Chemistry 446

INTRODUCTION TO BIOINORGANIC CHEMISTRY

             Fall 2009                       

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Instructor:            Dr. Keith M. Davies.     Office 410 OB-PW1

                               kdavies@gmu.edu      703-993-1075 

                               Ofice Hours:  Tu/Th 10:00-11:00, 1:30-2:00, and by appointment at 410 OB-PW1

 

Text:                    CHEM 446 Course Supplement. K. M. Davies (Copy Shop)

                             Recommended Text: Biological Inorganic Chemistry: Structure and Reactivity

                             by H. B. Gray, E. I. Stiefel, J. S. Valentine and I. Bertini,  University Science Books, 2007.

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Course Objectives

The application of principles of inorganic coordination chemistry and spectroscopic methods in understanding the structure and function of metal ion sites in biomolecules. Review of inorganic coordination chemistry, ligand field theory and metal binding in proteins. Bioinorganic topics covered will include transport and storage of metal ions (Fe, Cu, Zn) in biology; dioxygen activation, toxicity of oxygen species; dioxygen transport in mammals and lower organisms; the use of metal complexes as drugs, metal-related disease; nitric oxide biochemistry; electron transfer in biology by iron cytochromes, iron-sulfur clusters, copper enzymes. Cobalamins, nitrogenase and hydrogenase; hydrolytic enzymes.

Examinations and Grading  

Mid-Term Exam I

Sept. 24th

20%

Mid-Term Exam II

Oct. 22nd

20%

Mid-Term Exam III

Nov. 19th

20%

Problem Sets           10%

Final Exam (10:30-1:15)

Dec. 15th

          30%

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Course  Schedule

Sept 1

  

Introduction:  Occurrence, availability and roles of metallic elements.  Classification of metallobiomolecules

3

Fundamentals of inorganic coordination chemistry. Ligand structures, Complex stability, chelate effects, HSAB classification, solvation and macrocyclic effects.

 8

Review of protein structure and metal binding. Metal-binding amino acid residues, macrocyclic porphyrin and corrin ring structures. Hapticity (η) and bridging (μ).

10

Ligand field effects. High spin and low spin states. Magnetic and spectral properties.

15

Factors influencing thermodynamic stability and kinetic lability. Redox potentials, Latimer diagrams, substitution rates.

17

M.O.Theory  Diatomic oxygen species. Metal-ligand s and Π-interactions. 18-electron rule, organometallic structures.

22

 

24

Exam I

29

Metal transport and storage: Fe transport.  Transferrin. Iron storage.  Ferritin, Fe uptake and retrieval. Mossbauer spectroscopy. 

1

  Cu and Zn transport and storage. Metallothioneins and metallochaperones.

Oct

6

Dioxide transport.  Hb and Mb structure and O2     binding. pH effects. Spin states and cooperativity.   Fe2+- 1O2 vs. Fe3+ - 3O2 Inorganic model compounds, Hb variants.

8

O2 transport in hemocyanin and  hemerythrin

Dioxygen activation. Oxygen atom transfer by  cytochromes-P450, tyrosinase.

13

Columbus Day Holiday (No class).

15

Dioxygen reactivity and toxicity Toxicity of oxygen species,  detoxification enzymes. Superoxide dismutases, peroxidases and catalases. Disproportionation equilibria.

20

 

22

Exam II

27

Metals in Medicine. Cisplatin and 2nd generation Pt drugs.  

29

Metal deficiency and toxicity. Essential elements, Fe, Cu, Zn, chelation therapy. Toxicity of heavy metals, Hg, Pb, Cd, Cr, Al.  

Nov

 3

Nitric oxide biochemistry. Physiological roles of NO. Nitric oxide synthase enzymes

5

Electron Transfer in Biology. Metal cofactors. Iron cytochromes and iron-sulfur proteins, cytochrone-c oxidase,

10

Copper proteins.  epr spectroscopy

12

Marcus theoryProtein electron transfer

17

 

19

Exam III

24

Cobalamins. Structure of cobalt sites, B12-dependent isomerases and methyltransferases.

26

Thanksgiving Recess (Nov 26-30)

Dec

 1

Nitrogenase  Structure of nitrogenase enzyme: Iron protein, iron-molybdenum protein,    Mechanism of N2 reduction.  

3

Metal-dependant lyase and hydrolase enzymes Zinc enzymes, carbonic anhydrase, carboxypeptidase, alcohol dehydrogenase, Aconitase, urease.

 

 8

 Gp I, II metals, Na, K, Mg Biological messengers: Na+, K+, Ca2+ in communication, membrane transport mechanisms. Ion channels, Aquaporins

10

 Review

15

 Final Exam  10:30-1:15

   

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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)