Significant effect of intra-chain distribution of catalytic sites on catalytic activity in "clickase" single-chain nanoparticles

"Clickase" single-chain nanoparticles (Ck-SCNPs) are folded, enzyme-mimetic unimolecular polymeric nanoobjects containing copper (Cu) ions able to catalyze the azide-alkyne Huisgen cycloaddition reaction in water and/or selected organic solvents often in the presence of a reductant. Herein, we investigate the effect of morphology on catalytic activity of identical Ck-SCNPs either containing a homogeneous distribution of Cu catalytic sites (Ck-SCNPs1) or showing intra-chain clustering of Cu ions (Ck-SCNPs2). A model fluorogenic "click" reaction between 9-(azidomethyl)anthracene and phenylacetylene, which was catalyzed either by CkSCNPs1 or Ck-SCNPs2, was used to unravel the effect of intra-chain clustering on catalytic activity. This work paves the way to improve the catalytic activity of other metallo-folded SCNPs through control of the intra-chain distribution of catalytic sites.