Dynamic pH responsivity of triazole-based self-immolative linkers

The Cu(I)-catalyzed azide-alkyne ‘click’ reaction is used to generate triazole-based self-immolative linkers that can be reversibly paused and restarted throughout their elimination cascades. The formed 1,4-triazole ring expresses a pH-sensitive intermediate that can be switched dynamically between active and dormant states depending on the presence of acid or base, cleanly gating the release of payload in response to pH changes.