Ion Conductors Derived from Cholic Acid and Spermine:  Importance of Facial Hydrophilicity on Na⁺ Transport and Membrane Selectivity

Abstract

A series of ion conductors have been synthesized in which the degree of facial hydrophilicity has been systematically varied. Specifically, conjugates have been prepared from cholic acid and spermine in which the hydrophilic face of each sterol bears methoxy (1), hydroxy (2), carbamate (3), or sulfate groups (4). The ability of these conjugates to promote the transport of Na(+) across phosphatidylcholine membranes of varying thickness has been investigated by (23)Na NMR spectroscopy. Examination of observed activities in three different phosphatidylcholine membranes has provided evidence for membrane-spanning dimers as the transport-active species. In the thinnest membranes investigated, made from 1,2-dimyristoleoyl-sn-glycero-3-phosphocholine (C14), Na(+)-transport activity was found to increase, substantially, with increasing facial hydrophilicity. In thicker membranes, made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (C18), observed activities were found to decrease with increasing facial hydrophilicity; with a membrane of intermediate thickness, prepared from 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (C16), ion-conducting activity increased and then decreased, with continuous increases in facial hydrophilicity. The possible origins for these variations in activity are briefly discussed.

Mapping Interactions between Germinants and Clostridium difficile Spores

“…Methoxylated taurocholate analogs (3-methoxy-7,12-dihydroxytaurocholate [T09] and 3,7-dimethoxy-12-hydroxytaurocholate [T10]) were prepared following published procedures (3). Briefly, to a solution of taurocholate (1 equivalent) in dry 1,4-dioxane, methyl iodide (50 equivalents) and sodium hydride (4 equivalents) were added under nitrogen.…”

Transmembrane pores formed by synthetic p -octiphenyl β-barrels with internal carboxylate clusters: Regulation of ion transport by pH and Mg 2+ - complexed 8-aminonaphthalene-1,3,6-trisulfonate

“…It was, however, not possible to reach saturation under experimentally accessible conditions. The induced CD Cotton effect for ANTS was observed with transmembrane pore 1 4 in the presence (F) but not in the absence (E) of 20 mM Mg(OAc) 2 (Fig. 9).…”

“…The development of design strategies for the construction of easily variable active sites at the inner surface of transmembrane pores is the first step toward such organic chemistry within confined anisotropic space. In sharp contrast to breathtaking progress being made with biotechnologically modified natural pores (1), reliable and general design strategies for synthetic ion channels and pores with easily variable internal active sites do not exist (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Reasonably straightforward covalent synthesis of barrel-like macromolecules with the required Ϸ3.5-nm height and variably functionalizable interior of Ն1.0 nm diameter is not (yet) possible.…”

“…Reasonably straightforward covalent synthesis of barrel-like macromolecules with the required Ϸ3.5-nm height and variably functionalizable interior of Ն1.0 nm diameter is not (yet) possible. The more straightforward noncovalent syntheses (16)(17)(18)(19)(20) applied to barrellike supramolecules with ion channel activity is, with one possible exception (15), limited by apparent difficulties to position functional groups at internal concave surfaces (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). However, we have recently found that this trend toward ''peripheral crowding'' in supramolecular synthesis (16)(17)(18)(19)(20) can be bypassed in artificial ␤-barrels with p-octiphenyl ''staves'' and have used their rationally designed hydrophobic, ionophoric, and cationic interior to encapsulate guests with complementary characteristics in water and bilayer membranes (21,22).…”

Bile acid-polyamine conjugates as synthetic ionophores

“…These molecules could find use in the development of novel ionophoric devices. 4 The ultimate goal of this review is to discuss the recently designed pore forming amphiphiles/ionophores that can "punch" holes in the plasmamembrane of bacterial and fungal cells, but not in mammalian membranes. Such holes are expected to result in the rapid release of vital cellular constituents and ultimately in cell death.…”