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 thiosquaramides 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 pK_a 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.

A number of macrocyclic squaramide-containing receptors (MSQs) have been designed and synthesised and their interaction with a range of inorganic anions was studied in solution by ¹H NMR spectroscopy and ESI-HRMS. The binding data revealed remarkable binding of sulfate in aqueous mixtures from 0.5 to 50% v/v H₂O/DMSO-d₆. The larger [3]-MSQs were found to better match the size and shape of the sulfate ion than the [2]-MSQs, providing high affinity and selectivity for sulfate while other tetrahedral divalent anions such as selenate, phosphate species and chromate have substantially lower binding affinities. In mixtures of anions mimicking the composition of either nuclear waste or plasma, the [3]-MSQs were still able to bind sulfate ions with high affinity.

Large tumours contain regions with very low intracellular O₂ concentrations. Known as hypoxia, this feature of tumours yields a highly reducing environment owing to the presence of numerous oxygen sensitive reductase enzymes. The development of new optical chemosensors for these various reductases presents an ideal approach to visualise areas of hypoxia or highly reducing environments. Critical to the success of such chemosensors is the design of probes containing a bioreductively activated moiety that either ensures the selective retention of fluorescence within a hypoxic tissue or a probe that irreversibly releases a reporter fluorophore. This Feature Article aims to summarise the fluorescent tools that have been developed to image tumour hypoxia and the various reductase enzymes associated with the bioreduction process.