Inclusion complexes of beta-cyclodextrin with ionic liquid surfactants

The three kinds of ionic liquid (IL) surfactants, 1-dodecyl-3-methylimidazolium hexafluorophosphate (C(12)mimPF(6)), 1-tetradecyl-3-methylimidazolium hexafluorophosphate (C(14)mimPF(6)), and 1-hexadecyl-3-methylimidazolium hexafluorophosphate (C(16)mimPF(6)), were used to form the inclusion complexes (ICs) with beta-cyclodextrin (beta-CD). The surface tension measurements revealed that there were two kinds of inclusion formations, 1:1 and 1:2 (beta-CD/IL) stoichiometry for beta-CD-C(12)mimPF(6) and beta-CD-C(14)mimPF(6) ICs, and only 1:1 stoichiometry for beta-CD-C(16)mimPF(6) ICs. These inclusion compounds were further characterized by XRD, (13)C CP/MAS NMR, (1)H NMR, rotating frame nuclear Overhauser effect spectroscopy (ROESY), and thermogravimetry (TGA). The results showed that these ICs were fine crystalline powder. The host-guest system presented a channel-type structure, and each glucose unit of beta-CD was in a similar environment. It was suggested that hydrophobicity played a crucial role in supporting the formation of ICs. The decomposition temperature of these ICs was lower than those of their precursors. Furthermore, the possible inclusion structures were also speculated. These inclusion behaviors are likely to be used to recover ILs in the process of their preparation.     

Structure and dynamics of perfluoroalkane/beta-cyclodextrin inclusion compounds as studied by solid-state 19F MAS and 1H -->19F CP/MAS NMR spectroscopy

The molecular structure and dynamics of novel inclusion compounds (ICs) consisting of n-perfluoroalkane (PFA) guests and beta-cyclodextrin (beta-CD) host (PFA/beta-CD) have been investigated using 19F magic angle spinning (MAS) and 1H-->19F cross polarization (CP)/MAS NMR spectroscopy with the aid of thermal analyses, FT-IR spectroscopy, and X-ray diffraction method. The ICs of C9F20/beta-CD and C20F42/beta-CD were successfully obtained as precipitates from mixtures of respective PFAs and saturated aqueous solution of beta-CD. The wide-angle X-ray diffraction (WAXD) revealed that C9F20/beta-CD forms a channel-type crystallite, while C20F42/beta-CD is nearly amorphous at room temperature. The structural orders in both ICs increase at elevated temperatures. The 19F NMR signals obtained by the direct polarization (DP) method for PFA/beta-CD are resonated at higher frequencies than those for original PFA. This can be ascribed to the lower dielectric environment of the beta-CD cavity. Above 80 degrees C, 1H-->19F CP/MAS NMR technique revealed that C9F20 molecules undergo vigorous molecular motion and partly come out of the beta-CD channel. However, the guests hardly degrade or evaporate unless the host is pyrolytically decomposed above ca. 300 degrees C. The spin-lattice relaxation times in the laboratory frame for 19F (T1F) are almost identical for all the fluorines in PFA/beta-CD at each temperature, while significantly different values were observed for fluorines in neat PFA. This indicates that effective intramolecular spin diffusion occurs within a PFA molecule included in beta-CD.     

Demicellization of a mixture of cationic-anionic hydrogenated/fluorinated surfactants through selective inclusion by alpha- and beta-cyclodextrin

The interactions between alpha- and beta-cyclodextrin (alpha-/beta-CD) and an equimolar mixture of octyltriethylammonium bromide (OTEAB) and sodium perfluorooctanoate (SPFO) were studied by 1H and 19F NMR, surface tension, conductivity, and dynamic light scattering. It was shown that beta-CD could destroy the mixed micelles of OTEAB-SPFO by selective inclusion of SPFO. As beta-CD was added, the system was observed to undergo a process like this: beta-CD preferentially included SPFO to form 1:1 beta-CD/SPFO complexes. As the inclusion of SPFO was almost saturated, the mixed micelles broke and all OTEAB was released and exposed to aqueous surroundings. Then 1:1 beta-CD/OTEAB and 2:1 beta-CD/SPFO complexes significantly formed simultaneously. Contrary to beta-CD, alpha-CD exhibited selective inclusion to OTEAB and only weak association with SPFO. alpha-CD could also destroy the mixed micelles of OTEAB-SPFO; however, the demicellization ability of alpha-CD is much smaller than that of beta-CD. These conclusions were also well supported by the calculations of binding constants and DeltaG degrees . Different from the complexes of CD/conventional surfactants, the complexes of beta-CD/SPFO or alpha-CD/OTEAB formed by selective inclusion of CD in the mixed cationic-anionic surfactants may have contributed to the surface activity of the aqueous mixtures. The complexes of alpha-CD/OTEAB showed much more significant contribution to the surface activity than that of the complexes of beta-CD/SPFO.     

