Leveraging thiocarbonyls for the rapid release of COS/H2S from photocaged thionocarbamates

The controlled generation and delivery of hydrogen sulfide (H₂S), a critical biomolecule involved in various physiological and therapeutic processes, remain significant challenges, driving the need for innovative and responsive chemical tools. In this study, we developed thionocarbamate derivatives based on the boron dipyrromethene (BODIPY) scaffold, which rapidly release carbonyl sulfide (COS) upon photoactivation, allowing H₂S generation under physiological conditions. These systems exhibit an exceptional uncaging rate compared with other reported structures, enabling rapid and precisely controlled H₂S releases, as verified through live-cell imaging studies. In particular, the photolysis rate of the thionocarbamate derivatives was found to be more than 100-fold faster than the corresponding carbamates, a result that is explained through Density Functional Theory (DFT) calculations as arising from the thermodynamic instability of thiocarbonyls, offering a new strategy in photocage design. These results also highlight the potential of using thionocarbamate-based BODIPY derivatives as versatile tools for H₂S delivery, paving the way for their application in H₂S-related therapies and studies.