Formation of an inclusion complex

As described above, the most important reason for the increasing attention to cyclodextrins as enzyme models is the formation of inclusion complexes (the substrates are included in the cavities of cyclodextrins). 

Inclusion complexes are formed in aqueous solution. In most cases, substrates with poor solubility usually form stronger complexes with cyclodextrins, indicating that the transfer of the substrate from aqueous medium to the apolar cyclodextrin cavity is an important driving force for complex formation [3], 

Inclusion complexes are also formed in dimethylformamide and dimethyl sulfoxide, although they are less stable than those formed in aqueous solution [4], However, no inclusion complexes are formed in other organic solvents such as alcohol, ether, dioxane or pyridine. 

Capping of one side of the torus with an apolar moiety enhances the binding ability of a cyclodextrin. This effect is attributable to the increase in the apolar nature of the cavity due to the capping by the apolar groups. For example, capped )8-cyclodextrin (la) binds sodium l-anilino-8-naphthalenesulfonate 24 times better than parent -cyclodextrin [5]. The binding ability of another capped j8-cyclodextrin (lb) changes on photoirradiation, since the conformation of /8-cyclodextrin is varied due to the cis-trans photoisomerization of the azobenzene moiety [6]. 

One of the most important pieces of progress in recent years is the establishment of a method for the determination of the conformation of the inclusion complex in solution. The method, which takes advantage of the change of the H-chemical shifts of cyclodextrin on complex formation with the aromatic guest compound (mostly due to the anisotropic shielding effect of the aromatic ring of the guest), is briefly described as follows [7-9]. 

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Yamada, T., Komiya, T., and Akaki, M., Formation of an inclusion complex of anthocyanin with cyclodextrin, A,gric. Biol. Chem., 44, 1411, 1980. 

Research on the second strategy has been reported for several types of PRX materials. Most studies concern pPRXs formation between a-CD and polyesters (Table 1) [278-290]. A pPRX of a-CD/PLLA was firstly demonstrated by Tonelli and coworkers [282], Subsequently, we reported the pPRX formation of a-CDs and PLLA-b-PEG-b-PLLA triblock copolymer [288]. In this report, the formation of an inclusion complex and the stoichiometry of the amphiphilic biodegradable triblock... 

In a study of the formation of an inclusion complex between beta cyclodextrin and indole, the stability constant in aqueous solution was found, on the addition of formamide, to decrease, accompanied by a... 

Cyclophanes consist of a class of artificial hosts featured with well-defined hydrophobic cavities constructed by aromatic rings incorporated in their macrocy-clic structures, and also with high design versatility because they are totally synthetic.The first direct evidence of the formation of an inclusion complex with an organic guest was obtained for tetraazacyclophane 62, the cavity of which is constructed with diphenylmethane units bridged by tetramethylene chains. 

One of the simplest forms of guest encapsulation is the formation of an inclusion complex with a host containing a well-defined, preformed cavity. In this regard, the... 

Mechanism of Separation. There are several requirements for chiral recognition. (/) Formation of an inclusion complex between the solute and the cydodextrin cavity is needed (4,10). This has been demonstrated by performing a normal-phase separation, eg, using hexane—isopropanol mobile phase, on a J3-CD column. The enantiomeric solute is then restricted to the outside surface of the cydodextrin cavity because the hydrophobic solvent occupies the interior of the cydodextrin. (2) The inclusion complex formed should provide a rdatively "tight fit" between the hydrophobic species and the cydodextrin cavity. This is evident by the fact that J3-CD exhibits better enantioselectivity for molecules the size of biphenyl or naphthalene than it does for smaller molecules. Smaller compounds are not as rigidly held and appear to be able to move in such a manner that they experience the same average environment. (5) The chiral center, or a substituent attached to the chiral center, must be near to and interact with the mouth of the cydodextrin cavity. When these three requirements are fulfilled the possibility of chiral recognition is favorable. 

Electrostatic self-assembly was combined with supramolecular chemistry to obtain inclusion complexes of a polymeric nonlinear optical (NLO) active dye and modified [3-cyclodextrin with induced chromophore orientation [37], The polyanion is a N,N-diallyl-aniline and sodium-2-acrylamido-2-methylpropanesulfonate copolymer functionalized with pendant azo group. The modified /i-cyclodextrin oligo-cation was obtained by treatment of hcptakis(6-dco y-6-iodo-/i-cyclodcxtrin) with excess pyridine. A linear polyamine, chitosan, was also combined with the polyanion, for comparison. Films were deposited on glass slides by dipping them alternatively in aqueous solutions of the cation and the polyanion. UV-visible spectra indicate dye aggregation and suggest the formation of an inclusion complex of the dye with the cyclodextrin, thus isolating the chromophores. 

The size of the cavity plays a crucial role on the selectivity of the reaction. For example, when the esterification was performed with p-sulfonatocalix [4]arenes, the kcaiixarene/k HBS value for histidine was indeed increased from 24 to 86. 2H NMR studies supported the formation of an inclusion complex of caiixarenes with basic amino acids, and the reaction followed Michaelis-Menten kinetics. The specific rate enhancement observed for basic amino acids His 33, Lys 34 and Arg 35 is the result of a stabilization by the anionic sulfonate groups of the cationic intermediate, which can undergo esterification (see Scheme 13.8). In contrast, the formation of Phe 36, might proceed via simple acid catalysis. 