Preparation and Properties of Cyclodextrin Inclusion Complexes of Hyperoside

In order to improve the aqueous solubility and enhance the bioavailability of Hyperoside (Hyp), three inclusion complexes (ICs) of Hyp with 2-hydroxypropyl-β-cyclodextrin (2H-β-CD), β-cyclodextrin (β-CD), and methyl-β-cyclodextrin (M-β-CD) were prepared using the ultrasonic method. The characterization of the inclusion complexes (ICs) was achieved using Fourier-transform infrared spectroscopy (FTIR), scanning electronic microscopy (SEM), X-ray powder diffraction (XRPD), thin-layer chromatography (TLC), and ¹H nuclear magnetic resonance (¹H NMR). The effects of the ICs on the solubility and antioxidant activity of Hyp were investigated. A Job’s plot revealed that the Hyp formed ICs with three kinds of cyclodextrin (CD), all at a 1:1 stoichiometric ratio. The FTIR, SEM, XRPD, TLC, and ¹H NMR results confirmed the formation of inclusion complexes. The water solubility of the IC of Hyp with 2-hydroxypropyl-β-cyclodextrin was enhanced 9-fold compared to the solubility of the original Hyp. The antioxidant activity tests showed that the inclusion complexes had higher antioxidant activities compared to free Hyp in vitro and the H₂O₂–RAW264.7 cell model. Therefore, encapsulation with CDs can not only improve Hyp’s water solubility but can also enhance its biological activity, which provides useful information for the potential application of complexation with Hyp in a clinical context.     

Synthesis and spectral investigation of Al(III) catechin/beta-cyclodextrin and Al(III) quercetin/beta-cyclodextrin inclusion compounds

Al-catechin/beta-cyclodextrin and Al-quercetin/beta-cyclodextrin (beta-CD) inclusion compounds were synthesized and characterized by IR, UV-vis, 1H and 13C NMR and TG and DTA analyses. Because quercetin is sparingly soluble in water, the stability constants of the Al-quercetin/beta-CD and Al-catechin/beta-CD compounds were determined by phase solubility studies. The AL-type diagrams indicated the formation of 1:1 inclusion compounds and allowed calculation of the stability constants. The thermodynamic parameters were obtained from the dependence of the stability constants on temperature and results indicated that the formation of the inclusion compounds is an enthalpically driven process. The thermal decomposition of the solid Al-quercetin/beta-CD and Al-catechin/beta-CD inclusion compounds took place at different stages, compared with the respective precursors, proving that an inclusion complexation process really occurred.     

Synthesis and characterization of beta-cyclodextrin inclusion complex containing di(8-hydroxyquinoline) magnesium

The beta-cyclodextrin (beta-CD) inclusion complex containing di(8-hydroxyquinoline)magnesium was prepared. The product was characterized by NMR, IR, differential thermal thermogravimetric analysis (DT-TGA), spectrofluorimetry, and elemental analysis, indicating the formation of inclusion complex in which the quinoline rings of the guest were encapsulated within the beta-CD cavities. The Job's method provided 2:1 stoichiometry for the inclusion complex between beta-CD and di(8-hydroxyquinoline)magnesium. The association constant calculated with the modified Benesi-Hildebrand equation at 25 degrees C was determined. And the mean association constant was 3577 (L/mol)2, R.S.D. was 2.58%. The thermal stability and solubility of di(8-hydroxyquinoline)magnesium were improved when forming inclusion complex.     

