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Ph. D. Thesis Alexei Shamaev Final Nov 10 2015.pdf (10.17 MB)
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Synthesis, Photochemical Properties and DNA Binding Studies of DNA Cleaving Agents Based on Chiral Dipyridine Dihydrodioxins Salts
Author Info
Shamaev, Alexei E
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1445859853
Abstract Details
Year and Degree
2015, Doctor of Philosophy (Ph.D.), Bowling Green State University, Photochemical Sciences.
Abstract
Control of chemical reactions becomes especially challenging when chemical processes have to work within the complexity of biological environments. This is one of the reasons why the ability to design “caged” molecules with structure, reactivity, and biological activity that can be activated externally by light continues to draw significant attention, from both the practical and fundamental points of view. Possible applications of such molecules include design of molecular machines and switches, logic gate mimics, optical sensors, drug delivery systems, etc. Since “caged” molecules are of particular use for processes that occur in biochemical systems and in the environment, interesting light-sensitive systems, anti-cancer drugs, have been developed recently to control DNA cleavage. Caged molecules may interact with or bind with DNA and can be classified by their mechanism of action. Each of these classes of molecules has a different structure and interacts with DNA in a different way, but some molecules can combine several functionalities. The preponderance of caged molecules, anti-cancer drugs, capable of DNA cleavage or their metabolites incorporate Electron Transfer (ET) functionalities, which play important roles in physiological responses. These main groups include quinones (or phenolic precursors), metal complexes, aromatic nitro compounds (or reduced derivatives), and conjugated imines (or iminium species). Redox cycling with oxygen can occur giving rise to Oxidation Stress (OS) through generation of Reactive Oxygen Species (ROS) which can contribute to drug efficacy or can lead to undesirable toxicity. In some cases, ET results in interference with normal electron transport chains. In this work a series of caged molecules-chiral Pyrene Dihydridioxins (PDHD)-DNA chiral DNA intecalators and PDHD-metal complexes bearing masked o-quinone functionality activated through intramolecular ET were synthesized. The o-quinone release and intramolecular ET can be easily activated by UV-light. The mechanism of o-quinone release and intramolecular ET was studied in detail by methods of Ultrafast Transient Absortion Spectroscopy and supported by high-level quantum mechanical calculations. The binding properties of chiral intercalators based on PDHD to various DNA oligonucleotides were studied by various methods and DNA cleavage properties indicating strong binding and cleaving ability of the synthesized PDHDs. Also, a new method for synthesis of cyclohexa[e]pyrenes which possibly capable of intramolecular ET and electron transfer-oxidative stress (ET-OS) DNA cleavage was developed and partially accomplished.
Committee
Marshall Wilson (Advisor)
Jill Zeilstra-Ryalls (Other)
Thomas Kinstle (Committee Member)
Alexander Tarmovsky (Committee Member)
Pages
301 p.
Subject Headings
Biochemistry
;
Biomedical Research
;
Chemistry
;
Molecular Chemistry
;
Molecular Physics
;
Molecules
;
Organic Chemistry
;
Pharmaceuticals
;
Pharmacy Sciences
Keywords
synthesis of photoactive compounds
;
photoactivity
;
chiral separation
;
DNA binding
;
DNA cleavage
;
Drug-DNA interactions
;
femtosecond ultrafast spectroscopy
;
phoretic studies of DNA
;
mass-spectrometry of DNA
;
NMR of DNA
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Citations
Shamaev, A. E. (2015).
Synthesis, Photochemical Properties and DNA Binding Studies of DNA Cleaving Agents Based on Chiral Dipyridine Dihydrodioxins Salts
[Doctoral dissertation, Bowling Green State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1445859853
APA Style (7th edition)
Shamaev, Alexei.
Synthesis, Photochemical Properties and DNA Binding Studies of DNA Cleaving Agents Based on Chiral Dipyridine Dihydrodioxins Salts .
2015. Bowling Green State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1445859853.
MLA Style (8th edition)
Shamaev, Alexei. "Synthesis, Photochemical Properties and DNA Binding Studies of DNA Cleaving Agents Based on Chiral Dipyridine Dihydrodioxins Salts ." Doctoral dissertation, Bowling Green State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1445859853
Chicago Manual of Style (17th edition)
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Document number:
bgsu1445859853
Download Count:
973
Copyright Info
© 2015, some rights reserved.
Synthesis, Photochemical Properties and DNA Binding Studies of DNA Cleaving Agents Based on Chiral Dipyridine Dihydrodioxins Salts by Alexei E Shamaev is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Bowling Green State University and OhioLINK.