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TIME-RESOLVED SPECTROSCOPIC STUDIES OF PSORALENS, KHELLIN, VISNAGIN AND LUMICHROME AND DERIVATIVES DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Hannan Fersi, M.S. ***** The Ohio State University 2006 Dissertation Committee: Approved by Professor Matthew S. Platz, Advisor Professor Terry L. Gustafson _________________________________ Professor Anne B. McCoy Advisor Graduate Program in Chemistry Professor Stephen A. Sebo ABSTRACT Psoralens, coumarins and flavins are biologically active photosensitizers, which have been used in pathogen inactivation of blood products, cancer treatment and skin diseases. Laser flash photolysis (LFP) with UV-visible and infrared detection and Density Functional Theory (DFT) calculations were used to directly observe and identify the triplet states of psoralens, coumarins and lumichromes, and their intermediate derivatives, and to understand their chemical reactivity. The triplet-excited states of the parent psoralen as well as 8-methoxypsoralen, 5-methoxypsoralen and trimethylpsoralen were directly observed in acetonitrile using UV-visible or time-resolved infrared (TRIR) spectroscopy. TRIR spectra of trimethylpsoralen radical ions were also obtained. These experimental observations were supported by computational studies. The vibrational spectra of triplet visnagin and khellin, and their radical cations and anions were obtained upon 266 nm LFP in acetonitrile. Visnagin and khellin triplet excited states react with chloranil to form their radical cations and the chloranil radical anion. The radical cation of khellin and visnagin both present a vibrational band at 1136 cm-1. The excited states of khellin, visnagin and chloranil are all involved in the light induced electron transfer reaction. Khellin and visnagin triplets both react with anionic electron donors (NaI or KSCN) to form the related radical anions. Triplet visnagin reacts ii -1 with hydroquinone to form semiquinone radicals. The vibrational band at 1225 cm of the visnagin derived radical was assigned to a C-H rocking mode on the basis of DFT calculations. In the exploratory photochemistry of lumichrome and its oxides, both nanosecond and ultrafast laser flash photolysis with UV-visible and TRIR spectroscopy were used to observe the transient species generated photochemically from lumichrome (LC), lumichome-N-oxide (LCO) and lumichome-di-N-oxide (LCO2) and the data were interpreted with the aid of DFT calculations. The transient absorption spectra and the lifetimes of the triplet states of lumichrome, lumichrome N-oxide and lumichrome di-N- oxide were measured by LFP methods with UV-vis detection and TRIR spectroscopy upon 266 nm LFP in acetonitrile. The transient UV-vis spectra of 3LC*, 3LCO* and 3 * LCO2 were obtained upon 266 nm LFP in argon saturated acetonitrile and their lifetimes were determined to be about 1 µs in deoxygenated acetonitrile. The transient vibrational spectra of LC, LCO and LCO2 triplet excited states were obtained upon 266 nm and present similar features with strong IR bands assigned to the carbonyl C=O and C=N stretching vibrations as predicted by the DFT calculations. The singlet states of lumichrome, lumichome-N-oxide, lumichome-di-N-oxide, isoquinoline N-oxide and pyridine N-oxide were identified by picosecond time-resolved absorption spectroscopy. Time-correlated single photon counting (TCSPC) and fluorescence spectroscopy were used to determine the lifetimes of the singlet states and fluorescence quantum yields of these aromatic N-oxides as well as isoquinoline N-oxide (IQNO), pyridine N-oxide (PNO), riboflavin tetraacetate and riboflavin tetrabenzoate. iii To my mother and my sister Najira, iv ACKNOWLEDGMENTS The completion of my Ph.D. has been a long journey and I would like to take this opportunity to thank all the people who have helped make it a most memorable one. First, I wish to express my heartfelt gratitude to my adviser, Dr. Matthew Platz, for his guidance, patience and support. I really enjoyed working under his supervision. I thank Dr. Terry Gustafson, Dr. Anne McCoy and Dr. Stephen Sebo for serving as my dissertation committee. I wish to sincerely thank Dr. Larry Anderson and Dr. Sherwin Singer who helped guide, advise and encourage me through my academic experience at OSU. I thank Jin Wang, Drs. Gotard Burdzinski and Xiaofeng Shi for their valuable insights, assistance, and friendship. The Center for Chemical and Biophysical Dynamics provided ultrafast laser spectroscopic instruments for this work. I would like to thank Professor Terry Gustafson and Dr. Gotard Burdzinski of the CCBD for their help in the ultrafast spectroscopic measurements. I also thank the Ohio Supercomputer Center for providing the resources of my computational