Encapsulation of sodium nimesulide and precursors in beta-cyclodextrin

Crystalline 1:1 inclusion complexes with beta-cyclodextrin (beta-CD) and the sodium salt of nimesulide (4-nitro-2-phenoxymethanesulfonanilide), and the sodium salt of the derivative 2-phenoxymethanesulfonanilide, have been prepared by co-precipitation from aqueous solution. The presence of true inclusion complexes was supported by elemental analysis, thermogravimetry and powder X-ray diffraction. FTIR and 13C CP MAS NMR spectroscopy confirmed that no chemical modification of the guests occurred upon formation of inclusion complexes. The reaction of the precursors 2-phenoxynitrobenzene and 2-phenoxyaniline with beta-CD was also studied and crystalline inclusion complexes with a 2:1 (host-to-guest) stoichiometry were isolated. The interaction of the different guest species with beta-CD host molecules was studied theoretically by carrying out ab initio calculations. Favourable inclusion geometries were obtained for the four guests mentioned above. On the other hand, it was found that the inclusion of the neutral guests nimesulide and 2-phenoxymethanesulfonanilide was considerably less favourable. This is in agreement with the experimentally observed difficulty in isolating true inclusion complexes containing these guests and beta-CD. The calculated lower stability is attributed to the different steric hindrance arising from the different conformational preferences of neutral and anionic forms.     

Effect of added ionic liquid on aqueous Triton X-100 micelles

Addition of ionic liquids to aqueous surfactant solutions can alter/modify physicochemical properties of such systems in favorable manner. Changes in the properties of aqueous solutions of a useful nonionic surfactant Triton X-100 (TX-100) are assessed upon addition of 2.1 wt% of a common and popular ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6). It is shown that the solubility of 'hydrophobic' bmimPF6 in aqueous TX-100 increases with TX-100 concentration. This observation combined with the conductivity data strongly indicates partitioning of bmimPF6 into TX-100 micellar phase. Behavior of a variety of molecular absorbance [methyl orange, phenol blue, and N,N-diethyl-4-nitroaniline] and fluorescence [phenyl on the TX-100, pyrene, pyrene-1-carboxaldehyde, 2-(p-toluidino)naphthalene-6-sulfonate, and 1,3-bis-(1-pyrenyl)propane] probes further confirm this observation. Statistically insignificant increase in critical micelle concentration (cmc) and decrease in aggregation number (N(agg)) of TX-100 micelles are observed upon addition of 2.1 wt% bmimPF6. Based on the overall data, it is inferred that ionic liquid bmimPF6 partitions into the TX-100 micellar phase; presence of bmimPF6 both close to the core as well as in the palisade layer of TX-100 micelles is suggested. Presence of favorable interactions (e.g., H-bonding, dipole-induced dipole, among others) between bmimPF6 and TX-100 is proposed to be the reason for these observations.     

Study on inclusion interaction of piroxicam with beta-cyclodextrin derivatives

The inclusion behavior of piroxicam (PX) with beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and carboxymethyl-beta-cyclodextrin (CM-beta-CD) was investigated by using steady-state fluorescence and nuclear magnetic resonance (NMR) technique. The various factors affecting the inclusion process were examined in detail. The remarkable fluorescence emission enhancement upon addition of CDs suggested that cyclodextrins (CDs) were most suitable for inclusion of the uncharged species of PX. The stoichiometry of the PX-CDs inclusion complexes was 1:1, except for beta-CD where a 1:2 inclusion complex was formed. The formation constants showed the strongest inclusion capacity of beta-CD. NMR showed the inclusion mode of PX with CDs.     

Organic anion recognition of naphthalenesulfonates by steroid-modified beta-cyclodextrins: enhanced molecular binding ability and molecular selectivity

