Biomedical Applications of Pillararenes

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China Email houjl fudan.edu.cn 

Pillararenes (PA), a new kind of paracyclophane, were first synthesized in 2008 as pillar[5]arene (PA[5]) and were recognized as a new generation of supramolecular host because of their unique pillar structural feature, nanometer-sized ( 1.0nm) cavity, and multiple fiinctionalizable sites. In the last few years, these new types of compound have shown biomedical applications in the construction of artificial channels for transmembrane transport of physiologically active solutes and vesicles for drug delivery, which will be reviewed in this chapter. 

Numerous examples of artificial channels have been reported since the pioneering work of Tabushi using tetrachained cyclodextrin as a model. Of these examples, the macrocycles, such as crown ethers, calixarenes, cyclodextrins, and cucurbiturils, play an important role. The macrocycles provide not only the platforms for construction of whole channels but also the functional sites necessary to achieve transport selectivity and efficiency. From this viewpoint, pillararenes, new macrocycles with unique structural features, may also act as a platform for building such channels, which will give the channels new functions. This hypothesis has been systematically explored by us. 

Reproduced with permission from ref. 16. Copyright 2011, Wilw-VCH Verlag Gmbh Co. KGaA, Weinheim. 

Second, it possesses a cavity of 5.6 A width,which is suitable for the docking of water molecules, as demonstrated by the crystal structure of 11.1, and is close to the pore width of aquaporin. 

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Thus, macrocyclic amphiphiles are reviewed by Huang et al. with respect to cyclodextrins, calixarenes, cucurbiturils and pillararenes [1]. Similarly, Ma and Zhao present biomedical applications of supramolecular systems based on host-guest interactions, with a focus on cyclodextrins, calixarenes and cucurbiturils [2]. Sansone et al. published a review on calixarenes as multivalent ligands for biomolecular recognition [3]. 

Although pillararenes have been developed for several years, the chemistry of this family is beginning to blossom, as witnessed by the heightened interest in the field for the last several years. In particular, the efficient synthesis of the pillararene backbones and their subsequent direct functionalization have removed one of the major obstacles to pillararene chemistry and henceforth they will be available for exhaustive synthetic manipulations to pursue biomedical applications, including transmembrane transport and drug delivery, as we have demonstrated in this chapter. 

Ogoshi et al. in Chapter 8), supramolecular assemblies (Zhao et al. in Chapter 9), hybrid materials (Yang et al. in Chapter 10), and biomedical applications (Hou et al. in Chapter 11). In the final Chapter 12, Stoddart et al. review pillar[w]arene-related macrocyclic compounds, including their new fantastic macrocycles asar[n]arenes. It is hoped that the book will contribute to the further development of pillararene chemistry and the quest to discover new and exciting macrocyclic compounds. 

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