Cyclophane host molecules

The incorporation of hydrophobic subunits such as aryl, alkyl, napthyl, binaphthyl, etc., into a macrocyclic structural framework leads to synthetic host molecules containing large endolipophilic cavities which have the potential of accommodating neutral organic guest species. 

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Figure 2.63 Cyclophane host molecules containing quaternary ammonium and sulphonium groups (141, 144).

Dailey NK, Kou X, Bartsch RA et al (2003) Synthesis of new cyclophane host molecules and crystal stmctures of their compounds with hydrocarbon guests. J Incl Phen Macrocycl Chem 45 139-148... 

An example of the modular preparation of the cyclophane 3 from the substituted bipyridine 2 and a general tripeptide 1 is shown in Scheme 3-3. The host molecule 3 contains a pre-organized binding pocket. The overall basicity of such molecules also facilitates their intercalation within the lamellas of acidic zirconium phosphate, thus making this chemistry well suited for the desired application. 

Cyclophanes or 7r-spherands have played a central role in the development of supramolecular chemistry forming an important class of organic host molecules for the inclusion of metal ions or organic molecules via n-n interactions. Particular examples are provided by their applications in synthesis [80], in the development of molecular sensors [81], and the development of cavities adequate for molecular reactions with possible applications in catalysis [82]. The classical organic synthesis of cyclophanes can be quite complex [83], so that the preparation of structurally related molecules via coordination or organometallic chemistry might be an interesting alternative. 

While nature uses coenzyme-dependent enzymes to influence the inherent reactivity of the coenzyme, in principle, any chemical microenvironment could modulate the chemical properties of coenzymes to achieve novel functional properties. In some cases even simple changes in solvent, pH, and ionic strength can alter the coenzyme reactivity. Early attempts to present coenzymes with a more complex chemical environment focused on incorporating coenzymes into small molecule scaffolds or synthetic host molecules such as cyclophanes and cyclo-dextrins [1,2]. While some notable successes have been reported, these strategies have been less successful for constructing more complex coenzyme microenvironments and have suffered from difficulties in readily manipulating the structure of the coenzyme microenvironment. 

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

In addition to macrocyclic hosts discussed above, many other molecules capable of selective complexation have been synthesized. They belong to so-called macrocyclic chemistry [30] encompassing crown ethers discussed in this Chapter, cryptands 61-63 [21], spherands 70 [31], cyclic polyamines 71 [32], calixarenes 18 [5], and other cyclophane cages such as 72 [33] to name but a few. Hemicarcerand 5 [2b] discussed in Chapter 1 and Section 7.3 also belongs to this domain. Typical macrocyclic host molecules are presented in Chapter 7. 

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]. 

Diederich, F., Complexation of neutral molecules by cyclophane hosts. Angew. Chem., Int. Ed. Engl. 1988, 27, 362-386. 

Farthing also reported the synthesis of compound 6.8 Advancements in cyclophane receptor chemistry came in 1955, when Stetter and Roos recognized the ability of cyclophanes to form inclusion complexes. They reported what they thought to be cavity inclusion complexation of benzene in cyclophane 7.9 This opened the door to the study of inclusion complexation with cyclophanes. However, in the early 1980 s when the crystal structure of Stetter s complex was solved it was shown that the benzene was located between two host molecules and not inside the... 

Other Host Molecules - Building Three-Dimensional Cavities Cyclophanes are cyclic hosts made from aromatic rings that mainly recognize hydrophobic guest molecules. Three-dimensional cavities can be constructed by attaching tails, walls and caps to the cyclic hosts. 

F. Diederich, Complexation of Neutral Molecules by Cyclophane Hosts , Angew. Chem. Int Ed., 27,362 (1988)... 

Recently oxidative coupling reactions of a,a>-diethynyl compounds have been applied in the synthesis of cyclophanes, which are interesting functional host molecules. Whitlock and coworkers, - for example, have reported the synthesis of the water-soluble cyclophane (21), designed as an esterase mimic by the Eglington reaction of (20 Scheme 8). 

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