Transient Intermediates by Photodissociation and UV-Vis Action Spectroscopy in the Gas Phase

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In this project funded by the Chemical Structure, Dynamics & Mechanisms B Program of the Chemistry Division, Professor Frantisek Turecek of the Department of Chemistry at University of Washington, Seattle, is developing new methods for the generation and spectroscopic studies of highly reactive ionized components of nucleic acids. These intermediates play a role in radical reactions causing DNA damage. The goal of this research is to exploit the spectroscopic properties and energetics of these short-lived intermediates for the understanding of the early stages of ionization damage in DNA. DNA ionization adversely affects individuals engaged in high-altitude travel, space exploration, and work with radioactive materials, as well as materials used for the future development of DNA computing. The project addresses natural as well as synthetic DNA components and lies at the interface of physical, organic, and computational chemistry. Another part of the project is aimed at determining structure and interactions in biomolecular complexes of protein and DNA components. The project is therefore well suited to the education of scientists at the forefront of chemical research. The research group is dedicated to provide high levels of education and professional training for graduate and undergraduate students, as well as science outreach to K-12 students.These studies address two areas of chemistry where highly reactive intermediates play an important role. In one part of these studies, gas-phase ion chemistry methods are used to generate DNA nucleobase, nucleoside, and oligonucleotide cation radicals, as well as those from unnatural hachimoji bases, and obtain their UV-Vis photodissociation (UVPD) action spectra. This provides the first interference-free electronic spectra of isolated cation radicals relevant to reactive intermediates formed in the initial stages of DNA ionization damage. Advanced methods of ion chemistry are employed to generate radical intermediates that include multistage collision-induced electron transfer in transition metal complexes, which is an oxidative process, and electron-transfer dissociation of multiply charged non-covalent complexes, which is a reductive process. Cation-radicals of 61 amino-acid encoding DNA trinucleotides are generated and characterized to establish the DNA code of vulnerability to ionization damage and radical-driven rearrangements. The experimental studies are supported and complemented by large-scale computations, including Born-Oppenheimer molecular dynamics, ab initio thermodynamics, RRKM (Rice–Ramsperger–Kassel–Marcus) kinetics, excited electronic states, and vibronic spectra. Another part of these studies is aimed at developing new photosensitive tags to be incorporated into specific amino acid residues and utilized for photodissociative cross linking in gas-phase complexes of peptide ions with nucleosides. Tandem mass spectrometry is used to determine the crosslink sites in the photoproduct ions. The experimental studies are aided and complemented by BOMD (Born-Oppenheimer molecular dynamics) trajectory calculations to identify low-free energy conformers and track the dynamics of non-covalent interactions in the complexes.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.