Bioinorganic chemistry is a field that examines the role of metalsinbiology. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of metalloproteins as well as artificially introduced metals, including those that are non-essential, in medicine and toxicology. Many biological processes such as respiration depend upon molecules that fall within the realm of inorganic chemistry. The discipline also includes the study of inorganic models or mimics that imitate the behaviour of metalloproteins.[1]
As a mix of biochemistry and inorganic chemistry, bioinorganic chemistry is important in elucidating the implications of electron-transfer proteins, substrate bindings and activation, atom and group transfer chemistry as well as metal properties in biological chemistry. The successful development of truly interdisciplinary work is necessary to advance bioinorganic chemistry.[2]
A diverse collection of transporters (e.g. the ion pump NaKATPase), vacuoles, storage proteins (e.g. ferritin), and small molecules (e.g. siderophores) are employed to control metal ions concentration and bio-availability in living organisms. Crucially, many essential metals are not readily accessible to downstream proteins owing to low solubility in aqueous solutions or scarcity in the cellular environment. Organisms have developed a number of strategies for collecting and transporting such elements while limiting their cytotoxicity.
Many reactions in life sciences involve water and metal ions are often at the catalytic centers (active sites) for these enzymes, i.e. these are metalloproteins. Often the reacting water is a ligand (see metal aquo complex). Examples of hydrolase enzymes are carbonic anhydrase, metallophosphatases, and metalloproteinases. Bioinorganic chemists seek to understand and replicate the function of these metalloproteins.
Aerobic life make extensive use of metals such as iron, copper, and manganese. Heme is utilized by red blood cells in the form of hemoglobin for oxygen transport and is perhaps the most recognized metal system in biology. 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 in cytochrome c oxidase or small molecule oxidation in cytochrome P450 oxidasesormethane monooxygenase. 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. These systems include peroxidases, catalases, and superoxide dismutases. A complementary metalloprotein to those that react with oxygen is the oxygen evolving complex present in plants. This system is part of the complex protein machinery that produces oxygen as plants perform photosynthesis.
Myoglobin is a prominent subject in bioinorganic chemistry, with particular attention to the iron-heme complex that is anchored to the protein.
Bioorganometallic systems feature metal-carbon bonds as structural elements or as intermediates. Bioorganometallic enzymes and proteins include the hydrogenases, FeMoco in nitrogenase, and methylcobalamin. These naturally occurring organometallic compounds. This area is more focused on the utilization of metals by unicellular organisms. Bioorganometallic compounds are significant in environmental chemistry.[5]
Structure of FeMoco, the catalytic center of nitrogenase.
A number of drugs contain metals. This theme relies on 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. The most widely used anti-cancer drug is cisplatin. MRI contrast agent commonly contain gadolinium. Lithium carbonate has been used to treat the manic phase of bipolar disorder. Gold antiarthritic drugs, e.g. auranofin have been commercialized. Carbon monoxide-releasing molecules are metal complexes have been developed to suppress inflammation by releasing small amounts of carbon monoxide. The cardiovascular and neuronal importance of nitric oxide has been examined, including the enzyme nitric oxide synthase. (See also: nitrogen assimilation.) Besides, metallic transition complexes based on triazolopyrimidines have been tested against several parasite strains.[6]
Environmental chemistry traditionally emphasizes the interaction of heavy metals with organisms. Methylmercury has caused major disaster called Minamata disease. Arsenic poisoning is a widespread problem owing largely to arsenic contamination of groundwater, which affects many millions of people in developing countries. The metabolism of mercury- and arsenic-containing compounds involves cobalamin-based enzymes.
