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1.D.303.  The 4,6-dihydroxy-isophthalamide Multiple Stimuli Responsive Anionophore   (MSR-A) Family

Artificial ion transport systems have emerged as an important class of compounds that promise applications in chemotherapeutics as anticancer agents or to treat channelopathies. Stimulus-responsive systems that offer spatiotemporally controlled activity for targeted applications remain rare. Ahmad et al. 2024 utilized dynamic hydrogen bonding interactions of a 4,6-dihydroxy-isophthalamide core to generate a modular platform enabling access to stimuli-responsive ion transporters that can be activated in response to a wide variety of external stimuli, including light, redox, and enzymes, with excellent OFF-ON activation profiles. Alkylation of the two free hydroxyl groups with stimulus-responsive moieties locks the amide bonds through intramolecular hydrogen bonding and hence makes them unavailable for anion binding and transport. Triggering using a particular stimulus to cleave both cages reverses the hydrogen bonding arrangement, to generate a highly preorganized anion binding cavity for efficient transmembrane transport. Integration of two cages that are responsive to orthogonal stimuli enables multi-stimuli activation, where both stimuli are required to trigger transport in an AND logic process. This strategy provides a facile method to post-functionalize the highly active transporter core with a variety of stimulus-responsive moieties for targeted activation with multiple triggers.

Stimulus-controlled anion binding and transport by synthetic receptors has been reported (de Jong et al. 2023).  Artificial receptors for anionic species can mediate transmembrane transport. de Jong et al. give a full overview of the stimulus-controlled anion receptors that have been developed thus far, including their application in membrane transport. In addition to their potential operation as membrane carriers, the use of anion recognition motifs in forming responsive membrane-spanning channels is discussed. With this review article, de Jong et al. 2023 hope to increase interest in transmembrane transport among scientists working on host-guest complexes and dynamic functional systems.

 

References associated with 1.D.303 family:

Ahmad, M., T.G. Johnson, M. Flerin, F. Duarte, and M.J. Langton. (2024). Responsive Anionophores with AND Logic Multi-Stimuli Activation. Angew Chem Int Ed Engl 63: e202403314. 38517056
de Jong, J., J.E. Bos, and S.J. Wezenberg. (2023). Stimulus-Controlled Anion Binding and Transport by Synthetic Receptors. Chem Rev 123: 8530-8574. 37342028