Triazinium Ligation: Bioorthogonal Reaction of N1‐Alkyl 1,2,4‐Triazinium Salts**

Abstract

The development of reagents that can selectively react in complex biological media is an important challenge. Here we show that N1‐alkylation of 1,2,4‐triazines yields the corresponding triazinium salts, which are three orders of magnitude more reactive in reactions with strained alkynes than the parent 1,2,4‐triazines. This powerful bioorthogonal ligation enables efficient modification of peptides and proteins. The positively charged N1‐alkyl triazinium salts exhibit favorable cell permeability, which makes them superior for intracellular fluorescent labeling applications when compared to analogous 1,2,4,5‐tetrazines. Due to their high reactivity, stability, synthetic accessibility and improved water solubility, the new ionic heterodienes represent a valuable addition to the repertoire of existing modern bioorthogonal reagents.

Metal‐free click and bioorthogonal reactions of aggregation‐induced emission probes for lighting up living systems

“…Moreover, tailoring click reactions specifically for AIE research stands as an exciting direction as well. For instance, a few click handles have been reported to alter their hydrophilicity or solubility upon reaction [111]. Given that an AIEgen's fluorogenicity is intrinsically linked to its hydrophilicity, such reactions offer significant potential in designing unique AIE applications.…”