A synthetic ion channel with anisotropic ligand response.

Biological membranes play pivotal roles in the cellular activities. Transmembrane proteins are the central molecules that conduct membrane-mediated biochemical functions such as signal transduction and substance transportation. Not only the molecular functions but also the supramolecular properties of the transmembrane proteins such as self-assembly, delocalization, orientation and signal response are essential for controlling cellular activities. Here we report anisotropic ligand responses of a synthetic multipass transmembrane ion channel. An unsymmetrical molecular structure allows for oriented insertion of the synthetic amphiphile to a bilayer by addition to a pre-formed membrane. Complexation with a ligand prompts ion transportation by forming a supramolecular channel, and removal of the ligand deactivates the transportation function. Biomimetic regulation of the synthetic channel by agonistic and antagonistic ligands is also demonstrated not only in an artificial membrane but also in a biological membrane of a living cell.

Synthesis, guest-binding, and reduction-responsive degradation properties of water-soluble cyclophanes having disulfide moieties.

Water-soluble cationic cyclophane having diphenyl disulfide moieties (1a) was synthesized as a reduction-responsive degradable host. The stoichiometry for the complex of 1a with anionic fluorescence guests, such as 4,4'-bis(1-anilinonaphthalene-8-sulfonate) (Bis-ANS) and 4-(1-pyrene)-butanoic acid (PBA), was confirmed to be 1:1 host:guest by a Job plot. The binding constants (K) of 1a toward Bis-ANS and PBA were evaluated to be 6.7 × 10(3) and 4.5 × 10(4) M(-1), respectively, as confirmed by fluorescence spectroscopy. Reduction of disulfide bonds of 1a by dithiothreitol gave its reduced form having poor guest-binding affinity that led to release of the entrapped guest molecules to the bulk aqueous phase. Meanwhile, anionic cyclophane 1b, which was derived from 1a by a reaction with succinic anhydride, binds cationic anticancer drugs, such as daunorubicin hydrochloride (DNR) and doxorubicin hydrochloride (DOX), with a K of 2.1 × 10(3) and 7.5 × 10(2) M(-1), respectively. A similar reduction-responsive guest release feature was observed when DNR and DOX were employed as a guest for complexation with 1b.