Crystal packing patterns of cyclodextrin inclusion complexes

Cyclodextrin inclusion complexes crystallize in two basically different patterns, the cage and the channel type. The cage type occurs when cyclodextrins are packed crosswise (fishbone) or, if they are packed side-by-side, in layers and adjacent layers are displaced by about one half molecule. In each case, the internal cavity of one cyclodextrin is closed on both sides by neighbouring cyclodextrins. On the other hand, channel complexes are formed if cyclodextrins are stacked like coins in a roll so that cavities line up to produce long channels. In these crystal structures, cyclodextrins can be arranged in head-to-head or head-to-tail mode. In the smaller -cyclodextrin, cage type structures are formed with small, molecular guests whereas long molecular guests and ionic guest molecules induce channel type structures. The latter are generally preferred with the - and -cyclodextrin series which is probably due to the higher tendency for self aggregation in these two members of the cyclodextrin family.Part XXII of the series Topography of Cyclodextrin Inclusion Complexes. For part XXI, see ref. 6.     

人参皂苷与环糊精包合物的研究进展

人参皂苷是从人参、西洋参和三七中提取的主要活性成分,其药效价值相当高,但因其在水中几乎不溶,生物利用度极低,因此极大的限制了其在临床上的应用.环糊精具有独特的性质,其"腔内疏水、腔外亲水",可以选择性的包合人参皂苷等客体分子.环糊精与人参皂苷形成包合物后可以改变客体分子的某些物理化学性能,如水溶性、稳定性以及光学性质等,以此来提高其生物利用度.     

Electrospinning of polymer-free nanofibers from cyclodextrin inclusion complexes

The electrospinning of polymer-free nanofibers from highly concentrated (160%, w/v) aqueous solutions of hydroxypropyl-β-cyclodextrin (HPβCD) and its inclusion complexes with triclosan (HPβCD/triclosan-IC) was achieved successfully. The dynamic light scattering (DLS) and rheology measurements indicated that the presence of considerable HPβCD aggregates and the high solution viscosity were the key factors in obtaining electrospun HPβCD and HPβCD/triclosan-IC nanofibers without the use of any polymeric carrier. The HPβCD and HPβCD/triclosan-IC solutions containing 20% (w/w) urea yielded no fibers but only beads and splashes because of the depression of the self-aggregation of the HPβCD. The inclusion complexation of triclosan with HPβCD was studied by isothermal titration calorimetry (ITC) and turbidity measurements. The characteristics of the HPβCD and HPβCD/triclosan-IC nanofibers were investigated by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). It was found that the electrospinning of HPβCD/triclosan-IC solution having a 1:1 molar ratio was optimal for obtaining nanofibers without any uncomplexed guest molecules.     

Structure and spectroscopic properties of cyclodextrin inclusion complexes

We compare spectroscopic properties of higher order complexes of organic guests (e.g. naphthalene, phenols, indole, C₆₀ fullerene) with cyclodextrins (CDx) to results of molecular modeling investigations. Naphthalene 1:2 complexes with -CDx show high spectral resolution and peculiar triplet properties. Molecular simulations and calculation of the experimentally measured induced circular dichroism (ICD) provide detailed structural information.     

Synthesis, characterization and antitumor activity of 1,2-disubstituted ferrocenes and cyclodextrin inclusion complexes

Seven different ferrocene derivatives have been tested in vitro against Ehrlich ascites tumor cells. Neither ferrocene nor the monosubstituted derivative N,N-dimethylaminomethylferrocene showed cytotoxic activity (IC₅₀ > 1000 μM for 3 h treatments). Better results were obtained with 1,2-disubstituted derivatives. The IC₅₀ values ranged from 376.6 μM for 1,2-diformylferrocene to 71.2 μM for racemic 2-(N,N-dimethylaminomethyl)ferrocenecarboxamide. The latter derivative was also encapsulated in native β-cyclodextrin (CD), heptakis-2,3,6-tri-O-methyl-β-CD (TRIMEB) and 2-hydroxypropyl-β-CD (HPβCD) to give 1:1 (host:guest) inclusion compounds. The existence of true inclusion complexes in the solid state was confirmed by a combination of powder X-ray diffraction, thermogravimetric analysis, FTIR and ¹³C CP MAS NMR spectroscopy. The IC₅₀ value for the β-CD inclusion compound was identical to that obtained for the nonincluded ferrocene derivative. By contrast, the inclusion compounds comprising TRIMEB and HPβCD yielded IC₅₀ values of 25.2 and 20.0 μM, respectively. No obvious relationship could be established between the redox behavior of the compounds determined by cyclic voltammetry and the biochemical data.     

