Tuning Photoinduced Electron Transfer Efficiency of Fluorogenic BODIPY-α-Tocopherol Analogues

Fluorogenic analogues of α-tocopherol developed by our group have been instrumental in monitoring reactive oxygen species (ROS) within lipid membranes. Prepared as two-segment trap-reporter (chromanol-BODIPY) probes, photoinduced electron transfer (PeT) was utilized to provide these probes with an off/on switch mechanism warranting the necessary sensitivity. Herein, we rationalize within the context of Marcus theory of electron transfer how substituents on the BODIPY core and linker length joining the trap and reporter segments, tune PeT efficiency. DFT and electrochemical studies were used to estimate the thermodynamic driving force of PeT in our constructs. By tuning the redox potential over a 400 mV range, we observed over an order of magnitude increase in PeT efficiency. Increasing the linker length between the chromanol and BODIPY by 2.8 angstroms, in turn, decreased PeT efficiency 2.7-fold. Our results illustrate how substituent and linker choice enable "darkening" the off state of fluorogenic probes based on BODIPY fluorophores, by favoring PeT over radiative emission from the singlet excited state manifold. Ultimately, our work brings light to the sensitivity ceiling one may achieve in developing fluorogenic antioxidant analogues of α-tocopherol. The work provides general guidelines applicable to those developing fluorogenic probes based on PeT.