Aloka Srinivasan

HNO and NO release from a primary amine-based diazeniumdiolate as a function of pH

The growing evidence that nitroxyl (HNO) has a rich pharmacological potential that differs from that of nitric oxide (NO) has intensified interest in HNO donors. Recently, the diazeniumdiolate (NONOate) based on isopropylamine (IPA/NO; Na[(CH(3))(2)CHNH(N(O)NO)]) was demonstrated to function under physiological conditions as an organic analogue to the commonly used HNO donor Angelis salt (Na(2)N(2)O(3)). The decomposition mechanism of Angelis salt is dependent on pH, with transition from an HNO to an NO donor occurring abruptly near pH 3. Here, pH is shown to also affect product formation from IPA/NO. Chemical analysis of HNO and NO production led to refinement of an earlier, quantum mechanically based prediction of the pH-dependent decomposition mechanisms of primary amine NONOates such as IPA/NO. Under basic conditions, the amine proton of IPA/NO is able to initiate decomposition to HNO by tautomerization to the nitroso nitrogen (N(2)). At lower pH, protonation activates a competing pathway to NO production. At pH 8, the donor properties of IPA/NO and Angelis salt are demonstrated to be comparable, suggesting that at or above this pH, IPA/NO is primarily an HNO donor. Below pH 5, NO is the major product, while IPA/NO functions as a dual donor of HNO and NO at intermediate pH. This pH-dependent variability in product formation may prove useful in examination of the chemistry of NO and HNO. Furthermore, primary amine NONOates may serve as a tunable class of nitrogen oxide donor.

REACTION OF NITRIC OXIDE WITH THE IMINE DOUBLE BOND OF CERTAIN SCHIFF BASES

Reaction of nitric oxide with N-benzylidene-4-methoxyaniline produced 4-methoxybenzenediazonium nitrate and benzaldehyde. This may represent an example of the electrophilic reaction of NO with a double bond.

N -Nitrosated N -hydroxyguanidines are nitric oxide-releasing diazeniumdiolates

N-Hydroxyguanidines can be nitrosatively converted to zwitterionic diazeniumdiolates of crystallographically-confirmed structure H2N+C[NHR][N(O)NO]–, whose hydrolytic dissociation at physiological pH leads to both NO and N2O; the results appear to account for the formation of the ‘potential intercellular nitric oxide carrier’ produced on exposing NG- hydroxy-L-arginine (a metabolic intermediate in mammalian NO biosynthesis) to aerobic NO.