Cláudio N. Verani
Associate Professor
5101 Cass Ave, Room 143
Detroit, MI 48202
Email: [email protected]
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
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,
CHM 6070/7070: Advanced Bioinorganic Chemistry 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, 3rd ed., 2003
2. Gray, Stiefel, Valentine, and Bertini (editors) “Biological Inorganic Chemistry: Structure and
Reactivity” University Science Book; 1st ed. 2006. ~$78.00
3. J. C. Dabrowiak “Metals in Medicine” Wiley; 1st ed. 2010 ~$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, 2nd 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; 2nd edition (2007)
Other references will constitute of compiled sources in PPPs and research papers. Copies of
these publications can be downloaded with help of the Library’s E-journal finder list at
http://www.lib.wayne.edu/resources/journals/alphabetic/index.html
IV. Course Webpage.
A webpage for this course will be available on blackboard: http://blackboard.wayne.edu/.
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 2011 2
CHM 6070/7070: Advanced Bioinorganic Chemistry http://computing.wayne.edu/blackboard/aboutblackboard.php 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.
● 1st hour exam (25%)
February 7th.
nd
● 2 hour exam (25%)
March 9th.
● Seminar* (25%)
March 26th.
 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 1st or the 2nd 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 1st or the 2nd 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 2011 3
CHM 6070/7070: Advanced Bioinorganic Chemistry Meetings can be arranged at any convenient time by previous appointment. Communication
via email 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 5th 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 http://sdcl.wayne.edu/RegistrarWeb/Registrar/policies.htm for complete instructions.
X. Tentative Schedule
Week
#1
Month
January
#2
#3
#4
January
February
#5
#6
#7
#8
February
March
#9
# 10
# 11
Special event
# 12
# 13
April
# 14
# 15
Finals
Apr 27 -
Day
M 10
W 12
M 17
W19
M 24
W 26
M 31
W2
M7
W9
M 14
W 16
M 21
W 23
M 28
W2
M7
W9
14, 16
M 21
W 23
S 26
M 28
W 30
M4
W6
M 11
W 13
M 18
W 20
May 2
Topic
Source*
Introductions, syllabus, overview,
Infrared spectroscopy + Mass spectrometry
PPP‡
PPP
MLK holiday
UV-visible spectroscopy
EPR spectroscopy + X-ray diffraction
Pearson’s acidity + Ligand field theory
Molecular orbital theory
Mechanisms of inorganic reactions
Hour Exam # 1 + Biogeochemical cycles
Metals and proteins, cofactors & clusters
Metal ion transport & storage: transferrins, ferritins
Metal ion transport & storage: siderophores, chaperons
Hydrolytic chemistry: liase & hydrolases
Hydrolytic chemistry: urease & aconitase
Respiration & Photosynthesis: electron-transfer proteins
Respiration & Photosynthesis: dioxygen production
Respiration & Photosynthesis photosystem II
Hour Exam # 2 + Tips on presentations
Spring break
Oxygen metabolism: reactivity, dismutases, cytochrome
Hydrogen, carbon & sulfur metabolism: N-fixation
Research Seminars
4 extra classes
Metaloenzymes with radicals: free radicals, cobalamins
Metaloenzymes with radicals: galactose & amine oxidases
Metallodrugs and their action
Cancer I: Platina drugs
Cancer II: Ruthenium and gallium
Metals in the brain
Alzheimer: Copper and zinc
Diagnosis: Gadolinium
PPP
PPP
M&T (10-11)
M&T (10-11)
M&T (12)
Bertini (II)
Bertini (III/IV)
Bertini (VIII)
Bertini (VIII)
Bertini (IX)
Bertini (IX)
Bertini (X)
Bertini (X)
Bertini (X)
Bertini (XI)
Bertini (XII)
Bertini (XIII)
Bertini (XIII)
Dabrow (2)
Dabrow (3-4)
Dabrow (5)
PPP
Dabrow (7.2, 7.3)
Dabrow (8)
Cumulative Final exam
* Chapters indicated in parenthesis
‡
PowerPoint® presentation from various sources
Winter 2011 4
CHM 6070/7070: Advanced Bioinorganic Chemistry 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 2011 5