Apolar cavity

Cyclodextrins (CDs) have a wide range of application in the pharmaceutical field due to their unique structure, which allows them to include hydrophobic molecules in their apolar cavity and to mask the physicochemical properties of the included molecule. This results in the enhancement of drug bioavailability by improving aqueous solubility and the physical and chemical stability of the drug, masking undesired side effects such as irritation, taste, or odor, and overcoming compatibility problems or interactions between drugs and excipients. 

LI Separations in the reversed-phase mode — chiral recognition mechanisms and structural features of selectands. The primary mechanism of interaction between the macrocyclic selectors and the selectands in the reversed-pha.se mode (employing aqueous buffered mobile phases) is (partial) inclusion of hydrophobic molecules or parts of the molecules, such as (substituted) aromatic rings, into the apolar cavity of the CD. It is clear that the dimensions of the CD cavity play a dominant role to facilitate this... 

Furthermore, /8-cyclodextrin shows superb selectivity in the syntheses of 2.5-cyclohexadienones (12), which are important starting materials for the syntheses of physiologically active compounds, from / -substituted phenols, chloroform, and sodium hydroxide (Scheme 7) [25]. The selectivity of the production of 12 in the presence of /8-cyclodextrin is virtually 100%, in contrast to the formation of large amounts (about 4-8 times as large as 12) of ori/jo-formulated compound 13 in its absence. The remarkable selectivity in the present reaction is probably due to the formation of dichlorocarbene from chloroform and hydroxide ion in the cavity of /8-cyclodextrin. The / ara-substituted phenol should approach the cavity (and thus the carbene) from the side involving the para-ca.rhon, resulting in a selective reaction. The penetration of this apolar side in the apolar cavity should be more favorable than the penetration of the polar side by the phenoxide atom. 

Acridine and 2-acetylnaphthalene are examples of molecules that are emitting in polar and/or H-bonding solvents but nonemitting in apolar solvents. A decrease of fluorescence emission should be observed for these molecules following their inclusion in the relatively apolar cavity of the dextrins. 

Stead, CyDs merely offer their cavity as a hydrophobic and constrained reaction field. When substrate molecules are accommodated in the cavity, they take specific orientation there and thus two otherwise equivalent positions in these substrates can be clearly differentiated. Under these conditions, two reagents for bimolecular reactions are placed near each other with a specific mutual orientation. This situation is of course favorable for prompt and selective reactions. Other reactions are accelerated simply because the transition state is stabilized in the apolar cavity of CyD. Furthermore, the substrates and/or the products are protected from undesired side reactions (e.g. decomposition by other reagents). Therefore, notable specificity (regio-, stereo-, and enantio-selectivity), together with relatively high yields, are satisfactorily accomplished in CyD-catalyzed reactions. 

First, a ternary inclusion complex is formed from g-CyD, chloroform, and phenol or its derivative, in which the cavity of 3-CyD is largely occupied by chloroform. Phenol or its derivative in its anionic form penetrates shallowly in the cavity from the side involving the para carbon atom, since the inclusion of this apolar side in the apolar cavity is more favorable than the inclusion of the polar side... 

The particular three-dimensional CD structure with its hydrophilic surface and apolar cavity, impacts water solubility and the ability to partially or totally encapsulate hydrophobic molecules of appropriated size and shape in aqueous solution as well as in solid-state through the formation of a reversible host-guest complex (Fig. 2.3) [2]. 

Merski M, Shoichet BK (2013) The impact of introducing a histidine into an apolar cavity site on docking and ligand recognition. J Med Chem 56(7) 2874-2884. doi 10.1021/jm301823g... 

I. 922(5) to 1.944(7) A and the bond angle is 110.8°. A toluene molecule is guested in the intramolecular apolar cavity of each macrocycle, whereas two other molecules occupy intermolecular voids of the crystal lattice. These two molecules are rather disordered and this causes probably problems in the final refinement of the crystal structure. 

There are several similarities between the cyclodextrins and the cucurbiturils. They both come in different ring sizes they have an apolar cavity and rims lined with polar moieties that render them slightly soluble in aqueous solutions. Second they both have structures with a high degree of symmetry which makes selective functionalization, other than mono or complete, difficult. The most important similarity is that they both can complex organic molecules in their apolar cavity with size- and stmcture -dependent selectivity. The latter is the main reason that these molecules have become the most important receptors for supramolecular chemistry in water, with many practical applications. 

For compoimds 16, this conformation is in slow exchange (AG = 70-88 kJ/mol at 328K in CDCI3) with the 1,2,3-alternate conformation, the latter being less stable (AG° = 2-7 kJ/mol). ° Therefore it is possible to conclude that three important factors stabilize the flattened cone structure, viz. (i) the self-inclusion of the methoxy groups in the apolar cavity driven by CH-ti interactions, (ii) the presence of three bulky groups in 2,4,6 positions at the lower rim, and (iii) the presence of the ter/-butyl groups at the upper... 

The binding ability of the apolar cavity defined by die four aromatic nuclei of p-tert-butylcalix[4]arene toward neutral molecules was evidenced during the early elucidation of its solid state structure, since a toluene molecule was found into the cavity. ... 

It was therefore of great interest to exploit the 7t - donor apolar cavity of calix[4]arene for the complexation of neutral molecules both in solution and in the gas-phase. The binding ability of calbc[4]arenes (1 n = 4) toward neutral molecules is however very poor in solution and the reason for this is diat the intermolecidar CH/ii interactions involved in the complex formation are not strong enough to block the cone-to-cone ring inversion (see Figure 8) experienced by these macrocycles in solution. ... 

Inclusion of Neutral Molecules in the Apolar Cavity of Calixarenes... 

With the aim of obtaining evidences for the inclusion of neutral molecules inside the apolar cavity of calixarenes we previously synthesized a tetracarboxylic acid derivative 23 of p-rm-butylcalix[4]arene in the fixed cone conformation [13a]. The alkali metal salts of this acid were water soluble up to 5 x 10 M, but they were unable to complex neutral molecules such as benzene, toluene, xylenes and methanol which were easily included in the apolar cavity of this class of macrocycles in the solid state showing a well defined stoichiometry [6]. 

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