CHM4319: Bio-inorganic Chemistry – Fall 2010 (3 cr.)

Suggested prerequisites: a general background in inorganic chemistry, biochemistry, physical chemistry, structure and bonding, molecular biology.

Course Structure: This class will include both lecture, discussion and homework components. Since discussion and active learning will be important to the success of this course, classroom participation is expected. Assignments will be announced in advance so that you will have time to prepare. Throughout the semester, the class webpage will be updated with a class schedule to help you plan ahead.

Evaluation: You will be graded on exams, in-class tests, homework assignments, presentation and class participation.

Grading:

• Tests: 20%
• Homework (including in-class metalloprotein structure presentation): 30%
• Class participation: 5%
• Midterm and final exams: 45% total

Exams: There will be two in-class, closed-notes, close-books exams: mid-term (20% points) and final (25% points). Note that if you cannot make it to the midterm exam, you will have to provide a written proof (medical note) that you have a valid reason. In this case, the weight of the midterm (20%) will be transferred to the final exam.

Tests: there will be short (20-25 min.) tests (consisting of 3-5 problems (multiple choice problems and short-answer problems based on the recent lecture and reading material) at the end of ~each 4^th lecture.

Metalloprotein structure presentation: students will prepare presentations about a structure and function of a given metalloprotein. This will be a short (max 10 min.) powerpoint presentation to the class. Clarity, conciseness, and logical flow of the presentation and the ability to answer questions about the topic are important. The material of the student presentations will be included on the final exam.
The presentation should include the following information:

• when this protein was first isolated,
• what is the biological function of the protein,
• when this protein structure was solved, what is the resolution of the structure,
• what is the 3D description of the protein structure (CATH),
• how many metal sites does the protein structure contain and what is their position in the structure,
• (for each transition metal site) what is the metal ion description (oxidation state, spin state),
• (for each transition metal site) what is the metal site geometry,
• how does the protein achieve its biological function; what are the role(s) of each metal site(s) in the protein,
• (for each transition metal site) what spectroscopic features the metal site is (likely) to possess.

Class Participation: In active discussion, participation is expected of all, as the discussion is an integral component of the learning experience in a conference/workshop setting.

Course Outline

The topics and chapters will be discussed in the approximate order listed here. I will be rearranging and changing material a bit as the semester goes.

• Introduction to Bio-inorganic Chemistry
  • The chemical elements in biology. Metals in biological systems.
  • Fundamentals of biochemistry and molecular biology. Biological macromolecules. Proteins.
  • Computer tutorial: visualization of protein structures using UCSF Chimera.
  • Transition-metal complexes and chemical bonding.
    • Closed- and open-shell species. High- and low-spin complexes.
    • Hard and soft acids and bases (HSAB) theory.
    • Crystal field theory and ligand field theory. Spectrochemical series.
    • Periodic trends. Irving-Williams Series.
    • Protein residues as ligands for metal ions. Donor orbitals of coordinating residues.
    • DNA and RNA as Ligands.
  • Recurring structural motifs in bio-inorganic chemistry.
  • Kinetic effects and control. Elements of chemical kinetics and catalysis. Entatic state. Allosteric interactions.
• Physical Methods in Bio-inorganic Chemistry. Spectroscopic Characterization of Bio-inorganic species
  • X-Ray crystallography for solultion of protein structures. Use of synchrotron radiation. Resolution and quality.
  • NMR spectroscopy.
  • Vibrational spectroscopy (IR, Raman, resonance Raman). Isotopic perturbation.
  • X-Ray absorption spectroscopy (XAS) and extended X-ray absorption fine structure (EXAFS).
  • Electronic spectroscopy (UV-Vis and PES).
  • Electrochemistry.
  • Electron paramagnetic resonance (EPR) spectroscopy.
  • Other relevant methods (metal substitution, biomimetic models).
• Metal ion transport and storage
  • Transferrin
  • Ferritin
  • Siderophores
  • Metallothioneins
  • Cu-transporting ATPases
  • Metallochaperones
• Lewis acid catalysis and regulation.
  • Zinc enzymes.
• Electron transfer (ET) in biological systems.
  • ET Kinetics. Reorganization energy. Entatic state for ET. Marcus theory of electron transfer.
  • Electronic coupling. Two schools of thinking about long-range ET in proteins.
  • Bio-redox agents and ET mechanisms.
    • Copper ET sites. ET in blue copper proteins, nitrite reductases, multicopper oxidases and nitrous oxide reductases.
    • Iron ET sites (cytochromes, iron/sulfur sites).
  • Protein control of redox potentials.
• Nitrogen Cycle. Nitrogen fixation. Nitrification and denitrification.
  • Nitrogenase.
  • Nitrate reductase.
  • Nitrite reductase.
  • NO reductase.
  • Nitrous oxide reductase.
• Oxygen transport and transfer.
  • Cooperativity and dioxygen transport.
  • Hemoglogin family.
  • Hemocyanin family.
  • Hemerythrin family.
• Oxygen reactivity and toxicity. Antioxidant enzymes.
  • Superoxide dismutase (SOD)
  • Superoxide reductase (SOR)
  • Catalase
  • Peroxidase
• Toxicology.
• Inorganic medicinal chemistry.

