Conformational studies on adenine formation and spin properties of bio-related radicals
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] This dissertation summarizes a few different projects I have contributed to in Dr. Glaser's group during the past five years. The first part is chapter 2 and 3, which describe the results of theoretical studies related to adenine synthesis. The second part is chapter 4 on nitrogen dioxide and its natural extension chapter 5 on nitric oxide dioxygenases. The third part is about an anticancer drug tirapazamine from chapter 6 to chapter 8. In chapter 2 we explored the isomerization and thermodynamic preferences of nitirlium ion 8. Chapter 3 reports an unexpected phenomenon revealed in adenine formation calculations: the asymmetry of the N-inversion paths during the (Z)/(E) isomerization of 1H-purine-6(9H)-imine. Chapter 4 provides great demonstrations for spin delocalization and spin polarization effects. The spin-density distribution provides a practical connection to chemical reactivity because radical reactivity of the system tends to occur at positions with high α-spin concentration. The interaction between oxygenated heme protein and nitric oxide calculated in chapter 5 provides a perfect example for such reactions. Chapter 6, 7 and 8 describe results of a close collaboration with Prof. Gates group. Tirapazamine (TPZ) can cause hypoxia-selective, redox-activated DNA strand cleavage and nucleobase damage in solid tumors. A series of TPZ analogs were synthesized and studied in the Gates laboratory and possible reaction channels for their activation were studied with modern electronic structure methods by the Glaser group.
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