View source for Bioinorganic chemistry

{{Short description|Study of the role of metals in biology}}
{{for|the journal|Bioinorganic Chemistry (journal)}}
'''Bioinorganic chemistry''' is a field that examines the role of [[metal]]s in [[biology]]. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of [[metalloprotein]]s as well as artificially introduced metals, including those that are [[essential element|non-essential]], in [[medicine]] and [[toxicology]].  Many [[biological process]]es such as [[cellular respiration|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.<ref>Stephen J. Lippard, Jeremy M. Berg, ''Principles of Bioinorganic Chemistry'', University Science Books, 1994, {{ISBN|978-0-935702-72-9}}</ref>

As a mix of [[biochemistry]] and [[inorganic chemistry]], bioinorganic chemistry is important in elucidating the implications of electron-transfer [[protein]]s, 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.<ref>{{Cite journal|last1=Gumerova|first1=Nadiia I.|last2=Rompel|first2=Annette|date=2021-03-31|title=Interweaving Disciplines to Advance Chemistry: Applying Polyoxometalates in Biology|journal=Inorganic Chemistry|volume=60 |issue=9 |language=en|pages=6109–6114|doi=10.1021/acs.inorgchem.1c00125 |pmid=33787237 |pmc=8154434 |issn=0020-1669|doi-access=free}}</ref>

==Composition of living organisms==
About 99% of [[mammals]]' mass are the elements [[carbon]], [[nitrogen]], [[calcium]], [[sodium]], [[chlorine]], [[potassium]], [[hydrogen]], [[phosphorus]], [[oxygen]] and [[sulfur]].<ref name=Heymsfield>{{cite journal |vauthors=Heymsfield S, Waki M, Kehayias J, Lichtman S, Dilmanian F, Kamen Y, Wang J, Pierson R |title=Chemical and elemental analysis of humans in vivo using improved body composition models |journal=[[American Journal of Physiology]] |volume=261 |issue=2 Pt 1 |pages=E190–8 |year=1991 |pmid=1872381|doi=10.1152/ajpendo.1991.261.2.E190 }}</ref> The [[organic compound]]s ([[proteins]], [[lipids]] and [[carbohydrates]]) contain the majority of the carbon and nitrogen and most of the oxygen and hydrogen is present as water.<ref name=Heymsfield/>  The entire collection of metal-containing [[biomolecules]] in a [[Cell (biology)|cell]] is called the [[metallome]].

==History==
[[Paul Ehrlich]] used [[organoarsenic]] ("arsenicals") for the treatment of [[syphilis]], demonstrating the relevance of metals, or at least metalloids, to medicine, that blossomed with Rosenberg's discovery of the anti-cancer activity of [[cisplatin]] (cis-PtCl<sub>2</sub>(NH<sub>3</sub>)<sub>2</sub>).  The first protein ever crystallized (see [[James B. Sumner]]) was [[urease]], later shown to contain nickel at its [[active site]].  [[Cyanocobalamin|Vitamin B<sub>12</sub>]], the cure for [[pernicious anemia]] was shown crystallographically by [[Dorothy Crowfoot Hodgkin]] to consist of a cobalt in a [[corrin]] macrocycle.

==Themes in bioinorganic chemistry==
Several distinct systems are of identifiable in bioinorganic chemistry.  Major areas include:

===Metal ion transport and storage===
A diverse collection of [[Membrane transport protein|transporters]] (e.g. the ion pump [[NaKATPase]]), [[vacuole]]s, storage [[protein]]s (e.g. [[ferritin]]), and small molecules (e.g. [[Siderophore|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]].

===Enzymology===
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 [[metalloprotein]]s.  Often the reacting water is a ligand (see [[metal aquo complex]]).  Examples of [[hydrolase]] enzymes are [[carbonic anhydrase]], metallo[[phosphatase]]s, and [[metalloproteinase]]s.  Bioinorganic chemists seek to understand and replicate the function of these metalloproteins.

Metal-containing electron transfer proteins are also common.  They can be organized into three major classes: [[iron–sulfur protein]]s (such as [[rubredoxin]]s, [[ferredoxin]]s, and [[Rieske protein]]s), blue [[copper proteins]], and [[cytochrome]]s. These electron transport proteins are complementary to the non-metal electron transporters [[nicotinamide adenine dinucleotide]] (NAD) and [[flavin adenine dinucleotide]] (FAD). The [[nitrogen cycle]] make extensive use of metals for the redox interconversions.
[[Image:FdRedox.png|center|500px|thumb|4Fe-4S clusters serve as electron-relays in proteins.]]

