Inclusion-compound formation

Hersey, A., Robinson, B. H., and Kelly, H. C. 1986. Mechanisms of inclusion-compound formation for binding of organic dyes, ions and surfactantsitoyclodextrin studied by kinetic methods based on competition experimentsJ. Chem. Soc. Faraday Trar 1271-1287. 

First, CD complexation is selective, moreover highly stereoselective. CD inclusion processes are influenced mainly by hydrophobicity and shape of guest (G) molecule i.e. by the fit of the entire or at least part of complexed molecule to the CD (host) cavity.Thus ste-ric factors are of crucial importance for CD inclusion compounds formation and their stability. For that reason CD inclusion can be considered as a procedure... 

Inclusion-compound Formation Separation of constituents of a mixture is achieved by removing that component which happens to consist of molecules of the requisite size and shape. Molecules of this component alone get accomodated as guest species within the molecular structure of a host species while the latter is crystallising out from a solution of itself and the mixture. 

Fig. 7 Schematic diagram of the cyclodextrin-containing delivery system, (a) Components of the delivery system. The CDP condenses siRNA and protects it from degradation. The AD-PEG stabilizes the complexes in systemic circulation via inclusion compound formation. The AD-PEG-transferrin (Tf-PEG-AD) conjugate confers a targeting ligand to the complex, (b) Assembly of the targeted delivery systems. CDP, AD-PEG, and Tf-PEG-AD are combined and added to siRNA to generate stable complex. (Adopted from Cancer Research 2005 65 8984-8992)...

Although the isolation and purification of materials are very important processes in laboratory and industry, these are not easy to carry out and sometimes almost impossible. If the method of inclusion compound formation can be used, the process then becomes very simple and cheap. Furthermore, this method is easily applicable to the separation of isomers having very close boiling points, since molecular recognition of host and guest is mostly due to a size and shape relationship. 

Many studies of urea inclusion compounds have focused on practical applications, such as inclusion polymerization. stabilization of liquids or unstable solids in an isolated form, and molecular separation and chromatography. Chemists studying fatty acids, for example, routinely use urea inclusion compounds to carry out molecular separations. Among industrial examples, urea inclusion compound formation has been used by the petroleum industry in the dewaxing of certain oil fractions, although zeolites are now routinely used in such applications. Other applications include stabilization of diacyl peroxides and peroxy acids in laundry products, and the use of urea inclusion compounds as solid supports in gas-liquid chromatography. 

Interest in cyclomalto-oligosaccharides (Schardinger dextrins, cyclodextrins) as hosts and as potential catalysts has continued unabated. A book on the subject has appeared and there have been several reviews on inclusion compound formation with cyclomalto-oligosaccharides improving pharmaceutical formulations/ affecting the action of pesticides/ and being used in industry. ... 

Fig. 1. The principle of formation of an inclusion compound, (a) concave host (b) convex guest component (c) host—guest compound.

Examples of the hydroquinone inclusion compounds (91,93) are those formed with HCl, H2S, SO2, CH OH, HCOOH, CH CN (but not with C2H 0H, CH COOH or any other nitrile), benzene, thiophene, CH, noble gases, and other substances that can fit and remain inside the 0.4 nm cavities of the host crystals. That is, clathration of hydroquinone is essentially physical in nature, not chemical. A less than stoichiometric ratio of the guest may result, indicating that not all void spaces are occupied during formation of the framework. Hydroquinone clathrates are very stable at atmospheric pressure and room temperature. Thermodynamic studies suggest them to be entropic in nature (88). 

The formation of such materials may be monitored by several techniques. One of the most useful methods is and C-nmr spectroscopy where stable complexes in solution may give rise to characteristic shifts of signals relative to the uncomplexed species (43). Solution nmr spectroscopy has also been used to detect the presence of soHd inclusion compound (after dissolution) and to determine composition (host guest ratio) of the material. Infrared spectroscopy (126) and combustion analysis are further methods to study inclusion formation. For general screening purposes of soHd inclusion stmctures, the x-ray powder diffraction method is suitable (123). However, if detailed stmctures are requited, the single crystal x-ray diffraction method (127) has to be used. 

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. 

Molecular Design of Hosts for the Formation of Inclusion Compounds with Apolar Guests... 

Formation of Inclusion Compounds, Host-Guest Stoichiometries 56... 

Selectivity at formation of a respective inclusion compound and its thermal stability behavior might differ (cf. Tables 1 and 2), since for both representations different processes should be taken into consideration. Formation of a crystal inclusion compound is normally controlled by kinetics, whereas the thermal stability (decomposition property) is a result of thermodynamics. Thus, we speak of formation selectivity , on the one hand, and of binding selectivity , on the other. 

In case of the bianthrylmonocarboxylic acid 20, one may predict the formation of a lattice inclusion at least with dimethylformamide, but we did not succeed in obtaining it37. Instead a stable 1 1 stoichiometric inclusion compound of 20 is readily obtainable (Table 3). The bianthryldicarboxylic acid 21, which is a direct analogue of 1, is not available in sufficient quantity to be tested in respect to its lattice inclusion properties. 

Table 3). The crystal inclusion compounds of the protic solvents are distinguished by relatively high points of thermal decomposition and, as before, the inclusion compound with dimethylformamide exhibits the highest tendency of formation. This is the result of competitive experiments. 

According to the coordinatoclathrate predict, the Spiro compound 23 will not allow the formation of inclusion compounds with dimethylformamide and other polar solvents, but with benzene, tetrahydrofuran, and 1-bromopentane (Table 3). Due to the limited number of guest inclusions, a lattice cavity of rather restricted dimensions is suggested for 23 e.g. toluene, cyclohexane or dioxane are not suitable guest partners for 23, whereas lower homologues (cf. benzene, tetrahydrofuran) are readily included 37). The behavior of a reduced analogue of 23, the hydroxymethyl — substituted spiro compound 24, is in some way comparable since an inclusion compound with benzene is the only one known interestingly it is formed exclusively with optically resolved but not with racemic 24 49). 

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