Novel BODIPY-based fluorescent probes with large Stokes shift for imaging hydrogen sulfide

Abstract Hydrogen sulfide has important biomedical significance because it plays a regulatory role in a variety of physiological processes. In our previous work, we investigated the effect of substituents on Stokes shift of BODIPY and found that methoxy groups on phenyl substituents at 3,5-positions could expand the Stokes shift of BODIPY-based probes. In this study, taking hydrogen sulfide (H2S) as analyte, we designed and synthesized 4,4-difluoro-8-{4-(2,4-dinitrophenoxy)phenyl}-3,5-bis(2,4-dimethoxyphenyl)-4-bora-3a,4a-diaza-s-indancene (DMOEPB) and 4,4-difluoro-8-(4-nitrophenyl)-3,5-bis(2,4-dimethoxyphenyl)-4-bora-3a,4a-diaza-s-indancene (DMONPB) according to the same strategy. As expected, Stokes shifts of 49 nm and 51 nm were obtained respectively, which demonstrate the feasibility of the strategy in the synthesis of other fluorescent probes for the detection of small biomolecules. DMONPB can react with H2S to form the derivative with a fluorescence quantum yield of 0.13. An excellent linear relationship was observed in the range of H2S concentrations from 0 μM to 800 μM and the detection limit was 1.3 μM. Furthermore, it can be successfully applied to imaging of H2S in cells and tissues. For DMOEPB, the presence of m-dinitrophenyl did not cause the expected fluorescence quenching, which makes it impossible to perform bioimaging. We speculate that the strong electron-withdrawing property of nitro group is obviously weaker when the two benzene rings are separated at 8-position and are not conjugated with the fluorophore. It provides experience and lessons for designing the same type of turn-on probe.