Janus‐Like Squaramide‐Based Hosts: Dual Mode of Binding and Conformational Transitions Driven by Ion‐Pair Recognition

Abstract

New tripodal squaramide-based hosts have been synthesised and structurally characterised by spectroscopic methods. In 2.5 % (v/v) [D(6)]DMSO in CDCl(3), compound 4 formed dimeric assemblies [log K(dim)=3.68(8)] as demonstrated by (1)H NMR spectroscopy and UV dilution experiments. AFM and SEM analyses revealed the formation of a network of bundled fibres, which indicates a preferential mechanism for aggregation. These C(3)-symmetric tripodal hosts exhibited two different and mutually exclusive modes of binding, each one easily accessible by simultaneous reorientation of the squaramide groups. In the first, a convergent disposition of the NH squaramide protons allowed the formation of an array of N-H⋅⋅⋅X(-) hydrogen bonds with anions. In the second mode, reorientation of carbonyl squaramide groups allowed multiple C=O⋅⋅⋅H interactions with ammonium cations. The titration of 4 with different tetraalkylammonium iodides persistently showed the formation of 1:1 complexes, as well as 1:2 and 1:3 complexes. The corresponding stoichiometries and binding affinities of the complexes were evaluated by multi-regression analysis. The formation of high-order complexes, supported by ROESY, NOESY and mass spectrometry experiments, has been attributed to the insertion of NR(4)I ion pairs between the carbonyl and NH protons of the squaramide groups located in adjacent arms of 4. The observed effects reflect the induction of significant conformational changes in the hosts, mainly in relation to the relative orientation of the squaramide groups adapting their geometries to incoming ion-pair complementary substrates. The results presented herein identify and fully describe two different modes of ion-pair recognition aimed at directing conformational transitions in the host, therefore establishing a base for controlling more elaborate movements of molecular devices through ion-pair recognition.

Helical peptaibol mimics are better ionophores when racemic than when enantiopure

“…15,18 To model how these folded peptides might self-associate in a bilayer, changes in their 1 H NMR spectra were monitored as concentrated solutions in the apolar solvent CDCl 3 were progressively diluted. 19 However the concentration range studied for racemates (rac)-1 and (rac)-2 was limited by their lower solubility, as they had saturation concentrations (30 and 15 mM respectively) that were markedly lower than their enantiopure counterparts (150 and 75 mM respectively, e.g. see Figure 2a).…”

Amino acid-based squaramides for anion recognition

“…The squaramide-functional group has recently been exploited in supramolecular chemistry for the design of anion receptors (13)(14)(15)(16)(17)(18), self-complementary molecularrecognition motifs (19) and, most recently, by Gale and coworkers (20) where the squaramide motif was found to be a potent functionality for transmembrane anion transport of both chloride and bicarbonate. Notably, previous work indicates that the introduction of electron-withdrawing trifluoromethyl groups onto the squaramide aromatic substituents can be used to modify both lipophilicity and anion-binding affinity (10,13).…”

Synthesis and supramolecular self-assembly of glutamic acid-based squaramides

“…Besides, squaramides present a dual ability to recognize anions and cations through hydrogen bonding interactions, acting as ion sensors and transmembrane anion transporters [7]. This property has been crucial for the development of new drugs [8–9]. Moreover, these compounds have been recognized as bioisosters of ureas [10] exhibiting promising pharmacological properties [11] and being clinical candidates for the treatment of different diseases [1].…”