Potentiometric characterisation of cyclodextrin inclusion complexes of local anaesthetics

The complexation of several local anaesthetics by β and γ-cyclodextrins was studied by potentiometry with glass electrode. Tetracaine and dibucaine complexation constants were determined at 25°C in the presence of 0.1 M of NaCl. It was found that prilocaine and lidocaine complexes cannot be detected.     

Study of inclusion complexes of cyclodextrin by cyclic voltammetry

The inclusion complexes of a series of organometallic compound-cyclodextrin and aromatic compound-cyclodextrin have been studied by cyclic voltammetry using glassy carbon electrode. The variations of peak potential and peak current are showed on cyclic voltammogram when the electroactive guest molecules are complexed by cyclodextrins. Dissociation constants of cyclodextrin inclusion complexes have been calculated on the basis of this variation by both potential and current methods. According to the magnitude of dissociation constants the relationship between the stability of cyclodextrin inclusion complex and the degree of matching host molecule with guest molecule has been discussed.     

Inhibition of cyclodextrin acid hydrolysis by some inclusion complexes

Acidic hydrolysis of ??-cyclodextrin in the solution of hydrochloric acid containing some aliphatic alcohols was investigated. The reaction was carried out at 90 °C. It was observed that the rate of the reaction has decreased with the increase in concentration of a guest.     

Ability of the acetotoluides to form cyclodextrin inclusion complexes

Conclusion These series of experiments have shown that the -CD cavity was too small to allow stable inclusion complex formation. p-ACT is the isomer within this series that is best able to form inclusion complexes with -CD, then m-ACT and finally o-ACT. This would seem to indicate that the benzene ring of the molecule is the part of the structure most likely to penetrate the cavity since (a) -CD could not form stable complexes with any of the guest molecules and (b) less effective entry into the -CD cavity is the results of the acetamido group moving from p^–m^–o^– positions. Benzene ring penetration of the CD cavity is therefore required for stable inclusion complex formations in this group of compounds.     

Influence oftert-butyl alcohol on cyclodextrin inclusion complexes of pyrene

The effect oftert-butyl alcohol on complexes of pyrene and various cyclodextrins is investigated. The equilibrium constant for the complexation is derived from the fluorescence decay parameters. A greater than twofold enhancement of pyrene lifetime is observed in the presence oftert-butyl alcohol and -cyclodextrin or -cyclodextrin. As the number of hydroxyl groups decreases, substituted -cyclodextrins show smaller enhancements to both the fluorescence lifetime and the formation constant. These observations are explained by proposing that alcohol molecules are associated with the inclusion complex. This association increases the apparent hydrophobicity of the cyclodextrin cavity, protects the molecule from collisional quenching and deactivation, and provides additional rigidity to the system.     

环糊精包络物的循环伏安法研究

本文采用玻碳电极以循环伏安法研究了水溶液体系中二茂铁衍生物及芳香族衍生物与环糊精(α-CD, α-CD)的包络行为. 当电活性客体分子被包络时, 在循环伏安图上表现为峰电流和峰电位的变化, 用电流和电位法测定了包络物的解离常数, 并根据解离常数的大小次序探讨了主体分子与客体分子之间的匹配情况同包络物稳定性之间的关系.     

Photoproduction of remarkably stable benzylic radicals in cyclodextrin inclusion complexes

Photolysis of cyclodextrin inclusion complexes of diastereomers of ,′-dimethyldibenzyl ketone in the solid state resulted in stable benzylic radicals at room temperature. These radicals were characterized by their electron spin resonance (ESR) signals, emission and excitation spectra.     

环糊精与丹参酮IIA包合作用的研究

通过荧光光谱方法分别研究了丹参酮IIA在溶液的pH为7．5时与β—CD和γ—CD的包合常数,对客体的包结能力β-CD〉γ-CD;并利用热力学方法研究了温度对包合反应的影响,计算了包合过程的熵变、焓变及自由能变化;分子模拟方法进一步证实了该包合物的形成;采用超声波法制备了环糊精与丹参酮IIA的固体包合物,并用红外光谱对固体包合物进行了表征．     

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.     

Preparation and properties of cyclodextrin inclusion compounds of organometallic complexes. Ferrocene inclusion compounds

Inclusion compounds of ferrocene(FcH) and its derivatives with cyclodextrins(CDs; -CD, -CD, and -CD) were prepared. CD-ferrocene inclusion compounds were obtained in a crystalline state in high yield. -CD and -CD formed 11 stoichiometric inclusion compounds with ferrocene and its derivatives. -CD formed 21 (CD:guest) complexes with ferrocene and the monosubstituted derivatives, but did not form complexes with 1,1-disubstituted derivatives, -CD-FcH and -CD-FcH complexes are thermally stable and do not liberate ferrocene on heating at 100°C in vacuo. The cyclodextrin inclusion compounds were characterized by¹H-NMR, IR, UV, and CD spectra. A large positive induced Cotton effect was observed in the case of -CD-FcH complex, while the -CD-FcH complex showed a negative spectrum. The binding mode is discussed. -Cyclodextrin was found to form inclusion complexes in ethylene glycol, diethylene glycol, triethylene glycol, methyl cellosolve, ethyl cellosolve, methyl alcohol, and glycerine solutions. -CD also formed complexes in ethylene glycol solution. The binding of ferrocene by -CD is stronger in ethylene glycol than in dimethyl sulfoxide and dimethyl formamide.     

