2.B.101.  The pH-gated Cl--transporting Trazine-based Tripodal SemiCage (TTSC) Family

pH-gated chloride transport by a triazine-based tripodal semicage has been reported by Roy et al. 2017; Kumar and Madhavan 2023). Attachment of rigid 3,7-diazabicyclo[3.3.1]nonane arms to a planar triazine core formed a preorganized cavity (Fig. a below). This electron-rich cavity was capable of being protonated at acidic pH. Introduction of benzyl or pentafluorobenzyl groups at the ends of the rigid arms improved anion binding and membrane permeation (Fig. b below). An HPTS assay with vesicles showed that 4a has the highest transport activity. The compounds transport anions via a Cl/OH antiport mechanism with the anion transport trend being Cl ≫ SCN > Br > F > OAc > NO3 > ClO4. Mechanistic studies showed that the transport rate for Cl is higher than that for OH. Maximal chloride efflux was observed at pH 7 for 4a, and at pH 5.3 for 4b. These observations are attributed to the pKa values of 8.9 and 6.7 for compounds 4a and 4b, respectively (Kumar and Madhavan 2023).


 

References:

Kumar, N. and N. Madhavan. (2023). Small molecule-derived pH-gated ion transporters. Org Biomol Chem. [Epub: Ahead of Print]

Roy, A., D. Saha, P.S. Mandal, A. Mukherjee, and P. Talukdar. (2017). pH-Gated Chloride Transport by a Triazine-Based Tripodal Semicage. Chemistry 23: 1241-1247.