CHM 6070/7070 Advanced Bioinorganic Chemistry

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CHM 6070/7070 Advanced Bioinorganic Chemistry Mondays and Wednesdays, 4:30 5:50 PM Science & Engineering Library, Room 221 From January 10 to May 03, 2011 Prerequisite for undergraduates: CHM 3000 or

1 CHM 6070/7070 Advanced Bioinorganic Chemistry Mondays and Wednesdays, 4:30 5:50 PM Science & Engineering Library, Room 221 From January 10 to May 03, 2011 Prerequisite for undergraduates: CHM 3000 or CHM 3020 Tentative Syllabus Cláudio N. Verani Associate Professor 5101 Cass Ave, Room 143 Detroit, MI I. Description. This course will introduce advanced undergraduate and first year graduate students to concepts that underlie the way biological systems use metal ions and how bioinorganic chemists think about these systems. The course focuses on the following topics: (i) A review of pertinent instrumental techniques used to study bioinorganic systems (ii) An overview of the main theories relevant for transition metal behavior and ligand design (iii) Study of metal-containing biological systems and biomimetic metalrelated complexes (iv) Study of medicinal inorganic systems. II. Detailed Contents. 1. Pertinent Instrumental Techniques: (~3 weeks) Spectroscopic methods (Infrared, UV-visible, nuclear magnetic resonance, electron paramagnetic resonance spectroscopies), mass spectrometric methods, diffraction methods. 2. Bonding Theories and Transition Metal Behavior: (~3 weeks) Pearson s (hard/soft) acids and bases, ligand field theory, molecular orbital theory, inorganic reaction mechanisms 3. Metal-containing Biological Processes and Systems: (~7 weeks) Metal ions transport and storage: transferrins, ferritins, siderophores, methalothioneins, copper-transporting ATPases, metallochaperones. Hydrolytic chemistry: metal-dependent liase and hydrolase enzymes, urease, aconitase, catalytic nucleic acids. Respiration and Photosynthesis: electron-transfer proteins, electron-transfer trhough proteins, photosynthesis and respiration, dioxygen production, photosystem II. Oxygen metabolism: dioxygen reactivity and toxicity, superoxide dismutases and reductases, peroxidases and catalases, dioxygen carriers, activating enzymes, cytochrome c, multicopper oxidases, mechanistic considerations,

2 Hydrogen, carbon and sulfur metabolism: microbiology and biochemistry of hydrogen, reduction of carbon compounds, nitrogen fixation and nitrification, denitrification, sulfur metabolism, molybdenum and tungsten enzymes. Metaloenzymes with radical intermediates: free radicals, cobalamins, ribonucleotide reductases, Fe-S clusters, galactose oxidase, amine oxidases, lipoxygenase. Metal ion receptors and signaling: metalloregulatory proteins, zinc-binding domains, calcium in mammalian cells, nitric oxide, Metallodrugs and their action, Cancer: platina, ruthenium and gallium drugs Diabetes: Vanadium Alzheimer: Copper and zinc Diagnosis: Gadolinium 4. Study of Medicinal Inorganic Systems: (~3 weeks) Biomimetic complexes of the above mentioned systems; vanadium compounds as insulin mimics; overview of cellular targets for therapy (platinum-based drugs, gold-based agents, technetium radiopharmaceuticals, gadolinium chelates as MRI contrast agents), Treatment of Wilson and Menkes Diseases III. References. Textbooks: 1. Miessler & Tarr, (Selected chapters only) Inorganic Chemistry, Prentice-Hall, 3 rd ed., Gray, Stiefel, Valentine, and Bertini (editors) Biological Inorganic Chemistry: Structure and Reactivity University Science Book; 1 st ed ~$ J. C. Dabrowiak Metals in Medicine Wiley; 1 st ed ~$47.00 Shop for best prices! Other Sources: Frausto da Silva and Williams The Biological Chemistry of the Elements: The Inorganic Chemistry of Life" Oxford University Press, 2 nd edition (2001). Kaim and Schwederski Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life Wiley; (1994) Lippard and Berg "Principles of Bioinorganic Chemistry" University Science Books (1994) Metzler-Nolte and Schatzschneider Bioinorganic Chemistry: A Practical Course, Walter de Gruyter (2009) Roat-Malone Bioinorganic Chemistry: A Short Course Wiley-Interscience; 2 nd edition (2007) Other references will constitute of compiled sources in s and research papers. Copies of these publications can be downloaded with help of the Library s E-journal finder list at IV. Course Webpage. A webpage for this course will be available on blackboard: Announcements, grades, slides, homework and exercises, and other supplemental informationwill be provided via this site. New users to blackboard can visit the computing and information page at Winter

