Dual Fluorescence and Photoprototropic Characteristics of 2-Aminodiphenylsulphone-β-Cyclodextrin Inclusion Complex

The absorption and fluorescence spectral characteristics of 2-aminodiphenylsulphone (2ADPS) have been investigated in the presence of β-cyclodextrin (β-CDx) in water. Dual emission is observed upon the complexation of 2ADPS in β-CDx. The stoichiometry of the host:guest inclusion complex is found to be 2:1. Steady state and time-resolved fluorescence spectral analysis support the formation of 2:1 complex between β-CDx and 2ADPS. The large enhancement in fluorescence intensity of twisted intramolecular charge transfer (TICT) band in aqueous β-CDx solution is due to the decrease in non-radiative processes. The ground and the excited state pK_a values for the monocation-neutral equilibrium of 2ADPS in β-CDx are found to be different from the pK_a values in aqueous solution. In the presence of β-CDx, 2ADPS is found to be less basic in the ground and the excited states.     

Rigorous nonlinear regression analysis of phase solubility diagrams to obtain complex stoichiometry and true thermodynamic drug-cyclodextrin complexation parameters

This work reports rigorous nonlinear regression procedures aimed at analyzing various types of phase solubility diagrams (PSDs) corresponding to the different soluble and insoluble complex stoichiometries, which are generally encountered in drug-cyclodextrin (CD) complexation studies. These are depicted in final equations that can be modeled to fit experimental data of measured drug solubility against CD concentration utilizing simple spreadsheet software available for all PCs (i.e., the Solver Add-in in Microsoft Excel). They cover all types of guest/host phase solubility diagrams (A-, B_S-and B_I-types) allowing accurate estimation of soluble and insoluble complex stoichiometries generally encountered in drug/CD complexes (1:1, 2:1, 1:2, 2:2, 2:3, 3:2), the corresponding thermodynamic complex formation constants (K₁₁, K₂₁, K₁₂, K₂₂, K₂₃, K₃₂) and solubility product constants (K_sp) of saturated complexes.     

The complexation efficiency

Studies have shown that cyclodextrins form both inclusion and non-inclusion complexes and that several different types of complexes can coexist in aqueous solutions. In addition, both cyclodextrins and cyclodextrin complexes are known to form aggregates and it is thought that these aggregates are able to solubilize drugs through micellar-type mechanism. Thus, stability constants determined from phase-solubility profiles are rarely true stability constants for of some specific drug/cyclodextrin complexes. A more precise method for evaluation of the solubilizing effects of cyclodextrins is to determine their complexation efficiency (CE). CE can be determined by measuring the solubility of a given drug at 2–3 cyclodextrin concentrations in pure water or a medium constituting the pharmaceutical formulation such as parenteral solution or aqueous eye drop formulation. Based on the CE value the drug:cyclodextrin ratio in the complexation medium can be determined as well as the increase in the formulation bulk in a solid dosage form. Determination of CE is a simple method for quick evaluating the solubilizing effects of different cyclodextrins and/or the effects of excipients on the solubilization. Here we report the CE of 43 different drugs with mainly 2-hydroxypropyl-β-cyclodextrin but also with randomly methylated β-cyclodextrin as well as few other cyclodextrins. Calculation of CE, drug:cyclodextrin molar ratio and the increase in the formulation bulk is discussed, as well as the influence of the intrinsic solubility and drug lipophilicity on the CE.     

β-环糊精与有机胺之间包合作用的理论与实验研究

通过实验和理论计算方法研究了β-环糊精(CD)与乙二胺1及它的三个类似物: 二乙烯三胺2、三乙胺3和乙二胺四乙酸4之间的包合作用. 利用旋光法确定了β-CD与客体分子形成1:1型主–客体包合物, 在298.2 K下测定了包合物在水中的稳定常数(K). 采用半经验PM3方法考察了β-CD与短链脂肪胺1~7、环状脂肪胺8~11以及芳香胺12~13的分子间结合能力, 报道了β-CD与这些客体分子间的包合络合过程并讨论了这些包合体系之间的包合差异性. 变形能和水合能对包合体系的相互作用能的贡献均相当小. β-CD包合物的稳定性取决于主、客体分子之间的尺寸匹配. 对于β-CD与客体1~4形成的包合物而言, 旋光法测定的包合物的K值的顺序与PM3计算得到的包合物络合能绝对值的排序有很好的一致性.     

