Dynamic Control of the Self-Assembling Properties of Cyclodextrins by the Interplay of Aromatic and Host-Guest Interactions.

Tania Neva,José M García Fernández,Cédric Przybylski,Carmen Ortiz Mellet,Juan M Benito,Thais Carmona,Francisco Mendicuti

doi:10.3389/fchem.2019.00072

Abstract

The presence of a doubly-linked naphthylene clip at the O-2I and O-3II positions in the secondary ring of β-cyclodextrin (βCD) derivatives promoted their self-assembly into head-to-head supramolecular dimers in which the aromatic modules act either as cavity extension walls (if the naphthalene moiety is 1,8-disubstituted) or as folding screens that separate the individual βCD units (if 2,3-disubstituted). Dimer architecture is governed by the conformational properties of the monomer constituents, as determined by NMR, fluorescence, circular dichroism, and computational techniques. In a second supramolecular organization level, the topology of the assembly directs host-guest interactions and, reciprocally, guest inclusion impacts the stability of the supramolecular edifice. Thus, inclusion of adamantane carboxylate, a well-known βCD cavity-fitting guest, was found to either preserve the dimeric arrangement, leading to multicomponent species, or elicit dimer disruption. The ensemble of results highlights the potential of the approach to program self-organization and external stimuli responsiveness of CD devices in a controlled manner while keeping full diastereomeric purity.

Highlights

The incorporation of functional moieties into pre-existing cage molecules and macrocycles represents a powerful strategy to tailor their architectural, inclusion, self-assembling, stimulus responsiveness and biorecognition properties (Sansone and Casnati, 2013; Shetty et al, 2015; Gropp et al, 2017; Liu et al, 2017; Matsuoka and Nabeshima, 2018)
Compounds 4 and 5 were purposely conceived to avoid this and keep the toroidal βCD cavity characteristic of βCD undistorted, so that any effect in their supramolecular properties can be ascribed to the presence of the naphthalene component, devoid from additional effects on the βCD macroring topology
According to the available X-ray data for permethylated βCD 6 (Caira et al, 2004), the through-space distance between the O-2I and O-3II positions in the cyclooligosaccharide backbone is 3.4 Å, which can be accommodated by benzylic positions in either 1,8- or 2,3-disubstituted naphthylene clips without provoking any significant steric strain

Summary

Introduction

The incorporation of functional moieties into pre-existing cage molecules and macrocycles represents a powerful strategy to tailor their architectural, inclusion, self-assembling, stimulus responsiveness and biorecognition properties (Sansone and Casnati, 2013; Shetty et al, 2015; Gropp et al, 2017; Liu et al, 2017; Matsuoka and Nabeshima, 2018). A range of sophisticated molecular machines with programmed supramolecular behaviors have been designed by implementing this strategy, with applications in the fields of sensors, electronic or optical devices, natural ligand mimics, artificial catalysts or (bio) molecular carriers, among others (Jiménez Blanco et al, 2017; Webber and Langer, 2017; Yin et al, 2017; Guo et al, 2018; van Dijk et al, 2018; Yu et al, 2018; Zeng et al, 2018). The design of non-viral gene delivery systems (Ortiz Mellet et al, 2011; Gallego-Yerga et al, 2015; Evenou et al, 2018; Hong et al, 2018), antitoxins (Díaz-Moscoso et al, 2011; Joshi et al, 2011), nanocontainers (Gallego-Yerga et al, 2014b, 2017; Varan et al, 2017; Engel et al, 2018) and actuators (Smiljanic et al, 2006; Tan et al, 2014; Yang et al, 2014) highlights the potential of this tactic

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Results

Conclusion