Hydrolysis of thymidine boranomonophosphate and stepwise deuterium substitution of the borane hydrogens. 31 P and 11 B NMR studies


Journal Article

The α-P-boranophosphate nucleosides comprise a new class of modified nucleotides that may find use as therapeutic and DNA diagnostic agents. Hydrolysis of thymidine 5'-boranomonophosphate, d(p(B)T), has been studied in H2O and D2O using 1H, 31P, and 11B NMR spectroscopies. Although d(p(B)T) is quite stable at 25 °C, it hydrolyzes slowly at higher temperatures. At 50 or 60 °C, d(p(B)T) hydrolyzes first into thymidine (dT) and boranophosphate (O3P-BH33-), followed by subsequent hydrolysis of the O3P-BH33- to produce phosphonate and boric acid. A three-step deuterium substitution of the borane hydrogens in O3P-BH33- was detected in D2O by the presence of a 31P isotope shift. The 31P resonances shifted downfield by 0.14 ppm upon substitution of each of three 1H atoms by 2H. Exchange of the borane hydrogens with D2O occurs as sequential processes superimposed upon hydrolysis of O3P-BH33-. The hydrolysis and deuteration steps were characterized in terms of pseudo-first-order rate constants. Hydrolysis of O3P-BH33- is an order of magnitude slower than deuterium substitution.

Full Text

Duke Authors

Cited Authors

  • Li, H; Hardin, C; Shaw, BR

Published Date

  • July 17, 1996

Published In

Volume / Issue

  • 118 / 28

Start / End Page

  • 6606 - 6614

International Standard Serial Number (ISSN)

  • 0002-7863

Digital Object Identifier (DOI)

  • 10.1021/ja9540280

Citation Source

  • Scopus