Bioinorganic Chemistry   (141B1)

Academic year:

2019/2020.

Attendance requirements:

102B1

ECTS:

6

Study level:

Study program:

Teacher:

Milica R. Milenković, Ph.D.
associate professor, Faculty of Chemistry, Studentski trg 12-16, Beograd

Assistants:

—

Hours of instruction:

Weekly: four hours of lectures + two hours of labwork (4+0+2)

Goals:

Within this course students are introduced to the fundamentals of bioinorganic chemistry, medicinal chemistry and biomimetic chemistry, with a special emphasis on the mechanisms of enzyme-catalyzed reactions.

Outcome:

Students will master the fundamentals of bioinorganic chemistry.

Teaching methods:

Lectures, tutorials, term papers, experimental exercises.

Extracurricular activities:

—

Coursebooks:

Main coursebooks:

1. Ivano Bertini, Harry B. Gray, Edward I. Stiefel, Joan Selverstone Valentine, Biological Inorganic Chemistry, Structure and Reactivity, University Science Books, 2007.
2. Robert R. Crichton, Biological Inorganic Chemistry, A New Introduction to Molecular Structure and Function, Elsevier, 2012.
3. Wolfgang Kaim, Brigitte Schwederski, Axel Klein, Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life, An Introduction and Guide, Wiley, 2013.
4. Nils Metzler-Nolte, Ulrich Schatzschneider, Bioinorganic Chemistry, A practical course, Walter de Gruyter, 2009.
5. Joseph. J. Stephanos, Anthony W. Addison, Chemistry of Metalloproteins, Problems and Solutions in Bioinorganic Chemistry, Wiley, 2014.
6. Hermann Dugas, Bioorganic Chemistry, Springer, 1996.
7. Dušan Sladić, Bioorganska hemija. Mehanizmi enzimskih reakcija
8. Richard B. Silverman, The Organic Chemistry of Enzyme-Catalyzed Reactions, Academic Press, 2000.
9. Gareth Thomas, Medicinal Chemistry: An Introduction, Wiley, 2007.
10. Graham L. Patrick: An Introduction to Medicinal Chemistry, Oxford University Press, 2013.
11. Donald Voet, Judith G. Voet, Biochemistry, 4th Edition, Wiley, 2011.

Supplementary coursebooks:

• Recent review and scientific papers in this field.

Additional material:

—

Lectures:

0 points (4 hours a week)

Syllabus:

1. Introduction to the role of metals in biochemical processes (the role of metal ions and their complexes in metabolism, the application of metal complexes in medicine, the toxicity of metals and their compounds). Protein bioligands (amino acids as ligands). Non-protein bioligands, macrocycles: heme, chlorin, corrin. The abundance of bioelements in human body and their importance. Fundamentals of coordination chemistry necessary for understanding processes in biological systems. Fundamentals of enzyme catalysis. Experimental methods used in the study of the mechanisms of enzymatic reactions.
2. The role of alkali metal ions in the organism (ion channels, ion pumps, the membrane potential, the nerve impulse, ionophores).
3. The role of the alkaline earth metal ions in the organism (the skeleton, muscle contraction, Ca²⁺- the role in signal transduction, enolase, kinase (hexokinase), DNA and RNA polymerase, restriction enzymes, chlorophyll, calmodulin).
4. Nitrogen monoxide and its role in physiological and pathological conditions. NO synthase.
5. Zinc-containing enzymes - reaction mechanisms (carbonic anhydrase, carboxypeptidase A, class II aldolase, adenosine deaminase, alcohol dehydrogenase, alkaline phosphatase, purple acid phosphatase, Cu/Zn superoxide dismutase). The structural role of zinc (zinc finger).
6. The mechanisms of iron intake and its transport to eukaryotic and prokaryotic cells. Transferrin (Tf). Fe(III) binding site of transferrin. Siderophores. Ferritin. The role of iron in oxygen transport - hemoglobin, myoglobin, hemerythrin. Iron-containing enzymes - reaction mechanisms (the class I ribonucleotide reductases, Fe superoxide dismutase, aconitase, lysine-2,3-aminomutase, heme-dependent monooxygenases, α-keto acid-dependent dioxygenase). Iron–sulfur clusters. The role of iron-containing proteins in the mitochondrial electron transport chain.
7. Type I, II and III copper proteins (plastocyanin, galactose oxidase, hemocyanin, tyrosinase, catechol oxidase, polynuclear copper oxidases, cytochrome c oxidase).
8. Nickel-containing enzymes: non-redox enzymes (urease, acireductone dioxygenase and glyoxalase I) and redox enzymes (hydrogenase, CO dehydrogenase, acetyl-CoA synthase, methyl-CoA reductase, Ni superoxide dismutase).
9. Vitamin B12. Cobalt-containing enzymes (methylmalonyl-CoA mutase, class II ribonucleotide reductase).
10. Enzymes which contain molybdenum and tungsten. Xanthine oxidase. Sulfite oxidase. Dimethyl sulfoxide reductase. Nitrogenase.
11. Manganese-containing enzymes: non-redox enzymes (arginase) and redox enzymes (catalase, manganese superoxide dismutase, OEC (oxygen evolving complex)).
12. Enzyme models.
13. Drug discovery, design and development. Reversible enzyme inhibitors. Irreversible enzyme inhibitors. Drugs which affect DNA - antitumor and antiviral drugs. Pharmacokinetics. QSAR. Computers in medicinal chemistry. Antibacterial and antifungal agents. Rational approach to drug design.
14. The goals and principles of medicinal inorganic chemistry. The strategy in the design of metal-based drugs. Platinum complexes as antitumor agents. Cisplatin (the history of its discovery, action mechanism, cisplatin analogues). The complexes of palladium, ruthenium, gallium and gold as antitumor agents. The mechanisms of antitumor activity of metal complexes. Metal complexes in MRI diagnostics. Biological activity of organometallic compounds (ferrocene and other metallocenes). Chelating agents (Deferoxamine, Deferasirox, Clioquinol). Metal ions and neurodegenerative diseases.

Labwork:

10 points (2 hours a week)

Syllabus:

The synthesis of the complexes of transition metals with potentially bioactive ligands. An overview of the literature, synthesis, characterization (spectroscopic methods, magnetic measurements), investigating biological activity.

Semester papers:

20 points

Colloquia:

20 points

Written exam:

50 points