(A) Chemical structures of sphingosine Sph, clickable sphingosine cSph, and clickable and photoswitchable sphingosines caSph1, caSph2 and caSph3. (B) caSph1 undergoes reversable isomerization between its cis- and trans-configuration with UV (365 nm) and blue (470 nm) light, respectively. (C) Chemical synthesis of csSph1. See main text for details. (D) UV-Vis spectra of caSph1 (50 μM in DMSO) in its dark-adapted (trans, black), UV-irradiated (cis, violet) and blue irradiated (trans, blue) states. (E) caSph1 (50 μM in DMSO) undergoes isomerization to its cis-configuration with UV (365 nm) light, and this effect is completely reversed with blue (465 nm) light. Photoswitching was monitored by measuring the absorbance at 340 nm. (F) Dark-adapted caSph-1 (0.3 μM in HPLC eluent) was either kept in the dark or irradiated with UV or blue light and then analyzed by HPLC-MS-MS to determine the amounts of trans- and cis-isomers formed.