD signals of the guest upon inclusion complexation with the host. The inclusion constant of Na₂mnt/β-cyclodextrin was estimated to be (2.45 ± 0.15) × 10³ or (3.10 ± 0.11) × 10³ M^?1 in solution by these two fitting methods.     

Highly effective binding and inverse fluorescent behavior of palmatine and l-tetrahydropalmatine alkaloids by p-sulfonatocalixarenes

The effects of pressure and solvent were examined for the inclusion complexation of phenothiazine dyes and trans-4-[4-(dimethylamino)styryl]-1-methylpyridinium (St-4Me) with water-soluble p-sulfonatocalix[8]arene (Calix-S8). Depending on the bulkiness of the guest dyes, external pressures and solvent polarity increase the inclusion equilibrium constants of dyes with Calix-S8. From the pressure dependence of the inclusion equilibria, the reaction volumes for inclusion by Calix-S8 in the alcohol-water mixtures were estimated to be negative values (?19.8 to ?5.29 cm³ mol^?1 for the phenothiazine dyes and ?13.1 to ?9.85 cm³ mol^?1 for St-4Me). Analysis of the results of the high pressure indicated that the intrinsic volume change related to inclusion into the Calix-S8 cavity plays an important role in the inclusion of Calix-S8, depending on the bulkiness of the guest molecules. Based on ¹H NMR measurements, the structures of the inclusion complexes of Calix-S8 with phenothiazine dyes have been established and the differences in the inclusion behaviors of the phenothiazine dyes and St-4Me are discussed.     

Inclusion complexes of dihydroartemisinin with cyclodextrin and its derivatives: characterization,solubilization and inclusion mode

The characterization, inclusion complexation behavior and binding ability of the inclusion complexes of dihydroartemisinin with β-cyclodextrin and its derivatives, sulfobutyl ether β-cyclodextrin (SBE-β-CD), mono[6-(2-aminoethylamino)-6-deoxy]-β-cyclodextrin (en-β-CD) and mono{6-[2-(2-aminoethylamino)ethylamino]-6-deoxy}-β-cyclodextrin (dien-β-CD), were studied using phenolphthalein as a spectral probe. Spectral titration was performed in aqueous buffer solution (pH ca. 10.5) at 25 °C to determine the binding constants. The inclusion complexation behaviors were investigated in both solution and solid state by means of NMR, TG, XRD. The results showed that the water solubility and thermal stability of dihydroartemisinin were significantly increased in the inclusion complex with cyclodextrins (CDs). According to ¹H NMR and 2D NMR spectroscopy (ROESY), the A, B rings of dihydroartemisinin can be included into the cavity of CDs. The enhanced binding ability of CDs towards dihydroartemisinin was discussed from the viewpoint of the size/shape-fit concept and multiple recognition mechanism between host and guest.     

Synthesis and study of binuclear calix[4]arene Schiff base Co(II) complexes as catalyst in the presence of PhIO for the catalytic oxidation of olefin

The binuclear Co(II) complexes of calix[4]arene substituted 2-vanillin (R₁) and 2-hydroxy naphthaldimine (R₂), Schiff bases (Co₂L¹ and Co₂L²) have been synthesized, characterized and employed as models to mimic monooxygenase in the catalytical oxidation of olefins. The kinetic mathematical model (oxygen rebound mechanism) for olefin cleavage catalyzed by the complexes has been proposed. The results show that, compared to the calix[4]arene-free analogous, the mono and multinuclear complexes of calix[4]arene Schiff bases as catalyst exhibit high activity in the olefin catalytic oxidation.     

Inclusion of parabens in β-cyclodextrin: A solution NMR and X-ray structural investigation

A parallel study was conducted of the inclusion of alkyl parabens (guests) in the host β-cyclodextrin (β-CD). ¹H NMR data indicated an insertion of the guest phenyl ring into the β-CD cavity. The stoichiometry of each complex was 1:1, as determined by a continuous variation method that utilises the chemical shifts of the host protons. These chemical shifts were additionally used to determine the association constant yielding K values of 1631, 938, 460 and 2022 M^? 1 at 298 K for the methyl-, ethyl-, propyl- and butyl paraben solution state complexes, respectively. NOE experiments conducted on the methyl paraben solution complex indicated that the phenolic group of the guest was located at the secondary rim of the cyclodextrin cavity. Solid state structure analyses of the methyl and propyl paraben β-CD complexes were performed. Both complexes crystallised at ambient temperature in the space group C2, Z = 4 with a host to guest ratio of 1:1. Additionally, a second crystal structure between methyl paraben and β-CD is reported. This complex crystallised at 7^oC in the space group P1, Z = 2 with a 1:1 host–guest stoichiometry.

¹H NMR and solid state structure analyses were conducted on the inclusion of alkyl parabens in the host β-cyclodextrin. Both indicated an insertion of the guest phenyl ring into the β-CD cavity.     

Solubilizing effect of the p-phosphonate calix[n]arenes towards poorly soluble drug molecules such as nifedipine, niclosamide and furosemide

This article reports the solubilization of the practically water insoluble drug molecules such as nifedipine, niclosamide and furosemide by guest:host inclusion complexation with p-phosphonates calix[n]arenes as drug soluble agent. This complexation studies were carried out by using the phase solubility technique. From the obtained results, it was observed that the solubility of drug molecules was significantly increased in the presence of calix[n]arene host molecules. The increase in solubility of drugs by the calix[n]arene was most probably due to inclusion complexation between drug molecules and cavities of the calixarene skeleton similar to drug:cyclodextrin complexes.