CH3F8-15 Advanced Coordination and Bio-Inorganic Chemistry
Introductory description
N/A
Module aims
This module will examine the ways in which biological systems use the specific chemical properties offered by the full range of elements in the periodic table to perform a wide variety of functions, and how synthetic coordination compounds, including those with f-block elements, can be used in a bio-medical context. The module will introduce the chemical principles that govern the use of essential metal ions in biological systems, and selected examples will be discussed, to illustrate these principles. The impact of bio-inorganic chemistry on human health will be discussed in both the context of the consequences of aberrations in metal ion housekeeping and the use of metallo-based drugs.
Outline syllabus
This is an indicative module outline only to give an indication of the sort of topics that may be covered. Actual sessions held may differ.
INTRODUCTION
The importance of metal ions in biology and their relative abundances in the body. Natural
selection of the elements, chemical limitation imposed by biological systems.
Relevant coordination chemistry principles (hard and soft acids and bases, stability constants,
ligand exchange rates).
Biological Ligands: Proteins, Nucleic Acids and Nucleotides, Porphyrins, related ligands,
antibiotics.
PHYSICAL TECHNIQUES TO STUDY METAL ION-BIOMOLECULE INTERACTIONS Applictions of optical spectroscopies, NMR, EPR, X-ray absorption, Mössbauer spectroscopy
ION TRANSPORT AND SIGNALLING Importance of balanced distribution of elements, composition of cell membranes. Mechanisms of ion transport: Ionophores, Channels, Pumps.
UPTAKE AND STORAGE Why regulation of metal ion concentration is crucial in a biological system. Examples for metalloregulation; the iron cycle, siderophores, transferrin, ferritin.
CONTROL OF PROTEIN STRUCTURE AND DYNAMICS BY METAL IONS Calmodulin: tuning of protein structure and dynamics by metal binding. Cooperativity. Zinc fingers: structural role of zinc, composition of binding sites, roles of zinc fingers, sequence-specific DNA-recognition and artificial zinc fingers.
METALLOPROTEINS AND METALLOENZYMES: HYDROLYTIC ENZYMES Zinc. Properties and relevance to biology. Example carbonic anhydrase. The importance of coordination number, electrostatics, and the enzymatic cavity. Model complexes.
METALLOPROTEINS AND METALLOENZYMES: OXYGEN CARRIERS Dioxygen binding. Iron and copper. Haemoglobin and myoglobin: Structure, Physiological role, Oxygenation Equilibria, Oxygen Coordination, MO Interpretation, Model Systems. Haemerythrin and Haemocyanin.
METALLOPROTEINS AND METALLOENZYMES: REDOX CHEMISTRY Biological electron transfer: Redox active metal centres. Iron and copper. Importance and overview of range of standard potentials. Redox potentials and how to tune them. Iron-Sulfur Proteins: Rubredoxins, 2Fe Ferredoxins, Polynuclear Clusters. Heme proteins; Cytochromes, Cytochrome P-450. Non-heme Fe-binding enzymes: Methane monooxygenase and other oxygenases.
F-BLOCK (COORDINATION) CHEMISTY AND ELEMENTS IN MEDICINE Revision: Definition of the f elements; position in the periodic table Properties of the atoms and ions: ionisation energies, electrode potentials, metallic and ionic radii, preferred oxidation states and speciation (=> coordination chemistry), Electronic spectra and luminescence of lanthanide and actinide complexes, Magnetism Applications including lanthanides for bio-imaging/bio-sensing, and radioactivity of actinides.
Introduction to medicinal inorganic chemistry. Examples of metal-based drugs, diagnostic agents (=> inc. lanthanides), radionuclides in diagnosis and therapy. Metal-based anticancer drugs, including first, second and third generation platinum complexes. Interaction of anticancer drugs with DNA. Gold Complexes in the treatment of rheumatoid arthritis.
Learning outcomes
By the end of the module, students should be able to:
- Understand and rationalise roles that essential metal ions play in biological systems: Control of protein structure and dynamics, enzymatic catalysis, signalling.
