N-Methylation of Self-Immolative Thiocarbamates Provides Insights into the Mechanism of Carbonyl Sulfide Release.

ABSTRACT: Hydrogen sulfide (H₂S) is an important biomolecule, and self-immolative thiocarbamates have shown great promise as triggerable H₂S donors with suitable analogous control compounds; however, thiocarbamates with electron-deficient payloads are less efficient H₂S donors. We report here the synthesis and study of a series of N-methylated esterase-triggered thiocarbamates that block the postulated unproductive deprotonation-based pathway for these compounds. The relative reaction profiles for H₂S release across a series of electron-rich and electron-poor N-Me aniline payloads are examined experimentally and computationally. We show that thiocarbamate N-methylation does block some side reactivity and increases the H₂S release profiles for electron-poor donors. Additionally, we show that isothiocyanate release is not a competitive pathway, and rather that the reduced efficiency of electron-poor donors is likely due to other side reactions.

SUBMITTER: Levinn CM 

PROVIDER: S-EPMC8750613 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature