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

Abstract

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.