Initial Excited-State Structural Dynamics and Damage Kinetics of Nucleic Acid Derivatives and a Rhodopsin Analogue

  • Author / Creator
    Sasidharanpillai, Swaroop
  • Photochemical reactions resulting from the absorption of ultraviolet light are one of the main causes of DNA damage. For any excited-state photochemical reaction, it is the structural changes in the excited state after the absorption of the photon that ultimately decide the photochemical fate of the molecule. In this thesis, I have explored the initial excited-state structural dynamics of nucleic acid derivatives and a rhodopsin analogue to understand the structural distortions upon photon absorption and the correlation between the observed structural dynamics and the known photochemistry. Resonance Raman spectroscopy was used to probe the initial excited-state structural dynamics of 5,6-dimethyluracil, to understand the effect of mass changes at the C5 and C6 positions, and found that the observed initial excited-state structural dynamics are similar to those of thymine. This study showed that the methyl groups at the C5 and C6 positions are a major factor in determining how the initial excited-state structural dynamics are partitioned between the CH bending and C5=C6 stretching modes, which is directly related to the difference in the photochemistry of uracil and thymine. The resonance Raman-derived initial excited-state structural changes of homopentamer oligonucleotides lie along similar modes as in the corresponding nucleobases or nucleotides, but with smaller distortions. The smaller excited-state distortions suggest that the initial excited-state structural dynamics are restricted by the polymeric structure. The observed homopentamer homogeneous broadening is consistent with this model. The sequence dependence of UV-induced miRNA damage was also studied on a microarray platform. The results suggest that guanine provides a protective effect and sequences with cytosine and uracil are more susceptible to damage, although the errors are large. The visible resonance Raman spectroscopic studies on a rhodopsin analogue show similar initial molecular distortions along the C=C bond during the isomerization as in rhodopsin. The hydrogen out-of-plane (HOOP) mode is absent in N-alkyalated indanylidene-Pyrroline (NAIP), as expected due to the absence of C-H modes. The computed excited-state trajectories are consistent with the experimentally observed initial distortions along the C=C bond.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Doctor of Philosophy
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Chemistry
  • Supervisor / co-supervisor and their department(s)
    • Loppnow, Glen (Chemistry)
  • Examining committee members and their departments
    • Loppnow, Glen (Chemistry)
    • Alexander, Brown (Chemistry)
    • David, McCamant (Chemistry),
    • Wolfgang, Jaeger (Chemistry)
    • Charles, Lucy (Chemistry)