Kinetic and theoretical studies on the mechanism of alkaline hydrolysis of DNA

Naoya Takeda, Masahiko Shibata, Nobuo Tajima, Kimihiko Hirao, Makoto Komiyama

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18 Citations (Scopus)

Abstract

The reaction mechanism of alkaline hydrolysis of DNA has been investigated by kinetic analysis and density-functional-theory calculation. The rates of hydrolysis of thymidine 3'-monophosphate esters (including thymidylyl(3'-5')thymidine (Tp-OT)) monotonically decrease as the leaving groups get poorer. According to the theoretical calculation in which the solvent effects are incorporated, no intermediate is formed in the course of the reaction. In the alkaline hydrolysis of the activated Tp-OT analogues having good leaving groups, the 3',5'-cyclic monophosphate of thymidine is concurrently formed through the intramolecular attack by the 5'-alkoxide ion. In the hydrolysis of the native dinucleotide, however, this side reaction does not occur, since the transition state leading to the departure of its poor leaving group cannot be formed due to conformational restraint. These arguments are supported by the theoretical analysis on the hydrolysis of both dimethyl phosphate and its O(bridging)→ substituted analogue.

Original languageEnglish
Pages (from-to)4391-4396
Number of pages6
JournalJournal of Organic Chemistry
Volume65
Issue number14
DOIs
Publication statusPublished - 2000 Jul 14
Externally publishedYes

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ASJC Scopus subject areas

  • Organic Chemistry

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