2.B.103.  The Phenyl ThioSemiCarbazole Deriviative (PTSC-D) Family

Phenylthiosemicarbazoles (6) with an imine group adjacent to thiourea were reported to show a flat planar structure, presumably due to intramolecular H-bonding (Howe et al. 2016). The conformational locking of compound 6a-cis was confirmed because no change in the ¹H NMR chemical shift of the NH protons was observed upon titration with a chloride source in DMSO-d₆. These molecules function as ion carriers and co-transport H⁺/Cl⁻. Maximal ion transport was observed at pH 4.0 due to protonation of the imine and the resulting conformational freedom for compounds 6. 6a and 6b were found to be the most efficient among the compounds studied. The pH modulation was maximal for 6a, wherein the ratio of EC₅₀ at pH 7.2 to pH 4.0 was 640 compared to the 250 and ∼77 for 6b and 6c, respectively. The higher basicity of the imino-N of 6b than that of 6a resulted in the difference in the observed ion transport at pH 7. 7a–7c without an imine group showed no significant pH dependence.

  (a) Structures of phenyl semicarbazole ion transporters 6a–7c; (b) mechanism of pH-dependent conformationally driven Cl⁻ transport.