Cyclodextrin parent

The condensation reactions described above are unique in yet another sense. The conversion of an amine, a basic residue, to a neutral imide occurs with the simultaneous creation of a carboxylic acid nearby. In one synthetic event, an amine acts as the template and is converted into a structure that is the complement of an amine in size, shape and functionality. In this manner the triacid 15 shows high selectivity toward the parent triamine in binding experiments. Complementarity in binding is self-evident. Cyclodextrins for example, provide a hydrophobic inner surface complementary to structures such as benzenes, adamantanes and ferrocenes having appropriate shapes and sizes 12) (cf. 1). Complementary functionality has been harder to arrange in macrocycles the lone pairs of the oxygens of crown ethers and the 7t-surfaces of the cyclo-phanes are relatively inert13). Catalytically useful functionality such as carboxylic acids and their derivatives are available for the first time within these new molecular clefts. 

In contrast, the fluorescence spectra of the parent y-cyclodextrins (compounds y-CD1, y-CD2, y-CD3, y-CD4) exhibit both monomer and excimer bands in the absence of guests because the cavity is large enough to accommodate both fluorophores (Figure 10.38). The ratio of excimer and monomer bands changes upon guest inclusion. The ratio of the intensities of the monomer and excimer bands was used for detecting various cyclic alcohols and steroids (cyclohexanol, cyclo-dodecanol, i-borneol, 1-adamantanecarboxylic acid, cholic acid, deoxycholic acid and parent molecules, etc.). 

This interesting result strongly suggests that even for the substituted cyclodextrins the capacity of inclusion formation is much the same as for the parent cyclodextrin. Therefore, we may extend the basic concept of the structure of cyclodextrin inclusion to molecular design for the preparation of artificial enzymes having satisfactory substrate specificities and catalytic activities. 

In contrast to cyclodextrins, there is no parent cyclophane structure available in nature. Therefore, the design of the host molecule starts from the... 

Ono, N., et al. 2001. A moderate interaction of maltosyl-a-cyclodextrin with Caco-2 cells in comparison with the parent cyclodextrin. Biol Pharm Bull 24 395. 

Several prominent types of host molecule, such as the steroidal bile acids and the cyclodextrins, are chiral natural products that are available as pure enantiomers. Chemical modification of these parent compounds provides an easy route to the preparation of large numbers of further homochiral substances. Since all these materials are present as one pure enantiomer, it automatically follows that their crystalline inclusion compounds must have chiral lattice structures. It is not currently possible to investigate racemic versions of these compounds, but the examples discussed previously in this chapter indicate that very different behaviour could result. 

The solubility of a complex is generally greater than the solubility of the complexed compound, but less than the solubility of the cyclodextrin. If insufficient solubility has been achieved using unmodified cyclodextrins, greater solubility may be achieved with derivatives of cyclodextrins. Soluble derivatives, such as hydroxy-propyl-(3-cyclodextrin, can increase the solubility of insoluble drugs sufficiently to allow them to be administered parentally. Flunarizine, used to treat stroke victims, is very insoluble and, after oral administration, reaches therapeutic concentrations very slowly. When injected as a complex with hydroxypropyl-(3-cyclodextrin, a therapeutic concentration is achieved in the brain in minutes.78... 

It was found that B-cyclodextrin will form 1 1 complexes with the entire series of anti-inflammatory fanamates, with the exception of the parent compound anthranilic acid [56], Inclusion complexes could not be formed with a-cyclodextrin, indicating that the cavity of this host was too small to permit complexation. Formation of the inclusion complexes... 

The so-called parent cyclodextrins viz the alpha, beta, and other forms (Fig. 6) have properties that may have prevented widespread use as formulation adjuvants. The moderate solubility and the perceived need to form molar complexes meant that their use would be limited to low-dose, highly potent compounds. Furthermore, (3-cyclodextrin in particular could not be used parenterally because of renal nephrotoxicity. This was ascribed to its low solubility possibly associated with the propensity to form a molecular complex with cholesterol in vivo and precipitate... 

Like several other polyenes, natamycin forms an inclusion complex with gamma-cyclodextrin [7]. The complex shows biological activity1 and is much more soluble in water than the parent antibiotic. 

Cyclodextrins appear to be extremely biocompatible. They are unable to significantly permeate biological membranes and are not absorbed by the gastrointestinal tract yet do not induce a response from the body s immune system. Tests on rats indicate that LD50 values for the most toxic parent compound, /7-cyclodextrin, are greater than 5 g per kg of body weight when administered orally and 0.5 g per kg of body weight when administered intravenously. This low level of toxicity, coupled to the cyclodextrins ability to form inclusion complexes, makes them ideal excipients in pharmaceutical formulations. 

---