Thiobenzophenones: tunable hydrolysis-based donors for intracellular HS delivery

H 2 S, the third gasotransmitter, is involved in many physiological and pathological processes. Compounds that can release H 2 S slowly under physiological conditions are useful chemical tools for studying H 2 S biology as well as potential therapeutic reagents. Herein we demonstrate that thiobenzophenones are tunable structural motifs that release H 2 S upon spontaneous hydrolysis reaction under pH 7.4 and structural modifications enable the H 2 S release efficiency to be modulated. In addition, we demonstrate that 4,4′-diaminothiobenzophenone (1) may be used for intracellular H 2 S delivery based on bioimaging. Moreover, donor 1 exhibited negligeable cytotoxicity up to 200 μM and could mitigate H 2 O 2 -induced cellular stress. The preliminary results from our investigations may promote the further development of thiobenzophenones as new donor motifs for studying H 2 S biology. Thiobenzophenones are tunable structural motifs for intracellular H 2 S delivery through hydrolysis reaction.