Anion transport by ortho-phenylene bis-ureas across cell and vesicle membranes.

Ortho-Phenylene bis-ureas serve as anionophores in cells expressing halide-sensitive yellow fluorescent protein, as well as in synthetic vesicles. Activities can reach high levels, and are strongly dependent on the deliverability of the transporters.

A synthetic ion transporter that disrupts autophagy and induces apoptosis by perturbing cellular chloride concentrations.

Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.

Tris-ureas as transmembrane anion transporters.

Nine tris-urea receptors (L(1)-L(9)) have been synthesised and shown to coordinate to a range of anionic guests both by (1)H NMR titration techniques and single crystal X-ray structural analysis. The compounds have been shown to be capable of mediating the exchange of chloride and nitrate and also chloride and bicarbonate across POPC or POPC : cholesterol 7 : 3 vesicle bilayer membranes at low transporter loadings. An interesting dependency of anion transport on the nature of the cation is evidence to suggest that a M(+)/Cl(-) cotransport process may also contribute to the release of chloride from the vesicles.

Anion binding and transport properties of cyclic 2,6-bis(1,2,3-triazol-1-yl)pyridines.

A series of cyclic 2,6-bis-(1,2,3-triazolyl)-pyridine anion receptors with thiourea functionalities were synthesized by click reaction of 2,6-diazidopyridine with protected propargylamine followed by condensation of a bisthiocyanate derivative with a series of diamines. Their chloride binding affinities as well as their transport properties in POPC bilayers were examined. These receptors were found to function as anion carriers, which can mediate both Cl(-)/NO3(-) antiport and H(+)/Cl(-) symport, and the transport activity of these hosts were dominated by their lipophilicity.

Anion complexation, transport and structural studies of a series of bis-methylurea compounds.

A new family of bis-methylureas () have been synthesised and their ability to bind anions both in solution and in the solid state and to transport them through lipid membrane have been studied. From the solid state studies it has emerged that various conformations can be adopted by the receptors allowing the isolation of complexes of different stoichiometries (from 1 : 1 to 1 : 3). The transport studies highlighted the possibility to use bis-methylureas to mediate Cl(-) transport across membranes.

Highly effective yet simple transmembrane anion transporters based upon ortho-phenylenediamine bis-ureas.

Simple, highly fluorinated receptors are shown to function as highly effective transmembrane anion antiporters with the most active transporters rivalling the transport efficacy of natural anion transporter prodigiosin for bicarbonate.

Anion receptor chemistry: highlights from 2011 and 2012.

This review covers advances in anion complexation in the years 2011 and 2012. The review covers both organic and inorganic systems and also highlights the applications to which anion receptors can be applied such as self-assembly and molecular architecture, sensing, catalysis and anion transport.

Further insight into the coordination of 2,5-dicarbothioamidopyrroles: the case of Cu and Co complexes.

The coordination chemistry of 2,5-dicarbothioamidopyrrole ligands, namely N2,N5-dibutyl-3,4-diphenyl-1H-pyrrole-2,5-bis(carbothioamide) and N2,N5,3,4-tetraphenyl-1H-pyrrole-2,5-bis(carbothioamide), has been investigated with Cu(II) metal centres by means of X-ray crystallography. This resulted in the formation of the expected planar S,N,S' coordinated complex for the former ligand and unexpected ring-closure reactions, with formation of benzothiazole sidearms, for the latter. Both Cu(II) and Cu(I), used in large excess, were found to favour the ring-closure reaction, although the structural characterisation of the resulting complexes contained only Cu(II) cations, with varying coordination geometries ranging from square planar and square-based pyramidal to tetrahedral. By repeating the reaction using a slight excess of Cu(II) (2 : 1) two more different structures were obtained where the metal was coordinated to the original ligand, N2,N5,3,4-tetraphenyl-1H-pyrrole-2,5-bis(carbothioamide), or to the mixed ligand where only one of the thioamide substituents had converted to a benzothiazole. The essential role of Cu for the ring closure reaction was also established by comparing its complex with structural features of the analogous Co(II) complex, the latter revealing no ring closure to give benzothiazole substituents and co-crystallisation of a mixed Co(II)/Co(III) complex. Finally, the structure and photophysical properties of the corresponding 3,4-diphenyl-2,5-bis(benzothiozol-5-yl)-pyrrole ligand, obtained via treatment of the thioamide with K(3)[Fe(CN)(6)], were also investigated revealing a blue-centered emission.