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1.D.174.  The Synthetic Self-assembled 2-Hydroxy-N1,N3-diarylIsophthalamide (SSHI) Family

The isophthalamide core has been used to develop small-molecule ion transporters. The isopthalamide core was modified by functionalizing position 2 with a hydroxyl group to give 2-hydroxy-N1,N3-diarylisophthalamide connected to two identical aromatic side arms to vary the lipophilicity for better permeation and pKa values of the amide NHs (Malla et al. 2021). It was expected that the intramolecular C=O⋅⋅⋅H−O, and C−O⋅⋅⋅H−N interactions would provide a preorganized geometry of individual monomers. The intermolecular π-π stacking interactions among aromatic rings and hydrogen bonding interactions among amide moieties should lead to the aggregation of individual monomers in the membrane to form an active channel. Recognition sites for cations can be provided by either C−F or C=O moieties via cation-dipole interactions. Such systems are selective for M+/Cl ion transport. Channel formation was supported by planar bilayer conductance studies, and molecular dynamics simulation studies supported the dimeric self-assembly of individual monomers and M+/Cl selective nature of the channel (Malla et al. 2021).

References associated with 1.D.174 family:

Malla, J.A., M. Ahmad, and P. Talukdar. (2021). Molecular Self-Assembly as a Tool to Construct Transmembrane Supramolecular Ion Channels. Chem Rec. [Epub: Ahead of Print] 34766703