Amide-Based Naphthotubes as Biomimetic Receptors for Acetal Protection and Other Substrates in Water via Noncovalent Interactions

Abstract

Active compound protection can allow inherently unstable molecules to be stabilized and latent reactivity to be masked. Synthetic receptors are attractive in terms of providing such protection. Nevertheless, preserving the activity and functionality of organic molecules in water poses a challenge. Here, we show that biomimetic receptors, specifically amide naphthotubes and an amide anthryltube, allow the efficient preservation of functional organic molecules in water. In particular, the amide naphthotubes were found to extend the half-lives of acetal-containing substrates (“acetals”) against acid-catalyzed hydrolysis by up to 3000 times. This kinetic protection effect was ascribed to hydrogen bond-based recognition of the organic guests. A substrate dependence was seen that was further exploited to achieve the kinetic resolution of acetal isomers. To the best of our knowledge, the present study constitutes one of the most effective acetal protection strategies reported to date. The recognition-based protection approach reported here appears generalizable as evidenced by the protection of eight different substrates against six distinct chemical reactions. Based on the present findings, we propose that it is possible to design receptors that provide for the protection of specific substrates under a variety of reaction conditions including those carried out in water.