Two beta-cyclodextrin (beta-CD) derivatives bearing steroid groups (1 and 2) were synthesized by the condensation of mono(6-aminoethylamino-6-deoxy)-beta-CD with cholic acid and deoxycholic acid, respectively, and their original conformations and binding behavior to the organic anion of naphthalenesulfonate derivatives were investigated by using 1H NMR spectroscopy and spectrofluorometric titration in combination with computational methods. The 2D NMR experiments reveal that the steroid groups attached to the beta-CD rim could be deeply embedded in the beta-CD cavity to form the intramolecular (for 1) or intermolecular (for 2) inclusion complexes in aqueous solution. Upon complexation with naphthalenesulfonate derivatives, modified beta-CDs display two obviously different binding modes, that is, the competitive inclusion mode and the induced-fit inclusion mode, which is consistent with the results of molecular modeling study. The two modes and the strict size/shape fitting relationship between the hosts and guests reasonably explain the different binding behaviors and molecular selectivity of host beta-CDs 1 and 2 toward the naphthalenesulfonate guests. Therefore, the cholic acid- or deoxycholic acid-modified beta-CDs could effectively recognize the size/shape of guest molecules as compared with the parent beta-CD, giving good molecular selectivity up to 24.9 for the disodium 2,6-naphthalenedisulfonate/disodium 1,5-naphthalenedisulfonate pair by the host 1.     

Encapsulation of vortioxetine with cyclodextrins via host–guest inclusion complex: Synthesis,characterization, solubility,and in vitro dissolution studies

Drug solubility plays a significant role in the development of drug formulation. The objectives of this work are to improve the solubility and dissolution rate of vortioxetine (VT) by preparing its inclusion complexes (ICs) with β-Cyclodextrin (β-CD) and γ-Cyclodextrin (γ-CD). The ICs were prepared in 1:1 M ratio via recrystallization method and characterized by P-XRD, FT-IR, ¹H NMR, 2D NOESY, and DSC. Further, the crystal structure of VT-β-CD was analyzed by SC-XRD. P-XRD data obtained for ICs describe the crystalline pattern. The DSC analysis shows change in the thermal behavior of VT, CDs and ICs. FT-IR analysis shows shifting of frequencies in ICs when compared with the pristine VT drug and CDs. The 2D NOESY in DMSO-d⁶ indicates weak interaction between the VT and CD molecules. The crystal structure of VT-β-CD consists of one guest VT, one host CD, and nine water molecules in the crystal lattice. The solubility of ICs was significantly improved in distilled water, pH 1.2 acidic, and phosphate buffer pH 6.8 medium, as compared with the solubility of the pristine VT drug. The in vitro dissolution rate of ICs in different dissolution media was investigated, which was higher than that of the commercial product of VT.     

Tween80/BmimPF6/醇/甲苯体系的相行为

以环境友好型的Tween80为表面活性剂, 以醇(乙醇、正丁醇、正己醇、正辛醇、正癸醇和异戊醇)为助表面活性剂, 对离子液体1-丁基-3-甲基咪唑六氟磷酸盐(bmimPF6)和甲苯进行了微乳化实验, 绘制了不同条件下Tween80离子液体的微乳体系的拟三元相图, 考察了醇的种类、含量对单相微乳区的影响, 并用电导法研究了在乙醇为助表面活性剂情况下, 单相微乳区的结构转变. 结果表明, 当醇(异戊醇)固定时, 随着表面活性剂/醇的质量比增加, 单相微乳区的面积逐渐增大; 不同链长的直链醇对单相微乳区的面积影响与该醇在离子液体中的溶解情况有关, 单相微乳区的面积随着直链醇链长的增加而越小; 当乙醇作助表面活性剂时, 所得到的单相微乳区的面积最大, 且单相微乳区存在着O/IL(oil-in-ionic liquid)、双连续相和IL/O(ionic liquid-in-oil)三种微结构. 尤其对离子液体微乳体系的电导随油的含量的增加而最初增大的现象进行了解释, 这一现象是由于油主要起到减少离子液体中离子对或离子的积聚, 提高带电离子淌度的作用.     

Assembly behavior of inclusion complexes of beta-cyclodextrin with 4-hydroxyazobenzene and 4-aminoazobenzene

