Solute-cyclodextrin molecules

Cyclodextrin stationary phases utilize cyclodextrins bound to a soHd support in such a way that the cyclodextrin is free to interact with solutes in solution. These bonded phases consist of cyclodextrin molecules linked to siUca gel by specific nonhydrolytic silane linkages (5,6). This stable cyclodextrin bonded phase is sold commercially under the trade name Cyclobond (Advanced Separation Technologies, Whippany, New Jersey). The vast majority of all reported hplc separations on CD-bonded phases utilize this media which was also the first chiral stationary phase (csp) developed for use in the reversed-phase mode. 

Yamamoto and coworkers used two-dimensional, nuclear Over-hauser effect experiments (NOESY) to determine the proximity of particular protons situated on an included p-nitrophenolate ion to particular protons of a host alpha cyclodextrin molecule. The experiments showed cross-peaks connecting the H-3 resonance of alpha cyclodextrin to both meta and ortho proton resonances of the p-nitrophenolate ion, whereas H-5 of the alpha cyclodextrin gave a cross-peak only with the resonance of the meta proton thereof. As a consequence, it was unequivocally confirmed that the p-nitrophenolate ion is, in solution, preferentially included with its nitro group oriented to the narrow end of the alpha cyclodextrin... 

The terms in the denominator of the right side of Equation 1 include 0, the phase ratio A, stationary phase adsorption site and K, the association constant of a solute to the stationary phase binding site. The binding constant, K., can be evaluated graphically (by plotting 1/k versus [CD]) or by linear least squares. When complex equilibria are involved, Equation 1 deviates from linearity. In cases where two cyclodextrin molecules bind to a simple solute the correct pseudophase retention equation is (jl) ... 

A (CD )2-] using+ equations 7-15, cancelling [HA], letting X = 0[S](KTK K 1 /[H ] ) and rearranging gives an equation which describes the LC retention behavior of monoprotic solutes which complex two cyclodextrin molecules. 

To achieve chiral separations on CD CSPs, a part or all of the solute molecules must enter the cyclodextrin cavity. In most cases, the solutes that are successfully resolved contain an aromatic moiety at or adjacent to the stereogenic center, and it is the aromatic portion of the molecule that inserts itself into the chiral cavity of the cyclodextrin molecule to form the inclusion complex (66,67). The size of the aromatic moiety and cyclodextrin cavity determine which CD CSP will form the best inclusion complex, and single aromatic rings fit best in the ot-CD, naphthylrings in the p-CD and aromatic system larger than naphthyl in the -y-CD (68), In addition to the... 

Solid solubilizers such as the (3-cyclodextrins act by forming soluble inclusion complexes in aqueous solution. These molecules, as with surface active agents, are amphiphilic, meaning that they contain hydrophobic... 

The degree to which a solute molecule will be solubilized by a cyclodextrin molecule will depend on several properties. First the solute molecule must have a... 

When an aqueous solution of a-cyclodextrin is placed in contact with an ethereal iodine solution, reddish-brown crystals are formed at the surface having the composition (C6H,o05)6 l2-4H20. X-ray diffraction analysis indicates that the iodine molecule is colinear with the axis of the cyclodextrin. The closest contacts in the perpendicular direction to this axis take place between one of the iodine atoms and the C-5 and C-6 atoms, and the other iodine atom and the 0-4 oxygen atom. The environment is thus hydrophobic for the first, and hydrophilic for the second. The stacking on top of each other of the molecules in the crystal is such that the two apertures of the cavities of each cyclodextrin molecule are clogged by neighbouring molecules. This creates a cage-type structure (McMullan et al. 1973). 

Whereas the separation of racemates in the case of urea and TOT was achieved only by a chiral crystal lattice of the achiral or racemic host, respectively, the optically active cyclodextrins, available from the chiral pool, are able to differentiate a chiral guest within their intramolecular cavity. Therefore, they do not necessarily need the crystal lattice to form inclusion compounds. The guest is encapsulated, while is is in solution, too, if the guest by size and shape fits into the cavity of the specific cyclodextrin molecule (a- (26), P- (27), or y-cyclodextrins). 

The approach using cyclodextrin as a binding site has also been developed. Cyclodextrins are widely utilized in biomimetic chemistry as simple models for an enzyme because they have the ability to form inclusion complexes with a variety of molecules and because they have catalytic activity toward some reactions. Kojima et al. (1980, 1981) reported the acceleration in the reduction of ninhydrin and some dyes by a 1,4-dihydronicotinamide attached to 3 Cyclodextrin. Saturation kinetics similar to enzymatic reactions were observed here, which indicates that the reduction proceeds through a complex. Since the cavity of the cyclodextrin molecule has a chiral environment due to the asymmetry of D-glucose units, these chiralities are expected to be effective for the induction of asymmetry into the substrate. Asymmetric reduction with NAD(P)H models of this type, however, has not been reported. Asymmetric reduction by a 1,4-dihydronicotinamide derivative took place in an aqueous solution of cyclodextrin (Baba et al. 1978), although the optical yield from the reduction was quite low. Trifluoromethyl aryl ketones were reduced by PNAH in 1.1 to 5.8 % e.e. in the presence of 3-cyclodextrin. Sodium borohydride works as well (Table 18). In addition to cyclodextrin, Baba et al. also found that the asymmetric reductions can be accomplished in the presence of bovine serum albumin (BSA) which is a carrier protein in plasma. 

The inclusion complexes of cyclodextrins have been studied since about 30 years using chemical, spectroscopic, kinetic, potentiometric methods. The obtained data have led to the conclusion that the adduct formation of the cyclodextrin molecules in solution is due to their annular structure and that they provide space for the substrate molecules in their annular cavity. The only obvious requirement for inclusion is that the dimensions of the guest molecules must be small enough to fit into the cyclodextrin cavity. 

Room-temperature phosphorescence in solution has been observed in organized media containing micelles. With micelles, the analyte is incorporated into the core of the micelle, which serves to protect the triplet state. Cyclodextrin molecules, which are... 

Drug-CD-polymer complexation can be enhanced by brief heating of complexation media containing drug, CD and water-soluble polymer in an autoclave and cooling to room temperature. Such an effect is observed due to alteration in the hydration of the cyclodextrin molecule, and thus its three-dimensional structme, in aqueous solution [36]. 

For compounds which are quite similar (e.g. enantiomers), inclusion complexes formed with cyclodextrin (CD) molecules can lead to selective separation. Cyclodextrin molecules are uncharged and are therefore moved by the electroosmotic flow at a velocity (i eof.z)- Any racemic mixture which exists as ions in the solution may be... 

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