Bioinorganic chemistry

Bioinorganic chemistry studies the role of metals in biology. It also studies natural phenomena such as the behaviour of metalloproteins and artificially introduced metals in medicine and toxicology. Many biological processes such as respiration depend on some inorganic molecules. Bioinorganic chemistry also includes the study of inorganic models or mimics that imitate the way metalloproteins work. It is a mix of biochemistry and inorganic chemistry. Bioinorganic chemistry studies the implications for biology of electron-transfer proteins, substrate bindings and activation, atom and group chemistry as well as metal properties.

History

Paul Ehrlich used organoarsenic (“arsenicals”) for the treatment of syphilis. This demonstrated the relevance of metals, or at least metalloids, to medicine. Then Rosenberg discovered the anti-cancer activity of cisplatin (cis-PtCl₂(NH₃)₂). The first protein ever crystallized was urease. This has nickel at its active site. Vitamin B₁₂, the cure for pernicious anemia, was shown by crystallography by Dorothy Hodgkin to have a cobalt atom in a corrin macrocycle. The Watson-Crick structure for DNA demonstrated the key structural role played by phosphate-containing polymers.

Research areas

Some areas of interest in research are:

Metal ion transport and storage: this covers a diverse collection of ion channels, ion pumps (e.g. NaKATPase), vacuoles, siderophores, and other proteins and small molecules whose aim is to carefully control the concentration of metal ions in the cell (sometimes referred to as metallome).
Hydrolase enzymes: these include a diverse collection of proteins that interact with water and substrates. Examples of this class of metalloproteins are carbonic anhydrase, metallophosphatases, and metalloproteinases.
Metal-containing electron transfer proteins:
- iron-sulfur proteins such as rubredoxins, ferredoxins, and Rieske proteins
- blue copper proteins
- cytochromes
Oxygen transport and activation proteins: these make use of metals such as iron, copper, and manganese. Heme is used by red blood cells in the form of hemoglobin for oxygen transport. Other oxygen transport systems include myoglobin, hemocyanin, and hemerythrin. Oxidases and oxygenases are metal systems found throughout nature that take advantage of oxygen to carry out important reactions such as energy generation. Some metalloproteins are designed to protect a biological system from the potentially harmful effects of oxygen and other reactive oxygen-containing molecules such as hydrogen peroxide. A complementary metalloprotein to those that react with oxygen is chlorophyll, the basis of photosynthesis. Chlorophyll is a carbon ring pigment, similar to other porphyrin pigments such as heme. At the center of the chlorin ring is a magnesium ion. This system is part of the complex protein machinery that produces oxygen as plants do photosynthesis.
Bioorganometallic systems such as hydrogenases and methylcobalamin are biological examples of organometallic compounds. This area is more focused on the utilization of metals by unicellular organisms. Bioorganometallic compounds are significant in environmental chemistry.^[1]
The nitrogen metabolism pathways: these make use of metals. Nitrogenase is one of the more famous metalloproteins associated with nitrogen metabolism. More recently, the cardiovascular and neuronal importance of nitric oxide has been examined, including the enzyme nitric oxide synthase. (See also: nitrogen assimilation.)
Metals in medicine: this is the study of the design and mechanism of action of metal-containing pharmaceuticals, and compounds that interact with endogenous metal ions in enzyme active sites. This diverse field includes the platinum and ruthenium anti-cancer drugs, chelating agents, gold drug chaperones, and gadolinium contrast agents.
In mental health: some inorganic compounds have been found to treat certain disorders. For example, lithium carbonate has been used to treat mania in bipolar disorder.

References

↑ Sigel, A. (2010). Sigel, H.; Sigel, R.K.O. (eds.). Organometallics in Environment and Toxicology. Metal Ions in Life Sciences. Vol. 7. Cambridge: RSC publishing. ISBN 978-1-84755-177-1.

Other websites

More reading

Heinz-Bernhard Kraatz (editor), Nils Metzler-Nolte (editor), Concepts and Models in Bioinorganic Chemistry, John Wiley and Sons, 2006, ISBN 3-527-31305-2
Ivano Bertini, Harry B. Gray, Edward I. Stiefel, Joan Selverstone Valentine, Biological Inorganic Chemistry, University Science Books, 2007, ISBN 1-891389-43-2
Wolfgang Kaim, Brigitte Schwederski "Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life." John Wiley and Sons, 1994, ISBN 0-471-94369-X
Ivano Bertini, Harry B. Gray, Stephen J. Lippard, Joan Selverstone Valentine, "Bioinorganic Chemistry," University Science Books, 1994, ISBN 0-935702-57-1
Stephen J. Lippard, Jeremy M. Berg, Principles of Bioinorganic Chemistry, University Science Books, 1994, ISBN 0-935702-72-5
Rosette M. Roat-Malone, Bioinorganic Chemistry : A Short Course, John Wiley & Sons|Wiley-Interscience, 2002, ISBN 0-471-15976-X
J.J.R. Fraústo da Silva and R.J.P. Williams, The biological chemistry of the elements: The inorganic chemistry of life, 2nd Edition, Oxford University Press, 2001, ISBN 0-19-850848-4
Lawrence Que, Jr., ed., Physical Methods in Bioinorganic Chemistry, University Science Books, 2000, ISBN 1-891389-02-5

[1] Sigel, A. (2010). Sigel, H.; Sigel, R.K.O. (eds.). Organometallics in Environment and Toxicology. Metal Ions in Life Sciences. Vol. 7. Cambridge: RSC publishing. ISBN 978-1-84755-177-1.

[1]