Small-Molecule-Selective Organosilica Nanoreactors for Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions in Cellular and Living Systems.

Abstract

We reported the synthesis of a tris(triazolylmethyl)amine (TTA)-bridged organosilane, functioning as Cu(I)-stabilizing ligands, and the installation of this building block into the backbone of mesoporous organosilica nanoparticles (TTASi) by a sol-gel way. Upon coordinating with Cu(I), the mesoporous Cu^I-TTASi, with a restricted metal active center inside the pore, functions as a molecular-sieve-typed nanoreactor to efficiently perform Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions on small-molecule substrates but fails to work on macromolecules larger than the pore diameter. As a proof of concept, we witnessed the advantages of selective nanoreactors in screening protein substrates for small molecules. Also, the robust Cu^I-TTASi could be implanted into the body of animal models including zebrafish and mice as biorthogonal catalysts without apparent toxicity, extending its utilization <i>in vivo</i> ranging from fluorescent labeling to <i>in situ</i> drug synthesis.