1.D.209. The Pyridine-2,6-Dicarboxamide (PDA) Unit in a Macrocycle (PDA-MC-ACh) Family Chen et al. 2018 designed a unimolecular anion channel by combining three known motifs in the arena of synthetic channels (see figure below) Pyridine-2,6-dicarboxamide (PDA) units, embedded in a macrocycle (Yamnitz et al. 2010), were attached to lipophilic rods (Sisson et al. 2006). The authors hypothesized that PDA rings on phenylene ethylene oligomers (OPE 53_n) would stack on an edge of the rod and provide a pipeline for anion transport. OPE 53₃, estimated to be 3.3 nm long, was the top anion transporter (EC₅₀ = 0.36 μM in EYPC LUVs); it is selective for Cl⁻ and functions via H⁺/Cl⁻ co-transport. The linear relationship between k_obs for anion transport and concentration of OPE 53₃ suggested it functions as a unimolecular transporter (Davis et al. 2020). Voltage-clamp experiments were consistent with single channels, showing open lifetimes of seconds, and a large conductance of 0.6 nS was reported for OPE 53₃. Drawbacks associated with multi-step synthesis of OPE 53 may be outweighed by the pre-organisation of ion binding sites along a membrane-spanning rod. OPE 53. Schematic showing how OPE 53 (n = 3) enables ion flow across a membrane. Copyright 2018, Royal Society of Chemistry.
References:
Chen, S., , Y. Zhao, , C. Bao, , Y. Zhou, , C. Wang, , Q. Lin, , and L. Zhu,. (2018). A well-defined unimolecular channel facilitates chloride transport. Chem Commun (Camb) 54: 1249-1252.
Davis, J.T., P.A. Gale, and R. Quesada. (2020). Advances in anion transport and supramolecular medicinal chemistry. Chem Soc Rev. [Epub: Ahead of Print]
Sisson, A.L., M.R. Shah, S. Bhosale, and S. Matile. (2006). Synthetic ion channels and pores (2004-2005). Chem Soc Rev 35: 1269-1286.
Yamnitz, C.R., S. Negin, I.A. Carasel, R.K. Winter, and G.W. Gokel. (2010). Dianilides of dipicolinic acid function as synthetic chloride channels. Chem Commun (Camb) 46: 2838-2840.