Ditopic Receptors Based on Dihomooxacalix[4]arenes Bearing Phenylurea Moieties With Electron-Withdrawing Groups for Anions and Organic Ion Pairs.

Alexandre S Miranda,José R Ascenso,Mário N Berberan-Santos,Defne Serbetci,Neal Hickey,Paula M Marcos,Silvano Geremia

doi:10.3389/fchem.2019.00758

Abstract

Two bidentate dihomooxacalix[4]arene receptors bearing phenylurea moieties substituted with electron-withdrawing groups at the lower rim via a butyl spacer (CF3-Phurea 5b and NO2 Phurea 5c) were obtained in the cone conformation in solution, as shown by NMR. The X-ray crystal structure of 5b is reported. The binding affinity of these receptors toward several relevant anions was investigated by 1H NMR, UV-Vis absorption in different solvents, and fluorescence titrations. Compounds 5b and 5c were also tested as ditopic receptors for organic ion pairs, namely monoamine neurotransmitters and trace amine hydrochlorides by 1H NMR studies. The data showed that both receptors follow the same trend and, in comparison with the unsubstituted phenylurea 5a, they exhibit a significant enhancement on their host-guest properties, owing to the increased acidity of their urea NH protons. NO2-Phurea 5c is the best anion receptor, displaying the strongest complexation for F−, closely followed by the oxoanions BzO−, AcO−, and HS. Concerning ion pair recognition, both ditopic receptors presented an outstanding efficiency for the amine hydrochlorides, mainly 5c, with association constants higher than 109 M−2 in the case of phenylethylamine and tyramine.

Highlights

Anion recognition by synthetic receptors continues to attract much attention, as documented by the reviews published recently (Evans and Beer, 2014; Busschaert et al, 2015; Gale et al, 2016)
Macrocyclic compounds have been developed as anion receptors, in which the interactions are mainly established by hydrogen bond donor groups, such as ureas and thioureas, incorporated in Ditopic Dihomooxacalix[4]arenes for Anions and Organic Ion-Pairs the macrocycle scaffolds
We have reported the synthesis of a lower rim 1,3-disubstituted dihomooxacalix[4]arene receptor containing two phenylurea moieties and two n-butyl groups (Marcos et al, 2014a)

Summary

Introduction

Anion recognition by synthetic receptors continues to attract much attention, as documented by the reviews published recently (Evans and Beer, 2014; Busschaert et al, 2015; Gale et al, 2016). Macrocyclic compounds have been developed as anion receptors, in which the interactions are mainly established by hydrogen bond donor groups, such as ureas and thioureas, incorporated in Ditopic Dihomooxacalix[4]arenes for Anions and Organic Ion-Pairs the macrocycle scaffolds. Heteroditopic receptors, molecules capable of simultaneously bind both ions of a given ion pair, have been obtained and are an emerging area in supramolecular chemistry (Kim and Sessler, 2010; McConnell and Beer, 2012). These systems have important applications, as membrane transport agents, and in salt extraction and solubilisation. Alkylammonium moieties are a constant presence in compounds of biological interest, such as biogenic amines, trace amines and amino acids (Mutihac et al, 2011)

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Conclusion