Supramolecular Design Strategy of a Water-Soluble Diphenylguanidine-Cyclodextrin Polymer Inclusion Complex

Diphenylguanidine (DPG) is a widely used secondary accelerator for the vulcanization of natural rubber (NR) latex. However, its low water solubility and high toxicity limit its use in high-end NR products. In this study, a water-soluble inclusion complex of DPG and a β-cyclodextrin polymer (β-CDP), termed DPG-β-CDP, was prepared through supramolecular interactions and characterized using Fourier-transform infrared spectroscopy, ¹H NMR, scanning electron microscopy, and UV-vis spectroscopy techniques. In comparison with that of DPG, the water solubility of DPG-β-CDP was greatly enhanced because of the water-soluble host molecule. The molar ratio of DPG to the CD unit in β-CDP was determined to be 1:1. At 25 °C, the binding constant of DPG-β-CDP was found to be 9.2 × 10⁵ L/mol by UV-vis spectroscopy. The proposed method for forming inclusion complexes with high potential for use as water-soluble vulcanization accelerators is promising.     

Flow Injection and Batch Spectrophotometric Determination of Ibuprofen Based on its Competitive Complexation Reaction with Phenolphthalein‐β‐Cyclodextrin Inclusion Complex

Abstract

Rapid, simple, and accurate spectrophotometric method is presented for the determination of ibuprofen by batch and flow injection analysis methods. The method is based on ibuprofen competitive complexation reaction with phenolphthalein‐β‐cyclodextrin (PHP‐β‐CD) inclusion complex. The increase in the absorbance of the solution at 554 nm by the addition of ibuprofen was measured. Ibuprofen can be determined in the range 8.0×10^?6 ?3.2×10^?4 and 2.0×10^?5?5.0×10^?3 mol l^?1 by batch and flow methods, respectively. The limit of detection and limit of quantification were 6.19×10^?6 and 2.06×10^?5 mol l^?1 for batch and 1.77×10^?5 and 5.92×10^?5 mol l^?1 for flow method, respectively. The sampling rate in flow injection analysis method was 120±5 samples h^?1. The method was applied to the determination of pharmaceutical formulations.     

Preparation and Aggregation of Polypseudorotaxane from Dendronized Poly(methacrylate)‐Poly(ethylene oxide) Diblock Copolymer and α‐Cyclodextrin

Summary: Dendronized poly(methacrylate)‐poly(ethylene oxide) (PDMA₅₈‐b‐PEO₄₅) formed as a stoichiometric inclusion complex with α‐cyclodextrin. The incorporation of the rodlike PDMA blocks produced no apparent change in the crystal structure, but its steric hindrance on the PEO chain resulted in lower yield as compared with the pure PEO. Moreover, the architectural transition from rod–coil to rod–rod led to a morphological change from spindly aggregates to rods in a binary solvent mixture of N,N‐dimethylformamide and water.

Synthesis and self‐assembly of the α‐cyclodextrin‐[dendronized poly(methacrylate)‐poly(ethylene oxide)] (α‐CD‐PDMA‐PEO) polypseudorotaxane (PR).     

Study on Properties of Inclusion Complexation of Triclopyr Butoxy Ethyl Ester with Mixed Surfactant System

β‐cyclodextrin exhibits the property of forming inclusion complexes with various molecules. These complexes display improved properties in comparison with starting molecules in terms of their solubility and stability. In the present study, triclopyr butoxy ethyl ester, a selective systemic herbicide was utilized for forming inclusion complexes with β‐cyclodextrin in absence and presence of the nonionic: lauric acid monoethanolamide (C₁₂MEA)/anionic: α‐olefin sulfonate (AOS) mixed surfactant system. The objective of present work was to study the important physical properties like dissolution rate, dispersion stability and wettability in presence of mixed surfactant systems of inclusion complex of a herbicide. Coprecipitation method was used for inclusion complex formation, which was consequently characterized by analytical techniques such as x‐ray diffractometry (XRD), differential scanning calorimetry (DSC) and ultra‐violet spectroscopy (UV).     

