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 HSO4-. 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.

Tetraureido‐dihomooxacalix[4]arenes (tert‐butyl 4a and phenyl 4b) were synthesised and obtained in a partial cone conformation in solution and in the solid state, as confirmed by NMR and X‐ray diffraction studies. Their complexation ability towards halides, pseudo‐halides and oxoanions was assessed by 1H NMR and UV/Vis titrations. Structural and energetic insights of phenylurea 4b complexes were also obtained using molecular dynamics (MD) simulations. The binding data showed that the association constants are strongly dependent on the nature of the substituent (alkyl/aryl) at the urea unit. tert‐Butyl urea 4a is a much weaker receptor than phenylurea 4b, and showed association constants that decrease with decreasing of anion basicity. Phenylurea 4b is a highly efficient anion receptor, exhibiting a remarkable binding ability towards BzO– ion (log Kass = 4.81). In comparison to the phenylurea analogue bearing a butyl spacer and a cone conformation, receptor 4b containing a shorter spacer (three carbon atoms) and a partial cone conformation is more pre‐organized, displaying a strong enhancement of its binding efficiency. MD simulations have shown that the anions are preferentially bound to the urea moieties of the macrocycle lower rim, in agreement with the ROESY spectrum carried out with phenylurea 4b and BzO– anion.

Fluorescent dihomooxacalix[4]arene-based receptors 5a–5c, bearing two naphthyl(thio)ureido groups at the lower rim via a butyl spacer, were synthesised and obtained in the cone conformation in solution. The X-ray crystal structures of 1,3- (5a) and 3,4-dinaphthylurea (5b) derivatives are reported. Their binding properties towards several anions of different geometries were assessed by 1H-NMR, UV-Vis absorption and fluorescence titrations. Structural and energetic insights of the naphthylurea 5a and 5b complexes were also obtained using quantum mechanical calculations. The data showed that all receptors follow the same trend, the association constants increase with the anion basicity, and the strongest complexes were obtained with F−, followed by the oxoanions AcO− and BzO−. Proximal urea 5b is a better anion receptor compared to distal urea 5a, and both are more efficient than thiourea 5c. Compounds 5a and 5b were also investigated as heteroditopic receptors for biologically relevant alkylammonium salts, such as the neurotransmitter γ-aminobutyric acid (GABA·HCl) and the betaine deoxycarnitine·HCl. Chiral recognition towards the guest sec-butylamine·HCl was also tested, and a 5:2 selectivity for (R)-sec-BuNH3+·Cl− towards (P) or (M) enantiomers of the inherently chiral receptor 5a was shown. Based on DFT calculations, the complex [(S)-sec-BuNH3+·Cl−/(M)-5a] was indicated as the more stable.

The intrinsic electronic absorption and fluorescence properties of several dihomooxacalix[4]arenes are studied.