Colby College Digital Commons @ Colby Honors Theses Student Research 2005 The Synthesis of Biomimetic Tungsten and Molybdenum Complexes John Sterling Cole III Colby College Follow this and additional works at: https://digitalcommons.colby.edu/honorstheses Part of the Chemistry Commons Colby College theses are protected by copyright. They may be viewed or downloaded from this site for the purposes of research and scholarship. Reproduction or distribution for commercial purposes is prohibited without written permission of the author. Recommended Citation Cole III, John Sterling, "The Synthesis of Biomimetic Tungsten and Molybdenum Complexes" (2005). Honors Theses. Paper 298. https://digitalcommons.colby.edu/honorstheses/298 This Honors Thesis (Open Access) is brought to you for free and open access by the Student Research at Digital Commons @ Colby. It has been accepted for inclusion in Honors Theses by an authorized administrator of Digital Commons @ Colby. The Synthesis of Biomimetic Tungsten and Molybdenum Complexes John Sterling Cole III Colby College Department ofChemistry Waterville, ME 04901 United States ofAmerica May 2005 2 The Synthesis of Biomimetic Tungsten and Molybdenum Complexes John Sterling Cole III A Thesis submitted to the Chemistry Department at Colby College, Waterville, ME in partial fulfillment of the requirements for graduation with Honors in Chemistry May 18,2005 Approved: (Memor: Rebecca R. Conry, Associate Profes 0 ofChemistry) __----L..\\ (~\ D~ Date ~\.UD lww (Reader: Martin T Lemaire, Faculty Fellow ofChemisrry) ,~ WI '-'-1 ~ (" Date \ 3 Research papers are detailed records ofhow effort and time-even lives-have been spent, and a knowledgeable person by reading a research paper can judge the quality ofthe 'minds and hands' a/the author. --Donald J. Cram 4 Dedicated to my mom, dad, and grandpa I am a strong believer in humor, optimism, and balance. I learned many of my beliefs from my mom, dad, and grandpa. My mom has always put my sister and I before herself. She is extremely dedicated, compassionate, and thoughtful ofother people. She will always think. of others before herself and I have learned from her example how to put myself in other people's shoes. I would not have gotten to where I am today without her. My dad was brought up in rural Vermont and says that when he was very young he didn't have many friends because he lived so far from everyone. Nevertheless, it is he who shows compassion and genuine care toward people in subtle ways that most people never take the time to do. My maternal grandpa worked his way through medical school and became a successful vascular surgeon in Minnesota. Both my dad and grandpa became successful because of the way they treated people. It is the linle things that count. People appreciate acts of kindness in a world that can be entirely overwhelming at times. It is absolutely amazing how a small gesture like a smile at a busy airport can make all the difference in the world to one person. I have seen my dad smile and talk to a baggage checker when most people seem to pay no attention to the fact that there is actuaHy a person behind the check-in desk. This one act of kindness can make amazing things happen. Often times baggage checkers will release a huge sigh of relief, happy for once that there is not another stressed out, grumpy traveler in front ofthem, and they become more easygoing and helpful. This anitude toward life has practical implications for a doctor working with patients. Humor and optimism are important vehicles to make people feel at ease and secure, but balance is the key. To be a successful person, one must balance all aspects of life. r think a doctor in a community is held to a higher standard than an average citizen. I admire my grandpa who finds a balance between being confident and being a good listener to his patients. Patients trust their lives and their loved ones into a doctor's care, and this trust is secured by the way they are treated as well as by a successful diagnosis. A physician must be knowledgeable in all aspects ofmedicine and the human psyche while projecting a confident and calming persona. toward his patients. I strive to be like my mom, dad, and grandpa because they take on more than their responsibilities; they go the extra mile to be good people. 