Functional N-Substituted N-Thiocarboxyanhydrides as Modular Tools for Constructing H₂S Donor Conjugates

Area of Science:

• Organic Chemistry
• Chemical Biology
• Drug Delivery

Background:

• Hydrogen sulfide (H₂S) is an important signaling molecule with therapeutic potential.
• Developing efficient and controllable H₂S donors remains a challenge in chemical biology.

Purpose of the Study:

• To synthesize a new class of functional N-substituted N-thiocarboxyanhydrides (NTAs) capable of releasing COS/H₂S.
• To enable the conjugation of these NTAs to diverse molecular scaffolds for creating novel H₂S donors.

Main Methods:

• Developed a synthetic route for N-substituted NTAs with reactive functionalities.
• Utilized conjugation reactions such as olefin cross metathesis, thiol-ene, and copper-catalyzed azide-alkyne cycloaddition.
• Attached NTAs to small molecules, polymers, and a protein.

Main Results:

• Successfully synthesized a family of functional NTAs.
• Demonstrated the conjugation of NTAs to various targets, including a protein.
• All synthesized conjugates exhibited sustained H₂S release kinetics.

Conclusions:

• The developed NTAs provide a versatile platform for creating novel H₂S-releasing agents.
• The conjugation strategies allow for the targeted delivery of H₂S.
• The sustained release kinetics suggest potential therapeutic applications for these H₂S donors.