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

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-BH3^3-), followed by subsequent hydrolysis of the O3P-BH3^3- to produce phosphonate and boric acid. A three-step deuterium substitution of the borane hydrogens in O3P-BH3^3- 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-BH3^3-. The hydrolysis and deuteration steps were characterized in terms of pseudo-first-order rate constants. Hydrolysis of O3P-BH3^3- is an order of magnitude slower than deuterium substitution.

Duke Scholars

Author Barbara R. Shaw Chemistry