To further reveal the factors governing the supramolecular assembly of beta-cyclodextrin (beta-CD) inclusion complexes, two aggregates (1 and 2) were prepared from the inclusion complexes of beta-CD with 4-hydroxyazobenzene and 4-aminoazobenzene, respectively, and their binding behavior were investigated by means of X-ray analysis, UV-vis, NMR, and circular dichroism spectra in both solution and the solid state. The obtained results indicated that the beta-CD/4-hydroxyazobenzene complex 1 could form head-to-head dimers (triclinic system, space group P1) in the solid state, which were further self-assembled to a linear supramolecular architecture by the intra- and interdimer hydrogen bond interactions as well as the intradimer pi-pi interactions. However, when the included guest 4-hydroxyazobenzene was switched to a 4-aminoazobenzene, the resultant beta-CD/4-aminoazobenzene complex 2 (monoclinic system, space group P2(1)) could be self-assembled to a wave-type supramolecular aggregate under similar conditions. Furthermore, the combination of crystallographic and spectral investigations jointly revealed the inclusion complexation geometry of beta-CD with 4-hydroxyazobenzene and 4-aminoazobenzene in both solution and the solid state, which demonstrated that the disparity of substituents in the azobenzenes played an important role in the inclusion complexation and molecular assembly, affecting not only the structural features of aggregates but also the binding abilities of azobenzenes with beta-CD.     

Comparative study on the inclusion behavior between meso-tetrakis(4-N-ethylpyridiniurmyl)porphyrin and beta-cyclodextrin derivatives

5,10,15,20-Tetrakis(4-N-ethylpyridiniurmyl)porphyrin (TEPyP) formed 1:1 stoichiometry inclusion complexes with beta-cyclodextrin (beta-CD) and its derivatives including hydroxypropyl-beta-cyclodextrin (HP-beta-CD), sulfobutylether-beta-cyclodextrin (SBE-beta-CD) in basic aqueous solution. The supramolecular system was investigated by the methods of fluorescence, UV-vis absorption spectroscopy, nuclear magnetic resonance (NMR) technique. The inclusion ability of cyclodextrins exhibited remarkable difference for beta-CD, HP-beta-CD and SBE-beta-CD. Association constants as high as K=1.1 x 10(4) M(-1) in the case of HP-beta-CD/TEPyP and 2.0 x 10(5) M(-1) in the case of SBE-beta-CD/TEPyP complexes were determined, whereas a lower value (K=550 M(-1)) was given in the case of beta-CD/TEPyP. The results showed that hydrogen bonding and charge attraction play important roles in the processes of host-guest interaction. The interaction mechanism of inclusion processes could be explained by the analysis of NMR spectroscopy. The supramolecular assembly was formed. beta-CD and HP-beta-CD approached from the primary face of cavities of CDs.     

Spectroscopic investigations and crystal structure from synchrotron powder data of the inclusion complex of beta-cyclodextrin with atenolol

Inclusion complexes of atenolol with beta-cyclodextrin (beta-CD) in aqueous solution have been investigated with (1)H NMR and UV-vis spectroscopy. The stoichiometry of this inclusion complex was established to be equimolar (1:1) and its stability constant was determined by UV-vis spectroscopy. The crystal structure of the beta-CD-atenolol (1:1) inclusion compound has been solved from synchrotron powder diffraction data using direct-space search techniques. The crystal structure model and (1)H NMR data are in good agreement and, with support of Hyperchem MM+ molecular dynamics results, suggest which protons are likely to be involved in the inclusion process that leads to the supramolecular architecture of this guest-host complex.     

Inclusion complex of 2-naphthylamine-6-sulfonate with beta-cyclodextrin: intramolecular charge transfer versus hydrogen bonding effects

The photophysical characteristics of the ground and excited states of 2-naphthylamine-6-sulfonate (2-NA-6-S) were investigated in different solvents and in beta-cyclodextrin (beta-CD). The spectral shifts are well correlated with Kamlet-Taft relationship. Multiple linear regression analysis indicated that both non-specific dipolar interaction and specific hydrogen bonding interactions play competitive roles in determining the position of the absorption maximum, while the dipolar interaction is the dominating parameter in determining the emission maximum. For the Stokes shift, both the nonspecific interaction and the hydrogen donation property of the solvent are participating equally. The molecular encapsulation of 2-NA-6-S by beta-CD in aqueous solution has been studied by different spectroscopic techniques. Fluorescence measurements show that the dielectric constant of beta-CD experienced by the included 2-NA-6-S is intermediate between water and methanol. The changes observed in the absorption and fluorescence spectra of 2-NA-6-S upon inclusion in beta-CD allowed the association constant to be calculated and found to be 465+/-100 and 495+/-100 M-1, respectively. The changes observed for the chemical shifts of 2-NA-6-S and beta-CD 1H NMR spectra and the corresponding 1H NMR spectra of their mixture confirmed the formation of the inclusion complex and showed that 2-NA-6-S is encapsulated in beta-CD cavity in a tilted equatorial approach.     

