The Mechanism of Cleavage of RNA Phosphodiesters by a Gold Nanoparticle Nanozyme

The cleavage of uridine 3’‐phosphodiesters bearing alcohols with pK (a) ranging from 7.14 to 14.5 catalyzed by AuNPs functionalized with 1,4,7‐triazacyclononane‐Zn(II) complexes has been studied to unravel the source of catalysis by these nanosystems (nanozymes). The results have been compared with those obtained with two Zn(II) dinuclear catalysts for which the mechanism is fairly understood. Binding to the Zn(II) ions by the substrate and the uracil of uridine was observed. The latter leads to inhibition of the process and formation of less productive binding complexes than in the absence of the nucleobase. The nanozyme operates with these substrates mostly via a nucleophilic mechanism with little stabilization of the pentacoordinated phosphorane and moderate assistance in leaving group departure. This is attributed to a decrease of binding strength of the substrate to the catalytic site in reaching the transition state due to an unfavorable binding mode with the uracil. The nanozyme favors substrates with better leaving groups than the less acidic ones.