Inclusion complexes of α‐cyclodextrin and (AB)n block copolymers

Cyclodextrins thread onto polymer chains to form inclusion complexes, especially when the polymer is hydrophobic relative to the solvent. Selective threading might occur when the polymer architecture contains both hydrophobic and hydrophilic segments. α‐Cyclodextrin formed crystalline inclusion complexes with (AB)_n microblock copolymers, where the A block was a linear alkyl segment containing a single double bond and the B block was an exact length segment of poly(ethylene oxide). The complexes were isolated and characterized by solution and solid‐state NMR, X‐ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Each method confirmed complex formation and showed that the physical properties of the complexes were distinct from those of its individual components. The X‐ray data were consistent with known inclusion complexes having a channel or column crystal structure. The stoichiometry of the complex formation, 2.3 α‐cyclodextrin rings per polymer repeat unit, was determined by NMR analysis of the complexes and from an analysis of the inclusion complex yields. The data suggest that the inclusion complex stoichiometry is defined by the increasing insolubility of the polymer–cyclodextrin complex. Solid‐state NMR data were consistent with a preference for threading onto hydrophobic segments of the (AB)_n polymer. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2731–2739, 2001     

Effect of 1-n-Dodecanethiol on the Molecular Weight Distribution of Poly(methyl Methacrylate) Synthesized by Suspension Polymerization

Fractionation data of two poly(methyl methacrylate) samples prepared by suspension polymerization up to limiting conversion, in the presence of different amounts of 1-n-dodecanethiol, indicate that both samples have similar polydispersity factors, although the molecular weight distribution curve for the sample obtained with the highest chain transfer agent concentration is shifted to lower molecular weight values. The results obtained are qualitatively correlated with the high conversion polymerization theory proposed by Cardenas and O'Driscoll.     

Macromolecular Recognition by Polymer‐Carrying Cyclodextrins: Interaction of a Polymer Bearing Cyclodextrin Moieties with Poly(acrylamide)s Bearing Aromatic Side Chains

Summary: The interaction of a polymer bearing β‐cyclodextrin moieties (β‐CD polymer) with poly(acrylamide)s bearing aromatic side chains was investigated by viscometry to study the effect of collectivity (i.e., interactions at multi‐sites) in macromolecular recognition. The formation of inclusion complexes at multi‐sites caused a large difference in the size of interpolymer aggregates, even though the difference in association constants for complexation of native β‐CD with guest moieties was not very much large.

Conceptual illustration for interpolymer aggregates of β‐CD polymer with poly(acrylamide)s bearing naphthyl groups substituted on the (a) 1‐ and (b) 2‐positions (see Scheme 1 ).     

Complex formation of cyclodextrins with poly(propylene glycol) derivatives

The complex formation between cyclodextrins (CDs) and poly(propylene glycol) (PPG) derivatives is described. β‐CD and γ‐CD formed complexes with PPG derivatives such as 1‐naphthyl (1NA), 2‐naphthyl (2NA), 3,5‐dinitrobenzoyl, and 2,4‐dinitrophenyl PPG. α‐CD did not form complexes with these PPG derivatives. Although γ‐CD gave complexes with 9‐anthryl PPG (PPG9An), β‐CD did not efficiently form complexes with PPG9An. β‐CD did not form complexes with trityl PPG, demonstrating that trityl groups were too bulky to thread a β‐CD cavity. The emission spectra of the complexes showed that β‐CD bound a single 2NA moiety in its cavity and that γ‐CD included two 2NA moieties. In contrast, γ‐CD bound a single 1NA moiety in the cavity. X‐ray diffraction studies and ¹H NMR analysis showed that the CD molecules were stacked along a PPG chain to form a channel structure. The inclusion modes are discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4839–4849, 2000     