Biomineralization is the process by which living organisms produce minerals, often to harden or stiffen existing tissues. Such tissues are called mineralized tissues.[7][8][9] Examples include silicatesinalgae and diatoms, carbonatesininvertebrates, and calcium phosphates and carbonatesinvertebrates. Other examples include copper, iron and gold deposits involving bacteria. Biologically-formed minerals often have special uses such as magnetic sensors in magnetotactic bacteria (Fe3O4), gravity sensing devices (CaCO3, CaSO4, BaSO4) and iron storage and mobilization (Fe2O3•H2O in the protein ferritin). Because extracellular[10] iron is strongly involved in inducing calcification,[11][12] its control is essential in developing shells; the protein ferritin plays an important role in controlling the distribution of iron.[13]
The transition metals are usually present as trace elements in organisms, with zinc and iron being most abundant.[18][19][20] These metals are used as protein cofactors and signalling molecules. Many are essential for the activity of enzymes such as catalase and oxygen-carrier proteins such as hemoglobin.[21] These cofactors are tightly to a specific protein; although enzyme cofactors can be modified during catalysis, cofactors always return to their original state after catalysis has taken place. The metal micronutrients are taken up into organisms by specific transporters and bound to storage proteins such as ferritinormetallothionein when not being used.[22][23]Cobalt is essential for the functioning of vitamin B12.[24]
Many other elements aside from metals are bio-active. Sulfur and phosphorus are required for all life. Phosphorus almost exclusively exists as phosphate and its various esters. Sulfur exists in a variety of oxidation states, ranging from sulfate (SO42−) down to sulfide (S2−). Selenium is a trace element involved in proteins that are antioxidants. Cadmium is important because of its toxicity.[25]
^Maret, Wolfgang (2017). "Chapter 1. The Bioinorganic Chemistry of Lead in the Context of its Toxicity". In Astrid, S.; Helmut, S.; Sigel, R. K. O. (eds.). Lead: Its Effects on Environment and Health. Metal Ions in Life Sciences. Vol. 17. de Gruyter. pp. 1–20. doi:10.1515/9783110434330-001. ISBN9783110434330. PMID28731294.
^Sigel, A.; Sigel, H.; Sigel, R.K.O., eds. (2010). Organometallics in Environment and Toxicology. Metal Ions in Life Sciences. Vol. 7. Cambridge: RSC publishing. ISBN978-1-84755-177-1.
^Méndez-Arriaga JM, Oyarzabal I, et al. (March 2018). "In vitro leishmanicidal and trypanocidal evaluation and magnetic properties of 7-amino-1,2,4-triazolo[1,5-a]pyrimidine Cu(II) complexes". Journal of Inorganic Biochemistry. 180: 26–32. doi:10.1016/j.jinorgbio.2017.11.027. PMID29227923.
^Astrid Sigel, Helmut Sigel and Roland K.O. Sigel, ed. (2008). Biomineralization: From Nature to Application. Metal Ions in Life Sciences. Vol. 4. Wiley. ISBN978-0-470-03525-2.
^Weiner, Stephen; Lowenstam, Heinz A. (1989). On biomineralization. Oxford [Oxfordshire]: Oxford University Press. ISBN978-0-19-504977-0.
^Jean-Pierre Cuif; Yannicke Dauphin; James E. Sorauf (2011). Biominerals and fossils through time. Cambridge. ISBN978-0-521-87473-1.
^Anghileri, L. J.; Maincent, P.; Cordova-Martinez, A. (1993). "On the mechanism of soft tissue calcification induced by complexed iron". Experimental and Toxicologic Pathology. 45 (5–6): 365–368. doi:10.1016/S0940-2993(11)80429-X. PMID8312724.
^Dunn L, Rahmanto Y, Richardson D (2007). "Iron uptake and metabolism in the new millennium". Trends Cell Biol. 17 (2): 93–100. doi:10.1016/j.tcb.2006.12.003. PMID17194590.
^Maret, Wolfgang; Moulis, Jean-Marc (2013). "Chapter 1. The Bioinorganic Chemistry of Cadmium in the Context of its Toxicity". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel (ed.). Cadmium: From Toxicology to Essentiality. Metal Ions in Life Sciences. Vol. 11. Springer. pp. 1–30.
Heinz-Bernhard Kraatz (editor), Nils Metzler-Nolte (editor), Concepts and Models in Bioinorganic Chemistry, John Wiley and Sons, 2006, ISBN3-527-31305-2
Ivano Bertini, Harry B. Gray, Edward I. Stiefel, Joan Selverstone Valentine, Biological Inorganic Chemistry, University Science Books, 2007, ISBN1-891389-43-2
Wolfgang Kaim, Brigitte Schwederski "Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life." John Wiley and Sons, 1994, ISBN0-471-94369-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, ISBN0-19-850848-4
Lawrence Que, Jr., ed., Physical Methods in Bioinorganic Chemistry, University Science Books, 2000, ISBN1-891389-02-5
