Bioinorganic Chemistry   (152H2)

Academic year:

2024/2025.

Attendance requirements:

There are no requirements.

ECTS:

9

Study level:

Study programs:

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 exercises + three hours of labwork (4+2+3)

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, theoretical exercises, labwork, colloquia, semmester papers.

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. A. Messerschmidt, R. Huber, K. Wieghardt, T. Poulos: Handbook of Metalloproteins, John Wiley & Sons, Inc. 2001.
5. Hermann Dugas: Bioorganic Chemistry, Springer, 1996.
6. Dušan Sladić: Bioorganska hemija. Mehanizmi enzimskih reakcija
7. Richard B. Silverman: The Organic Chemistry of Enzyme-Catalyzed Reactions, Academic Press, 2000.
8. Gareth Thomas: Medicinal Chemistry: An Introduction, Wiley, 2007.
9. Graham L. Patrick: An Introduction to Medicinal Chemistry, Oxford University Press, 2013.
10. Donald Voet, Judith G. Voet: Biochemistry, 4th Edition, Wiley, 2011.
11. Recent reviews and scientific papers dealing with metalloenzymes and enzyme mimetics.

Supplementary coursebooks:

1. G. G. Hammes: Spectroscopy for the biological sciences, Wiley & Sons, Inc. 2005.
2. R S. Drago: Physical Methods for Chemists, Surfside Scientific Publiser, 1992.
3. ˛. °. şŢÓĐÝ, ˛. ˛. ťăÚŢŇ: źĐÓÝŐâŢĺŘÜŘď, ÎÖÝëŮ ÄŐÔŐŕĐŰěÝëŮ ĂÝŘŇŐŕáŘâŐâ, şĐäŐÔŕĐ äŘ×ŘçŐáÚŢŮ Ř ÚŢŰŰŢŘÔÝŢŮ ĺŘÜŘŘ, ŔŢáâŢŇ ÝĐ ´ŢÝă, 2013.
4. A. Antić-Jovanović: Molekulska spektroskopija - spektrohemijski aspeÚt, Univerzitet u Beogradu - Fakultet za fizičku hemiju, Beograd, 2016.
5. R. R. Crichton, Ricardo O. Louro: Practical Approaches to Biological Inorganic Chemistry, Elsevier, 2019.

Additional material:

—

Lectures:

0 points (4 hours a week)

Syllabus:

1. Introduction to the role of metals in biochemical processes. 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 (muscle contraction, Ca²⁺- the role in signal transduction, enolase, hexokinase, calmodulin). Photosynthesis.
4. Nitrogen monoxide and its role in physiological and pathological conditions. NO synthase.
5. Zinc-containing enzymes (carbonic anhydrase, carboxypeptidase A, class II aldolase, adenosine deaminase, alcohol dehydrogenase, alkaline phosphatase, purple acid phosphatase, CuZn superoxide dismutase).
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 (the class I ribonucleotide reductases, Fe superoxide dismutase, aconitase, lysine-2,3-aminomutase, heme-dependent monooxygenases, α-keto acid-dependent dioxygenase, biotin synthase). Iron–sulfur clusters.
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-CoM reductase, Ni superoxide dismutase). Wood–Ljungdahl pathway.
9. Vitamin B12. Cobalamin-dependent enzymes (methylmalonyl-CoA mutase, class II ribonucleotide reductase, methionine synthase).
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 (manganese 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. 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. Metal ions and neurodegenerative diseases.

Exercises:

0 points (2 hours a week)

Syllabus:

1. NMR spectroscopy of proteins
2. IR and Raman spectroscopy
3. Mössbauer spectroscopy
4. EPR spectroscopy
5. Magnetochemistry
6. X-ray absorption spectroscopy (EXAFS and XANES)
7. Mass spectrometry of proteins
8. Electronic absorption spectroscopy
9. Fluorescence spectroscopy

Labwork:

10 points (3 hours a week)

Syllabus:

1. Synthesis, characterization and catalytic activity of catalase, superoxide dismutase and peroxidase mimetics ([Mn(salen)Cl] complex and ferrite nanomaterials).
2. Isolation and electronic absorption spectra of plant pigments.
3. Investigation of the effect of metal ions on bromelain activity.

Semester papers:

20 points

Colloquia:

20 points

Written exam:

50 points