Role of Lipophilicity in the Activity of Hexameric Cyclic Peptoid Ion Carriers

Two families of hexameric cyclic peptoids decorated with linear N-alkyl and alternated N-alkyl/N-benzyl side chains (2 a-d and 3 a-c, respectively) were designed and synthesized in order to correlate their logP values (from 2.55 to 6.83) to their ionophoric activities. The present contribution confirms the general ability of hexameric cyclic peptoids to behave as efficient cation carriers, corroborates their preference for Na+ ion, among the tested alkali metals, and suggests a Na+/H+ antiport transport mechanism (rate limited by the transport of the proton) for these new ionophores. Our observations indicate that in order to attain an efficient ionophoric activity, a narrow range of liphophilicity is required (4<5). Moreover, to gain information on the solid state stucture of ionophoric cyclic peptoids with linear N-side chains, X-ray crystallographic studies were performed on exemplar compound 2 a. Crystal structure of compound 2 a confirms the tendency of ionophoric cyclopeptoids with linear N-side chains to form layered assemblies.

Automated summary

Two families of hexameric cyclic peptoids with different alkyl side chains were synthesized and their ionophoric activities were studied, showing a preference for Na+ ions and a potential Na+/H+ antiport transport mechanism. X-ray crystallographic studies on linear N-side chain ionophoric cyclic peptoids revealed a tendency to form layered assemblies.