1.D.282.  Photodynamically-modulated Membrane Mobility Regulates a Synthetic Transporter (PMM-ST) Family

Artificial transmembrane transport systems can have their activities switched in response to environmental stimuli, which has been achieved mostly by modulating the substrate binding affinity. Bos et al. 2024 demonstrated that the activity of a synthetic anion transporter can be controlled through changes in the membrane mobility and incorporation. The transporters─equipped with azobenzene photoswitches─poorly incorporate into the bilayer membrane as their thermally stable (E,E,E)-isomers, but incorporation is triggered by UV irradiation to give the (Z)-containing isomers. The latter isomers, however, are found to have a lower mobility and are therefore the least active transporters. This opposite effect of E-Z isomerization on transport capability offers unique photocontrol as is demonstrated by in situ irradiation studies during the used transport assays. These results help to understand the behavior of artificial transporters in a bilayer and are highly important to future designs, with new modes of biological activity and with the possibility to direct motion, which may be crucial toward achieving active transport.

Tren-based tris-thiourea transporters [tren = tris(2-aminoethyl)amine], which were previously developed by Gale and co-workers (see Bos et al. 2024) (and for which the transport mechanism is well understood) with azobenzene photoswitches. In such a transporter, the impact of E/Z isomerization on the binding properties would be minimal. Conversely, owing to the large change in the dipole moment of azobenzene upon isomerization, and resultantly a large difference in solubility between the E and the Z-isomer, membrane mobility and incorporation were expected to be largely influenced. An additional benefit of the tren-based scaffold is that it allows appendage of up to three azobenzene groups to enhance these expected effects. Thus, Bos et al. 2024 describe the azobenzene-appended tren-based tris-thiourea transporters 1 and 2 (see Scheme 1A in this reference), whose isomers can be interconverted by UV and visible light. The half-lives of the photogenerated, metastable state of these two compounds are different. That is, the thiourea substitution in the benzylic position in 2 is known to afford higher thermal stability of azobenzene as compared to the direct substitution in 1. The photogenerated Z-containing isomers of these transporters are better incorporated into the lipid bilayer membrane, while their mobility—and with that their transport activity—is lower than the corresponding (E,E,E)-isomers (Scheme 1B). These opposing effects of isomerization on the transport capability are shown to give unprecedented control of the transport process (see Bos et al. 2024).