Thiobenzophenones: tunable hydrolysis-based donors for intracellular H2S delivery

H2S, the third gasotransmitter, is involved in many physiological and pathological processes. Compounds that can release H2S slowly under physiological conditions are useful chemical tools for studying H2S biology as well as potential therapeutic reagents. Herein we demonstrate that thiobenzophenones are tunable structural motifs that release H2S upon spontaneous hydrolysis reaction under pH 7.4 and structural modifications enable the H2S release efficiency to be modulated. In addition, we demonstrate that 4,4′-diaminothiobenzophenone (1) may be used for intracellular H2S delivery based on bioimaging. Moreover, donor 1 exhibited negligeable cytotoxicity up to 200 μM and could mitigate H2O2-induced cellular stress. The preliminary results from our investigations may promote the further development of thiobenzophenones as new donor motifs for studying H2S biology.