Evaluation of host-guest complex formation between a benzimidazolic derivative and cyclodextrins by UV-VIS spectrophotometry and differential scanning calorimetry

Interactions between a benzimidazolic derivative, omeprazole (OME), beta-cyclodextrin (βCD) and a chemically modified βCD, methyl-beta-cyclodextrin (MβCD) were investigated in aqueous solution by UV-VIS spectroscopy and in solid state by differential scanning calorimetry (DSC). Phase solubility studies were used to evaluate the complexation in aqueous solution. The two solubility diagrams obtained were A_L type, indicating the formation of a drug-cyclodextrin complex with 1:1 stoichiometry. The complex of OME with MβCD showed a higher stability constant (K _S) than those with βCD. Some evidences of inclusion complexation in solid state were obtained from DSC. Only in thermal curves of OME-βCD lyophilized product and in OME-MβCD spray-dried and lyophilized systems the melting point of the drug disappeared completely suggesting the possible formation of an inclusion complex.     

Fluorescence properties of (R)- and (S)-[1,1′-binaphthalene]-2,2′-diols solutions and their complexes with cyclodextrins in aqueous medium

Steady-state and time-resolved fluorescence techniques were used to study (R)- and (S)-[1,1′-binaphthalene]-2,2′-diol (1,1′-binaphthol or BINOL) dilute solutions of different polarity solvents, as well as their inclusion complexes with α- and βcyclodextrins (CDs) in water. BINOLs in dilute water solutions exhibited a surprisingly high fluorescence anisotropy that was explained as being due to the formation of fairly large order π–π stacking aggregates in aqueous polar media. Stoichiometries, formation constants and the changes of enthalpy and entropy upon inclusion were also obtained by measuring the variation of the fluorescence intensity with [CD] and temperature. Results agree with the formation of 1:1 stoichiometry complexes, but the association constants are rather low and very similar for both enantiomers. Molecular mechanic calculations in the presence of water were employed to study the formation of BINOL complexes with both α- and βCDs. For the most stable structures of any of the complexes only a small portion of the guests, in agreement with thermodynamics parameters and quenching experiments, penetrates inside the CD cavities. Driving forces for 1:1 inclusion processes may be dominated by non-bonded van der Waals host:guest interactions. The low guest:host binding constants and poor enantioselectivity of α- and βCDs for BINOLS may be a consequence of the BINOL aggregation in water.     

Fluorescence Sensing and Selective Binding of a Novel 4,4′‐Sulfonyldianiline‐Bridged Bis(β‐cyclodextrin) for Bile Salts

A novel 4,4′‐sulfonyldianiline‐bridged bis(β‐cyclodextrin (CD)) 2 was synthesized, and its complex stability constants (K_s) for the 1 : 1 inclusion complexation with bile salts, i.e., cholate (CA), deoxycholate (DCA), glycocholate (GCA), and taurocholate (TCA) have been determined in phosphate buffer (pH 7.2) at 25° by fluorescence spectroscopy. The result indicated that 2 can act as efficient fluorescent sensor and display remarkable fluorescence enhancement upon addition of optically inert bile salts. Structures of the inclusion complexes between bile salts and 2 were elucidated by 2D‐NMR experiments, indicating that the anionic tail group and the D ring of bile salts penetrate into one CD cavity of 2 from the wide opening deeply, while the phenyl moiety of the CD linker is partially self‐included in the other CD cavity to form a host–linker–guest binding mode. As compared with native β‐CD 1 upon complexation with bile salts, bis(β‐CD) 2 enhances the binding ability and molecular selectivity. Typically, 2 gives the highest K_s value of 26200 M ^?1 for the complexation with CA, which may be ascribed to the simultaneous contributions of hydrophobic, H‐bond, and electrostatic interactions. These phenomena are discussed from the viewpoints of multiple recognition and induce‐fit interactions between host and guest.     

