A p-tert-Tutyldihomooxacalix[4]arene Based Soft Gel for Sustained Drug Release in Water.

Hao Guo,Chaoguo Yan,Ying Han,Jin Wang,Runmiao Zhang

doi:10.3389/fchem.2020.00033

Abstract

P-tert-butyldihomooxacalix[4]arene is a well-known calix[4]arene analog in which one CH2 bridge is replaced by one -CH2OCH2- group. Thus, dihomooxacalix[4]arene has a slightly larger cavity than that of calix[4]arene and usually possesses a more flexible cone conformation, and the bridged oxygen atom might provide additional binding sites. Here, we synthesized a new functional p-tert-butyldihomooxacalix[4]arene 1 through Ugi reaction with good yield (70%), starting from condensed p-tert-butyldihomooxacalix[4]arene O-alkoxy–substituted benzaldehydes, benzoic acid, benzylamine, and cyclohexyl isocyanide. Proton nuclear magnetic resonance spectroscopy (1H NMR), 13C NMR, IR, and diffusion-ordered 1H NMR spectroscopy (DOSY) methods were used to characterize the structure of 1. Then soft gel was prepared by adding 1 into cyclohexane directly. It shows remarkable thermoreversibility and can be demonstrated for several cycles. As is revealed by scanning electron microscopy (SEM) images, xerogel showed highly interconnected and homogeneous porous network structures, and hence, the gel is suitable for storage and controlled release.

Highlights

We designed and synthesized a novel functionalized p-tert-butyldihomooxacalix[4]arene 1 with two H-bonding sites through Ugi reaction (Scheme 1), which was prepared with good yield (70%)
The soft gel was constructed by adding 1 into cyclohexane, heating the mixture, and leaving it cooled in the refrigerator for 2 min. 1-based gel showed remarkable thermoreversibility, and this can be demonstrated for several cycles
When the temperature cooled to 25◦C, 1 could form a gel in cyclohexane (Figure 1, under, sample j) but could not form a gel in methanol, ethanol, pentanol, tert-butanol, acetonitrile, ethyl acetate, tetrahydrofuran, toluene, and hexane, as the samples flowed under gravity (Figure 1, under, samples a, b, c, d, e, f, g, h, k)

Summary

Introduction

The designed and prepared macrocyclic hosts [mainly including crown ethers (Liu et al, 2017; Morrison et al, 2017), cyclodextrins (Zhang et al, 2018; Larsen and Beeren, 2019), calixarenes (Wang et al, 2015; Tian et al, 2019), cucurbiturils (Kim et al, 2007; Wu et al, 2018; Xiao B. et al, 2019), and pillar[n]arenes (Xue et al, 2012; Sun et al, 2018; Chen et al, 2019; Ogoshi et al, 2019; Xiao T. et al, 2019)] and the investigations of their host–guest properties are the foundation of the development of supramolecular chemistry (Zheng et al, 2012; Yao et al, 2018; Zhang et al, 2019). Investigations about supramolecular gels based on p-tert-butyldihomooxacalix[4]arene and their applications are rarely reported

Methods

Results

Conclusion