聚(二甘氨酸乙酯)磷腈的合成及其生物相容性

氨基酸酯基取代的聚磷腈由于具有优良的水解性能并能降解成无毒产物, 因而成为一类非常有吸引力的生物医用材料. 采用两步法合成了聚(二甘氨酸乙酯)磷腈(PEGP). 首先采用开环聚合的方法制备中间体聚二氯磷腈, 再利用亲核取代方法合成PEGP. 通过红外光谱、核磁共振及元素分析等确证了产物的结构. 用蒸汽压下降法测得PEGP的分子量为12959, 用DSC法测得其玻璃化转变温度为-21.5 ℃. 采用体外细胞培养的方法评价了肝癌细胞HepG2和人工合成纤维细胞在PEGP薄膜表面的生长性能. 结果表明, 该材料不但没有细胞毒性, 反而具有良好的促进细胞生长的能力, 显示聚(二甘氨酸乙酯)磷腈在组织工程和再生医学中的潜在应用价值.     

Host–Guest Interaction Study of Resveratrol With Natural and Modified Cyclodextrins

The aim of this work is to increase the stability and water solubility of resveratrol by complexation with different cyclodextrins. Furthermore, physical–chemical properties of each inclusion compound were investigated. Complexes of resveratrol with cyclodextrins both native (α, β, γ) and modified (2-hydroxypropyl-β-cyclodextrin, dimethyl-β-cyclodextrin) were obtained by using the suspension method. An inclusion complex with β-cyclodextrin was also prepared by using the microwave. Solid state characterization of the products was carried out using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (DRX); solution studies were performed by UV–Vis spectrophotometry and ¹H-NMR spectroscopy. Phase solubility profiles with all cyclodextrins employed were classified as A_N type, indicating the formation of 1:1 stoichiometric inclusion complexes. Stability constants (K _c) from the phase solubility diagrams were calculated. Stability studies in the solid state and in solution were performed; the photodegradation by UV–Vis spectrophotometry was monitored. The isomerization rate trans to cis, in ethanol solution, decreased with inclusion. The dissolution studies revealed that resveratrol dissolution rate was improved by the formation of inclusion complexes.     

Effect on the Solubility,Wettability, and Dispersibility of the β‐CD‐Deltamethrin Inclusion Complex in Presence of Mixed Surfactant (C14MEA/AOS) Blend

An inclusion complex formation using β‐cyclodextrin (β‐CD) as the host molecule and deltamethrin as guest molecule was a first step towards improvement in conventional insecticide formulations. β‐CD‐deltamethrin inclusion complex formation in the absence and presence of the nonionic myrisitic acid monoethanolamide (C₁₄MEA)/anionic α‐olefin sulfonate C₁₂‐C₁₄ (AOS) mixed surfactant system was comparatively studied. The co‐evaporation method was used for complex formation, which was subsequently characterized by analytical methods such as FTIR and XRD techniques. Important physical properties such as solubility, dispersion stability, and wettability were also studied.     

Preference Prediction for the Stable Inclusion Complexes between Cyclodextrins and Monocyclic Insoluble Chemicals Based on Monte Carlo Docking Simulations

Cyclodextrins (CDs) are useful functional excipients, which are being used to camouflage undesirable pharmaceutical characteristics, especially poor aqueous solubility, through the inclusion complexation process with insoluble drugs. The selection of more efficient cyclodextrin is important to improve the bioavailability of drugs. In this study, the complexing and solubilizing abilities toward poorly water-soluble monocyclic molecules of natural CDs (α-CD, β-CD, and γ-CD) were investigated using Monte Carlo (MC) docking simulations studies. These theoretical results closely agree with the experimental observation of the complex stability in water of the various guests–CD complexes. Host preferences, based on the experimentally determined stability constants between host CDs and guest molecules, show excellent correlation with the calculated interaction energies of corresponding complexes. The inclusion complex with the lower MC docking interaction energy shows a higher value of stability constant than that of the other complex, and the prediction accuracy of the preferred complex for 21 host–guest pairs is 100%. This result indicates that the MC docking interaction energy could be employed as a useful parameter to select more efficient cyclodextrin as a host for the bioavailability of insoluble drugs. In this study, β-CD shows greater solubilizing efficacies toward guest molecules than those of α-CD and γ-CD, with the exception of one case due to the structure of a guest molecule containing one lipophilic cyclic moiety. The surface area change of CDs and hydrogen bonding between the host and guest also work as major factors for the formation of the stable complex.     