Effect of the acyl group and the dodecylsulfonate chain on the inclusion of pyrene inside the cavity of β-cyclodextrin

The solubilization of pyrene in aqueous solution of β-cyclodextrin (β-CD) or its derivatives such as β-CD-hexanoyl, β-CD-benzoyl and β-CD-dodecylsulfonate was investigated by spectrophotometry. Linear and non-linear regression methods were used to estimate the association constants (K₁). A 1:1 stoichiometric ratio and different effects of the hexanoyl, benzoyl and dodecylsulfonate groups on the association constant were observed for the binary inclusion complex between pyrene and β-CD. The formation constant was shown to decrease when β-CD was modified by a dodecylsulfonate chain. The value of K₁ was 190 ± 10 L mol⁻¹ for the [pyrene/β-CD] complex and 145 L mol⁻¹ for the [pyrene/β-CD-dodecylsulfonate] complex. Partitioning of the pyrene molecules between the dodecylsulfonate chains and cyclodextrin cavities can explain the decrease in the association constant value. In the cases of β-CD-hexanoyl and β-CD-benzoyl derivatives, no association constants were detected. Results suggest that the high hydrophobicity of the hexanoyl and benzoyl groups prevents the inclusion of pyrene molecules inside the cyclodextrin cavity.     

Inclusion complexation of diclofenac with natural and modified cyclodextrins explored through phase solubility, 1H-NMR and molecular modeling studies

Guest–host interactions were examined for neutral diclofenac (Diclo) and Diclofenac sodium (Diclo sodium) with each of the cyclodextrin (CD) derivatives: α-CD, β-CD, γ-CD and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), all in 0.05 M aqueous phosphate buffer solution adjusted to 0.2 M ionic strength with NaCl at 20 °C, and with β-CD at different pHs and temperatures. The pH solubility profiles were measured to obtain the acid–base ionization constants (pK _as) for Diclo in the presence and absence of β-CD. Phase solubility diagrams (PSDs) were also measured and analyzed through rigorous procedures to obtain estimates of the complex formation constants for Diclo/CD and Diclo sodium/CD complexation in aqueous solutions. The results indicate that both Diclo and Diclo sodium form soluble 1:1 complexes with α-, β-, and HP-β-CD. In contrast, Diclo forms soluble 1:1 Diclo/γ-CD complexes, while Diclo sodium forms 1:1 and 2:1 Diclo/γ-CD, but the 1:1 complex saturates at 5.8 mM γ-CD with a solubility product constant (pK _sp = 5.5). Therefore, though overall complex stabilities were found to follow the decreasing order: γ-CD > HP-β-CD > β-CD > α-CD, some complex precipitation problems may be faced with aqueous formulations of Diclo sodium with γ-CD, where the overall concentration of the latter exceeds 5.8 mM γ-CD. Both ¹H-NMR spectroscopic and molecular mechanical modeling (MM⁺) studies of Diclo/β-CD indicate the possible formation of soluble isomeric 1:1 complexes in water.     

Inclusion complexes of 2-phenoxyethanol and alkoxyethanols in cyclodextrins: an 1H NMR study

The association in aqueous solutions of small amphiphilic molecules [2-phenoxyethanol, PhE₁, and some α-n-alkyl-ω-hydroxyoligo(oxiethylenes], C₄E₁, C₄E₂ and C₆E₂) with β-cyclodextrin (βCD), heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) was investigated by ¹H NMR spectroscopy. The upfield shifts observed for the H3 and H5 NMR signals due to anisotropic shielding confirm that the host–guest associations are of inclusion type. The stoichiometries and the apparent inclusion constants, K _app, were determined by ¹H NMR spectroscopy using the H5 and H3 signals. The relative differences in the K _app values for βCD inclusion complexes seem to reflect the hydrophobic/hydrophilic balance of the guests. The K _app values for the PhE₁ inclusion complexes can be related to the degree of methylation and hydrophobicity variation within the considered hosts. In addition, a comparative study between βCD and TRIMEB inclusion complexes using 2D ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) NMR spectra provides structural features for these complexes which are inaccessible by other experimental methods.     

