Photochemical Sciences Ph.D. Dissertations

Title

Studies of Photoinduced DNA Damage by Phenanthrene Dihydrodioxin and Light-driven Electron Delocalization in Pyridinium Molecules

Date of Award

2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Photochemical Sciences

First Advisor

R. Marshall Wilson (Advisor)

Second Advisor

Farida Selim (Other)

Third Advisor

Pavel Anzenbacher (Committee Member)

Fourth Advisor

Alexander Tarnovsky (Committee Member)

Abstract

Ever since the discovery of the DNA molecular structure, this molecule became a desirable target for the researchers aiming to develop anticancer drugs and therapies. The main emphasis of this dissertation was placed on the design, development and studies of photochemical properties of a novel photo activated DNA damaging agent. Upon light irradiation of compound the release of highly reactive 9,10-phenanthrenequinone was observed. Studies of phenanthrene dihydrodioxin interaction with DNA demonstrated the intercalative mode of binding and slightly preferential binding affinity to the AT-rich DNA sequences. The synthesized agent induced a partial transition from B to Z form of DNA. The phenanthrene dihydrodioxin compound proved to be an efficient single-strand DNA photocleaver upon visible light irradiation. This further demonstrates the potential of photomasked ortho-quinones as efficient DNA damaging agents.

This work also describes an unusual transformation from pyridinium substituted methane to the corresponding gem-diol in the mild conditions in the presence of air. Proposed mechanism of the reaction involves the formation of reactive oxygen species (ROS). ROS are known to be highly toxic to biomolecules, including DNA. It is demonstrated in this work that the production of ROS intermediates in the reaction of the gem-diol formation can lead to DNA damage in the dark.

In the continuous interest of our research group, a series of bis(pyridinium) and bis(3-carboxamidepyridinium) alkane salts were synthesized in order to study through-space electron delocalization and formation of dimer radical cation species upon electrochemical and photoreduction. Investigation of photoinduced charge separation is important for the development of artificial photosynthetic systems and molecular electronics. Studies of unsubstituted and meta-substituted pyridines connected by the alkyl linker of different length provided additional information on the efficiency of the pyridinium dimers in delocalizing the electron density. The systems were studied by means of cyclic voltammetry and transient absorption spectroscopy.

Link to Full Text
COinS