work. I would like to thank all my friends, who made the last six years more enjoyable, particularly, Dr. Mariano Avila-Escobedo and Dr. Rajni Tyagi for their unending support, v and ensuring that there was never a dull moment in my life in Columbus, OH. I also thank Nathalie Dardare and Abraham Levy Solomon whose mails and phone calls helped me keep my mental health. I thank my best friend, Hota Okio, for her tremendous enthusiasm, support and friendship through the last twenty years. I feel very privileged to have such a great friend. Finally, I wish to express my heartfelt gratitude to my family for their unconditional support and love and for providing within me the guidance and character to accomplish all that I have; Jeffrey Clogston, for being an excellent friend. I deeply appreciate your patience, understanding, love and support at all times; I thank my sisters, Nora, Fayelle, Yasmine-Syrine, my brother Lassad for providing great joy in my life through your extraordinary cheerfulness and vitality. I love you all very much. And my final thanks go to my parents and my sister Najira for their unconditional support, endless love and for providing an example as tremendous human beings; your dedication and inspiration is the force aiding me the most. vi VITA 1997................................................................DEUG Sciences de la Matiere, Universite Claude Bernard, Lyon I, France 1999 . Maitrise de Chimie Chysique, Universite Claude Bernard, Lyon I, France 2002 . M. S. in Physical Chemistry The Ohio State University, Columbus, Ohio 2000 - present . Graduate Teaching and Research Associate, The Ohio State University, Columbus, Ohio PUBLICATIONS Fersi, H.; Platz, M.S., Nanoseconds Time-Resolved Infra-Red Studies of Visnagin and Khellin, J. Phys. Chem. A, 2005, 109:41, 9206 - 9212 Cherezov, V.; Fersi, H.; Caffrey, D., Crystallization Screens. Compatibility with the Lipidic Cubic Phase for In Meso Crytallization of Membrane Proteins, Biophys. J., 2001, 81:225-242. FIELDS OF STUDY Major Field: Chemistry - Physical Chemistry vii TABLE OF CONTENTS Page Abstract…...……………………………………………………………………………... ii Dedication……………………………………………………………………………...…iv Acknowledgements………………………………………………………………………..v Vita………………………………………………………………………………….…...vii List of Tables……………..……………………………………………………………..xiii List of Figures.…………………………………………………………………………...xv List of Schemes………………………………………………………………………....xxiv Chapters: 1. Introduction ............................................................................................................. 1 2. Experimental.......................................................................................................... 15 2.1 Nanosecond laser flash system (LFP) with UV-Vis detection................. 15 2.2 Time-resolved infrared spectroscopy (TRIR) ........................................... 16 2.3 Ultrafast transient UV-Vis spectroscopy .................................................. 17 2.4 UV-Vis and fluorescence measurements .................................................. 18 2.5 Density functional calculations................................................................. 20 2.6 References................................................................................................. 21 3. Nanosecond laser flash photolysis of psoralen and its derivatives triplet excited states ...................................................................................................................... 22 3.1 Introduction ............................................................................................... 22 3.2 Experimental ............................................................................................. 29 3.2.1 Materials........................................................................................ 29 3.2.2 Time-resolved infrared spectroscopy............................................ 29 3.3 Results and discussion ................................................................................. 30 viii 3.3.1 Time-resolved with UV-Vis detection.......................................... 31 3.3.2 Time-resolved infrared spectroscopy studies................................ 42 3.4 Conclusions ............................................................................................. 56 3.5 References ............................................................................................... 57 4. Nanosecond laser flash photolysis studies of lumichrome and its oxides triplet excited states......................................................................................................... 60 4.1 Introduction..............................................................................................
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