Cyclodextrins and the liquid-liquid phase distribution of progesterone, estrone and prednicarbate

The purpose of the present work was to investigate the interaction of drugs and octanol with hydroxypropyl β- (HPβCD) and γ- (HPγCD) cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD) and randomly methylated-β-cycoldextrin (RMβCD) and to describe the interaction by theoretical models. The poorly soluble steroid drugs progesterone, estrone and prednicarbate were used as model compounds in this study. Hexane and chloroform were also investigated in combination with HPβCD. Octanol formed a complex with all cyclodextrins and the saturation of the aqueous solution with this solvent therefore had a significant effect on the solubilization and extraction potential of cyclodextrins. Hexane had less affinity for cyclodextrins, but the drugs were poorly soluble in this solvent and it could therefore not be used in phase-distribution investigations. Previously we have derived equations that can be used to account for the competitive interaction between two guest compounds that compete for space in the cyclodextrin cavity. These equations were rearranged to calculate the complexation efficacy from phase-solubility data. An equation was derived that obtains intrinsic solubility (S ₀) and intrinsic partition coefficient (P) from the slopes of the phase-solubility and phase-distribution profiles. Investigation of the data showed that the results could not be sufficiently explained by the “classical” drug/cyclodextrin complex model that recognizes the possibility of competitive interactions but ignores any contribution from higher order complexes or aggregation of the cyclodextrin complexes. Relative difference in solubilization potential of different cyclodextrins cannot be translated to relative differences in extraction efficacy. Thus, for these three steroid compounds, RMβCD and SBEβCD gave the best solubilization potential whereas the best extraction efficacy was observed with HPγCD.     

Effect of self-aggregation of γ-cyclodextrin on drug solubilization

The purpose of this study was to investigate the physicochemical properties of drug-saturated aqueous cyclodextrin (CD) solutions. Phase solubility profiles of different drugs were determined in aqueous solutions containing γ-cyclodextrin (γCD) and/or hydroxypropyl-γ-cyclodextrin (HPγCD) in absence or presence of water-soluble polymers. ¹H-NMR and turbidity analysis were performed as well as permeation studies. Phase solubility diagrams showed that the observed γCD content (1–20% w/v) was only slightly different from the theoretical values for aqueous solutions that had been saturated with indomethacin, diclofenac sodium or amphotericin B, all displayed A-type profiles, while it was less than the theoretical value in solutions that had been saturated with corticosteroids (hydrocortisone and dexamethasone) that displayed B_S-type profiles. In the latter case self-assemble of drug/CD complexes decreased the overall CD solubility. Water-soluble polymers enhanced aqueous solubility of the drugs tested by stabilizing the drug/CD complexes, i.e. enhancing their stability constants, without affecting the observed aqueous γCD solubility. When the drug solubility leveled off (the B_S-type profiles) the amount of dissolved γCD increased and approached the theoretical values. Hydrocortisone formed partial inclusion complex with γCD and HPγCD and no non-inclusion or aggregates could be detected in diluted solutions by ¹H-NMR. Both permeation and turbidity studies showed that formation of dexamethasone/γCD complex promoted CD aggregation. All these observations indicate that CD aggregate formations play a role in CD solubilization of lipophilic and poorly water-soluble drugs and that the water-soluble polymers enhance the complexation efficiency of γCD and HPγCD by stabilizing the self-assembled drug/CD nanoparticles and promote non-inclusion complex formation.     

Competitive Molecular‐/Ion‐Recognition Responsive Characteristics of Poly(N‐isopropylacrylamide‐co‐benzo‐12‐crown‐4‐acrylamide) Copolymers with Benzo‐12‐crown‐4 as Both Guest and Host Units

Novel dual molecular‐ and ion‐recognition responsive poly(N‐isopropylacrylamide‐co‐benzo‐12‐crown‐4‐acrylamide) (PNB₁₂C₄) linear copolymers with benzo‐12‐crown‐4 (B12C4) as both guest and host units are prepared. The copolymers exhibit highly selective sensitivities toward γ‐cyclodextrin (γ‐CD) and Na⁺. The presence of γ‐CD induces the lower critical solution temperature (LCST) of PNB₁₂C₄ copolymer to shift to a higher value due to the formation of 1:1 γ‐CD/B12C4 host‐guest inclusion complexes, while Na⁺ causes a negative shift in LCST due to the formation of 2:1 “sandwich” B12C4/Na⁺ host‐guest complexes. Regardless of the complexation order, when γ‐CD and Na⁺ coexist with PNB₁₂C₄, competitive complexation actions of B12C4 as both guest and host units toward γ‐CD and Na⁺ finally form equilibrium 2:2:1 γ‐CD/B12C4/Na⁺ composite complexes, and the final LCST values of PNB₁₂C₄ copolymer reach almost the same level. The results provide valuable guidance for designing and applying PNB₁₂C₄‐based smart materials in various applications.

