Novel spectroscopic probes of sunscreens, initial excited-state structural dynamics and DNA photodamage.

摘要

This thesis discusses developing new tools to probe DNA damage resulting from photoinduced chemical processes and probing the initial excited-state structural dynamics of nucleic acids and sunscreen agents. The results of this thesis show that UV resonance Raman spectroscopy (UVRRS) is an information-rich probe of chemical compositions in in situ analysis of sunscreen formulations. The results indicate that 244-nm excited UV resonance Raman spectra can provide a limit of detection of 0.23% w/w of sunscreen active ingredients (AIs), far below typical active ingredient (AI) concentrations in sunscreen formulations.;Since DNA does not exist in isolation in cells, the role of a UV-absorbing amino acid, tryptophan, in UV-induced DNA photodamage was explored using molecular beacons (MBs) to detect the damage. The results indicate that tryptophan protective effects on DNA far outweighs their photodamage potential.;However, MBs are expensive and they have some technical limitations, despite their exquisite sensitivity. Therefore, a new DNA damage detection method was developed based on smart probes (SPs). These probes are shown to be sensitive and sequence specific for detecting DNA photodamage.;UVRRS was used to probe the photostability of sunscreens, by determining the initial excited-state structural dynamics of Benzophenone-3 (BZ3), a common sunscreen active ingredient. Only minor excited-state structural distortions were obtained, based on the low displacement values, suggesting an inherently stable molecule. The largest structural change occurs along the carbonyl stretch, suggesting a strong interaction with the methanol solvent and a dissipative decay path for the molecule. Similarly, to gain an insight into how the structure of nucleic acids determine their photochemistry, UVRRS was used to probe the initial excited-state structural dynamics of 9-methyladenine (9-MeA). As for BZ3, the initial excited-state structural dynamics obtained for 9-MeA, are low, and much lower than for pyrimidine bases, providing a strong evidence for the photochemical stability of this purine base analog, compared to pyrimidines.