2.B.102.  The  Dimeric Melamine-substituted 3,7-Diazabicyclo[3.3.1]Nonane H+/Cl- Co-transporter (DMDN-C) Family

A dimeric melamine-substituted 3,7-diazabicyclo[3.3.1]nonane (5) H+/Cl co-transporter has been described (Shinde and Talukdar 2017).The crystal structure of 5 showed that two of the bispidine units are protonated. Ion transport studies using the HPTS assay in the presence of the proton transporter FCCP indicated that 5 preferentially transports H+ over OH ions. The transport study in the presence of valinomycin (K+ transporter) as well as the dependence of ion transport rates on the nature of extravesicular anions confirmed cooperative H+/Cl symport. Chloride transport was further confirmed using a lucigenin dye and a Cl ion-selective electrode. Cl efflux was maximal at pH 7.0, but decreased at a higher pH of 8.0 and a lower pH of 5.8. This pH dependence of chloride efflux was due to the protonation of the triazine ring N-atom at pH 7, which enhances chloride binding. Further lowering of pH resulted in the protonation of the other nitrogen atoms of the ring. This results in strong repulsion and loss of the dimeric anion-binding conformation (Kumar and Madhavan 2023).

  Enhanced chloride transport by bis-melamine derivative 5 at pH 7.



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

Shinde, S.V. and P. Talukdar. (2017). A Dimeric Bis(melamine)-Substituted Bispidine for Efficient Transmembrane H /Cl Cotransport. Angew Chem Int Ed Engl 56: 4238-4242.