Inclusion complexes, formation

4- tert-Butyl benzoate Ibuprofen anion 1-Adamantane carboxylate 

CA(S)[= l and CA(L)W Simple precipitation l-Octanol 1-Butanol Oleic acid 16, 64 

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Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

The theory and development of a solvent-extraction scheme for polynuclear aromatic hydrocarbons (PAHs) is described. The use of y-cyclodextrin (CDx) as an aqueous phase modifier makes this scheme unique since it allows for the extraction of PAHs from ether to the aqueous phase. Generally, the extraction of PAHS into water is not feasible due to the low solubility of these compounds in aqueous media. Water-soluble cyclodextrins, which act as hosts in the formation of inclusion complexes, promote this type of extraction by partitioning PAHs into the aqueous phase through the formation of complexes. The stereoselective nature of CDx inclusion-complex formation enhances the separation of different sized PAH molecules present in a mixture. For example, perylene is extracted into the aqueous phase from an organic phase anthracene-perylene mixture in the presence of CDx modifier. Extraction results for a variety of PAHs are presented, and the potential of this method for separation of more complex mixtures is discussed. 

Table 6. Host-guest inclusion complex formation by solid-solid reaction...

The conclusions of the preceding discussion can be briefly summarized as follows. The formation of inclusion complexes in both the crystalline state as well as in solution has been convincingly demonstrated by spectral and kinetic techniques. Whereas the crystalline complexes are seldom stoichiometric, the solution complexes are usually formed in a 1 1 ratio. Although the geometries within the inclusion complexes cannot be accurately defined, it is reasonable to assume that an organic substrate is included in such a way to allow maximum contact of the hydrophobic portion of the substrate with the apolar cycloamylose cavity. The hydrophilic portion of the substrate, on the other hand, probably remains near the surface of the complex to allow maximum contact with the solvent and the cycloamylose hydroxyl groups. The implications of inclusion complex formation for specificity and catalysis will be elucidated in subsequent sections of this article. 

The inability of y-CD to complex with POx under the same conditions as for / -CD indicates the failure of POx to meet the prerequisite for inclusion complex formation that the polymer chain fits well into the CD cavity and is hydrophobic enough to stabilize the complex. 

Inclusion complex formation with fluorescent NBD-guests corroborated internal hydrophobicity of /3-barrel hosts and potential for intratoroidal catalysis <2002CH18>. 

Buvari-Barcza A, Rohonczy J, Rozlosnik N et al. (2001) Aqueous solubilization of [60]fullerene via inclusion complex formation and the hydration of C60. J Chem Soc Perkin Trans. 2 191-196. 

The participation of van der Waals forces in inclusion-complex formation is also found to be consistent with crystal structure analyses. Interatomic distances between the guest and the cyclodextrin thus determined are characteristic of van der Waals interactions. Hydrogen bonding between the guest and the hydroxyl groups of the cyclodextrin has also... 

Thus, it seems that both the hydrophobic interactions and the van der Waals interactions undoubtedly play a part in inclusion-complex formation, although the relative contribution of each type of interaction may vary with the chemical properties of the guest this would account for the ability of the cyclodextrins to form complexes with a wide variety of guest molecules. The existence of a close spatial fit between the guest and the cyclodextrin cavity is, however, a necessary requirement for the formation of a stable inclusion-complex. 

Until 1984, all of the stopped-flow and temperature-jump kinetic studies of alpha cyclodextrin inclusion-complex formation were explainable in terms of a single-step, binding mechanism. According to this mechanism, the observed rate constant, kobs, (for stopped-flow) and the reciprocal relaxation time, 1/t, (for temperature-jump) should show a linear dependence on the edpha cyclodextrin concentration. Sano and coworkers, however, in the case of the iodide-alpha cyclodextrin interaction, and Hersey and Robinson,in the case of various azo dye-alpha cyclodextrin interactions (see Fig. 7), found that certain guest species exhibit a limiting value of kobs and 1/t at high concentrations of alpha cyclodextrin. This behavior can most simply be explained in terms of a mechanism of the type,... 

