The Characterization of Synthetic Ion Channels and Pores

The structural classification of synthetic ion channels and pores differentiates between (macro)molecules and different classes of supramolecules [2]. Unimolec-ular synthetic ion channels and pores are usually hollow, often helical (macro)mol-ecules that are long enough to span common lipid bilayer membranes (2-4 nm). 

Transport of ions and molecules (filled circles) across lipid bilayer membranes (grey) by (a) ion channels and pores (b) carriers (c) endovesiculators and (d) fusogens (empty black symbols). 

Virtual vertical cutting of this unimolecular barrel gives the barrel-stave , horizontal cutting the barrel-hoop , horizontal and vertical cutting the barrel-rosette motif (Fig. 11.2). More complex motifs that include modification of the lipid bilayer are summarized as micellar pores. 

The barrel-stave architecture is a classic for both biological and synthetic ion channels and pores (Fig. 11.3). Whereas barrel-hoop motifs have received considerable attention, barrel-rosette ion channels and pores are just beginning to emerge. The more complex micellar (or toroidal ) ion channels and pores are, on the one hand, different from detergents because the micellar defects introduced into the lipid bilayer are only transient. Micellar pores differ, on the other hand, from membrane-spanning (i.e. transmembrane ) barrel-stave pores because (a) they disturb the bilayer suprastructure and (b) they always remain at the membrane-water interface. A representative synthetic barrel-stave pore is shown in Fig. 11.3 [3, 4] comprehensive collections of recently created structures can be found in pertinent reviews [2], 

Two main methods exist to characterize synthetic ion channels and pores [2], Conductance experiments in planar or black lipid membranes (BLMs) reveal the 

---

S. Matile and N. Sakai, The characterization of synthetic ion channels and pores, in Analytical Methods in Supramolecular Chemistry, ed. C. A. Schalley, John Wiley Sons, Wein-heim, 2007, pp. 391-418. 

Determination of the pH profile of a synthetic ion channel or pore early on is important to focus the further, often time consuming in-depth characterization on the pH of relevant activity [19, 21]. pH sensitivity is usually introduced with acidic or basic functional groups with a pKa near the pH of interest. Synthetic ion channels and pores with multiple acids or bases in the ion-conducting pathway exhibit parabolic pH profiles (Fig. 11.6). With fractional activity normalized between minima and maxima (7 = 0 at pHmin, T = 1 at pHmax), characteristics such as pHmax,... 

Fig. 11.10. Synthetic multifunctional ion channels and pores either (A) open or (B) close in response to chemical stimulation. Dose response curves for (A) ligand gating or (B) blockage are characterized by effective (EC50) or inhibitory concentrations (/C50) and Hill coefficients (n). (C) Woodhull analysis of the voltage dependence of blockage reveals the depth of molecular recognition. (D) The special case of blockage by permeant electrolytes is described by /C50 and gwAX (the maximal conductance).

---