Light-induced isomerization between the E and Z isomers of 7 was tested with several different LEDs in an aqueous solution. As a result, light with 505 nm is most effective in switching the azobenzene unit from E to Z, while the reverse isomerization proceeds best with 400 nm light. The different isomers of 7 are shown in Scheme 2. Hence, we can selectively switch between E and Z using visible light. The bathochromic effect of tetra-ortho-fluorination allows avoiding UV light, which may harm living cells and has limited tissue penetration. Consequently, using a tetra-orthofluorinated azobenzene renders 7 more biocompatible. Photochromic switching was investigated in several different media (Milli-Q ® water, PBS++ buffer, and Leibovitz's L-15 medium (L15)) at two temperatures (25 °C and 37 °C) using 505 nm and 400 nm LEDs (which are most effective for switching, see SI). Figure shows the UV/Vis spectra of 7 in pure Milli-Q ® water at 25 °C. As indicated by the UV/Vis absorption spectrum, irradiation of 7 with a 505 nm LED is sufficient to isomerize from the thermally more stable isomer E to Z. In comparison, a 400 nm LED induces the reverse process. The same behavior was observed in all three media (Milli-Q ® water, PBS++ buffer, L15 cell medium) at both temperatures (25 °C and 37 °C), as described in the SI. Hence, the lightinduced isomerization is also fully retained at the conditions used for the cell assays (L15 cell medium, 37 °C). Since the steric repulsions within the azobenzene moiety are less pronounced in the E-isomer, it is lower in energy and most predominantly present in the thermal equilibrium before irradiation. To determine, whether the Z-isomer thermally switches back to the more stable E-isomer, UV/Vis spectra were measured in 5 min intervals over the course of 860 min after 7 has been converted to the Z-isomer by light exposure. The UV/Vis spectra do not change over time, indicating that the azobenzene moiety remains in the Z-form throughout the entire 860 min, so no thermal re-isomerization occurs within this time frame. To further investigate whether the Z-isomer gets thermally converted to the E-isomer at all, a long-time kinetic UV/Vis measurement was performed over 29 days (for further details, see SI). We observed minor changes in the absorption spectrum over time, albeit on the timescale of weeks to months. This implies that thermal Z to E isomerization takes place to a small extent over several weeks. However, this time scale is much longer than experiments on cells typically require. Consequently, we conclude that the cAMP derivative 7 is photoswitchable between bistable isomers with negligible thermal re-isomerization within the time of typical cell culture experiments. Accordingly, the conformation of 8-azo-cAMP is precisely controlled by the optical switching without any noticeable thermal re-equilibration.