Molecular hosts cyclophane

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 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. 

The steroid cyclophane also provides a sizable and well-desolvated hydro-phobic cavity in aqueous media in a manner as observed for the octopus cyclophane. The molecular recognition ability of the steroid cyclophane is inferior to that of the octopus cyclophane in aqueous solution due to the structural rigidity of steroid segments of the former host. When the steroid cyclophane is embedded in the bilayer membrane to form a hybrid assembly, however, the steroid cyclophane becomes superior to the octopus cyclophane with respect to functions as an artificial cell-surface receptor, performing marked guest discrimination. 

The cage-type cyclophane furnishes a hydrophobic internal cavity for inclusion of guest molecules and exercises marked chiral discrimination in aqueous media. The host embedded in the bilayer membrane is capable of performing effective molecular recognition as an artificial cell-surface receptor to an extent comparable to that demonstarated by the host alone in aqueous media. 

Figure 7-19. Three examples of supramo-lecules formed from the assembly of two molecular species. In 7.33, the 1,4-butane-dioic acid is specifically hydrogen bonded to the bisamide. In 7.34, rc-stacking interactions between the cationic cyclophane and the host 1,4-dimethoxybenzene stabilise the structure, whilst in 7.35 the cavity of the ct-cyclodextrin host is the correct size for the benzaldehyde guest. In each case, hydrogen atoms have been omitted for clarity carbon atoms are grey, nitrogen atoms white and oxygen atoms black.

Forman, J. E., Barrans, R. E., Dougherty, D. A., Circular-dichroism studies of molecular recognition with cyclophane hosts in aqueous-media. J. Am. Chem. Soc. 1995, 117, 9213-9228. 

Very recently, nice recognition of free and AT-acetylated amino acids (Gly, Ala, Phe) and some structurally related guests by a dicationic cyclophane-type A/,Ar -dibenzylated chiral derivative (4) of a bisisoquinoline alkaloid S,S-(+)-tetrandine (3 DBT) has been studied by NMR titration in water [31]. In contrast to other macrocyclic hosts, DBT shows high affinity and large enan-tioselectivity (K(S)/K(R)> 10) toward the smaller N-acetylalanine and binds the larger phenylalanine more weakly and nonselectively. The binding specificity of DBT was rationalized on the basis of molecular mechanics calculations. 

The study of pyridinophanes resulted in joint publications on the complexation of water and the encapsulation of halocarbons within pyridino-crown hosts. Additional professional exchanges occurred over the years in which both groups were pursuing mutual synthetic interests in heterocyclic chemistry, stereochemistry, and cyclophanes. Central to those interests was a better understanding of molecular inclusion and recognition phenomena, now more uniquely defined as an aspect of supramolecular chemistry. 

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