Cyanostilbenes as selective chloride carriers relying on CH-anion interactions

Achieving selectivity is one of the challenges in the development of anion receptors for transmembrane transport. Selectivity can be obtained by larger molecular designs to efficiently encapsulate the anion, or by the use of alternative binding motifs rather than the more commonly used NH-based hydrogen bond donors. Here we present a series of small chloride receptors based on α-cyanostilbenes, using CH-based hydrogen bonds. Upon varying the substituents, we found that the compound with four trifluoromethyl groups and a nitro group in addition to the two cyano groups showed the highest chloride affinity and chloride transport rates, outperforming reported triazole-based compounds. Furthermore, this compound showed clear selectivity for the transport of chloride over hydroxide, bicarbonate, and fluoride anions. The activity, selectivity, and deliverability of this compound makes it a promising candidate for therapeutic applications of chloride channelopathies.