Formation of diazoate intermediate upon nitrous acid and nitric oxide treatment of 2'-deoxyadenosine

Bioorg Med Chem Lett. 2009 Feb 1;19(3):788-91. doi: 10.1016/j.bmcl.2008.12.012. Epub 2008 Dec 9.

Abstract

When 2'-deoxyadenosine was treated with HNO(2) or NO, a small amount of a previously unidentified product was formed. The product was also formed by the reaction of 2'-deoxyadenosine with isoamyl nitrite in tetrahydrofuran as a major product. The product was identified as a diazoate derivative of 2'-deoxyadenosine, a reaction intermediate. At the initial stage of the HNO(2) or NO reaction, the concentration of the diazoate was greater than or comparable to 2'-deoxyinosine, a deamination product of 2'-deoxyadenosine. The diazoate was fairly stable and decomposed with a half-life of 66h at pH 7.4 and 37 degrees C. These results suggest that the diazoate can be formed in cellular nucleosides or DNA with biologically relevant dose of HNO(2) and NO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Chemistry / methods
  • Chemistry, Pharmaceutical / methods*
  • Chromatography, High Pressure Liquid
  • Deoxyadenosines / chemistry*
  • Drug Design
  • Humans
  • Hydrogen-Ion Concentration
  • Models, Chemical
  • Nitric Oxide / chemistry*
  • Nitrous Acid / chemistry*
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Temperature
  • Time Factors

Substances

  • Amines
  • Deoxyadenosines
  • Nitric Oxide
  • 2'-deoxyadenosine
  • Nitrous Acid