Lectures, Tests and Exams

Password is needed to access the files below. The PDF files will be posted ~24 hours before the corresponding lectures.

September 9	Course Outline. Introduction.
September 14	Fundamentals of biochemistry and molecular biology. Biological macromolecules. Proteins. Protein structures and their classifications. Metal coordination in proteins.
September 16	Metal coordination in proteins. Amino acid protonation states. Open-shell and closed-shell species. Oxygen reactivity.
September 21	Visualization of protein structures. UCSF Chimera computer tutorial. Part 1. A short summary of commands.
September 23	Visualization of protein structures. UCSF Chimera computer tutorial. Part 2. A short summary of commands.
September 28	X-ray radiation and structure resolution in protein structures. Identification of the metal coordination environment in proteins. Homework assignment #1. Test #1
September 30	Reactive oxygen species (ROSs) and the enzymes that handle ROSs. Naming enzymes. Chemical bonding in molecules. Ionic and covalent interactions. Electronegativity and orbital energies..
October 3	Covalent/donor-acceptor interactions. Electronegativity and orbital energies. Hardness and softness of chemical species. Chemical bonding in transition metal species. Crystal field theory. High- and low-spin states. Irving-Williams series. Spectroscopic methods in bio-inorganic chemistry. Absorption spectra. Tanabe-Sugano diagrams. Crystal field theory vs. molecular orbital theory. Homework assignment #1 is due at midnight, Oct.6.
October 5	Metal coordination in proteins. Absorption spectra. Introduction to Crystal field theory.
October 10	Absorption spectra. Introduction to Crystal field theory. Spectrochemical series of ligands.
October 12	Iron sites in proteins. Diiron catalytic centres and their involvement in dehydrogenation vrs hydroxylation.
October 17	Iron sites in proteins. High-, intermediate- and low-spin sites. Ferromagnetically and anti-ferromagnetically coupled systems. Test #2.
October 19	Discussion of problems from Test #2.
October 31	MIDTERM EXAM
November 1	Discussion of problems in the midterm exam.
November 6	Iron sites in proteins. Properties of iron-sulfur clusters and iron heme sites. The catalytic cycle for P450 proteins. Homework #2
November 8	Electron transfer (ET) in biology. ET proteins. Contributions to the ET function. Redox potentials, reorganization energy and electronic coupling.
November 13	Electron transfer in proteins. Contributions to the ET function. Electron tunnelling and hopping. Superexchange mechanism. ET Pathways. Mononuclear and binuclear copper sites for ET. Their strucural and spectroscopic properties. Homework #2 is due
November 15	Electron transfer in proteins. Contributions to the ET function. Electron tunnelling and hopping. Superexchange mechanism. ET Pathways.
November 20	Transport and storage of metal ions in biology. Chapters 5 and 8 of BIC for home reading.
November 22	Mononuclear Cu sites for electron transfer in proteins. The electronic structure, spectroscopic properties (abs, EPR, rRaman, XAS) and function.
November 27	Binuclear Cu sites for electron transfer in proteins. The electronic structure, spectroscopic properties (abs, EPR, rRaman, XAS) and function.
November 29	Metalloproteins for oxygen metabolism. Dioxygen carriers. Dioxygen activating enzymes. Cytochrome c oxidase and multi-copper oxidases. Test #3.
December 1	Follow-up to Test #3. Dioxygen carriers. Dioxygen activating enzymes. Cytochrome c oxidase and multi-copper oxidases. Denitrification and denitrification enzymes. Nitrogen fixation and nitrification. Hydrogen metabolism and hydrogenases.
December 3	Assignment #3: protein structure presentations.
TBA	FINAL EXAM

CHM4319 Main Page