Light-Induced Hydrogen Sulfide Release from o-Naphthoquinone Methide Precursors (NQMPs)

Hydrogen sulfide (H₂S) is one of the important gasotransmitters, a family of small gaseous signaling molecules. According to recent publications, hydrogen sulfide possesses anti-inflammatory,¹ anti-tumor,² cardiovascular protective,³ and antioxidant⁴ activities. However, the biological response to H₂S strongly depends on H₂S concentration and the specific site in the system.⁵ The use of H₂S gas or inorganic sulfides is problematic due to the toxicity and non-specific systemic action. Therefore, finding efficient approaches to the delivery of hydrogen sulfide to the target location at the right concentration with appropriate rate is vital for the understanding of the biology, as well as realizing the clinical potential of hydrogen sulfide. ⁶ Among other strategies, using photocaged H₂S donors is a promising approach, as it provides spatiotemporal control of H₂S release.⁷ In our group, H₂S-releasing agents that are based on o-naphthoquinone methide precursors (NQMPs) were designed and synthesized, and their ability to release H2S under UV irradiation was studied. Comparing to other photolabile H₂S donors, these NQMPs-based H₂S donors demonstrated much higher yield of H₂S. Thus, irradiation of these donors in the presence of thiols allows for achieving over 90% of photo-release efficiency. The intermediates and byproducts formed during these photoreactions were characterized, allowing us to gain an insight into the mechanistic pathways.

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