Four new linear oligoesters containing a diphenylacetylene unit were prepared by fragment coupling sequences and the ion channel forming ability of the compounds was investigated. Activity in vesicles was very strongly controlled by overall length; the longest compound was effectively inactive. Planar bilayer studies established that all compounds are able to form channels, but that regular step changes in conductance depend on the location of the diphenylacetylene unit within the oligoester and on the electrolyte. The intrinsic fluorescence of the diphenylacetylene unit was used to probe aggregation and membrane localization. Both monomer (320 nm) and excimer (380 nm) emissions are quenched by copper ions; quenching of the excimer emission from an aqueous aggregate is very efficient. Time-dependent changes in the intensities of monomer and excimer emission show slow transfer of diphenylacetylene units from an aqueous aggregate to a membrane-bound monomer with subsequent growth of emission from a membrane-bound excimer. The latter species is not quenched by aqueous copper ions. The implications of these species and processes for the mechanism of ion channel formation by simple oligoesters are discussed.
The synthesis and membrane activity of a suite of linear oligoesters containing a common diphenylacetylene unit core and differing in the hydroxyl terminus are reported. Active compounds formed high-conductance channels efficiently in both vesicle and planar bilayers, with one compound showing a very unusual slow loss of transport activity over a 20-30 min period. Steady-state and time-resolved fluorescence studies establish the rapid partition of active compounds to the bilayer and identify at least three types of membrane-associated species by their differing fluorescence lifetimes. The change in the distribution of species is correlated with the slow loss of activity. The results are interpreted in terms of an aggregate within a single bilayer leaflet that is nonetheless competent to transport ionic species through the bilayer. The properties of such structures, revealed by these compounds, appear to be consistent with commonly observed behaviors of other synthetic ion channels.
Compact, fluorescent uracil aglycones and derivatives suitable for incorporation into the oligonucleotide mimic peptide nucleic acid (PNA) have been prepared by Sonogashira/CastroStephens coupling to monosubstituted phenylacetylenes. Cyclic 6-(phenyl)furo[2,3-d]pyrimidin-2(3H)-ones were accessed by the Ag + -catalyzed cyclization of the 5-alkynyluracil precursors. Although this reaction was sluggish, it gave quantitative chemical yields. Electron-rich alkynes, such as p-methoxyphenylethyne, cyclize much more rapidly than electron-deficient alkynes. Adjustment of the reaction conditions permitted the synthesis of p-nitrophenylfuranouracil in excellent yield.
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