CHM4319: Bio-inorganic Chemistry – Fall 2011 (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: 30% (5% homework 1; 5% homework 2; 20% presentation)
• Class participation: 5%
• Midterm and final exams: 45% total

=====================|=====|=====
STUDENT   HOMEWORK 1 |  2  |  3
=====================|=====|=====
...1322	     8.0    2.0    20
...7883	     7.0    2.0    20
...1920	     9.0    2.0    17
...2826	     9.5    3.0    20
...2233	     6.0    3.0    16
...2089	     9.8    2.0    14
...2780	     8.5    2.0    14
...2470	     9.0    3.0    15
=====================|=====|=====
"PERFECT"   10.0     | 4.0 |  20

Exams: There will be two in-class, closed-notes, close-books exams: mid-term (15% points) and final (30% points). 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 will be transferred to the final exam.

Tests: there will be short (20 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.

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 8	Course Outline. Introduction.
September 13	Fundamentals of biochemistry and molecular biology. Biological macromolecules. Proteins. Protein structures and their classifications.
September 15	No lecture
September 20	Protein structures and their classifications
September 22	X-ray radiatiion and diffraction. Protein structures and resolution.
September 27	Visualization of protein structures. UCSF Chimera computer tutorial. A short summary of commands
September 29	Metal coordination in proteins. Amino acid protonation states. Identification of the metal coordination environment in proteins. Open-shell and closed-shell species. Oxygen electron structure.
October 4	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 6	Covalent/donor-acceptor interactions. Electronegativity and orbital energies. Hardness and softness of chemical species. Irving-Williams series.	Example questions for Test 1
October 11	Metal coordination in proteins. Spectroscopic methods in bio-inorganic chemistry. Absorption spectra. Ligand-field and charge transfer transitions. Introduction to Crystal field theory. Spectrochemical series of ligands. High-spin and low-spin states. Tanabe-Sugano diagrams.	Homework assignment #1
October 13	Crystal field theory vs. molecular orbital theory.	Test #1
October 18	Iron sites in proteins. Properties of iron-sulfur proteins. Ferromagnetically and anti-ferromagnetically coupled systems. Redox potentials.	Homework #1 is due by 11 PM
October 20		Example questions for Midterm Exam
November 1		MIDTERM EXAM
November 3	Iron sites in proteins. Properties of iron heme sites. The catalytic cycle for P450 proteins.
November 8	Dioxygen carriers	Homework #2
November 10	Dioxygen carriers (cont'd)	Example questions for Test 2
November 15	Dioxygen activating enzymes. Tyrosinase. Methane monooxygenase (MMO).
November 17	Electron transfer (ET) in biology. ET proteins. Redox potentials. Cytochrome c oxidase.	Homework #2 is due by 11 PM Test #2
November 22		How to prepare your metalloprotein structure presentation EXAMPLE: Nitrate Reductase
November 24	Electron transfer (ET) in proteins. Reorganization energies. Electronic coupling. Electron tunnelling and hopping. Superexchange mechanism. ET Pathways. Nitrite reductase and multi-copper oxidases.	Example questions for Final Exam
November 29	Spectroscopic methods in bio-inorganic chemistry. Resonance Raman spectroscopy. EPR.
December 1	Zn fingers. Cu chaperon. Stellacyanin. Cytochrome cH. Galactose oxidase. Amine oxidase. DMSO reductase. Lipoxygenase.
December 6	Mono- and bi-nuclear Cu sites for electron transfer in proteins. The electronic structure and spectroscopic properties (abs, EPR, rRaman, XAS). Robin-Day Classification.
not covered	Transport and storage of metal ions in cells.
December 18		FINAL EXAM

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