Deltamides and Croconamides: Expanding the Range of Dual H‐bond Donors for Selective Anion Recognition

Abstract

Dual H-bond donors are widely used as recognition motifs in anion receptors. We report the synthesis of a library of dual H-bond receptors, incorporating the deltic and croconic acid derivatives, termed deltamides and croconamides, respectively, and a comparison of their anion binding affinities (for monovalent species) and Brønsted acidities to those of the well-established urea and squaramide dual H-bond donor motifs. For dual H-bonding cores with identical substituents, the trend in Brønsted acidity is croconamides>squaramides>deltamides>ureas, with the croconamides found to be 10-15 pK units more acidic than the corresponding ureas. In contrast to the trends displayed by ureas, deltamides and squaramides, N,N'-dialkyl croconamides displayed higher binding affinity to chloride than the N,N'-diaryl derivatives, which was attributed to partial deprotonation of the N,N'-diaryl derivatives at neutral pH. A number of differences in anion binding selectivity were observed upon comparison of the dual H-bond cores. Whereas the squaramides display similar affinity for both chloride and acetate ions, the ureas have significantly higher affinity for acetate than chloride ions and the deltamides display higher affinity for dihydrogenphosphate ions than other oxoanions or halides. These inherent differences in binding affinity could be exploited in the design of anion receptors with improved ability to discriminate between monovalent anions.

Extraction and transport of sulfate using macrocyclic squaramide receptors

“…) did not lead to isolation of the desired product. In the absence of an anion or in the presence of anions such as ClO 4 À , I À , BF 4 À that are known to only weakly coordinate to squaramides, 30,40,41 no reaction occurred. In the presence of Cl À and SO 4…”

“…, which bind to squaramides with relatively high affinities, mixtures of products were observed but all attempts to isolate desired macrocycle 2 (or other discrete species) from these reactions failed. We hypothesize that Cl À and SO 4 2À may bind strongly to the reactants in the non-polar conditions used, [40][41][42][43][44] locking them into conformations that do not favour cyclisation, thus promoting the formation of linear oligomers, whereas the weaker binding to H 2 PO 4 À allows interconversion of conformers to allow cyclisation to progress.…”

Chemiresistors for the Real‐Time Wireless Detection of Anions

“…Experimental p K a values were determined by UV‐vis titration with TBA benzoate in DMSO (Figures S19–S21, Supporting Information) . Theoretical p K a values of the selectors were calculated by DFT using the SMD implicit solvation model, wherein the solution phase Gibbs free energies were calculated by combining free energies of solvation in DMSO with the gas phase free energies (Supporting Information). The experimental and computational p K a values are within 1 p K a unit and a consistent order of the selectors with 2 < 3 < 1 ( Table 3 ).…”

Investigating the effects of structure on sulfate recognition by neutral dipeptide receptors

“…resulting from increased electron withdrawing groups on the phenyl ring appended to the squaramide. (24,26) All receptors exhibited high affinity and selectivity for SO4 2in this solvent system, with Ka >10 4 M -1 regardless of structural differences in the peptidic scaffold or the number of electron withdrawing groups on the phenyl substituent appended to the squaramide. To study the effect the differences in design have on the binding ability of the receptors for SO4 2-, investigations in water-DMSO mixtures with concentrations of water greater than 20% need to be undertaken.…”

“…(18-21) However, Kubik and co-workers have recently reported a water soluble bis-macrocyclic peptide that binds to chloride, bromide, iodide and sulfate ions through hydrogen bonding interactions in water, although this receptor does not discriminate between these anions (sulfate logK = 3.31; iodide logK = 3.62). (22) Squaramides were first employed as an anion binding motif in 1997 by Costa and coworkers(23) and since then have been shown to have improved anion affinities when compared to analogous urea and thiourea derivatives, (24)(25)(26)(27) and also to be potent transmembrane anion transporters. (26) We have recently described a number of squaramide based receptors including a macrocyclic receptor which exhibited strong affinity and selectivity for sulfate in 33% v/v H2O/DMSO.…”