We report on the eligibility of tetraphosphonate resorcinarene cavitands for the molecular recognition of amino acids. We determined the crystal structure of 13 complexes of the tetraphosphonate cavitand Tiiii[H, CH3, CH3] with amino acids. (1)H NMR and (31)P NMR experiments and ITC analysis were performed to probe the binding between cavitand Tiiii[C3H7, CH3, C2H5] or the water-soluble counterpart Tiiii[C3H6Py(+)Cl(-), CH3, C2H5] and a selection of representative amino acids. The reported studies and results allowed us (i) to highlight the noncovalent interactions involved in the binding event in each case; (ii) to investigate the ability of tetraphosphonate cavitand receptors to discriminate between the different amino acids; (iii) to calculate the Ka values of the different complexes formed and evaluate the thermodynamic parameters of the complexation process, dissecting the entropic and enthalpic contributions; and (iv) to determine the solvent influence on the complexation selectivity. By moving from methanol to water, the complexation changed from entropy driven to entropy opposed, leading to a drop of almost three orders in the magnitude of the Ka. However, this reduction in binding affinity is associated with a dramatic increase in selectivity, since in aqueous solutions only N-methylated amino acids are effectively recognized. The thermodynamic profile of the binding does not change in PBS solution. The pivotal role played by cation-π interactions is demonstrated by the linear correlation found between the log Ka in methanol solution and the depth of (+)N-CH3 cavity inclusion in the molecular structures. These findings are relevant for the potential use of phosphonate cavitands as synthetic receptors for the detection of epigenetic modifications of histones in physiological media.

The stepwise synthesis of ionizable p-tert-butylcalix[5]arenes 1a·H and 1b·H, featuring a fixed cone cavity endowed with a carboxyl moiety at the narrow rim, is described. Single-crystal X-ray analyses have shown that in the solid state 1a·H and 1b·H adopt a cone-out conformation with the carboxylic OH group pointing in, toward the bottom of the aromatic cavity, as a result of a three- or two-center hydrogen-bonding pattern between the carboxyl group and the phenolic oxygen atom(s). The affinity of amines for calix[5]arene derivatives 1a·H and 1b·H was probed by (1)H NMR spectroscopy and single-crystal X-ray diffraction studies. These carboxylcalix[5]arenes are shown to selectively recognize linear primary amines--over branched, secondary, and tertiary amines--by a two-step process involving a proton transfer from the carboxyl to the amino group to provide the corresponding alkylammonium ion, followed by binding of the latter inside the cavity of the ionized calixarene. Proton transfer occurs only with linear primary amines, that is, when the best size and shape fit between host and substrate is achieved, while the other amines remain in their noncompeting unprotonated form. The role of the solvent in the ionization/complexation process is discussed. Structural studies on the n-BuNH(2) complexes with 1a·H and 1b·H provide evidence that binding of the in situ formed n-BuNH(3)(+) substrate to the cavity of the ionized macrocycle is ultimately secured, in the case of 1a·H, by the formation of an unprecedented salt-bridge interaction.

Two novel triptycene quinoxaline cavitands (DiTriptyQxCav and MonoTriptyQxCav) have been designed, synthesized, and applied in the supramolecular detection of benzene, toluene, ethylbenzene, and xylenes (BTEX) in air. The complexation properties of the two cavitands towards aromatics in the solid state are strengthened by the presence of the triptycene moieties at the upper rim of the tetraquinoxaline walls, promoting the confinement of the aromatic hydrocarbons within the cavity. The two cavitands were used as fiber coatings for solid-phase microextraction (SPME) BTEX monitoring in air. The best performances in terms of enrichment factors, selectivity, and LOD (limit of detection) values were obtained by using the DiTriptyQxCav coating. The corresponding SPME fiber was successfully tested under real urban monitoring conditions, outperforming the commercial divinylbenzene-Carboxen-polydimethylsiloxane (DVB-CAR-PDMS) fiber in BTEX adsorption.

Three novel tetra(thio)ureido dihomooxacalix[4]arene anion receptors (phenylurea 4a, phenylthiourea 4b, and tert-butylurea 4c) were synthesized and obtained in the cone conformation in solution, as shown by NMR studies. The X-ray crystal structure of 4c is reported. The host-guest properties of these receptors toward several anions were investigated by H NMR titrations. Phenylurea 4a displayed a very efficient binding toward the spherical F and Cl anions, and the linear CN (log K = 3.46, 3.50, and 4.02, respectively). In comparison to related bidentate phenylurea dihomooxacalix[4]arenes, tetraphenylurea 4a is more preorganized and the higher number of hydrogen bond donor sites provides a remarkable enhancement of its binding efficiency.

In contrast to sulfonato-calix[4]arene (sclx4), which mediates close-packed assemblies, the higher charge carboxylate-containing sclx4mc induced a crystalline framework of cytochrome c.