2.B.105.  The Pyridyl-linked Benzimidazolyl hydrazone H⁺/Cl⁻ coTransporter (P-BH-T) Family 

Pinaki Talukdar and co-workers reported pyridyl-linked benzimidazolyl hydrazones 11–13 as H⁺/Cl⁻ co-transporters (top figure below; Mondal et al. 2021). The pyridyl N in the more favourable imino tautomer gets protonated, enhancing the chloride affinity of the molecule. The efficiency of the HCl transporter (11) with an EC₅₀ value of 0.000022 mol% is 5-fold higher than that of the natural transporter prodigiosin.

Protonation of the pyridine N-center gives rise to transport of HCl by transporter 11.

Pinaki Talukdar and the group have reported bis(amido)imidazole (14) that transports the Cl⁻ ion in its protonated form (Shinde and Talukdar 2019).  H NMR binding studies with the deprotonated form showed negligible binding of the Cl⁻ ion. The protonated receptor 14a·HPF₆ showed anion binding with the affinities following the trend Cl⁻ (K_a = 8041 ± 55 M⁻¹) > Br⁻ (K_a = 7215 ± 256 M⁻¹) > I⁻ (K_a = 2245 ± 187 M⁻¹). Imidazole N can be protonated under physiological conditions as it has a pK_a of ∼6.4–7.0. The most efficient chloride transporter 14a has an EC₅₀ value of 8.73 mol% with a selectivity order of Cl⁻ > F⁻ ≈ AcO⁻ > SCN⁻ > I⁻ ≈ Br⁻ > ClO₄⁻ > NO₃⁻. Mechanistic studies showed H⁺/Cl⁻ symport via a carrier mechanism.

  Bis(amido)imidazole derivatives show H⁺/Cl⁻ co-transport in the protonated state.

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