1.D.87.  The Helical Peptide-modified Pillar[5]arene Pore-forming (Pilararene) Family 

1,4-Dimethoxypillar[5]arene (DMpillar[5]arene), the first pillararene, was reported by Ogoshi et al. 2008 who catalyzed dimethoxybenzene using a Lewis acid with paraformaldehyde to obtain 1,4-dimethoxypillar[5]arene. The methoxy groups of DMpillar[5]arene were deprotected to give a cylindrical or 'pillar' in shape compound composed of aromatic or 'arene' moieties. Multiple chemists refer to the macrocycle as 'pillarene'.  Pillararenes are composed of hydroquinone units linked by methylene bridges at para-positions. Its features a symmtrical pillar architecture with two identical cavity gates. Pillar[5]arene is the most conformationally stable member in this family. Due to the close proximity of many electron-rich hydroquinones, the cavity of pillararenes are able to form strong association complexes with electron-poor species. Also, derivatives of the pillararenes can be generated by modifying the hydroxyl groups at all positions or selectively on one or two positions (Strutt et al. 2011).

Five unimolecular tubular channels with different lengths (2.4 -4.0 nm) can be formed (Xin et al. 2017). The varying lengths of these channels have significant impact on their transmembrane transport properties, which are directly correlated with their antimicrobial activities and inversely correlated with their haemolytic toxicities. The longer channels transport cations (i.e., H+ and K+) most efficiently. By further structural optimization, these new channels can reach high antimicrobial activity with low haemolytic toxicity, with the potential to serve as systemic antibiotics (Xin et al. 2017).



This family belongs to the Arene Artificial Ion Transporter Superfamily.

 

References:

Ogoshi, T., S. Kanai, S. Fujinami, T.A. Yamagishi, and Y. Nakamoto. (2008). para-Bridged symmetrical pillar[5]arenes: their Lewis acid catalyzed synthesis and host-guest property. J. Am. Chem. Soc. 130: 5022-5023.

Strutt, N.L., R.S. Forgan, J.M. Spruell, Y.Y. Botros, and J.F. Stoddart. (2011). Monofunctionalized pillar[5]arene as a host for alkanediamines. J. Am. Chem. Soc. 133: 5668-5671.

Xin, P., Y. Sun, H. Kong, Y. Wang, S. Tan, J. Guo, T. Jiang, W. Dong, and C.P. Chen. (2017). A unimolecular channel formed by dual helical peptide modified pillar[5]arene: correlating transmembrane transport properties with antimicrobial activity and haemolytic toxicity. Chem Commun (Camb) 53: 11492-11495.