Inclusion complexes, modified

Cyclodextrins are cyclic oligosaccharides forming inclusion complexes with a wide variety of organic and inorganic compounds. The formation of inclusion complexes modifies the physicochemical parameters of the guest molecule, resulting in modified retention behavior. The aims of this entry are to provide a short overview of the chemistry and physicochemistry of cyclodextrins and of their applicatiou for improving separatioD, with special emphasis on the separation of enantiomer pairs of pharmaceuticals and euvirou-meutal pollutauts. 

Immobilization. The abiUty of cyclodextrins to form inclusion complexes selectively with a wide variety of guest molecules or ions is well known (1,2) (see INCLUSION COMPOUNDS). Cyclodextrins immobilized on appropriate supports are used in high performance Hquid chromatography (hplc) to separate optical isomers. Immobilization of cyclodextrin on a soHd support offers several advantages over use as a mobile-phase modifier. For example, as a mobile-phase additive, P-cyclodextrin has a relatively low solubiUty. The cost of y- or a-cyclodextrin is high. Furthermore, when employed in thin-layer chromatography (tic) and hplc, cyclodextrin mobile phases usually produce relatively poor efficiencies. 

The milder metal hydnde reagents are also used in stereoselective reductions Inclusion complexes of amine-borane reagent with cyclodexnins reduce ketones to opucally active alcohols, sometimes in modest enantiomeric excess [59] (equation 48). Diisobutylaluminum hydride modified by zmc bromide-MMA. A -tetra-methylethylenediamme (TMEDA) reduces a,a-difluoro-[i-hydroxy ketones to give predominantly erythro-2,2-difluoro-l,3-diols [60] (equation 49). The three isomers are formed on reduction with aluminum isopropoxide... 

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. 

These interesting results are attributed to the formation of an alkene/ cyclodextrin inclusion complex as well as the solubility of the chemically modified cyclodextrin in both phases. Prior to this study, hydroformylation in the presence of unmodified cyclodextrins had been studied by Jackson, but the results were rather disappointing.174... 

In contrast to the reactions of the cycloamyloses with esters of carboxylic acids and organophosphorus compounds, the rate of an organic reaction may, in some cases, be modified simply by inclusion of the reactant within the cycloamylose cavity. Noncovalent catalysis may be attributed to either (1) a microsolvent effect derived from the relatively apolar properties of the microscopic cycloamylose cavity or (2) a conformational effect derived from the geometrical requirements of the inclusion process. Kinetically, noncovalent catalysis may be characterized in the same way as covalent catalysis that is, /c2 once again represents the rate of all productive processes that occur within the inclusion complex, and Kd represents the equilibrium constant for dissociation of the complex. 

Monflier and co-workers recently described a new approach based on the use of chemically modified /3-cyclodextrins to peform efficiently the functionalization of water-insoluble olefins in a two-phase system. These compounds behave as inverse phase transfer catalysis, i.e., they transfer olefins into the aqueous phase via the formation of inclusion complexes.322... 

There are several cases that have addressed molecular recognition of chiral drugs by modified CDs127 as well as inclusion complexes of cationic, anionic and neutral organic compounds128 in order to understand the role of hydrophobic and electrostatic interactions between the functional groups on host and guest. 

Decene was hydrocarboxylated with a [PdClaj/TPPTS catalyst in acidic aqueous solutions (pH adjusted to 1.8) in the presence of various chemically modified cyclodextrins (Scheme 10.11) [18]. As in most cases, the best results were obtained with DiOMe-P-CD. In an interesting series of reactions 1-decene was hydrocarboxylated in 50 50 mixtures with other compounds. Although all additives decreased somewhat the rate of 1-decene hydroformylation, the order of this inhibitory effect was 1,3,5-trimethylbenzene < cumene < undecanoic acid, which corresponds to the order of the increasing stability of the inclusion complexes of additives with p-CD, at least for 1,3,5-trimethylbenzene (60 M ) and cumene (1200 M ). These results clearly show the possible effect of competition of the various components in the reaction mixture for the cyclodextrin. 

The reactivity of molecules bound to surfaces, located at various kinds of interfaces, solubilized in microheterogeneous media, or incorporated as "guests" in various "hosts" as inclusion complexes has been the subject of much recent study. Indeed the structure of the medium, the nature of "solubilization sites" and reactivity in these environments have all been the focus of independent or interrelated investigations (1-12). Photochemistry has played a major role in these studies both in terms of studies of the media and also in terms of modified or controlled reactivity (1,5,8,9). In the course of these investigations numerous questions have arisen many of these have developed from differing pictures of solute-environment interactions which are furnished by different studies using different molecules as "probes" (5,10-12). Controversies arising... 

The formation of CD inclusion complexes is favored in aqueous media, and hence most of the early chiral resolutions were carried out in the reversed-phase mode. However with the development of various derivatives of CDs, normal and polar organic mobile phases could also be used. The selectivities of these modes increase in the following order normal > polar organic > reversed phase. This is due to certain advantages associated with the normal and polar organic phase modes. Now that all three mobile phase modes can be used, optimization on these phases can be achieved by varying a number of parameters such as composition of the mobile phase, use of organic modifiers, mobile phase pH, flow rate, and temperature. The details of the optimization of the chiral resolution on these CSPs are presented next. 

Valeur et al. have modified every glucosyl subunit of the primary rim of P-CD with naphthoate donor groups [374], At pH > 8, the emission spectrum of 36 is composed of naphthoate monomer and excimer fluorescence, the ratio of which readily allows surfactant concentrations to be ascertained. Ionic strength and competition binding experiments strongly point toward a micelle complex rather than a 1 1 inclusion complex. Aggregates between 36 and cationic sur-... 

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. 

Inclusion properties of molecular nanotubes composed of crosslinked a-cyclodextrin was investigated [47], Induced circular dichroism was used to probe the formation and dissociation of complexes between the nanotubes and azobenzene modified polyethylene glycol), either with or without a hydrophobic alkyl chain. The inclusion complex between the nanotubes and polymers formed at room temperature, and the polymers dissociated from the nanotubes with increasing temperature. 

The inclusion complexation of spiropyrans in cyclodextrins has also been explored as a means to control photochromic reactions.1591 Distinct differences in complexation of sulfonic acid-modified spiropyrans to various cyclodextrins were observed and the closed spiropyran form bound to (3-cyclodextrin was stable towards photochemical ring-opening. 

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