Morphological change of poly (ε‐caprolactone) with a wide range of molecular weight via formation of inclusion complex with α‐cyclodextrin

The effect of molecular weight of poly(ε‐caprolactone) (PCL) on the formation and stability of inclusion complexes (ICs) between α‐cyclodextrin (α‐CD) and PCL was investigated by FTIR, WAXD, and DSC measurements. ICs between α‐CD and PCLs with a wide range of number‐average molecular weight, M_n = 1.21 × 10⁴ – 1.79 × 10⁵, were prepared by mixing the aqueous solution of CD and acetone solution of PCL followed by stirring at 60 °C for 1h and at the room temperature for 1 day. FTIR, WAXD, and DSC measurement showed the PCL chains were included into the α‐CD cavity, and the crystallization of PCL was suppressed in the α‐CD cavity. Stoichiometry and yield of each IC varied with the molecular weight of guest PCL, and the effect of IC formation on the crystallization behaviour of guest polymer decreased with the increase of molecular weight of guest polymer. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 1433–1440, 2005     

Crystal structures of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin complexes with (R)- and (S)-Flurbiprofen

Hepatakis(2,3,6-tri-O-methyl)--cyclodextrin (TM--CDx) forms crystalline complexes with (R)-Flubiprofen (R-FP), C₆₃H₁₁₂O₃₅C₁₅H₁₃O₂F·H₂O, and (S)-Flurbiprofen (S-FP), C₆₃H₁₁₂O₃₅C₁₅H₁₃O₂F. The crystal structures were determined by X-ray analysis. Crystals of both compounds are orthorhombic and the space group isP2₁2₁2₁ with cell dimensions:a=15.092(2),b=21.714(3), andc=28.269(4) Å for theR-FP complex, anda=15.271(2),b=21.451(3) andc=27.895(3) Å for theS-FP complex. The macrocyclic ring of TM--CDx is markedly distorted because of the inability to form intramolecular hydrogen bonds and the steric hindrance involving methyl groups. In both complexes, the phenyl group is inserted into the host cavity from the O(2), O(3) side, which is wider than the O(6) side. The biphenyl moiety ofR-FP is fixed in theR-configuration within the host cavity. The phenyl group ofS-FP is disordered, andR-andS-configurations are statistically distributed with equal probability. TM--CDx molecules are stacked along theb axis to form a column structure. The TM--CDx molecule is laterally shifted with respect to the column axis, and a half of the guest molecule protrudes outside from the crevis of the column. The carboxyl group ofR-FP forms a hydrogen bond with water located outside the host cavity, while the carboxyl group ofS-FP is hydrogen-bonded to an oxygen atom of an adjacent TM--CDx. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82064 (24 pages).     

Formation of Inclusion Complexes between Cyclodextrins and Carbaryl and Characterization of the Complexes

The solubility of carbaryl increased with increasing concentrations of-CD, G₂--CD, and M--CD. The result suggests theformation of soluble inclusion complex. Solubility increase was highestin M--CD-carbaryl, being 18.4 fold higher than that of carbaryl when 100 mM M--CD was used. The apparent formation constant for the complex calculated from phase solubility diagram was 223.18 M^-1. The preparation of the complex in solid form for characterization was successful by kneading andfreeze-drying. The DSC curves for kneading and freeze-drying mixture didnot show the endothermic peak characteristic of carbaryl, but a small new endothermic peak was observed. FTIR analysis showed a shift of the major peak of carbonyl group in carbaryl molecule from 1717 to 1744 and 1734 cm^-1 in kneading and freeze-dried mixtures, respectively. M--CD-carbaryl complex demonstrated higher dissolution rate, higher thermal and UV stability but lower toxicity than its parent carbaryl compound.     

