Design of fast redox-controlled self-immolative selenium-based cysteine surrogates

The self-immolation of N-selenoethyl cysteine derivatives into cysteine exhibits a strong Thorpe-Ingold effect. Notably, the gem-dimethyl substitution alpha 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.