Chemistry 446
INTRODUCTION TO BIOINORGANIC
CHEMISTRY
Fall 2011
Art and Design Building 2003, T/R
12:00-1:15 pm ________________________________________________________________________________________________________________________________
Instructor:
Dr. Keith M. Davies.
kdavies@gmu.edu 703-993-1075
Office Hours:
Tu/Th 10:30-11:30, 1:30-2:30
ST1 331; M/W/F
410 Occoquan (PW1) by
appointment Text:
CHEM 446-Introduction to Bioinorganic Chemistry-Course Supplement (Copy Shop-University.
Bookstore)
Recommended Reading: Biological Inorganic Chemistry: Structure
and Reactivity
by
H. B. Gray,
E. I. Stiefel,
J. S. Valentine and
I. Bertini, University Science Books,
2007. Prerequisites:
CHEM 463, CHEM 313. Students may
take this course concurrently with CHEM
463. ___________________________________________________________________________________________________________________
Course Outline and Objectives
Bioinorganic
chemistry considers the roles of inorganic elements in biological processes. It
applies fundamental principles of inorganic chemistry (particularly transition
metal coordination chemistry and ligand field theory) to understanding the
structure and function of metal ion sites in biomolecules. It also examines a
variety of metal-related topics ranging from metal toxicity and the use of metal
complexes as drugs to oxidative stress from reactive oxygen species and the
bioregulatory functions of nitric oxide.
Mid-Term Exam I
Sept. 22 22%
Mid-Term Exam II
Oct. 25 22%
Mid-Term Exam III
Nov. 29 22%
Final Exam
(10:30-1:15)
Dec. 15
___________________________________________________________________________________________________________________ Make-Up Exam Policy There will be no “make-up”
exams given. An absence from one exam will be excused if adequate
documentation is provided. (e.g. a note from a physician). For an
excused absence, the mid-term exam% for the course will be determined from the
other mid-terms and final (i.e. the point values of the other exams will
be increased proportionately). The University requires that all students take a
final exam.
___________________________________________________________________________________________________________________
Course Schedule
30
Sept
Introduction: Occurrence,
availability and roles of metallic elements. Classification of
metallobiomolecules
1
Fundamentals of inorganic coordination chemistry.
Ligand structures, complex stability, chelate effects, HSAB classification,
solvation and macrocyclic
effects.
6
Review of protein structure and metal binding.
Metal-binding amino acid residues, macrocyclic porphyrin and
corrin ring structures. Hapticity
(η) and bridging (μ) modes.
8
Ligand field effects. High spin and
low spin states. Magnetic and spectral properties.
13
Thermodynamic stability and kinetic lability. Redox
potentials, Latimer diagrams, substitution
rates.
15
M.O.Theory Diatomic oxygen
species. Metal-ligand s and
Π-interactions. Organometallic structures, Π-acid ligands, 18-electron rule
20
Metal transport and storage: Fe
uptake and transport, transferrin.
22
27
Exam I
29
Iron storage, ferritin, Fe
uptake and retrieval. Mossbauer
spectroscopy. Siderophore iron transport.
Cu and Zn transport and storage. Metallothioneins and
metallochaperones.
Oct
4
Dioxide transport.
Hb and Mb structure and O2 binding. pH effects. Spin states and
cooperativity. Fe2+- 1O2 vs. Fe3+-
O2- Inorganic model compounds, Hb variants.
6
O2
transport in hemocyanin and hemerythrin.
Dioxygen activation. Oxygen
atom transfer by cytochromes-P450, tyrosinase.
11
Columbus Day Holiday (No class).
13
Dioxygen toxicity
Toxicity of oxygen species, detoxification enzymes. Termodynamics
of disproportionation equilibria. Superoxide
dismutases.
Peroxidases and catalases.
18
Anticancer Therapeutic
Agents.
Cisplatin and 2nd generation Pt drugs.
Organometallic anticancer
transition metal complexes.
20
25
Exam II
27
Metal deficiency and toxicity.
Essential elements, Fe, Cu, Zn, chelation therapy. Toxicity of heavy
metals, Hg, Pb, Cd, Cr, Al.
Nov
1
Nitric oxide biochemistry.
Physiological roles of NO. Nitric oxide synthase enzymes. NO donor compounds
3
Electron Transfer in Biology. Metal
cofactors. Iron cytochromes and iron-sulfur clusters, cytochrone-c
oxidase,
8
Copper proteins. epr spectroscopy. Marcus electron
transfer theory. Protein
electron transfer
10
Nitrogenase Structure of
nitrogenase enzyme: Mechanism of N2 reduction.
15
Hydrogenases structure and reactivity.
17
Cobalamins. Structure of
coenzyme B 12 coenzyme sites.
22
Mechanism of B12-dependent isomerases and methyltransferases.
Thanksgiving Recess (Nov 23-26)
29
Dec
Exam III
1
Metal-dependant hydrolase enzymes
Zinc enzymes, carbonic anhydrase, carboxypeptidase, alcohol
dehydrogenase. Aconitase, urease.
6
Membrane transport of metal
ions.
Gp I, II metals, Na, K,
Mg, Ca as biological messengers: Ionophores,
gramicidin,
ion channels, aquaporins.
8
Last day of class. Review
Bioinorganic Chemistry Texts: On
reserve in Johnson Center library:
H. B. Gray,
E. I. Stiefel,
J. S. Valentine and
I. Bertini, Biological Inorganic Chemistry: Structure
and Reactivity (University Science Books, 2007)
Bertini, I.; Gray, H. B.; Lippard,
S. J.; Valentine, J. S.
Bioinorganic Chemistry
(University Science
Books; 1994)
Kaim, W. and Schwederski, B.
Bioinorganic
chemistry : inorganic elements in the chemistry of life : an introduction and
guide (Wiley, 1994)
Cowan, J. A.
Inorganic Biochemistry: An
Introduction (Wiley-VCH: New York,
1997)
Lippard, S. J. and Berg, J. M.
Principles of
Bioinorganic Chemistry (University Science Books; 1994).
Roat-Malone, R. M. Bioinorganic Chemistry: A
Short Course (Wiley, 2002)
Examinations and Grading
34%
15
Final Exam
10:30-1:00