3 for more information about access and use of blackboard. V. Lectures. During the lectures, presentation and clarification of the contents will take place. Attending lecture, participating in classroom discussions, and taking notes is fundamental to succeed in the class. Questions will be addressed during lecture and office hours will be available. The student is responsible for learning the material presented. While most of the contents will be covered in lectures, some material may be covered only by assigned readings. VI. Evaluation. 1 st hour exam (25%) February 7 th. 2 nd hour exam (25%) March 9 th. Seminar* (25%) March 26 th. Group 30-minute talk, PowerPoint presentation & questions on a given topic not discussed in the classroom. See suggested topics on section XI. Other possibilities are the work of a particular group, or topics related to the research interest of the student within the WSU inorganic division (however, the work developed by Allen, Brock, Endicott, Verani, or Winter, as well as any other WSU group are not recommended). Final exam (25%) Determined by the university * Details will be discussed accordingly The final scores will be sorted out in groups and given an equivalent Letter Grade. If no clear cut offs are reached, the single highest grade will be assigned as equals to 4.00 and the remaining grades will be converted accordingly to the WSU graduation system, where 4.0 is equivalent to A, 3.67 is equivalent to A-, 3.33 is equivalent to B+, 3.0 is equivalent to B, 2.67 is equivalent to B-, 2.33 is equivalent to C+ and 2.00 is equivalent to C. If a student misses either the 1 st or the 2 nd hour exam, the lowest grade obtained in any of the three hour exams will replace the missing grade. The third hour exam will not be replaced and the student will receive a failing grade. VII. Academic Honesty. Students are expected to exhibit academic honesty and integrity at all times. Cheating on course work or any other form of academic dishonesty is abhorrent to the academic process and will not be tolerated under any circumstances. Cheating will not be tolerated and is likely to lead to expulsion from the University according to the rules of the College of Arts and Science and the Wayne State University. VII. Registration Policy: Unregistered students will not be allowed in the classroom. VIII. Attendance Policy: Students are encouraged to attend every class. Very often points are stressed in class that elucidate exam questions. However, attendance will not be taken and will not be considered for grading purposes. Attendance at exams is mandatory. Students are responsible for obtaining notes of missed lectures from classmates, they will not be provided by the course instructor, nor will the instructor take significant time to explain material during office hours that the student has not received due to a missed lecture. If a student misses either the 1 st or the 2 nd hour exam, the lowest grade obtained in any of the three hour exams will replace the missing grade. The third hour exam is cumulative and will not be replaced. The student will receive a failing grade. IX. Office Hours, Communication Policy, and Course Withdrawals Winter

