Multistate Redox-Switchable Ion Transport Using Chalcogen-Bonding Anionophores

Abstract

Synthetic supramolecular transmembrane anionophores have emerged as promising anticancer chemotherapeutics. However, key to their targeted application is achieving spatiotemporally controlled activity. Herein, we report a series of chalcogen-bonding diaryl tellurium-based transporters in which their anion binding potency and anionophoric activity are controlled through reversible redox cycling between Te oxidation states. This unprecedented in situ reversible multistate switching allows for switching between ON and OFF anion transport and is crucially achieved with biomimetic chemical redox couples.

Photo‐ and Redox‐Regulated Transmembrane Ion Transporters

“…Recently Langton and co-workers reported a Te based ionophore capable of reversible switching in ON to OFF (and viceversa), or OFF to ON to OFF multi-state switching modes. [62] This was achieved by careful control over the tellurium oxidation state in a small family of tellurium biaryl compounds, 50-55 (Figure 28a). The telluride and tellurone (Te II and Te VI , respectively) do not bind chloride, as revealed by NMR binding titrations, and are inactive transporters.…”

“…The redox‐responsive ion transporters discussed thus far are examples of irreversible OFF to ON switching. Recently Langton and co‐workers reported a Te based ionophore capable of reversible switching in ON to OFF (and vice‐versa), or OFF to ON to OFF multi‐state switching modes [62] . This was achieved by careful control over the tellurium oxidation state in a small family of tellurium biaryl compounds, 50 – 55 (Figure 28a).…”

Exploiting the Catenane Mechanical Bond Effect for Selective Halide Anion Transmembrane Transport

“…[34] In addition, we and others have demonstrated that sigma-hole based recognition strategies in anionophore design endow these host systems with unique selectivity profiles, which suggests this originates from an intrinsic property of the non-covalent interaction employed. [35][36][37][38][39][40][41][42][43][44][45][46][47] The development of anionophores capable of selective chloride transport over hydroxide and other oxoanions is particularly important in the context of biological systems which typically contain multiple anionic species. Achieving non-protonophoric chloride anion selectivity (Cl À > OH À / H + ) is also necessary to avoid disruption of cellular pH gradients for therapeutic applications.…”

Solution Studies of a Water-Stable, Trivalent Antimony Pnictogen Bonding Anion Receptor with High Binding Affinities for CN–, OCN–, and OAc–

“…Up to three of these sites can be induced. The stabilizing interaction that results from an electron donor interacting with this site has been termed a pnictogen bond (PnB), in analogy to the closely related halogen (XB) and chalcogen (ChB) bonds − which have been employed in the design of anion receptors. ,− ,− An important feature of these supramolecular interactions that distinguishes them from formal Lewis acids such as BX 3 , AlX 3 , or PnX 5 (Pn = pnictogen, X = halogen) is that they form with minimal geometric reorganization which results in reversible PnB, ChB, or XB formation without an activation barrier. , These receptors have been applied to form supramolecular capsules to mimic biological molecules, as cross-membrane anion transporting agents, ,,, and as catalysts in substitution reactions. , …”