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.

Three (bola)amphiphilic spirooxazines have been synthesized and their photochromism has been characterized. The large biphotochromic structure of 2 significantly affects its conformational flexibility and the rate constants for thermal ring closure are particularly dependent on the lipid phase state. Two comprehensive ion permeation studies were performed to examine the effect of spirooxazine inclusion and isomerization on membrane permeability. In all cases, the open-ring isomers of these spirooxazines are more disruptive in bilayer membranes than their closed-ring isomers. Further, the rate of ion permeation and net release are highly dependent on the lipid bilayer phase state and the relative position of the photochromic moiety in the bilayer membrane. Moreover, the difference in potassium ion permeability under UV and visible irradiation is more pronounced than previously reported photoresponsive membrane disruptors with reversible photocontrols.

A synthetic route for the preparation of amphiphilic asymmetrical dithienylethenes that incorporate methyl groups at the 4- and 4′-positions and an aryl group at one of the reactive carbons has been developed. The presence of a bulky aryl substituent ensures a relatively large change in molecular geometry upon photoisomerization, whereas the presence of methyl groups provide enhanced photostability. Notably, a substituent effect was systematically revealed en route to the preparation of the dithienylethene precursors. In particular, this formal substitution reaction was significantly inhibited due to steric hindrance, stemming from the presence of aryl and methyl groups at the alpha positions of the preformed thienyl carbanionic carbon, and an aryl group on the monosubstituted perfluorocyclopentene derivative.