Thiophene Esters Are Not Selective for H2S and Undergo Thiol and Esterase Cleavage.

Hydrogen sulfide (H2S) fluorescent probes are important tools for imaging and understanding H2S in biology. One significant requirement for such probes is that they are highly selective for H2S over competing analytes, which are often present at much higher levels than endogenous H2S. Different approaches have been used to generate selective H2S probes, and recently, highly selective probes using 2-thiophene esters have been reported. We report here that in contrast to prior reports, thiophene ester probes are not selective for H2S but rather report on both biothiols and esterase activity. We do demonstrate, however, that the rate of reactivity toward H2S can be enhanced by incorporating an ortho aldehyde, leading to an 85-fold rate enhancement. We anticipate that this work will further clarify effective approaches for selective H2S detection and also advance strategies for improving the selectivity of electrophilic probes for H2S and other related nucleophiles.