     

A Microcalorimetric Study of Host–Guest Complexes of α-Cyclodextrin with Alkyl Trimethyl Ammonium Bromides in Aqueous Solutions

Interactions between α-CD and three alkyl trimethyl ammonium bromides, a homologues series of surfactants, in aqueous solutions have been investigated with titration microcalorimetry at 298.15 K. The results are discussed in the light of the amphiphilic interaction and the iceberg structure of water molecules existing around the hydrophobic tail of the surfactant. The stoichiometry of the host–guest complex changes from 1:1 to 2:1, as the number of carbon atoms (n) in the hydrophobic chain, C_nH_2n+1, increases from 8 to 14. All the complexes are quite stable, with the apparent experiential stability constants being β₁ = 2.65 × 10³ dm³-mol⁻¹, β₂ = 4.85 × 10⁶ dm⁶-mol⁻², β₂ = 6.50 × 10⁶ dm⁶-mol⁻², respectively for n = 8, 12, 14. All the complexation processes are shown to be enthalpy driven, and the standard enthalpy effect (−ΔH⁰) increases while standard entropy change (ΔS⁰) decreases with elongation of the hydrophobic chain.     

2D and 1D Coordination Polymers with the Ability for Inclusion of Guest Molecules: Nitrobenzene, Benzene, Alkoxysilanes

The complexation reactions of the electron rich, linear and bi-functional ligand, 9,10-bis(4-pyridyl)anthracene, with metal salts Cd(NO₃)₂, CdI₂, CoI₂ and CuI in the presence of guest molecules nitrobenzene, benzene and alkoxysilanes were studied. The single crystal analyses of the complexes reveal that an electron deficient guest molecule such as nitrobenzene consistently templated the open two-dimensional network with grid dimensions of ca. 15 × 15Å. On the other hand the presence of benzene or alkoxysilane templated1D-zigzag chains and/or 2D-grid layers. The crystal structures revealthe importance of host–guest interactions in tailoring the network architectures ofcoordination polymers.     

Inclusion Complex of 4-Hydroxycoumarin with Cyclodextrins and Its Characterization in Aqueous Solution

The physicochemical properties of 4-hydroxy-7-methoxy-3-phenyl-2H-chromen-2-one (4HC) and β-cyclodextrins (CDs) inclusion complexes were investigated. The phase solubility profile of 4HC with β-cyclodextrin derivatives was classified as A_L-type. Stability constants for complexes with 1:1 molar ratios were calculated from the phase solubility diagrams and indicate the following trend: DMβCD>HPβCD>βCD. The highest value of the binding constant was for 4HC-DMβCD; the binding association constant (K _a) for this complex was determined at different temperatures and the thermodynamic data indicate that 4HC-DMβCD association is mainly an entropically driven process. ¹H NMR and ROESY were carried out, revealing that 4HC is embedded in the apolar cavity of DMβCD with the 4OH group buried in the cyclodextrin cavity with the phenyl group outside, near the primary rim. These results are in agreement with ORAC_FL values; the decrease in the antioxidant activity of 4HC-DMβCD is explained by the effective protection of the hydroxyl group due to complexation.     

On Chloralose-Cyclodextrin Complexes by ESI-Mass Spectrometry

α-Chloralose is a useful mild anaesthetic, providing stable but not deep anaesthesia. Host–guest complexes of α-chloralose with α-, β- and γ-cyclodextrin (CD) were studied using electrospray ionisation (ESI-MS) mass spectrometry and molecular modelling (MD). As it is currently administered, chloralose is transported in a convenient water-soluble complex, and released to react on a physiological level with the reactor sites. It is believed that the chloraloses (α and its isomer β) are encapsulated within the CD cavity. However, the ESI spectra did not reveal such the presence of inclusion compounds. Searching of alternative mechanisms of transportation of these anaesthetic agents, we found that outer-cavity complexes of inserted chloraloses, as found from MD calculations, do have a reasonable stability.     