===Toxicity===
Several metal ions are toxic to humans and other animals. The bioinorganic chemistry of lead in the context of its toxicity has been reviewed.<ref>{{cite book|last1= Maret |first1= Wolfgang|chapter= Chapter 1. The Bioinorganic Chemistry of Lead in the Context of its Toxicity|publisher= de Gruyter|date= 2017|series= Metal Ions in Life Sciences|volume=17|pages= 1–20|title=Lead: Its Effects on Environment and Health|editor1-last=Astrid|editor1-first= S.|editor2-last=Helmut|editor2-first=S.|editor3-last=Sigel |editor3-first= R. K. O.|doi=10.1515/9783110434330-001|pmid= 28731294|isbn= 978-3-11-043433-0}}</ref>

===Oxygen transport and activation proteins===
{{Main|Transition metal dioxygen complex}}
Aerobic life make extensive use of metals such as iron, copper, and manganese.  [[Heme]] is utilized by [[red blood cell]]s 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]].  [[Oxidase]]s and [[oxygenase]]s 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 oxidase]]s or [[methane 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 [[peroxidase]]s, [[catalase]]s, and [[superoxide dismutase]]s.  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 [[Oxygen evolution|produces oxygen]] as plants perform [[photosynthesis]].
[[Image:Myoglobin.png|right|220px|thumb|Myoglobin is a prominent subject in bioinorganic chemistry, with particular attention to the iron-heme complex that is anchored to the protein.]]

===Bioorganometallic chemistry===
[[Bioorganometallic chemistry|Bioorganometallic]] systems feature metal-carbon bonds as structural elements or as intermediates. Bioorganometallic enzymes and proteins include the [[hydrogenase]]s, [[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]].<ref>{{cite book |editor-last=Sigel |editor-first=A. |editor2=Sigel, H. |editor3=Sigel, R.K.O. |title=Organometallics in Environment and Toxicology|publisher=RSC publishing|location=Cambridge|year=2010|series=Metal Ions in Life Sciences|volume=7|isbn=978-1-84755-177-1}}</ref>

[[File:FeMoco cluster.svg|thumb|right|160px|Structure of [[FeMoco]], the catalytic center of nitrogenase.]]

===Metals in medicine===
{{Main|Metals in medicine}}
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 [[neuron]]al 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.<ref name="pmid29227923">{{cite journal  |vauthors=Méndez-Arriaga JM, Oyarzabal I, etal |title=In vitro leishmanicidal and trypanocidal evaluation and magnetic properties of 7-amino-1,2,4-triazolo[1,5-a]pyrimidine Cu(II) complexes |journal= Journal of Inorganic Biochemistry|volume=180 |pages=26–32 |date=March 2018 |pmid=29227923 |doi=10.1016/j.jinorgbio.2017.11.027 }}</ref>

===Environmental chemistry===
{{main|Environmental chemistry}}
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===
{{main|Biomineralization}}
Biomineralization is the process by which living organisms produce [[mineral]]s, often to harden or stiffen existing tissues. Such tissues are called [[mineralized tissues]].<ref>{{cite book
 |title=Biomineralization: From Nature to Application|editor=Astrid Sigel, Helmut Sigel and Roland K.O. Sigel|publisher=Wiley|year=2008|series=Metal Ions in Life Sciences|volume=4
 | isbn=978-0-470-03525-2}}</ref><ref name=Weiner1989>{{cite book 
 |author1=Weiner, Stephen |author2=Lowenstam, Heinz A. | title=On biomineralization
 | publisher=Oxford University Press 
 |location=Oxford [Oxfordshire] |year=1989 |isbn=978-0-19-504977-0}}</ref><ref>{{cite book|title=Biominerals and fossils through time|author1=Jean-Pierre Cuif |author2=Yannicke Dauphin |author3=James E. Sorauf |publisher=Cambridge|year=2011| isbn=978-0-521-87473-1}}</ref>  Examples include [[silicates]] in [[algae]] and [[diatoms]], [[carbonate]]s in [[invertebrates]], and [[calcium phosphates]] and [[calcium carbonate|carbonates]] in [[vertebrates]]. Other examples include [[copper]], [[iron]] and [[gold]] deposits involving bacteria. Biologically-formed minerals often have special uses such as magnetic sensors in [[magnetotactic bacteria]] (Fe<sub>3</sub>O<sub>4</sub>), gravity sensing devices (CaCO<sub>3</sub>, CaSO<sub>4</sub>, BaSO<sub>4</sub>) and iron storage and mobilization (Fe<sub>2</sub>O<sub>3</sub>•H<sub>2</sub>O in the protein [[ferritin]]). Because extracellular<ref>{{cite journal|vauthors=Gabbiani G, Tuchweber B|title=The role of iron in the mechanism of experimental calcification|journal=J Histochem Cytochem|year=1963|volume=11|issue=6|pages=799–803|doi=10.1177/11.6.799|doi-access=free}}</ref> iron is strongly involved in inducing calcification,<ref>{{Cite journal
| doi = 10.1038/nature02631
| pmid = 15295599
| year = 2004
| last1 = Schulz | first1 = K.
| last2 = Zondervan | first2 = I.
| last3 = Gerringa | first3 = L.
| last4 = Timmermans | first4 = K.
| last5 = Veldhuis | first5 = M.
| last6 = Riebesell | first6 = U.
| title = Effect of trace metal availability on coccolithophorid calcification.
| volume = 430
| issue = 7000
| pages = 673–676
| journal = Nature 
|bibcode = 2004Natur.430..673S | url = https://epic.awi.de/id/eprint/13015/1/Sch2004bl.pdf
}}</ref><ref>{{Cite journal
| pmid = 8312724
| year = 1993
| last1 = Anghileri | first1 = L. J.
| last2 = Maincent | first2 = P.
| last3 = Cordova-Martinez | first3 = A.
| title = On the mechanism of soft tissue calcification induced by complexed iron
| volume = 45
| issue = 5–6
| pages = 365–368
| journal = Experimental and Toxicologic Pathology
 | doi=10.1016/S0940-2993(11)80429-X
| bibcode = 1993EToxP..45..365A
}}</ref> its control is essential in developing shells; the protein [[ferritin]] plays an important role in controlling the distribution of iron.<ref name='Jackson2007'>{{Cite journal | doi = 10.1186/1471-2148-7-160 | title = Dynamic expression of ancient and novel molluscan shell genes during ecological transitions | year = 2007 | last1 = Jackson | first1 = D. J. | last2 = Wörheide | first2 = G. | last3 = Degnan | first3 = B. M. | journal = BMC Evolutionary Biology | volume = 7 | issue = 1 | article-number = 160| pmid = 17845714 | pmc = 2034539  | bibcode = 2007BMCEE...7..160J | doi-access = free }}</ref>

