cod. 1006027

Academic year 2023/24
1° year of course - Second semester
- Giorgio PELOSI
Academic discipline
Chimica generale e inorganica (CHIM/03)
Attività formative affini o integrative
Type of training activity
48 hours
of face-to-face activities
6 credits
hub: PARMA
course unit

Learning objectives

At the end of the course the students will have acquired skills that allow them to critically read papers in the field of bioinorganic chemistry and to join groups working in the field of Bioinorganic Chemistry. In particular, with reference to the Dublin Indicators, the students will have pursued and reached the below reported targets.

Knowledge and understanding: at the end of the course of Bioinorganic Chemistry the students will have acquired the fundamental concepts of inorganic chemistry in biological systems and will be able to discuss the subject in English. Particular care will be given to the correct use of the technical language.

Knowledge application: the course equippes the students with the tools to study and understand the role of metals in biological systems. Students are encouraged to read scientific papers and the reading comprehension is constantly checked.

Communication skills: the course leads to the acquisition of the technical language that allows the students to communicate internationally with specialists both in the field of chemistry and molecular biology using a formally correct language.

Making judgements: with the intellectual tools provided in the course, the student will be able to use the principles of bioinorganic chemistry to think critically and tackle problems relevant to the same field.

Learning skills: at the end of the course the students should have acquired the concepts of bioinorganic chemistry and should be able to study by themselves without problems on advanced level bioinorganic chemistry texts and be able to expand, with a good level of independence, their knoweldge in the field.


Basic knowledge of coordination chemistry and biochemistry and possibly a B2 level of English

Course unit content

The course is made up of three parts and requires 6ECTS of student’s activity.

Part 1: Chemical concepts relevant to understand biological processes.
– The cycles of the main elements involved in the functioning of living organisms
– Summary of the main metalloenzymes and metalloproteins studied in the course
– Proteins and nucleic acids from a structural perspective

Part 2: Physical methods in the study of metalloproteins: biocrystallography.
– Protein crystallography: preparing crystals, preliminary characterization, reciprocal lattice, data collection, solution of the phase problem, refinement and structure
– Protein data bank
– use of Chimera to display proteins

Part 3: Bioinorganic chemistry
– Roles of metalloproteins in cells: choice, uptake and assembly of metal containing units in biology
– Control and use of of ion concentration in the cell
– Influence of metals in folding and cross linking in biomolecules
– Interactions between metal ions and complexes in biomolecules
– Electron transport proteins
– Nonredox activation mechanisms and interactions with substrates
– Atom and atom groups transfer chemistry
– Metals in medicine

Full programme

UNIT 1 Development of Bioinorganic Chemistry
An overview. Elementogenesis The abundance of the elements necessary for life Many metals play a fundamental role in biological processes. Evolution of life: Miller-Urey’s, Wächtershäuser’s and the “clay organism” scenarios A comparison between the atmospheres of Mars, the Earth and Venus: the Great Oxygenation Event A recap of how a cell looks like: organelles and their functions. Archaea, bacteria and eukarya Bioelements and their cycles The Carbon/Oxygen/Hydrogen Cycles Photosynthesis - The Oxygen Catastrophe and its implications on the bioavailability of some elements - Respiration Hydrogenases The Nitrogen Cycle All the enzymes involved in the nitrogen cycle contain metals The Sulfur Cycle Sulfate reducing bacteria (SRB) (anaerobic) and Sulfide-oxidizing bacteria (aerobic) The Phosphorus Cycle Metalloproteins and Metalloenzymes: an overview Transport and storage -Transferrin, albumin and metallothioneins -Ferritin, ceruloplasmin and hephaestin Oxygen transport -myoglobin, haemoglobin, haemerythrin, myoemerythrin, haemocyanin Electron transfer -Iron-sulfur cluster proteins, cytochromes, blue copper proteins Structural roles -Aspartate transcarbamoylase, zinc fingers and zinc in Superoxide Dismutase Hydrolytic enzymes -Carbonic anhydrase, Carboxypeptidase A, Alkaline phosphatase, Thermolysin Redox enzymes -Oxidation (cytochrome P-450), Reduction (ribonucleotide reductase (Fe)), Dehydrogenation (alcohol dehydrogenase (Zn)) Rearrangement promoting enzymes -Isomerases (vitamin B12 dependent)

UNIT 2. Thermodynamic and kinetic concepts: coordination chemistry in bioinorganic chemistry
Equilibria in water solution The Effect of Metal Ions on the pKa of Ligands Chelate effect Lewis HSAB theory Ligand-Field Theory The basics, the Spectroscopic Series, the Ligand Field Stabilization Energy Effects of the d orbitals splitting on UV-Vis spectra and magnetism The Irving Williams series Tuning of the Redox Potentials Influence of the donor atoms and the geometry of the metal centre on its redox potential Non-innocent ligands Biopolymer effects Cooperativity and allosteric interactions Site organization in multicentre enzymes Surface recognition sites and electron transfer pathways Access channels to the active site Hydrophobic environment Residues with specific charges and with hydrogen bonds near the metal centre Entatic or “rack state” Kinetic aspects Ligand exchange rate and mechanisms Electron transfer reactions

UNIT 3. Proteins and nucleic acids from a structural perspective
Amino acids and their role as metal ligands Common protein secondary and supersecondary structures SCOP Structural Classification of Proteins Common structures found in metalloproteins: globins, four helix bundles, antiparallel β-sheets barrels, Greek key protein, Jelly/Swiss roll. Role of metal ions in the structure stabilization of DNA and tRNA