Noncovalently-Bound Cyclodextrin Dimers and Related Compounds. (Review)

In the review noncovalently-bound cyclodextrin (CD) dimers, i. e., CD host-guest 2:1 complexes as well as CD self-assembled inclusion oligomers, are briefly characterized, showing methods of their investigations; the properties and possible applications of these species are also described. __________ Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1603–1624, November, 2005.     

抗抑郁化合物SIPI5838和环糊精分子非共价复合物的研究

报道了用电喷雾电离质谱(ESI-MS), 并结合紫外分光光度法及溶解度实验, 研究一种新型的具有自主知识产权的抗抑郁化合物SIPI5838与α-环糊精(CD)和β-环糊精(CD)分子生成的非共价复合物. 质谱测量结果表明, 在溶液中, SIPI5838分子可以与环糊精分子之间生成非共价复合物, 且两者之间的配比关系为1∶1. 这些非共价复合物的形成可以显著地提高这种抗抑郁化合物在水溶液中的溶解度, 使得它作为高效的口服或注射药物成为可能. 另外, 还用紫外分光光度法和溶解度实验对液相中非共价复合物的形成进行了辅助研究, 这些结果均显示了非共价复合物的生成. 根据溶解度实验结果, 计算了SIPI5838和两种环糊精分子在液相中的生成常数, 它们分别为SIPI5838-β-环糊精: 1.83×103 mol－1•L, SIPI5838-α-环糊精: 3.15×101 mol－1•L. 两种非共价复合物的稳定程度为β-环糊精-SIPI5838＞α-环糊精-SIPI5838.     

抗抑郁化合物SIP15838和环糊精分子非共价复合物的研究

报道了用电喷雾电离质谱(ESI-MS),并结合紫外分光光度法及溶解度实验,研究一种新型的具有自主知识产权的抗抑郁化合物SIPI5838与α-环糊精(CD)和β-环糊精(CD)分子生成的非共价复合物.质谱测量结果表明,在溶液中,SIPI5838分子可以与环糊精分子之间生成非共价复合物,且两者之间的配比关系为1:1.这些非共价复合物的形成可以显著地提高这种抗抑郁化合物在水溶液中的溶解度,使得它作为高效的口服或注射药物成为可能.另外,还用紫外分光光度法和溶解度实验对液相中非共价复合物的形成进行了辅助研究,这些结果均显示了非共价复合物的生成.根据溶解度实验结果,计算了SIPI5838和两种环糊精分子在液相中的生成常数.它们分别为SIPI5838-β-环糊精:1.83×103 mol-1·L,SIPI5838-α-环糊精:3.15×101mol-1·L.两种非共价复合物的稳定程度为β-环糊精-SIPI5838>α-环糊精-SIPI5838.     

环糊精包结物包结比的测定

由于环糊精具有“外亲水,内疏水”的独特性质,它可以包结许多物质而形成主客体配合物,从而改变物质的特性,所以被广泛应用于各行各业中,包结物的包结比是决定包络物性质的一个重要参数,在查阅大量文献的基础上,总结出环糊精包结反应过程中测定主客体间的包结比的方法,并对其进行了较详细的介绍。     

Improvement of some pharmaceutical properties of nocloprost by β- and γ-Cyclodextrin Complexation

Inclusion complexation of nocloprost, a potent antiulcer prostaglandin derivative, with -, -, and -cyclodextrins (CyDs) in aqueous solutions has been studied by the solubility method and¹³C-NMR spectroscopy. The steric requirement of host-guest interaction was reflected in the magnitude of the stability constants and the thermodynamic parameters of the inclusion complexes. Solid complexes of nocloprost with - and -CyDs in a molar ratio of 1 : 2 were obtained on the basis of aBs-type phase solubility diagram. The X-ray diffraction data suggested that nocloprost is included in the cylindrical channel formed by coaxial alignment of -CyD molecules to give a channel type structure. Release and thermal behavior of the solid complexes was examined and compared with nocloprost itself. The results indicated that the -CyD complex may have great utility among the three CyDs, being a rapid dissolving form of nocloprost with improved thermal stability.