Synthetic transporters for sulfate: a new method for the direct detection of lipid bilayer sulfate transport

Abstract

The transmembrane transport of anions by small synthetic molecules is a growing field in supramolecular chemistry and has focussed mainly on the transmembrane transport of chloride. On the other hand, the transport of the highly hydrophilic sulfate anion across lipid bilayers is much less developed, even though the inability to transport sulfate across cellular membranes has been linked to a variety of genetic diseases. Tris-thioureas possess high sulfate affinities and have been shown to be excellent chloride and bicarbonate transporters. Herein we report the sulfate transport abilities of a series of tris-ureas and tristhioureas based on a tris(2-aminoethyl)amine or cyclopeptide scaffold. We have developed a new technique based on 33 S NMR that can be used to monitor sulfate transport, using 33 S-labelled sulfate and paramagnetic agents such as Mn 2+ and Fe 3+ to discriminate between intra-and extravesicular sulfate. Reasonable sulfate transport abilities were found for the reported tris-ureas and tris-thioureas, providing a starting point for the development of more powerful synthetic sulfate transporters that can be used in the treatment of certain channelopathies or as a model for biological sulfate transporters.

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

“…These are hydrophilic species 15 that are typically not transported through POPC membranes. 16 Therefore, we infer that under these experimental conditions, anion antiport should not contribute to the efflux of chloride from the liposome. Studies involving compound 5 were also carried out when the external sulphate anion was replaced by either NO 3 − or HCO 3 − (as the sodium salts).…”

“…These species are known to act primarily as anion exchangers (e.g., Cl − for HCO 3 − and Cl − for SO 4 2− ), rather than as ion pair cotransporters. 2,16 …”

Anion recognition by cyclic peptides

“…Somewhat surprisingly, the affinity of the preorganised cryptand 52 for sulfate ions in the more competitive 25% v/v H 2 O/DMSO-d 6 The high sulfate selectivity and affinity observed for receptors 46, 52 and 53 and their apparent ability to shield this anion from the environment led to an examination of their ability to function as transmembrane anion transporters. 81 This study used a new technique to monitor sulfate transport, using 33 S-labelled sulfate and paramagnetic agents such as Mn 2+ and Fe 3+ to discriminate between intra-and extravesicular sulfate by 33 S NMR experiments. Cryptand 53 was the only cyclic peptide based receptor that was found to function as an anion transporter and this was attributed to its cage-like structure that offers nine hydrogen bonds to its anionic guest and screens the anion from the membrane environment.…”

Recognition and Extraction of Cesium Hydroxide and Carbonate by Using a Neutral Multitopic Ion‐Pair Receptor

“…For example, in the case of the highly hydrated sulfate anion (SO 4 2− ; ΔG hyd = −1018 kJ·mol −1 ), [3] notable progress has been made in the areas of through-membrane transport, liquid-liquid extraction, and selective crystallization. [4] This has led us to consider whether it might be possible to exploit anion recognition for the purpose of adjusting pH. However, the recognition and extraction of both anionic carbonate and monoanionic hydroxide has remained elusive, perhaps because of their high hydration energies (−1315 kJ·mol −1 and −430 kJ·mol −1 for CO 3 2− and OH − , respectively), [3] strong basicity, and potential nucleophilicity.…”