Artificial Ion Channel Formed by Cucurbit[n]uril Derivatives with a Carbonyl Group Fringed Portal Reminiscent of the Selectivity Filter of K⁺Channels

Abstract

Novel artificial ion channels (1 and 2) based on CB[n] (n = 6 and 5, respectively) synthetic receptors with carbonyl-fringed portals (diameter 3.9 and 2.4 A, respectively) can transport proton and alkali metal ions across a lipid membrane with ion selectivity. Fluorometric experiments using large unilamellar vesicles showed that 1 mediates proton transport across the membranes, which can be blocked by a neurotransmitter, acetylcholine, reminiscent of the blocking of the K+ channels by polyamines. The alkali metal ion transport activity of 1 follows the order of Li+ > Cs+ approximately Rb+ > K+ > Na+, which is opposite to the binding affinity of CB[6] toward alkali metal ions. On the other hand, the transport activity of 2 follows the order of Li+ > Na+, which is also opposite to the binding affinity of 2 toward these metal ions, but virtually no transport was observed for K+, Rb+, and Cs+. It is presumably because the carbonyl-fringed portal size of 2 (diameter 2.4 A) is smaller than the diameters of these alkali metal ions. To determine the transport mechanism, voltage-clamp experiments on planar bilayer lipid membranes were carried out. The experiments showed that a single-channel current of 1 for Cs+ transport is approximately 5 pA, which corresponds to an ion flux of approximately 3 x 107 ions/s. These results are consistent with an ion channel mechanism. Not only the structural resemblance to the selectivity filter of K+ channels but also the remarkable ion selectivity makes this model system unique.

The determination of the ion selectivity of synthetic ion channels and pores in vesicles

“…For an organic chemist entering the field without BLMs, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] LUVs provide a user friendly and, according to the comparative studies discussed below, valid alternative. Among several possible methods to determine anion/cation selectivity of synthetic ion channels in vesicles, the HPTS assay worked best in our hands (Fig.…”

Synthesis and X-ray Structure of the Inclusion Complex of Dodecamethylcucurbit[6]uril with 1,4-Dihydroxybenzene

“…The chemistry of cucurbit[n]uril (Q[n]s) has expanded dramatically with the discovery of cucurbituril(Q [6]) and its homologues (Q [5], Q [7], Q [8], and Q [10]) [1][2][3]. Recently, the direct functionalization of CB[n] [4][5][6] and introduction of building blocks for the preparation of Q[n] derivatives [7][8][9] and analogues [10][11] providing CB[n]s with solubility in both organic and aqueous solution has further expanded the range of the research and applications, which have been summarized in related reviews [12][13][14][15][16][17][18][19].…”

“…Recently, the direct functionalization of CB[n] [4][5][6] and introduction of building blocks for the preparation of Q[n] derivatives [7][8][9] and analogues [10][11] providing CB[n]s with solubility in both organic and aqueous solution has further expanded the range of the research and applications, which have been summarized in related reviews [12][13][14][15][16][17][18][19]. More recently, we have found that the solubilities of substituted cucurbit[n]urils (SQ[n]s) are dependent upon the kind, position and number of substituent groups on the substituted cucurbit[n]urils Q[n]s [20].…”

“…Since the discovery in 1992 of the first substituted Q[n], decamethylcucurbit [5] [8]. In this work, a similar approach to substituted cucurbituril synthesis is reported (Scheme 1), whereby one mole equivalent of monomethylglycoluril (1) was added to four mole equivalent of dimethylglycoluril (2) in 12 M HCl with the addition of formaldehyde to produce a mixture of methyl-substituted cucurbit[n=5,6]urils (Me-SQ [5,6]).…”

“…In this work, a similar approach to substituted cucurbituril synthesis is reported (Scheme 1), whereby one mole equivalent of monomethylglycoluril (1) was added to four mole equivalent of dimethylglycoluril (2) in 12 M HCl with the addition of formaldehyde to produce a mixture of methyl-substituted cucurbit[n=5,6]urils (Me-SQ [5,6]). From this mixture a very rare dodecamethycucurbit [6]uril (DDMeQ [6] shown in Scheme 2) can be obtained in moderate yield (compared to the yield of 0.2% in the literature method [22]).…”