A neutralization-reionization mass spectrometry and computational analysis of 3-hydroxypyridine, 2-hydroxypyridine/2-(1H)pyridone, and uracil
Free radical damage to DNA has been studied since the early years of radiobiology, when it became well established that DNA, and specifically the purine and pyrimidine bases are critical cellular target for radiation-induced damage. Cytosine and uracil are of key importance since the observation that cytosine deaminates to form uracil at a finite rate in vivo. Although a detailed mechanism has not been well established, it has been observed that radical damage increases mutations such as the C to A point mutation which occurs if uracil is left in the replicating DNA strand. This dissertation focuses on both modeling studies for the pyrimidine base radicals by examining the 3-Hydroxypyridine and the 2-Hydroxypyridine/2-(1H)Pyridone system as well as the more complicated uracil system by neutralization-reionization mass spectrometry.Neutralization - reionization mass spectrometry (NRMS) is a technique that allows the characterization of radical stability and dissociation pathways by femtosecond electron collisions of the corresponding ion with a target gas, typically dimethyldisulfide. Ab initio and density functional theory help characterize the protonation sites in addition to the radical and ion stabilities. Kinetic modeling, such as RRKM is useful in determining which expected fragmentation pathways could occur on the time scale of the experiment. These computational techniques aid in interpretation of the NRMS spectra.
- Chemistry