Study on the inclusion complexes of cryptotanshinone with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin

The inclusion complexes of beta-cyclodextrin (beta-CD) and HP-beta-cyclodextrin (HP-beta-CD) with a kind of tanshinone, cryptotanshinone (CTan) were investigated by using spectrophotometry. Stable inclusion complexes were established in solution and in solid state and were characterized by UV, IR and 1H NMR spectra, respectively. The optimum pH for inclusion is about 7.5. Stoichiometry of the inclusion complex is 1:1. The stabilities of beta-CD and HP-beta-CD to CTan were in the order: beta-CD相似文献   

Preparation and study on the solid inclusion complex of cloxacillin sodium with beta-cyclodextrin

The interaction of cloxacillin sodium with beta-cyclodextrin (beta-CD) has been studied by several analytical techniques, including (1)H NMR, fluorescence spectroscopy, infrared spectroscopy. In this paper, solid inclusion complex of cloxacillin sodium with beta-CD was synthesized by the coprecipitation method. In addition, the characterization of the inclusion complex has been proved by fluorimetry, infrared spectroscopy and 1D, 2D NMR. The experimental results confirmed the existence of 1:1 inclusion complex of cloxacillin sodium with beta-CD. The formation constant of complex was determined by fluorescence method and (1)H NMR. Spacial configuration of complex has been proposed on 2D NMR technique.     

Structure and intramolecular flexibility of beta-cyclodextrin complex with (-)-epigallocatechin gallate in aqueous solvent

The probable structure of the inclusion complex of beta-cyclodextrin (beta-CD) and (-)-epigallocatechin gallate (EGCg) in D2O was investigated using several NMR techniques. EGCg formed a 1:1 complex with beta-CD, in which the A ring and a portion of the C ring of EGCg were included at the head of the phenolic hydroxyl group attached to C7 of EGCg in the beta-CD cavity from the wide secondary hydroxyl group side. In the 1:1 complex with beta-CD, EGCg maintained the conformation in which the B and B' rings of EGCg took pseudoequatorial and pseudoaxial positions with respect to the C ring, respectively. The structure of the inclusion complexes of beta-CD and EGCg obtained from NMR experiments supported those determined from AM1 semiempirical SCF MO calculations well.     

A comparative study on the binding behaviors of beta-cyclodextrin and its two derivatives to four fanlike organic guests

Four fanlike organic compounds, 1-ethoxybenzene (EOB), 1-butoxybenzene (BOB), 1-dodecyloxybenzene (DOB), and 1-(dodecyloxy)-2-methoxybenzene (DOMB), were chosen as guests, and beta-cyclodextrin (beta-CD) and its two derivatives, mono(2-O-2-methyl)-beta-CD and mono(2-O-2-hydroxy-propyl)-beta-CD, were chosen as hosts. Energy changes involved in host-guest inclusion processes were clearly obtained by applying semiempirical PM3 calculations. According to this, probable structures of the host-guest inclusion complexes were proposed. The inclusion systems in aqueous solution were investigated by UV-vis spectroscopy and nuclear magnetic resonance ((1)H NMR) titration, and the formation constants (K) of the inclusion complexes were determined using the Benesi-Hildebrand equation. Moreover, two solid inclusion complexes of beta-CD with EOB and DOB were prepared and characterized by Fourier transform infrared spectra, X-ray powder diffraction, (1)H NMR, electrospray ionization mass spectrometry, and thermogravimetric analyses. Results showed that the host-guest stoichiometries in the inclusion complexes were all 1:1 both in solid state and in aqueous solution. As for the same host, the values of K increased in the order EOB < BOB < DOB, in strong association with the fan handle in the fanlike molecules; that is to say, the K values increased with increasing carbon chain length of substituent on benzene ring. In addition, the K values of DOMB complexes were larger than those of DOB complexes for the same CD, indicating that the introduction of an extra o-methoxyl group on DOB further stabilized the CD inclusion complexes. The decomposition activation energies of EOB-beta-CD and DOB-beta-CD were very similar but significantly larger than that of free beta-CD.