1.D.56 The α-Aminoisobutyrate (Aib) Oligomeric Nanopore (AibNP) Family
An iterative synthesis of α-aminoisobutyric acid (Aib) oligomers was used to create a library of homologous rigid-rod 310-helical foldamers, which have incrementally increasing lengths and functionalizable N- and C-termini (Jones et al. 2016). This library was used to probe the inter-relationship of foldamer length, self- association strength, and ionophoric ability. Although foldamer self- association in nonpolar chloroform increased with length, with an approximately 14-fold increase in dimerization constant from Aib6 to Aib11, ionophoric activity in bilayers showed a stronger length dependence, with the observed rate constant for Aib11 approximately 70-fold greater than that of Aib6. The strongest ionophoric activity was observed for foldamers with >10 Aib residues, which have end-to-end distances greater than the hydrophobic width of the bilayers used ( approximately 2.8 nm); X-ray crystallography showed that Aib11 is 2.93 nm long. These studies suggest that being long enough to span the membrane is more important for good ionophoric activity than strong self- association in the bilayer. Planar bilayer conductance measurements showed that Aib11 and Aib13, but not Aib7, could form pores (Jones et al. 2016). This pore-forming behavior provides evidence that Aibm (m >/= 10) building blocks can span bilayers.