Kinetic solvent deuterium isotope effect in transesterification of RNA models

Noora Virtanen, Lauri Polari, Maria Välilä, Satu Mikkola*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)

Abstract

2-Methylbenzimidazole ribonucleoside arylphosphates (1a,b) and alkylphosphates (2a,b) were synthesized as RNA model compounds containing a minimised number of exchangeable protons. Intramolecular transesterification of these substrates was studied in H2O and D2O solutions over a wide pL range and apparent kinetic solvent deuterium isotope effects of the alkaline cleavage of both substrates and of the cleavage and isomerisation of 2a under neutral and acidic conditions were determined. The observed K H2O/kD2O of 4.9 obtained for the alkaline cleavage of the arylphosphate 1b can be primarily attributed to the ΔpK of the attacking nucleophile. The alkyl leaving group in 2a brings about an additional 1.5-fold isotope effect (kH2O/kD2O of 7.1 observed), which, considering the pL-dependence of the reaction, can not be explained by a process involving a proton transfer. Differences in solvation of the transition state are tentatively suggested as a source of the difference. In contrast to alkaline cleavage, under neutral and acidic conditions the cleavage and isomerisation of 2a showed no apparent solvent isotope effect. Several examples found in the literature show that intramolecular proton transfer from phosphate to the leaving group in pre-equilibria may not necessarily result in an observable solvent isotope effect. This may also explain the results obtained in the present work, since intramolecular proton transfer processes take place in transesterification reactions of 2a under neutral and acidic conditions. Relevance of the results obtained in the base catalysed cleavage to hammerhead ribozyme reaction is briefly discussed.

Original languageEnglish
Pages (from-to)385-397
Number of pages13
JournalJournal of Physical Organic Chemistry
Volume18
Issue number5
DOIs
Publication statusPublished - May 2005
MoE publication typeA1 Journal article-refereed

Keywords

  • Phosphodiester bonds
  • RNA
  • Solvent isotope effect
  • Transesterification

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