Abstract
The chemical roles of lanthanides in biology are increasingly recognized, yet remain largely unexplored. Unlike most lanthanides, cerium is redox-active and readily adapted for chemical transformation. Herein, we report a cerium-mediated oxidative thiol-ene coupling between cysteine-derived thiols and styrenes under aqueous conditions, yielding β-hydroxysulfide products. Building on this reactivity, we developed a site-selective cysteine modification strategy using a 17-amino acid cerium-binding sequence. Only cysteines optimally positioned near the vacant coordination site undergo efficient and rapid labeling, particularly with electron-deficient styrene derivatives. This work demonstrates cerium-mediated biological activity and highlights its potential as a reactive center for site-selective bioconjugation and broader biochemical and synthetic applications.