Photocontrol of ion permeation in lipid vesicles with amphiphilic dithienylethenes

Abstract

The integration of photochromic dithienylethenes (DTEs) with lipid vesicles as photoresponsive membrane disruptors for ion transport applications has been examined. We have synthesized three amphiphilic DTEs 1-3 that incorporate a terminally charged alkyl chain, and contain methyl or phenylethynyl substituents at the reactive carbons. Our photochromic reactivity studies suggest that the inclusion of a single alkyl chain favors the photoactive antiparallel conformation of DTEs, given the significant improvement in the cyclization quantum yield over previous phenylethynyl derivatives. Our ion permeation studies show that the open-ring isomers of these DTEs are more disruptive than the closed-ring isomers in the four lipid vesicle systems studied, regardless of their lamellar phase at room temperature. In addition, a steric effect was clearly observed as DTEs incorporating the comparatively smaller methyl group exhibited lower rates of ion permeation than the bulkier phenylethynyl group. In all cases, UV irradiation led to a reduction in ion permeability. In fact, the methyl analog exhibited a significant reduction in ion permeability in gel-phase lipid vesicles upon UV exposure. Also, the hexyl chain derivatives had a greater effect on membrane permeability than the dodecyl derivative owing to their relative position in the bilayer membrane of lipid vesicles.

Synthesis of amphiphilic asymmetrical dithienylethenes with aryl groups at the reactive carbons

“…The coupling of 17 with 18 was expected to produce the precursor to the DTE dimer; however, this coupling reaction, like that for 1 and 3, was unsuccessful. As discussed earlier, our group reported a coupling yield of 42% for the equivalent monomer without methyl groups at the 4-and 4'-positions 2. If we assume that the presence of methyl substituents reduces the relative coupling yield by ~43%, an upper limit of ~24% (i.e., 42%-(0.43  42%)) is estimated for the coupling yield of the dimer precursor.…”

“…2,4-Dibromo-3-methylthiophene was prepared in a linear synthesis consisting of two steps from 3-methylthiophene with a 50% yield, 5,6 and 4-(6-(N,Ndimethylamino)hexyl)phenylboronic acid was prepared in a linear synthesis consisting of five steps from 6-aminohexanoic acid with a 35% yield. 2 After stirring at 100 °C for 6 h, the reaction mixture was allowed to cool to room temperature and poured into water (20 mL) to give a biphasic mixture. This mixture was extracted with ethyl acetate (3  35 mL).…”

“…The starting material, 6-(4-(4,5-dibromothiophen-2yl)phenyl)-N,N-dimethylhexan-1-amine, was prepared in a convergent synthesis consisting of seven steps with a 16% yield. 2,[5][6][7] Purification of the crude product by column chromatography This method is similar to that used for 9. The starting material, 3-bromo-2-(4-t-butylphenyl)-5phenylthiophene, was prepared in a linear synthesis consisting of five steps from thiophene with a 75% yield.…”

“…Moreover, to the best of our knowledge, the corresponding asymmetrical DTEs have never been reported. Our group recently reported a coupling reaction yield of 42% for the preparation of a non-methylated asymmetrical DTE with phenylethynyl substituents at the 2-and 2'-positions, and the same substituents at the 5-and 5'-positions as proposed for 1 2. The coupling yield for the analogous symmetrical DTE with phenyl substituents at the 5-and 5'-positions was higher at 54% 7.…”

“…For example, we have recently reported on the inclusion of a series of amphiphilic asymmetrical DTEs in the bilayer membrane of lipid vesicles. 2 We have shown that these molecular photoswitches can be used to control membrane permeability in vesicles. Notably, a substituent effect was clearly observed as DTEs incorporating comparatively smaller methyl groups at the reactive carbons (i.e., the 2-and 2'-positions of the thiophene rings) exhibited lower rates of ion permeation than bulkier phenylethynyl groups.…”