Tuning lipophilicity for optimizing the H2S sensing performance of coumarin–merocyanine derivatives

Abstract

Hydrogen sulfide (H₂S) is an endogenous signaling molecule involved in various physiopathological processes; coumarin-based merocyanines have been successfully utilized for developing fluorescent H₂S sensors. However, subtle changes in the chemical structure of merocyanines could induce distinct difference in the H₂S sensing behavior. Investigation of the structure–property relationship of merocyanine dyes is of great importance for the development of ideal sensors with desirable performance. In this work, a series of coumarin/merocyanine (CMC) hybrid fluorescent probes with different lipophilicities have been developed. By altering the N-alkyl chain, the reaction rate with H₂S and intracellular distribution of CMC sensors are optimized. The results showed that increasing the lipophilicity by attaching longer N-alkyl chains leads to a faster sensing response as well as a higher efficiency of the mitochondrial targeting ability. By virtue of rapid sensing of H₂S and impressive mitochondrial co-localization ability, CM-NC₆ could monitor H₂S levels via a dual channel ratiometric mode. In addition, CM-NC₆ is also capable of in vivo imaging of exogenous H₂S. The work provided a powerful strategy for developing H₂S sensors with optimized performance, which would be helpful for understanding the complicated roles of H₂S in various physiological processes.