Solution chemistry effects on the analysis of DNA by matrix-assisted laser desorption/ionization mass spectrometry

The mass spectrometric analysis of oligonucleotides is now performed using electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI). However, the processes involved in the production of gas-phase ions by these ionization methods are not well characterized. In this paper, we report investigations into the role of oligonucleotide solution-phase behavior on the subsequent gasphase behavior of the oligonucleotide. Characterization of mononucleotide ion intensity as a function of solution pH, determination of the gas-phase acidity of mononucleotides in order to identify the site(s) of deprotonation, and the use of organic bases to reduce cation adducts without the formation of the ammonium salt of the oligonucleotide were studied. The results of these studies show that the ionization process is likely influenced to a great extent by the gas-phase properties of oligonucleotides, although there are several important solution phase factors to be considered when analyzing oligonucleotides via MALDI-MS.