5 Acknowledgements I would like to thank Professor Conry for her constant guidance, knowledge, and friendship throughout this research project and Professor Lemaire for being my reader. Past members of the Conry group were instrumental in getting this project to where it is today. Isaac Newton once said that: "If! have seen further it is by standing on ye shoulders of Giants." Those giants are A. Alex Tipton, Alexis Bond, Jessica Hayward, Laura Olenick, and Eric Bergh. Thank you for your dedication and hard work on this project. My family has been very supportive throughout my education and I want to especially thank my mom and dad for working tirelessly to give me such a wonderful well-rounded head and education. I would like to thank my sister Kristy, who I have always looked up to ever since I was a little boy, for being a dependable friend and role model. Colby College has given me so much over these past four years and I will always hold the school and the Chemistry Department in the highest regard. Thank you Professor Millard, Professor Shattuck, Professor King, Professor Pratt, Professors Shari and Steve Dunham, Professor Thamattoor, Professor Lemaire, Professor Katz, Professor Rowe, Brenda, Lisa, Ms. Mac, Harry, Jane, and Professor Mundy. You are what make Colby College great! Thank you for taking the time to get to know your students, it makes a big difference. 6 Table of Contents Quote. 3 Dedication 4 Acknowledgements 5 Vitae 7 Table of Figures 8 Abstract. 9 Introduction Section I-Introduction to Bioinorganic Chemistry 1.1 Tungsten Enzymes 10 1.2 Molybdenum Enzymes 13 1.3 The Catalytic Mechanism ofAldehyde Ferredoxin Oxidoreductase (AOR) 14 Section 2-The Small Model Complex 2.1 Model Tungsten Complexes 15 2.2 Structural Considerations for Preparing Model Complexes 17 2.3 Previous Molybdenum Reactions of Relevance " 18 Results and Discussion 3.1 Synthetic Plan for the Ligand Precursor, LH2 20 3.2 Contributions to the Ligand Precursor Synthesis Made by Others 22 3.3 Synthesis and Characterization of the Ligand Precursor LH2•..•....•....•..•.•.........23 3.4 Synthesis and Characterization of the Ligand Precursor L'H 26 3.5 Metal-Containing Starting Material Syntheses 28 3.6 Coordination Chemistry ofL'H 30 Conclusions 32 Methods and Materials 33 References .39 7 VITAE John Cole was born in Edina, Minnesota on April 30, 1982 to JaM and Sue Cole. He has an older sister named Kristy who has always been a best friend. John was raised in Edina until third grade, then Ladue, Missouri until eighth grade, and finally Glencoe, Illinois. These moves have taught him a lot about making new friends and fitting in new situations. He graduated from New Trier Township High School in the top half of his class and was an All-American swimmer his senior year in high school. He entered Colby College in the fall of 200 1 eager to fmd a major where he could excel and fit into a small closely knit community. He found that in the chemistry department, joining a group of24 enthusiastic majors in his class and forming great relationships with his professors. He began his research with Dr: Shari Dunham in anal}'1ical chemistry. Working over the summer at Colby and during the fall of his junior year lead to the publication of the paper titled "Evaluation of various calcium-fortified high moisture commercial products for improving the calcium content of crickets, Acheta domesricus" which was coauthored with Finke, M.D. and Dunham, S.D. and appeared in the Journal ofHerpetolOgical Medicine and Surgery. He began his thesis research with Dr. Rebecca Conry in January of his junior year. With his hard work., persistence, and dedication he has proved to be a capable chemist. He loves Colby and the Chemistry department and will miss them neXt year. He will graduate from Colby College on May 22,2005 with a B.A. in Chemistry, with an emphasis on Biochemistry. In September, he will attend Rush Medical College in Chicago where he will begin his M.D. program with aspirations to someday practice orthopedic surgery in Chicago. 8 Table of Figures Introduction Scheme 1. Reactions that tungsten enzymes catalyze by family ll Figure 1. The crystal structure of the AOR enzyme ofPyrococcusfuri()sus.....12 Figure 2. Active site of common metalloenzymes where M = Mo or W 13 Figure 3. [MO(dithiolene)2]2- complexes 16 Figure 4 Active site for AFO enzyme from the X-ray crystal structure (left) and the target small molecule synthetic tungsten(Vl) model complex (right) 18 Figure 5. Product of direct linking reaction using propane-linking arm 21 Results and Discussion Figure 6. Structure ofthe practice compound .- 23 Figure 7. IH NMR spectrum of the second product isolated from the column after the deprotection reaction (eq 10) 25 Figure 8. The new target ligand precursor L'H 26 Figure 9. 1H NMR spectrum of biphenyl-2-thiol-2'-mercapto-alpha-para­ xylene 28 Scheme 2. Synthesis of bis-acetylacetonate dioxotungsten(VI) 29 Scheme 3. Synthesis of bis-acetylacetonate dioxomolybdenum(Vl) 29 Figure 10. IH NMR spectrum of the reaction between 8 and L'H in CD2Ch after two days 31 9 Abstract The synthesis of novel biornimetic molybdenum and tungsten compounds that are potential model complexes for molybdenum and tungsten oxidase enzymes is being pursued.