New Transmembrane Polyene Bolaamphiphiles as Fluorescent Probes in Lipid Bilayers

Abstract

The former view of the cell lipid membrane as a somewhat random and disordered distribution of lipids and proteins has given way to one characterized by a complex lateral organization, with nm-sized domains in which specific lipids and proteins are assembled to carry out a particular process. [1] The study of the morphology, composition, regulation, and persistence time of these structures is an experimental challenge that has been taken up by fluorescence probe methods. In the case of lipid ± lipid and lipid ± protein interactions, the dependence of the resonant transfer of electronic excitation on the proximity of donor and acceptor probe molecules can provide very useful information in the 10-nm range. [2] We have previously developed a series of fluorescent fatty acids that contain five conjugated double bonds at the end of a flexible linear chain. [3] These probes accurately report the changes in order and dynamics of the lipid environment in artificial and natural membranes. Furthermore, the large spectral overlap of the polyene absorption with the tryptophan fluorescence from membrane proteins and peptides is very convenient for energy-transfer experiments. However, the mobility of the energy-accepting polyene group in fluid bilayers may introduce some uncertainty into the distance evaluation. This would also be the case in other possible applications of the probes, such as the detection of oxidizing radicals by fluorescence quenching. To restrict the mobility of the chromophore, a linear structure with two polar terminal groups, that is, a bolaform amphiphile similar to the membrane lipids of Archaebacteria [4] would be ideal, with the additional advantage of precisely locating the sensing group of the probe in the bilayer. Bolaamphiphiles can be constructed with the appropriate length to reach both external membrane surfaces with the distal polar groups, and with a sensitive group in the lipophilic central part of the molecule. [5] Some transmembrane bolaamphiphiles have been produced previously for altering specific membrane properties: for example, compounds with p-benzoquinone or anthraquinone groups to change the redox behavior, [6] or conjugated polyenes derived from the natural product bixine to modify the charge-transfer rate across the bilayer. [7] Furthermore, bolaamphiphiles that contain photochemically reactive benzophenone [8] or diazirine [9] groups, or emitting fluorene [10] or anthracene groups, [11] have been also synthesized. A different but interesting fluorescent bolaform structure was also produced by linking two rhodamine 101 dye molecules with a C 32 linear chain. [12] Herein we describe the synthesis of symmetrical bolaamphiphiles with four, five, or six conjugated double bonds in the center of the molecule, with terminal methyl ester (4) or carboxylic acid (5) groups (Scheme 1), and with the appropriate length for spanning the lipid bilayer (Figure 1). The intermediates in the synthesis of the former compounds are conjugated polyenediyne diesters 3 that might also be useful t...

Lignin–polypropylene composites. II. Plasma modification of kraft lignin and particulate polypropylene

“…However, the opposite result was the case. Independent of this result, our earlier FRET experiments with related TM units already confirmed their extended self‐assembly inside the vesicle membrane (for details, see the Supporting Information) 22…”

Fluorescent Polyene Ceramide Analogues as Membrane Probes

“…The design of the probes was based on the combination of a conjugated pentaene group as fluorophore ,− and a doxyl carboxylic acid as a fluorescence quencher. The conformationally flexible butyric acid was used as a scaffold to append the above moieties, as indicated in Scheme .…”

Bolaamphiphiles

“…Cross-coupling of polyene diiodides and alkynes and the Stille reaction between two polyene iodide molecules and a bis(tributylstannyl)ethane were reasonably successful in syntheses of long-chain bolas. A C28 bola was, for example, isolated in a 60% overall yield . Asymmetric coupling of hydro- and fluorocarbon segments was achieved by simple mixing of an ω-iodofluorocarbon sulfonate and 10-undecenoic acid in an acetonitrile/water mixture in the presence of dithionite .…”