GENERAL AND SPECIFIC ACID-BASE CATALYSIS OF THE HYDROLYSIS AND INTERCONVERSION OF RIBONUCLEOSIDE 2'-PHOSPHOTRIESTERS AND 3'-PHOSPHOTRIESTERS - KINETICS AND MECHANISMS OF THE REACTIONS OF 5'-O-PIVALOYLURIDINE 2'-DIMETHYLPHOSPHATES AND 3'-DIMETHYLPHOSPHATES



: KOSONEN M, LONNBERG H

Publisher: ROYAL SOC CHEMISTRY

: 1995

Royal Society of Chemistry. Journal: Perkin Transactions 2

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2

: J CHEM SOC PERK T 2

: 6

: 1203

: 1209

: 7

: 0300-9580

DOI: https://doi.org/10.1039/p29950001203


Kinetics of the hydrolysis and interconversion of 5'-O-pivaloyluridine 2'- and 3'-dimethylphosphates in the pH range 0-9 have been studied. At pH < 2, both reactions are first order in hydronium ion concentration, the hydrolysis being three times as fast as the interconversion. The interconversion, however, becomes hydroxide-ion-catalysed at pH as low as 2.5, whereas the hydrolysis remains pH independent to pH 7, and becomes then base-catalysed. Both reactions are susceptible to general-base catalysis, the Brosted beta values based on carboxylate ions being 0.75. These observations suggest that the monocationic, phosphorane intermediate, obtained by the attack of 2'-OH on the phosphotriester monocation, is decomposed to the hydrolysis and isomerization products at a comparable rate. By contrast, the monoanionic phosphorane, obtained by the attack of 2'-O- on the neutral phosphotriester, predominantly gives isomerization products; the methoxide ion leaves 10(5) times less readily than the sugar oxyanions, 2'-O- or 3'-O-. Accordingly, the pH-independent hydrolysis appears to consist of consecutive specific base/acid catalysis. The buffer-catalysed reactions are Suggested to proceed by general-base-catalysed attack of 2'-OH on neutral phosphotriester, followed by general-acid-catalysed decomposition of the phosphorane intermediate to either hydrolysis or isomerization products. The mechanisms of the hydrolysis and isomerization of the internucleosidic phosphodiester bonds are discussed on these bases.



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