Mechanism of general acid-base catalysis in transesterification of an RNA model phosphodiester studied with strongly basic catalysts

Organic & Biomolecular Chemistry
David Octavio Corona-MartínezA K Yatsimirsky

Abstract

Using 80% vol aqueous DMSO as the reaction medium for transesterification of an RNA model substrate 2-hydroxypropyl 4-nitrophenyl phosphate allows one to observe catalysis in buffer mixtures composed of highly basic components such as guanidines, amidines or alkylamines, which provide up to 10(3)-fold accelerations over the background reaction in the 0.01-0.1 M concentration range. The rate law k(obs) = k(1)[B] + k(2)[B][BH(+)] was established indicating contributions from both simple general base catalysis and the reaction involving concerted action of neutral (B) and protonated (BH(+)) forms of the buffer. The catalytic efficiency of guanidinium and amidinium cations is 10 times larger than that of more acidic ammonium cations. Rate constants k(1) and k(2) obey the Brønsted equations with the slopes 0.77 and 0.69 respectively. Proton inventory for k(2) (B = guanidine) in D(2)O/H(2)O mixtures gives two fractionation factors phi(1) = 0.48 and phi(2) = 1.26 for normal and inverse isotope effects respectively. The former results from the proton transfer to B and the latter from the binding of guanidinium cation to the phosphate group as follows from observation of an inverse solvent isotope effect for the binding of guanidinium a...Continue Reading

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Citations

Sep 21, 2012·The Journal of Organic Chemistry·David Octavio Corona-MartínezAnatoly K Yatsimirsky
Oct 24, 2012·Organic & Biomolecular Chemistry·Riccardo SalvioRocco Ungaro
Aug 22, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bokun Cho, Ming Wah Wong
Sep 6, 2013·Chembiochem : a European Journal of Chemical Biology·Andrei KhorobrykhG Charles Dismukes
Mar 5, 2015·Chemistry : a European Journal·Claudia Savelli, Riccardo Salvio
May 9, 2015·Journal of Inorganic Biochemistry·Irma Sánchez-LombardoDebbie C Crans
Feb 5, 2015·The Journal of Organic Chemistry·Silvia AlvarezJavier Pérez-Castells
Sep 1, 2016·The Journal of Organic Chemistry·Riccardo SalvioAlessandro Casnati
May 27, 2011·The Journal of Organic Chemistry·Riccardo SalvioLuigi Mandolini
Mar 1, 2012·The Journal of Organic Chemistry·Laura BaldiniRocco Ungaro
May 3, 2018·Beilstein Journal of Organic Chemistry·Satu MikkolaHarri Lönnberg

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