Design of Fast Redox-Controlled Self-Immolative Selenium-Based Cysteine Surrogates

The self-immolation of <i>N</i>-selenoethyl cysteine derivatives into cysteine exhibits a strong Thorpe-Ingold effect. Notably, the gem-dimethyl substitution α to the selenium atom achieved rate accelerations up to 252-fold, enabling Cys unmasking through C-N bond cleavage within minutes. These investigations offer valuable insights into the mechanism of selenoethyl arm breakdown and new redox-sensitive Cys surrogates.