Crystal structure of a polyfunctional macrocyclic K⁺ complex provides a solid-state model of a K⁺ channel

Abstract

Molecular channels are thought to be important in ion exchange processes across membranes, and biophysical and physiological data point to the existence of ion-specific Na⁺ and K⁺ pores (see, for example, refs 1,2). The nature and structure of these entities, as well as the molecular mechanism of ion flow through channels, are still largely unknown, whereas cation transport via facilitated diffusion by natural or synthetic carrier molecules has been extensively investigated in both natural and model membrane systems^3–5. The formation of transmembrane cation channels has been studied mainly with linear peptides (gramicidin A, alamethicin; refs 3,7, and refs 6,8 and refs therein). The cylindrical macrotricyclic molecules are suitable model species for investigating both the synthetic construction of molecular channel subunits and their cation binding properties as they form cation inclusion complexes of cryptate type and undergo intramolecular cation jump processes^9–11. We report here the crystal structure of the potassium complex (1, 1.5 KBr, 3.5 H₂O) of the chiral macrocyclic tetracarboxamide 1, a member of a group of functionalized macrocyclic polyethers^12,13 which strongly bind alkali and ammonium cations¹⁴. This structure presents a solid-state model of a molecular channel, in which the macrocyclic units are organized in a polymolecular stack and the K⁺ cations are located alternatively inside and on top of successive macrocycles, as in a frozen picture of potassium ion propagation through the stack.