- Understand the rationales for the selection of metal ions to perform biological functions.
- Identify metal-binding portions of biomolecules, recognise and describe the differences between metal sites in small molecule complexes and proteins.
- Understand the principles of metal ion homeostasis: metalloregulation of gene expression and translation, metal ion transport through membranes and cytosols.
- Understand and rationalise the effects that the binding of metal ions to proteins and nucleic acids has on the structure and dynamics of biomolecular structures.
- Understand and rationalise the mode of actions of metal ions in hydrolytic and redox metalloenzymes.
- Understand and rationalise the impact of metal binding residues and protein environment (coordination numbers and geometry, hydrophobic and electrostatic effects) on reactivity of metal ions.
- Understand and rationalise the mode of action and design features of selected metallodrugs.
Indicative reading list
Shriver/Atkins, 6th edition, Chapters 22 (f-block), 26 (Bio-inorganic Chemistry) and 27 (Metals in
Medicine)
Lippard, S J, Berg J: ‘Principles of bioinorganic chemistry’, QD 2400.L4
Biological Inorganic Chemistry: Structure and Reactivity
by I. Bertini, H.B. Gray, E.I. Stiefel, J.S. Valentine (Editors), University Science Books, U.S. (2006).
J J R Frausto da Silva and R J P Williams, The Biological Chemistry of the Elements, Clarendon
Press, Oxford, 1991. QD 2400.S4
W Kaim and B Schwederski, Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life,
Wiley, 1994. QD 2400.K2
Metals in Medicine
by James C Dabrowiak, Wiley & Sons Ltd., 2009
Further reading matter is available on the Moodle site.
Interdisciplinary
e.g. co taught with another department or with an industry perspective, bridges two or more disciplinary concepts, ideas, etc.
Subject specific skills
Problem solving
Critical thinking
Transferable skills
Problem solving
Critical thinking
Study time
| Type | Required |
|---|---|
| Lectures | 24 sessions of 1 hour (16%) |
| Practical classes | 4 sessions of 1 hour (3%) |
| Private study | 122 hours (81%) |
| Total | 150 hours |
Private study description
Self study, directed reading, and revision
Costs
No further costs have been identified for this module.
You must pass all assessment components to pass the module.
Students can register for this module without taking any assessment.
Assessment group B1
| Weighting | Study time | |
|---|---|---|
| Online Examination | 100% | |
|
||
Feedback on assessment
Cohort level examination feedback provided via Moodle.
Pre-requisites
To take this module, you must have passed:
Courses
This module is Optional for:
- Year 4 of UCHA-F107 Undergraduate Master of Chemistry (with Intercalated Year)
-
UCHA-F109 Undergraduate Master of Chemistry (with International Placement)
- Year 3 of F109 MChem Chemistry (with International Placement)
- Year 3 of F111 MChem Chemistry with Medicinal Chemistry (with International Placement)
-
UCHA-4M Undergraduate Master of Chemistry Variants
- Year 3 of F105 Chemistry
- Year 3 of F109 MChem Chemistry (with International Placement)
- Year 3 of F126 MChem Chemistry with Med Chem (with Prof Exp)
- Year 3 of F125 MChem Chemistry with Medicinal Chemistry
- Year 3 of F106 MChem Chemistry with Professional Experience
- Year 4 of UCHA-F127 Undergraduate Master of Chemistry with Medicinal Chemistry(with Intercalated Year)
This module is Option list A for:
-
UCHA-4 Undergraduate Chemistry (with Intercalated Year) Variants
- Year 4 of F101 Chemistry (with Intercalated Year)
- Year 4 of F122 Chemistry with Medicinal Chemistry (with Intercalated Year)
-
UCHA-3 Undergraduate Chemistry 3 Year Variants
- Year 3 of F100 Chemistry
- Year 3 of F100 Chemistry
- Year 3 of F121 Chemistry with Medicinal Chemistry
- Year 3 of UCHA-F110 Undergraduate Master of Chemistry (with Industrial Placement)
- Year 3 of UCHA-4M Undergraduate Master of Chemistry Variants