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Kinetic solvent deuterium isotope effect in transesterification of RNA models
Author(s) -
Virtanen Noora,
Polari Lauri,
Välilä Maria,
Mikkola Satu
Publication year - 2005
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.883
Subject(s) - chemistry , kinetic isotope effect , intramolecular force , deuterium , solvation , cleavage (geology) , solvent , transesterification , isomerization , nucleophile , photochemistry , medicinal chemistry , methanol , stereochemistry , organic chemistry , catalysis , physics , geotechnical engineering , quantum mechanics , fracture (geology) , engineering
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 H 2 O and D 2 O solutions over a wide p L 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 H 2 O / k D 2 Oof 4.9 obtained for the alkaline cleavage of the arylphosphate 1b can be primarily attributed to the Δp K of the attacking nucleophile. The alkyl leaving group in 2a brings about an additional 1.5‐fold isotope effect ( k H 2 O / k D 2 Oof 7.1 observed), which, considering the p L –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. Copyright © 2004 John Wiley & Sons, Ltd.