Thermoanalytical method for studying the guest content in cyclodextrin inclusion complexes

The interaction of cypermethrin with β-cyclodextrin was investigated using different (coprecipitation, suspension, kneading and ‘melting in solution’) complexation methods and qualifying the resulted complexes by UV-spectrophotometry, thermal methods (TG, DTG and DSC) and X-ray powder diffraction. The total guest content of complexes can be measured by UV-spectrophotometry in aqueous ethanol solution, while the uncomplexed guest fraction of samples can be determined by DSC based on a previous calibration curve, which was found between the melting enthalpy change of cypermethrin and the guest content of physical mixture samples. The combination of both analytical methods enables the determination of really complexed guest content.     

Constrained polymer chain behavior observed in their non-stoichiometric cyclodextrin inclusion complexes

Much has been learned from inclusion compounds (IC’s) formed between guest polymers and host cyclodextrins (CDs) [polymer-CD-ICs] by examining the properties of the fully covered guest polymers, as well as those coalesced neat bulk samples of guest polymers obtained upon removal of the host CDs. However, what can be gained from studying the properties of the restrained unthreaded portions of polymer chains that “dangle” from non-stoichiometric (n-s)-polymer-CD-IC’s? We attempt to assist in answering this question by observing (n-s)-polymer-CD-IC’s formed between amorphous atactic-poly(methyl methacrylate) (PMMA) and γ-CD, as well as the IC formed between a synthesized poly(ε-caprolactone)-poly(propylene glycol)-poly(ε-caprolactone) (PCL-PPG-PCL) triblock copolymer and β-CD, which was presumed to have threaded and unthreaded PPG and PCL blocks. Though our (n-s)-PMMA-γ-CD-IC samples were found to exhibit extremely heterogeneous behaviors, glass transition temperature increases of up to 27?°C above that of neat PMMA were observed. X-ray diffraction data indicates modest γ-CD crystallinity at partial coverages of PMMA, with a crystal structure similar to that of the IC with full coverage. On the other hand, XRD, DSC and FTIR data revealed an almost total disruption of PCL block crystallinity upon complexation of PCL-PPG-PCL with β-CD, suggesting either partial threading and coverage of the PCL blocks by β-CD or their partial mixing with the PPG blocks covered with β-CD.     

Stretching a polymer brush by making in situ cyclodextrin inclusion complexes

The interaction between poly(ethylene oxide) (PEO) chains grafted onto polystyrene latex particles and alpha-, beta-, and gamma-cyclodextrins (CD) was studied by small-angle neutron scattering. The particles were contrast-matched to the solvent in order that only the scattering from the polymer layers was detected. The signal from the layers was fitted to a double-exponential volume fraction profile. The effects of adding cyclodextrin on the polymer profile are shown as a function of cyclodextrin concentration. The polymer layers are seen to extend on addition of CD, which is consistent with a complexation between the grafted PEO and the CD molecules. The effect is the strongest with alpha-CD.     

Physicochemical characterization of coumestrol/β-cyclodextrins inclusion complexes by UV–vis and FTIR-ATR spectroscopies

The inlcusion behaviour of unsubstituted β-cyclodextrin (β-CyD) and (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD), in solution and solid state was studied with regards to a poorly water-soluble bioflavonoid, coumestrol (Coum), namely 7,12-dihydroxycoumestan, well-known for its anti-oxidant, anti-inflammatory, anti-fungal and anti-viral activities. Phase-solubility measurements were performed to evaluate in solution the complexation of the two cyclodextrins, i.e. β-CyD and HP-β-CyD. The stoichiometry and stability constants of the Coum/β-CyD and Coum/HP-β-CyD complexes were calculated by the phase-solubility method, after which drug–cyclodextrin solid systems were prepared by co-precipitation. In solid phase, the formation of inclusion complexes was confirmed by Fourier transform infrared spectroscopy in attenuated total reflectance (FTIR-ATR) geometry. In particular, complexation mechanisms were explained by the significant differences revealed in the FTIR-ATR spectra of physical mixtures with respect to those of the complexes; the use of deconvolution and curve fitting was determinant.