KL Larsen, T Endo, H Ueda, W Zimmermann. Inclusion complex formation... 

Lelievre and Gareil (31) studied chiral separations of nonsteroidal anti-inflammatory drugs (carprofen, flurbiprofen, indoprofen, ketoprofen, naproxen, propafenone, and suprofen) and determined the acidity and inclusion complex formation constants of these chiral compounds with different neutral CDs (/3-CD, HP-/3-CD, DM-/3-CD, TM-/3-CD, and HP-y-CD). In... 

X-ray crystallography has a long history as a powerful technique for investigating the structure of CDs and their complexes in the solid state. The first experimental evidence of the inclusion complex formation ability of CDs in the solid state was obtained by Hyble et al. in 1965 using this technique (74). X-ray studies of CD complexes have been summarized in several recent reviews (75,76). However, few studies relevant to chiral CE have been published (69,70). This may be for the following reasons (1) X-ray crys-... 

Free-Energy Change in Inclusion Complex Formation"... 

Spherands, hemispherands, and other similar macrocycles capable of inclusion complex formation [33]... 

The n values used here are derived from di-n-butylether/water partition coefficients since the ether phase was thought to better simulate the environment of the cavity of cyclodextrins. Eq 38 indicates that the principal driving force for the inclusion complex formation with P-cyclodextrin is the dehydration from surroundings of the guest molecule. 

In Eq. 39, substituents, the dimension of which is larger than 5.1 A in terms of the sum of the opposite-pair Bj values, are not included, since their log (1/Kd) values are much lower than those expected from the correlation for others. They are supposed not to be accomodated into the cavity of the a-cyclodextrin, the diameter of which is 4.5-5 A. Thus, the inclusion complex formation with a-cyclodextrin is more limited than that with P-cyclodextrin and the extent of dehydration is less significant. The term B in Eq. 39 implies that the larger the minimum width of substituents the maximum diameter of which is less than 5.1 A, the more uniform would be the van der Waals interaction with the cavity wall resulting in the more stable inclusion complex. 

In an aqueous medium these wtermolecular attractive interactions make a strong contribution to biopolymer self-association and inclusion complex formation, as well as to the flocculation of biopolymer-coated colloidal particles. // //Y/molecular hydrophobic interactions commonly influence the level of folding/unfolding of macromolecules as well as their detailed conformations. 

Host-Guest Inclusion Complex Formation between Surfactant Stilbenes and Amylose... 

The stabilization of a substratS)(as the result of inclusion complex formation occurs noncova-lently and may be the result of either a microsolvent effect ora conformational effect (Szejtli, 1982). The kinetic method utilizes this reduction in rate of the reactioiScrfhen ligand is present to obtain information about the nature of the complex. The basic assumption is that the decreased reactivity is the sole result of complexation, the compleSdsfeing less reactive than frtafeThe kinetic scheme can be represented as Scheme 8.1 ... 

The chiral resolution using cyclodextrins as mobile phase additives is also controlled by a number of chromatographic parameters as in case of CSPs. The chiral resolution occurred by the formation of diastereoisomeric inclusion complex formation and, hence, the composition of the mobile phase, pH, concentration of cyclodextrins, and temperature are the most important controlling parameters. 

Miyazaki, I., et al. 1995. Physicochemical properties and inclusion complex formation of 8-cyclodextrin. Eur J Pharm Sci 3 153. 

Surfactants were found to induce phosphorescence from 1-bromonaphthalene in aerated aqueous solutions of (3-CD [22], In the case of the 1 1 inclusion-complex formation between 7-cyclodextrin and acenaphthene in aqueous solution, bromoalcohols such as 2,3-dibromopropane-l-ol or 2-bromoethanol induced a decrease of the fluorescence and an enhancement of room-temperature phosphorescence of acenaphthene [23],... 

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