Thiobenzophenones: tunable hydrolysis-based donors for intracellular H2S delivery

Abstract

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.