Solvolysis Mechanisms of RNA Phosphodiester Analogues Promoted by Mononuclear Zinc(II) Complexes: Mechanisic Determination upon Solvent Medium and Ligand Effects

The solvolysis mechanisms of RNA phosphodiester model 2-(hydroxypropyl)-4-nitrophenyl phosphate (HpPNP) catalyzed by mononuclear zinc­(II) complexes are investigated in the paper via a theoretical approach. The general-base-catalyzed (GBC) and specific-base-catalyzed (SBC) mechanisms are thoroughly discussed in the paper, and the calculations indicate a SBC mechanism (also named as the direct nucleophilic attack mechanism) when the cyclization of HpPNP is promoted by the Zn:[12]­aneN₃ complex ([12]­aneN₃ = 1,5,9-triazacyclododecane). The ligand effect is considered by involving two different catalysts, and the results show that the increasing size catalyst provides a lower energy barrier and a significant mechanistic preference to the SBC mechanism. The solvent medium effect is also explored, and reduced polarity/dielectric constant solvents, such as light alcohols methanol and ethanol, are more favorable. Ethanol is proven to be a good solvent medium because of its low dielectric constant. The computational results are indicative of concerted pathways. Our theoretical results are consistent with and well interpret the experimental observations and, more importantly, provide practical suggestions on the catalyst design and selection of reaction conditions.