The bis(dioxolanyl)oxazolidinone 33 has been prepared from D-mannitol and evaluated as a chiral auxiliary <02MT749> and the diamine 34 has been examined as a ligand for rhodium catalysed asymmetric hydrogenation of diethyl itaconate <02JOU104>. Deracemisation of 2-benzylcyclohexanone by formation of an inclusion complex with the TADDOL compound 35 has been described and the mechanism clarified by X-ray structure determination of the complex <02T3401>. A production process for the bis(phosphine oxide) 36 has been patented <02USP6472539>. 

In a mixture containing a 2 1 molar ratio of 1 and II the NDI proton signal of 1 and all the protons of II are shifted upheld by 0.09 and 0.08 ppm, respectively, while in a similar mixture containing 1-ester and II the same protons are shifted upheld by only 0.04 ppm (Fig. 37). This behaviour is consistent with the formation of an inclusion complex between 1 and II, where the pyrene molecules are shielded by the naphthalene aromatic cores of the NDIs, which in turn are shielded by the pyrenes complexed inside the nanotube. Spectrum d in Fig. 37 shows that, although there is some... 

In a test tube, dissolve 4-mcthyl(/V-bcnzyl )azacalix[3]arene (34, 36 mg, 0.05 mmol) in toluene (5 mL) to give a colourless solution. In a second test tube, dissolve C60 (7 mg, 0.01 mmol) in toluene (5 mL), heating if necessary, to give a characteristic purple solution. Add the solution of the macrocycle to the Cgo solution and heat briefly. The purple solution will slowly turn pale brown if left standing at room temperature for several days indicating the formation of an inclusion complex of Cgo-... 

Enantiomeric resolution of solutes that fit within the molecular cavity, which is chiral, results in the formation of an inclusion complex (Ref. 169 and Fig. 4). In general, the enantiomers are separated on the basis of formation constants of the host-guest complexes. The enantiomer that forms the more stable complex has a greater migration time because of this effect. The chiral recognition mechanism for cyclodextrin enantioseparation has been discussed in several works (163-168). 

A photostabilizing effect by complex formation with cyclodextrins has been reported for a number of biologically active compounds (Zejtli et al., 1980 Uekama et al., 1983 Ammar and El-Nahhas, 1995 Chen et al., 1996 Lin et al., 2000 Bayomi et al., 2002, Tpnnesen et al., 2002). However, formation of an inclusion complex does not necessarily lead to a stabilization of the guest molecule. This is clearly... 

Figure 121. Interaction of free drug molecules (Df) with the cavity of cyclodextrins. The formation of an inclusion complex can lead to either stabilization of the drug or catalysis of its breakdown.

The self-diffusion coefficients reflect the molecular mobility in solution and are sensitive to temperature, solvent viscosity, and molecular mass. Similarly to other spectral parameters, the apparent self-diffusion coefficient is the weighted average for all species remaining in the equilibrium. Thus, when a small guest molecule interacts with a bigger host molecule its apparent diffusion coefficient decreases, allowing us to detect the formation of an inclusion complex. Moreover, the dependence of the self-diffusion coefficient of guest on the host molar fraction allows us to determine the association constant similarly to the chemical shift titration. 

In normal phases HPLC (polar columns), the least polar component of the mobile phase have priority to be encapsulated in the CD cavity and cannot be easily replaced by another compound. The chiral separation is the result of the structure of the analyte and the competitive reactions between the stationary CDs and the components of the mobile phase. A mobile phase of water-organic hquid mixture is used in RP HPLC and the selectivity is the result of the formation of an inclusion complex of CDs with the hydrophobic part of the analyte. Sometimes, especially in some HPLC with polar organic phases, instead of the inclusion complexation, chiral separations are mainly dependent on the analyte interaction with secondary hydroxyl groups on the outer rim of the CD [31]. 

CDs could effectively change UV/VIS spectral properties of guest by complexing the guest. Usually, the intensity and position of the absorption bands in the spectrum are varied after the formation of an inclusion complex. Due to the hydrophobic... 

NMR spectroscopy prove the formation of an inclusion complex. When the guest molecule is enclosed in the CD cavity, the resonance signals of protons located inside the cavity (3H and 5H) are shifted in the spectrum. The signals of protons located on the outer side of the cavity (2H, 4H, 6H) remain relatively unaffected. 

The chemical equation for the reaction of formation of an inclusion complex between the gable conformation of DPM and a symmetrical guest G, is... 

These. supramolecular catalysts showed high substrate selectivity in competition hydrogenation experiments and exceptional activity in the hydroformylation reactions. In contrast to the simple methylated P-cyclodextrin previously mentioned, even internal and cyclic olefins were converted into aldehydes. Such improvements were explained with the formation of an inclusion complex at the phase boundary, with the cylodextrin host fixing the substrate in the proximity of the catalytically active metal center (Fig. 

A method based on the formation of an inclusion complex between aflatoxins and cyclodextrins (CDs) has been recently developed [72], and specific CDs are added to mobile phase (water-methanol), including aflatoxins in their cyclic structure, enhancing AFBl and AFGl fluorescence [73],... 

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