University of New Orleans ScholarWorks@UNO University of New Orleans Theses and Dissertations Dissertations and Theses Spring 5-16-2014 X-Ray Structure Analysis and Topological Charge Density Studies of Gossypol Derivatives Carlos Zelaya [email protected] Follow this and additional works at: https://scholarworks.uno.edu/td Part of the Physical Chemistry Commons Recommended Citation Zelaya, Carlos, "X-Ray Structure Analysis and Topological Charge Density Studies of Gossypol Derivatives" (2014). University of New Orleans Theses and Dissertations. 1841. https://scholarworks.uno.edu/td/1841 This Dissertation is protected by copyright and/or related rights. It has been brought to you by ScholarWorks@UNO with permission from the rights-holder(s). You are free to use this Dissertation in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Dissertation has been accepted for inclusion in University of New Orleans Theses and Dissertations by an authorized administrator of ScholarWorks@UNO. For more information, please contact [email protected]. X-Ray Structure Analysis and Topological Charge Density Studies of Gossypol Derivatives Submitted to the Graduate Faculty of the University of New Orleans in partial fulfillment of the requirements for the degree of A Dissertation Doctor of Philosophy in Chemistry Physical by Carlos A. Zelaya B.S. University of New Orleans, 2006 B.A. University of New Orleans 2006 M.S. University of New Orleans 2011 May, 2014 Copyright 2014, Carlos Zelaya ii Dedication The following is dedicated to my parents Carlos Alfonso Zelaya Sr. and Dalia Zelaya for their unselfish dedication to their son in all aspects of life. Both of my parents came to the United States, as immigrants, not only to find a better life for themselves but to give their children a greater opportunity for an enriching life. Through their hard work and love, my parents have fulfilled the promise of giving their children a more meaningful life. Without them I would have never had the opportunities offered to me. Without them I would not be. I would also like to dedicate this dissertation to Evelyn, Claudia, and Eric Zelaya. Not only have I been blessed with superb parents but with loving siblings. My love for my daughter, Mia Elisia, who has given me the desire to become a more conscious and humble man. No greater gift can be bestowed upon a man than that of a beautiful child. Mia you have been my greatest joy, and the reason I wish to live my life in full. Most importantly, I dedicate all my work to GOD. iii Acknowledgements I would first like to take the opportunity to thank Dr. Michael Dowd and Professor Edwin Stevens. Dr. Dowd has exhibited a tremendous amount of patience and understanding throughout the years that have made him an excellent mentor. Dr. Dowd’s thorough and complete understanding of chemical engineering, crystallography, chemistry, and computational analysis have been impressive. He’s ability to examine and solve scientific problems via analysis have had a profound impact on my understanding on what being a scientist entails. Professor Stevens has been a tremendous teacher, mentor, and scientist. His ability to teach mathematics, physics, and its application to physical chemistry, theoretical chemistry, and chemical physics has been exemplary. Professor Stevens’ passion for learning is not only integral to his well being but thankfully contagious. I would also like to thank Professor Steve Rick, who has been my principle instructor in the majority of my course work. Dr. Rick always had an open door policy and has taken considerable time, not only to teach but has made sure that I, the student, understood the material thoroughly. Scott Pelitire, from Dr. Dowd’s research group, has also taken great care in teaching a multitude of instrumentation, problem solving skills, laboratory techniques, and scientific application. Mr. Pelitire has not only been an outstanding scientist but a genuine friend. iv Table of Contents List of Figures .................................................................................................................... vi List of Tables .................................................................................................................... vii Abstract ............................................................................................................................ viii Introduction ..........................................................................................................................1 Methods..............................................................................................................................72 Results ................................................................................................................................74 Discussion ........................................................................................................................105 Conclusion .......................................................................................................................124 References ........................................................................................................................127 Vita ...................................................................................................................................151 v List of Figures Figure 1.1 Gossypol Structure .............................................................................................2 Figure 1.2 6',6'-Dimethoxygossypol (MG) ..........................................................................4 Figure 1.3 Di(propylamino)gossypol (PAG) .......................................................................5 Figure 1.4 Critical Points & Curvature ..............................................................................29 Figure 1.5 Electron Charge Density of Diborane 1 ...........................................................31 Figure 1.6 Electron Charge Density of Diborane 2 ...........................................................32 Figure 1.7 Trehalose ORTEP .............................................................................................58 Figure 1.8 Static & Residual Maps of Trehalose ...............................................................61 Figure 1.9 Trehalose Gradient Trajectory Maps ................................................................64 Figure 3.1 Di(3-phenylpropylamino)gossypol ORTEP (Low Temp.)...............................75 Figure 3.2 Di(3-phenylpropylamino)gossypol ORTEP (Room Temp.) ............................76 Figure 3.3 Di(t-butylamino)gossypol ORTEP (ordered) ...................................................78 Figure 3.4 Di(t-butylamino)gossypol ORTEP (disordered) ..............................................79 Figure 3.5 Di(3-hydroxypropylamino)gossypol ORTEP ..................................................81 Figure 3.6 Di(propylamino)gossypol ORTEP ...................................................................82 Figure 3.7 Di(propylamino)gossypol ORTEP ...................................................................83 Figure 3.8 Di(methoxy)gossypol ORTEP..........................................................................84 Figure 3.9 Experimental Static Deformation Density (MG) .............................................90 Figure 3.10 Experimental Static Deformation Density (PAG) ..........................................91 Figure 3.11 Experimental Aldehyde Deformation Density (MG) .....................................92 Figure 3.12 Experimental Alcohol Deformation Density (MG) ........................................94 Figure 3.13 Experimental Alcohol Deformation Density (PAG) ......................................95 Figure 3.14 Amine Bond Experimental Deformation Density (PAG) ..............................96 Figure 3.15 Experimental Electrostatic Potential (MG) ....................................................99 Figure 3.16 Experimental Electrostatic Potential (PAG) .................................................100 Figure 4.1 Residual Density of MG .................................................................................116 Figure 4.2 Residual Density of PAG ...............................................................................117 Figure 4.3 Aldehyde Gradient Trajectories of MG ..........................................................119 Figure 4.4 Gradient Trajectories & Electron Density of MG ..........................................120 vi List of Tables Table 1 MG Bond Critical Points ....................................................................................101 Table 2 PAG Bond Critical Points ...................................................................................103 Table 3 DMG VS PAG Bond Critical Points ..................................................................121 Table 4 Naphthalene VS DMG VS PAG Bond Critical Points .......................................123 vii Abstract Gossypol and gossypol derivatives are natural byproducts of a variety of cotton plant species that poses interesting chemical, biological, and medicinal properties that are currently heavily researched. Supporting evidence suggest that gossypol and gossypol derivatives act on the Bcl-2 proteins that have been linked to certain cancers. Gossypol amine