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.
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− (Ka = 8041 ± 55 M−1) > Br− (Ka = 7215 ± 256 M−1) > I− (Ka = 2245 ± 187 M−1). Imidazole N can be protonated under physiological conditions as it has a pKa 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.
References associated with 2.B.105 family:
Mondal, A., J.A. Malla, H. Paithankar, S. Sharma, J. Chugh, and P. Talukdar. (2021). A Pyridyl-Linked Benzimidazolyl Tautomer Facilitates Prodigious H/Cl Symport through a Cooperative Protonation and Chloride Ion Recognition. Org Lett 23: 6131-6136. 34319120
Shinde, S.V. and P. Talukdar. (2019). Transmembrane H/Cl cotransport activity of bis(amido)imidazole receptors. Org Biomol Chem 17: 4483-4490. 30984952