title: Infrared multiphoton dissociation of duplex DNA/drug complexes in a quadrupole ion trap.
abstract: Noncovalent duplex DNA/drug complexes formed between one of three 14-base pair non-self-complementary duplexes with variable GC content and one of eight different DNA-interactive drugs are characterized by infrared multiphoton dissociation (IRMPD), and the resulting spectra are compared to conventional collisionally activated dissociation (CAD) mass spectra in a quadrupole ion trap mass spectrometer. IRMPD yielded comparable information to previously reported CAD results in which strand separation pathways dominate for complexes containing the more AT-rich sequences and/or minor groove binding drugs, whereas drug ejection pathways are prominent for complexes containing intercalating drugs and/or duplexes with higher GC base content. The large photoabsorptive cross section of the phosphate backbone at 10.6 mum promotes highly efficient dissociation within short irradiation times (<2 ms at 50 W) or using lower laser powers and longer irradiation times (<15 W at 15 ms), activation times on par with or shorter than standard CAD experiments. This large photoabsorptivity leads to a controllable ion activation method which can be used to produce qualitatively similar spectra to CAD while minimizing uninformative base loss dissociation pathways or instead be tuned to yield a high degree of secondary fragmentation. Additionally, the low-mass cutoff associated with conventional CAD plays no role in IRMPD, resulting in richer MS/MS information in the low m/z region. IRMPD is also used for multiadduct dissociation in order to increase MS/MS sensitivity, and a two-stage IRMPD/IRMPD method is demonstrated as a means to give specific DNA sequence information that would be useful when screening drug binding by mixtures of duplexes.
authors.affiliation: Department of Chemistry and Biochemistry, 1 University Station A5300, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Brodbelt
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D017785:Photons; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D004247:DNA