UNIT 4. Protein crystallography
Preparing crystals. Preliminary characterization. Reciprocal lattice (unit cell, asymmetric unit, symmetry elements, space groups) Data collection (Ewald sphere, number of collectible data, effect of a change in wavelength) Solution of the phase problem: Multiple Isomorphous Replacement (MIR), Molecular Replacement (MR), Multiwavelength Anomalous Dispersion (MAD), Direct methods Structure refinement, Resolution and R index Protein Data Bank and use of Chimera to display the metal centres of proteins

UNIT 5. Homeostasis of metal ions in cells: uptake, storage and metal uptake control
Alkaline and alkaline earth metals. Pumps, channels and ionophores Iron in bacteria. Siderophores. Enterobactin. Fur (iron uptake regulator) protein. Iron in higher organisms: transferrin and ferritin. Regulation through the Iron Responsive Element Binding Protein Copper homeostasis. Copper chaperones (COX17, ATOX1 and CCS). Regulation: ACE1 and MAC1 Mercury: bacterial detoxification. The Mer operon. Roles of proteins MerR, MerA, MerB and MerP

UNIT 6. Influence of metals in folding and cross linking in biomolecules
Aspartate Transcarbamoylase, Zinc fingers (TFIIIA), Calcium binding proteins (Calmodulin) Thermodynamic and kinetic control on the ion selection Application of the Ligand Field Stabilization Energy Principle of electroneutrality in protein metal sites Polynuclear sites

UNIT 7. Oxygen transport and oxygen activation
Reactivity and toxicity of O2 Haemoglobin, myoglobin, haemerythrin, myoemerythrin, haemocyanin. Model systems. Transition metal ions as stable radicals Mono- and dioxygenases. Cytochrome P450, Methane Monooxygenase, Catechol dioxygenaseUNIT 8. Electron transport proteins Normal reduction potential. Parameters that influence the potential range in electron transfer proteins. Cytochromes (Haem-containing proteins classified according to the apical donors), Fe-S cluster proteins(classified according to the number of Fe and S) and blue copper proteins

UNIT 9. Nonredox activation mechanisms and interactions with substrates
Carbonic anhydrase (lyase), Carboxypeptidases (hydrolytic enzymes), Thermolysin (a case of convergent evolution), Alkaline phosphatase (hydrolytic enzymes), Alcohol dehydrogenase (an oxidoreductase* containing zinc – a non redox metal)

UNIT 10. Atom and atom groups transfer chemistry
Cobalamine containing enzymes: mutase activity, 1,2 shifts in diol dehydratases and methylation of sulfur in methionine synthase

UNIT 11. Metals in medicine
Cancer: cisplatin and analogues. Radiotherapy with boron derivatives and slow neutrons Reumatoid arthritis: auranofin Diabetes: vanadium derivatives Imaging agents: rare earths compounds Therapies against hypertension: nitric oxide releasing compounds Bismuth and its history in the treatment of heartburn Lithium in the treatment of dipolar disorders


D. Rehder. 2014. Bioinorganic Chemistry, Oxford University Press, Oxford, UK
H. B. Gray, E. I. Stiefel, J. S. Valentine, I. Bertini. Biological Inorganic
Chemistry: Structure and Reactivity . University Science Book. Mill Valley,
S J Lippard, J M Berg. 1994. Principles of Bioinorganic Chemistry.
University Science Books Mill Valley, California
R. M. Roat-Malone. 2002. Bioinorganic Chemistry: A Short Course. John
Wiley & Sons, New Jersey, USA.
W Kaim, B Schwederski. 1995. Bioinorganic Chemistry. John Wiley &
Sons, New York
D.E. McRee. 1999. Practical Protein Crystallography. Academic Press. San

Teaching methods

The lessons are designed to be held in the classroom. The classrooms are large enough to host all the students according to ministerial safety rules.
Nevertheless, to facilitate those who may not be able to attend physically, there will also be the possibility to attend live streaming the lessons via Teams or to watch the recording. The recorded lessons will be available on the platform Elly only for a few days after the live lecture.
It is worth noticing that the course is based on live lectures and that, if there will be technical problems, these will not interfere with the programmed schedule. The material presented during the lessons will be available online at the site
During the lectures questions concerning the subject under discussion will be posed and students are incouraged to intervene or ask further questions.

Assessment methods and criteria

The exam is in two parts:

1. the oral communication skills are tested through a presentation (15 min) of an article of bioinorganic chemistry in the presence of the whole class. The other students are invited to pose questions or to make considerations. This part contributes to the final evaluation for 2 points.

2. The written part is made up of ten questions divided into 3 parts (1 hour):
the first one regards the concepts of coordination chemistry applied to biological systems (2 questions, 3 points each),
the second one is about biocrystallography (2 questions, 3 points each ) and
the third one concerns bioinorganic chemistry (6 questions, 3 points each).

The exam is passed only if the student has gathered at least 18 points and has obtained for each section at least half of the associated points (3 for the first and the second section and 6 for the third section). If the sum of the points exceeds 30 the student is assigned a 30/30 e lode.

Other information

The reference books are available in the department library. The Chimera software used for the visualization of proteins and also the Protein Data Bank files are free of charge and can be downloaded from the internet.
The lecturer can be contacted by e-mail for further explanations and guidance at