Cavitands type hosts

ELECTROCHEMISTRY OF INCLUSION COMPLEXES FORMED BY CAVITAND-TYPE HOSTS... 

For quite some time most synthetic efforts to prepare cavitand-type hosts led to compounds that were only soluble in low polarity solvents. Because of their potential biological relevance, interest on the synthesis of water-soluble cavitands developed quickly, but only recently a number of accessible hosts has become available. We will describe here recent work done by us on Gibb s octaacid, deep-cavity cavitand58 and Rebek s water-soluble cavitand.59 The structures of these compounds are shown in Fig. 3.10. 

Figure 3.10 Structures of water-soluble cavitand-type hosts Gibb s octaacid (host 5) and Rebek s cavitand (host 6).

Further examples of cavitand-type structures include hw-cyclo-triveratrylene derivatives such as (257) (Gabard Collet, 1981 Canceill, Lacombe Collet, 1986) and the bowl-shaped hosts represented by (258) - the base of the bowl is formed by the four methyl groups. Once again, the shape of these molecules is maintained by conformational constraints. Cavitand (258) is able to accommodate simple solvent molecules such as dichloromethane and chloroform. Moreover, its cavity is large enough to form inclusion complexes with up to four molecules of water (Moran, Karbach Cram, 1982). 

A further category of cavitands are the calixarenes (Gutsche, Dhawan, No Muthukrishnan, 1981 Gutsche Levine, 1982). Structure (255) illustrates an example of this type which is readily prepared by treatment of 4-f-butylphenol with formaldehyde and base. The compound may exist in other conformations besides the saucer-shaped one illustrated by (255). Similarly, f-butyl-calix[4]arene (256 R = CH2COOH) has an enforced hydrophilic cavity in the shape of a cone the alkali and ammonium salts of this host are soluble in water (Arduini, Pochini, Reverberi Ungaro, 1984). 

The complexation of anionic species by tetra-bridged phosphorylated cavitands concerns mainly the work of Puddephatt et al. who described the selective complexation of halides by the tetra-copper and tetra-silver complexes of 2 (see Scheme 17). The complexes are size selective hosts for halide anions and it was demonstrated that in the copper complex, iodide is preferred over chloride. Iodide is large enough to bridge the four copper atoms but chloride is too small and can coordinate only to three of them to form the [2-Cu4(yU-Cl)4(yU3-Cl)] complex so that in a mixed iodide-chloride complex, iodide is preferentially encapsulated inside the cavity. In the [2-Ag4(//-Cl)4(yU4-Cl)] silver complex, the larger size of the Ag(I) atom allowed the inner chloride atom to bind with the four silver atoms. The X-ray crystal structure of the complexes revealed that one Y halide ion is encapsulated in the center of the cavity and bound to 3 copper atoms in [2-Cu4(//-Cl)4(//3-Cl)] (Y=C1) [45] or to 4 copper atoms in [2-Cu4(/U-Cl)4(/U4-I)] (Y=I) and to 4 silver atoms in [2-Ag4(/i-Cl)4(/i4-Cl)] [47]. NMR studies in solution of the inclusion process showed that multiple coordination types take place in the supramolecular complexes. 

Molecular recognition is a term often used to describe the ability of a host molecule to bind a specific type of guest, typically from a mixture.47 The 3-D hosts (i.e., cavitands) are more apt at this task than are flat, 2-D hosts (i.e., coronands). The concept of molecular recognition is reminiscent of Fischer s48 lock and key ... 

A holand has recently been described by Reinhoudt and coworkers which was constructed by the assembly of two caEx[4]arenes and two resorcinol-based cavitands (schematically shown in Figure 20) [32]. This extremely rigid host has a shielded hole of nanosize dimensions, with an estimated hole volume of Inm. Reinhoudt and coworkers have also reported the synthesis of a cryptocalix[6]arene (Figure 21), and studied its dynamic behavior [33]. A novel type of stereoisomerism has been reported in carcaplexes of dimethylacetamide and iV-methylpyrroEdone with a calix[4]arene-based carcerand. This isomerism... 

Fig. 4 Exemplary cases of enforced cavity hosts and their supramolecular compounds (guests symbolized in broken rings) (a) Cleft-type (b) tweezer-type (c) spherand (d) cyclophane (monocyclic) (e) cyclophane ibicyclic) (f) cavitand (g) carcerand (h) calixarene (calix[4]arene) (i) resorcarene (j) cryptophane (k) cyclodextrin (P-cyclodextrin) and (1) cucurbituril.

Up till now, a very high number of reports have been published about results achieved in preparation and testing of different molecules that were found applicable as ionophore in ISEs. Crown ethers [20], calixarenes [21], cryptands [22], podands [23], or other cavitand host species are among the most often prepared and studied types of molecules in this respect. 

The same velcrand has also been shown to engender cavitand-mediated endo-cytosis [188]. The authors demonstrated selective, controlled endocytosis of a trimethylammonium-tagged fluorescein to several types of living human cells with little observed cytotoxicity. This approach therefore represents a novel method of small-molecule trans-membrane transport controlled by host-guest complementarity. 

This review of state-of-the-art cavitand chemistry demonstrates that after being initiated by Cram, the field has expanded considerably in large part because of the ease of functionalizing the two-position of resorcinarenes and cavitands, and because of the wide nature of the bridging group used to form these hosts. In particular, the last decade has seen a veritable explosion of variety and hence application of cavitands, from the very fundamental to the wholly applied. One is forced to conclude that the future is very bright for this unique type of host. 

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