Preparation and characterization of cyclodextrin complexes of doxycycline hyclate for improved photostability in aqueous solution

Doxycycline hyclate is Biopharmaceutical Classification System, class I drug (high solubility and high permeability), but it is associated with poor photostability. It is in the class of tetracycline antibiotic, which is used to treat various infections, but its bioavailability is compromised due to its sensitivity to light and aqueous instability. In this paper, the influence of inclusion complexation with different cyclodextrins, i.e., αCD, γCD, HPβCD and RMβCD, on the photostability of doxycycline hyclate in aqueous media was investigated. Host–guest inclusion complexes were prepared by freeze- drying method. The prepared complexes were characterized for drug content, SEM, XRPD, in vitro permeation studies and photostability studies. XRPD showed diffused peaks for most of the complexes, while SEM showed irregularly shaped particles. The formulation D20 (Drug: γCD in 1:20 molar ratio) showed the highest % drug content (83.72?±?1.2%), and the formulations D1 (Drug: αCD in 1: 2 molar ratio) showed the lowest % drug content among all the CD complexes. It was found that the photodegradation of the drug was reduced significantly upon complexation. For Drug: CD complexes, the photostability of the aqueous solution of drug/CD complexes was found to be in the order of γCD?>?RMβCD?>?HPβCD?>?αCD with maximum photostability shown by Drug: γCD (1:20 molar ratio) complex. The obtained results suggested that cyclodextrin complexation can be used as an alternative approach for increasing the photostability of doxycycline hyclate.

     

Synthesis of Mono-Amino Substituted γ-CD: Host–Guest Complexation and In Vitro Cytotoxicity Investigation

Cyclodextrins (CDs) are cyclic oligosaccharides which can trap hydrophobic molecules and improve their chemical, physical, and biological properties. γ-CD showed the highest aqueous solubility with the largest cavity diameter among other CD types. The current study describes a direct and easy method for nucleophilic mono-aminos to be substituted with γ-CD and tested for their ability to host the guest curcumin (CUR) as a hydrophobic drug model. The mass spectrometry and NMR analyses showed the successful synthesis of three amino-modified γ-CDs: mono-6-amino-6-deoxy-cyclodextrine (γ-CD-NH₂), mono-6-deoxy-6-ethanolamine-γ-cyclodextrine (γ-CD-NHCH₂CH₂OH), and mono-6-deoxy-6-aminoethylamino)-γ-cyclodextrin (γ-CD-NHCH₂CH₂NH₂). These three amino-modified γ-CDs were proven to be able to host CUR as native γ-CDs with formation constants equal to 6.70 ± 1.02, 5.85 ± 0.80, and 8.98 ± 0.90 mM⁻¹, respectively. Moreover, these amino-modified γ-CDs showed no significant toxicity against human dermal fibroblast cells. In conclusion, the current work describes a mono-substitution of amino-modified γ-CDs that can still host guests and showed low toxicity in human dermal fibroblasts cells. Therefore, the amino-modified γ-CDs can be used as a carrier host and be conjugated with a wide range of molecules for different biomedical applications, especially for active loading methods.     

Complexation of dodecyl‐substituted poly(acrylate) by linked β‐cyclodextrin dimers and trimers in aqueous solution

Two‐dimensional NOESY ¹H NMR, isothermal titration calorimetric (ITC), and rheological studies of host–guest complexation by β‐cyclodextrin, β‐CD, and the β‐CD groups of the linked β‐CD dimers, β‐CD₂ur and β‐CD₂su and trimers, β‐CD₃bz and β‐CDen₃bz, of the dodecyl, C12, substituents of the 3.0% substituted poly(acrylate), PAAC12, in aqueous solution are reported. Complexations by β‐CD, β‐CD₂ur, β‐CD₂su, β‐CD₃bz, and β‐CDen₃bz of the C12 substituents of PAAC12 in 0.2 wt % solution exhibit complexation constants 10^?4K₁₁ (298.2 K) = 0.83, 5.80, 4.40, 15.0, and 1.50 dm³ mol^?1, respectively. (The corresponding ΔH₁₁ and TΔS₁₁ show a linear relationship.) The rheologically determined zero‐shear viscosities of 3.3 wt % aqueous solutions of PAAC12 alone and in the presence of β‐CD, β‐CD₂ur, β‐CD₂su, β‐CD₃bz, and β‐CDen₃bz (where the β‐CD groups and C12 substituents are equimolar) are 0.016, 0.03, 0.12, 0.25, 0.12, and 0.08 Pa s (298.2 K), respectively, and show PAAC12 to form interstrand cross‐links through complexation. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1278–1286