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

Dissecting the chloride–nitrate anion transport assay

A systematic study of chloride vs. nitrate selectivity across six anion transporters has revealed a good correlation between the selectivities of their anion binding and membrane transport properties. This work reveals the limitations of the chloride–nitrate exchange assay and shows how new approaches can be used to measure anion uniport.ARC, JSPS, University of Sydney, Kyushu Universit

High-affinity anion binding by steroidal squaramide receptors

Exceptionally powerful anion receptors have been constructed by placing squaramide groups in axial positions on a steroidal framework. The steroid preorganizes the squaramide NH groups such that they can act cooperatively on a bound anion, while maintaining solubility in nonpolar media. The acidic NH groups confer higher affinities than previously-used ureas or thioureas. Binding constants exceeding 1014?M?1 have been measured for tetraethylammonium salts in chloroform by employing a variation of Cram’s extraction procedure. The receptors have also been studied as transmembrane anion carriers in unilamellar vesicles. Unusually their activities do not correlate with anion affinities, thus suggesting an upper limit for binding strength in the design of anion carrier

Chloride anion transporters inhibit growth of methicillin-resistant: Staphylococcus aureus (MRSA) in vitro

A series of aminopyrrolic receptors were tested as anion transporters using POPC liposome model membranes. Many were found to be effective Cl(−) transporters and to inhibit clinical strains of Staphylococcus aureus growth in vitro. The best transporters proved effective against the methicillin-resistant Staphylococcus aureus (MRSA) strains, Mu50 and HP1173. Tris-thiourea tren-based chloride transporters were also shown to inhibit the growth of S. aureus. in vitro

Chloride anion transporters inhibit growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro

A series of aminopyrrolic receptors were tested as anion transporters using POPC liposome model membranes. Many were found to be effective Cl– transporters and to inhibit clinical strains of Staphylococcus aureus growth in vitro. The best transporters proved effective against the methicillin-resistant Staphylococcus aureus (MRSA) strains, Mu50 and HP1173. Tris-thiourea tren-based chloride transporters were also shown to inhibit the growth of S. aureus. in vitro.<br/

pH-regulated nonelectrogenic anion transport by phenylthiosemicarbazones

Gated ion transport across biological membrane is an intrinsic process regulated by protein channels. Synthetic anion carriers (anionophores) have potential applications in biological research, however, previous reported examples are mostly nonspecific, capable of mediating both electrogenic and electroneutral (non-electrogenic) transport processes. Here, we show the transmembrane Cl? transport studies of synthetic phenylthiosemicarbazones mimicking the function of acid-sensing (proton-gated) ion channels. These anionophores have remarkable pH-switchable transport properties with up to 640-fold increase in transport efficacy on going from pH 7.2 to 4.0. This “gated” process is triggered by protonation of the imino nitrogen and concomitant conformational change of the anion binding thiourea moiety from anti to syn. By using a combination of two cationophore-coupled transport assays, with either monensin or valinomycin, we have elucidated the fundamental transport mechanism of phenylthiosemicarbazones which is shown to be non-electrogenic, inseparable H+/Cl? cotransport. This study demonstrates the first examples of pH-switchable non-electrogenic anion transporter

Thiosquaramides: pH switchable anion transporters

The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquar-amides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH

Full elucidation of the transmembrane anion transport mechanism of squaramides using in silico investigations

A comprehensive experimental and theoretical investigation of the transmembrane chloride transport promoted by four series of squaramide derivatives, with different degrees of fluorination, number of convergent N-H binding units and conformational shapes, is reported. The experimental chloride binding and transport abilities of these small synthetic molecules in liposomes were rationalised with quantum descriptors and molecular dynamics simulations in POPC bilayers. The tripodal tren-based compounds, with three squaramide binding motifs, have high chloride affinity, isolating the anion from water molecules within the membrane model and preventing its release to the aqueous phase, in agreement with the absence of experimental transport activity. In contrast, the symmetrical monosquaramides, with moderate chloride binding affinity, are able to bind and release chloride either in the aqueous phase or at the membrane interface level, in line with experimentally observed high transport activity. The PMF profiles associated with the diffusion of these free transporters and their chloride complexes across phospholipid bilayers show that the assisted chloride translocation is thermodynamically favoured

Acylthioureas as anion transporters: the effect of intramolecular hydrogen bonding

Small molecule synthetic anion transporters may have potential application as therapeutic agents for the treatment of diseases including cystic fibrosis and cancer. Understanding the factors that can dictate the anion transport activity of such transporters is a crucial step towards their application in biological systems. In this study a series of acylthiourea anion transporters were synthesised and their anion binding and transport properties in POPC bilayers have been investigated. The transport activity of these receptors is dominated by their lipophilicity, which is in turn dependent on both substituent effects and the formation and strength of an intramolecular hydrogen bond as inferred from DFT calculations. This is in contrast to simpler thiourea systems, in which the lipophilicity depends predominantly on substituent effects alone