Stimuli-Responsive Anion Transport through Acylhydrazone-Based Synthetic Anionophores

Abstract

Photoswitchable acylhydrazone-based synthetic anionophores are reported. Single-crystal X-ray structure and 1 H NMR titration studies confirmed the chloride binding in solid and solution states. The ion transport activity of 1a was greatly attenuated through a phototriggered E to Z photoisomerization process, and the photoisomerized deactivated state showed high kinetic stability due to an intramolecular hydrogen bond. Switchable "OFF−ON" transport activity was achieved by the application of light and acid-catalyzed reactivation process.

Progress and prospects toward supramolecular bioactive ion transporters

“…Recently, highly selective methods, including stimuli-responsive protransporters, have been developed by several research groups including us to achieve control over the locus of action of the anionophores. 61,79,85,[87][88][89][90][91][92][93][94][95][96][97][98][99][100] Taken together, synthetic ion transport systems undoubtedly possess immense potential to be used as therapeutic agents in curing life-threatening diseases like cystic fibrosis and cancer. This field has grown rapidly, and new systems with improved efficiencies have recently been reported.…”

“…We realized that acylhydrazone moiety could be tuned to generate a suitable binding site for the recognition of anions. Based on this understanding, we designed a class of acylhydrazone-based ion carriers 89 as shown in Fig. 28.…”

“…Recently, highly selective methods, including stimuli-responsive protransporters, have been developed by several research groups including us to achieve control over the locus of action of the anionophores. 61,79,85,87–100…”

Multistate Redox-Switchable Ion Transport Using Chalcogen-Bonding Anionophores

“…However, from a clinical perspective, it is highly desirable to develop anion transporter systems that exhibit controllable behavior (i.e., stimuli-responsive activity as a means of selectively targeting specific tissue). To this end, photoswitchable systems have demonstrated considerable promise, wherein modulation of anion binding behavior by light-induced isomerization in mobile carrier and membrane-anchored systems − can effectively switch ON or OFF anion transport. However, another potential strategy toward achieving spatiotemporally controlled anion transport is developing anionophores that are responsive to the target cell’s intrinsic physiological environment .…”

Reversible Stimuli‐Responsive Transmembrane Ion Transport Using Phenylhydrazone‐Based Photoswitches

“…Acylhydrazones, especially those derived from pyridine‐2‐aldehyde, possess high thermal stability in the photoisomerized Z ‐state because of the formation of six‐membered intramolecular hydrogen bonding between the acylhydrazone N−H and the pyridine nitrogen [8] . Very recently, we have demonstrated the stimuli‐responsive anion transport by a class of acylhydrazones whose activity can be minimized by light and regained upon back‐isomerization in the presence of an acid stimulus [5e] . However, acylhydrazones require harmful bio‐incompatible UV radiations (∼312 nm) for the photoisomerization process.…”