Hydrophobic cyclophanes

HOST-GUEST INTERACTIONS WITH HYDROPHOBIC CYCLOPHANES IN AQUEOUS MEDIA... 

Figure 16.13 Example of a dendritic cyclophane used by Diederich etal. [172] as a receptor for hydrophobic guest molecules...

There are several types of natural and synthetic molecular hosts, such as cyclodextrin and cyclophane, that are shaped to accommodate neutral and charged organic molecules in the three-dimensional cavity. The inclusion complexation by molecular hosts is driven by various weak forces like van der Waals, hydrophobic, hydrogen bonding, ion-dipole, and dipole-dipole interactions, and therefore the molecular recognition process seems much more complicated. In expanding the scope of the present theory, it is intriguing and inevitable to perform the extrather-... 

Cyclophanes consist of a class of artificial hosts featured with well-defined hydrophobic cavities constructed by aromatic rings incorporated in their macrocy-clic structures, and also with high design versatility because they are totally synthetic.The first direct evidence of the formation of an inclusion complex with an organic guest was obtained for tetraazacyclophane 62, the cavity of which is constructed with diphenylmethane units bridged by tetramethylene chains. 

Nitrogen-bearing cyclophanes like 351 [16] and 352 [17] bind larger organic anions in water due to superposition of the hydrophobic effect and electrostatic attraction. The phenanthridinium hosts like 351 have been found to form the most stable nucleotide complexes known so far. On the other hand, free tetrapyrrolic porphyrins do not bind anions since their cavity is too small to take advantage of the convergent N-H dipoles for the complex stabilization [18]. However, expanded diprotonated porphyrins like sapphyrin 353 were shown to form stable complexes with phosphate [19a] and halide [19b] anions. 

Some authors based their approach to selective binding of the more lipophilic a-amino acids in water on hydrophobic effects using water-soluble, cavity-containing cyclophanes for the inclusion of only the apolar tail under renouncement of any attractive interaction of the hosts with the zwitterionic head . Kaifer and coworkers made use of the strong affinity of Stoddart s cyclobis(paraquat-p-phenylene) tetracation 33 for electron-rich aromatic substrates to achieve exclusive binding of some aromatic a-amino acids (Trp, Tyr) in acidic aqueous solution [48]. Aoyama et al. reported on selectivities of the calix[4]pyrogallolarene 34 with respect to chain length and t-basicity of aliphatic and aromatic amino acids, respectively [49]. Cyclodextrins are likewise water-soluble and provide a lipophilic interior. Tabushi modified )S-cyclodextrin with a 1-pyrrolidinyl and a carboxyphenyl substituent to counterbalance the... 

Fig. 3A-C. Space-filling models of artificial receptors, each being capable of providing a large hydrophobic cavity A octopus cyclophane 4 B steroid cyclophane 6 C cage-type cyclophane 8...

In order to construct a hydrophobic three-dimensional cavity that is in-tramolecularly limited in space, we have prepared cage-type cyclophanes by linking macrocyclic rings. First we prepared a macropolycyclic host, which is constructed with two rigid macrocyclic skeletons of different size, tetraaza[3.3.3.3]paracyclophane as the larger one and tetraazacyclotetradecane as the smaller one, and four flexible hydrocarbon chains that connect the two macrocycles [40]. The flexibility of four hydrocarbon chains connecting the two macrocycles allows the induced-fit host-guest interaction in aqueous media. 

The cage-type peptide cyclophanes (7 and 8) exhibit discrimination toward steroid hormones, as effected by hydrophobic and n-n interactions. In addition, the chirality-based discrimination between a- and -estradiol as well as between D- and L-amino acids bearing an aromatic moiety is performed on the basis of their capacity of forming efficient hydrogen bonding with the host molecules in aqueous media [41, 43]. 

Fig. 7A-C. Schematic representations for guest-binding modes of hybrid assemblies formed with peptide lipid 9 and octopus (3 and 4) and steroid (5 and 6) cyclophanes a guest molecule is located in the hydrogen-belt domain (A for 11 and 12 each bound to 3 and 4 B for 11 and 12 bound to 6 and 5, respectively) a guest molecule is located in the hydrophobic domain (C for 11 and 12 bound to 5 and 6, respectively)...

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