4 Meetings can be arranged at any convenient time by previous appointment. Communication via is welcomed and will be employed routinely along the course. Due to the impossibility of easy recording and tracking, telephone calls and messages will not be answered. April 20, 2011 is the last day to withdraw from this class. Failure to withdraw officially before Final Exam Study Day will result in an F. There is no longer an X grade. Students who request course withdrawals beginning with the 5 th WEEK of the term will now receive one of these notations: WP Withdrawal with a passing grade earned to date WF Withdrawal with a failing grade earned to date WN Withdrawal never attended, or no graded work to date None of these notations affect GPA. The new withdrawal policy does not affect tuition and fees, since there is no tuition cancellation provision for withdrawn courses. The Instructor can also choose to Deny the request to withdraw. The request to withdraw can be made on Pipeline. It is located under the Student tab, Registration menu, and then select Withdraw from a Class. Please go to for complete instructions. X. Tentative Schedule Week Month Day Topic Source* # 1 January M 10 W 12 Introductions, syllabus, overview, Infrared spectroscopy + Mass spectrometry # 2 M 17 W19 MLK holiday UV-visible spectroscopy # 3 M 24 W 26 EPR spectroscopy + X-ray diffraction Pearson s acidity + Ligand field theory M&T (10-11) # 4 January February M 31 W 2 Molecular orbital theory Mechanisms of inorganic reactions M&T (10-11) M&T (12) # 5 M 7 W 9 Hour Exam # 1 + Biogeochemical cycles Metals and proteins, cofactors & clusters Bertini (II) Bertini (III/IV) # 6 M 14 W 16 Metal ion transport & storage: transferrins, ferritins Metal ion transport & storage: siderophores, chaperons Bertini (VIII) Bertini (VIII) # 7 M 21 W 23 Hydrolytic chemistry: liase & hydrolases Hydrolytic chemistry: urease & aconitase Bertini (IX) Bertini (IX) # 8 February March M 28 W 2 Respiration & Photosynthesis: electron-transfer proteins Respiration & Photosynthesis: dioxygen production # 9 M 7 Respiration & Photosynthesis photosystem II W 9 Hour Exam # 2 + Tips on presentations # 10 14, 16 Spring break # 11 M 21 W 23 Oxygen metabolism: reactivity, dismutases, cytochrome Hydrogen, carbon & sulfur metabolism: N-fixation Bertini (XI) Bertini (XII) Special event S 26 Research Seminars 4 extra classes # 12 M 28 W 30 Metaloenzymes with radicals: free radicals, cobalamins Metaloenzymes with radicals: galactose & amine oxidases Bertini (XIII) Bertini (XIII) # 13 April M 4 W 6 Metallodrugs and their action Cancer I: Platina drugs Dabrow (2) Dabrow (3-4) # 14 M 11 W 13 Cancer II: Ruthenium and gallium Metals in the brain Dabrow (5) # 15 M 18 W 20 Alzheimer: Copper and zinc Diagnosis: Gadolinium Dabrow (7.2, 7.3) Dabrow (8) Finals Apr 27 - May 2 Cumulative Final exam * Chapters indicated in parenthesis PowerPoint presentation from various sources Winter

5 XI. Topics for Seminar The following topics are an integral part of the books of Bertini et al and Dabroviak. The information containied in those sources is suppose to be complemented by classic and recent papers on the subject. 1. Biomineralization (Bertini IV) 2. Storage and transport: methalothioneins, copper-transporting ATPases (Bertini VIII.4, VIII.5) 3. Hydrolytic chemistry: catalytic nucleic acids (Bertini IX.5) 4. Respiration and Photosynthesis: electron-transfer through proteins, photosynthesis and respiration (Bertini X.2, X.3) 5. Oxygen metabolism: peroxidases and catalases, dioxygen carriers, activating enzymes, multicopper oxidases, mechanistic considerations (Bertini XII.3-7) 6. Hydrogen, carbon and sulfur metabolism: microbiology and biochemistry of hydrogen, reduction of carbon compounds, sulfur metabolism, molybdenum+tungsten enzymes. (Bertini XII.1-2, XII.5-7) 7. Metaloenzymes with radical intermediates: ribonucleotide reductases, Fe-S clusters, lipoxygenase (Bertini XIII.3-4, XIII.6) 8. Metal ion receptors and signaling: metalloregulatory proteins, Zn domains (Bertini XIV.1, XIV.2) 9. Metal ion receptors and signaling: Ca in cells, nitric oxide (Bertini XIV.3, XIV.4) 10. Cisplatin and cancer (Dabrowiak 3) 11. Gold complexes for arthritis (Dabrowiak 6) Winter

CCHEMISTRY 366. Inorganic Chemistry with Emphasis on Bioinorganic, Medicinal & Materials Chemistry

CCHEMISTRY 366. Inorganic Chemistry with Emphasis on Bioinorganic, Medicinal & Materials Chemistry CCHEMISTRY 366 Inorganic Chemistry with Emphasis on Bioinorganic, Medicinal & Materials Chemistry Instructor: North Building Office Hours: to be decided by class, probably Tuesday after class or by appointment.