==Types of inorganic substances in biology==

===Alkali and alkaline earth metals===
[[Image:Monensin2.png|210 px|thumb|left|Like many antibiotics, [[monensin]]-A is an ionophore that tightly bind Na<sup>+</sup> (shown in yellow).<ref name=Green>{{Greenwood&Earnshaw2nd}}</ref>]]
The abundant inorganic elements act as [[ion]]ic [[electrolyte]]s. The most important ions are [[sodium]], [[potassium]], [[calcium]], [[magnesium]], [[chloride]], [[phosphate]], and [[bicarbonate]]. The maintenance of precise [[ion gradient|gradients]] across [[cell membrane]]s maintains [[osmotic pressure]] and [[pH]].<ref>{{cite journal |author=Sychrová H |title=Yeast as a model organism to study transport and homeostasis of alkali metal cations |url=http://www.biomed.cas.cz/physiolres/pdf/53%20Suppl%201/53_S91.pdf |journal=Physiol Res |volume=53 |pages=S91–8 |year=2004 |issue=Suppl 1 |doi=10.33549/physiolres.930000.53.S91 |pmid=15119939}}</ref> Ions are also critical for [[nerve]]s and [[muscle]]s, as [[action potential]]s in these tissues are produced by the exchange of electrolytes between the [[extracellular fluid]] and the [[cytosol]].<ref>{{cite journal |author=Levitan I |title=Modulation of ion channels in neurons and other cells |journal=Annu Rev Neurosci |volume=11 |pages=119–36 |year=1988 |pmid=2452594 |doi=10.1146/annurev.ne.11.030188.001003}}</ref> Electrolytes enter and leave cells through proteins in the cell membrane called [[ion channels]]. For example, [[muscle contraction]] depends upon the movement of calcium, sodium and potassium through ion channels in the cell membrane and [[T-tubule]]s.<ref>{{cite journal |author=Dulhunty A |title=Excitation-contraction coupling from the 1950s into the new millennium |journal=Clin Exp Pharmacol Physiol |volume=33 |issue=9 |pages=763–72 |year=2006 |pmid=16922804 |doi=10.1111/j.1440-1681.2006.04441.x}}</ref>

===Transition metals===
The [[transition metal]]s are usually present as [[trace element]]s in organisms, with [[zinc]] and [[iron]] being most abundant.<ref>{{cite book 
|last1=Dlouhy |first1=Adrienne C. |last2=Outten|first2=Caryn E. 
|editor1-first=Lucia|editor1-last=Banci |series=Metal Ions in Life Sciences |volume=12 
|pages=241–78 |chapter= The Iron Metallome in Eukaryotic Organisms
|title=Metallomics and the Cell |year=2013 |publisher=Springer |isbn=978-94-007-5560-4|doi=10.1007/978-94-007-5561-1_8|pmid=23595675 |pmc=3924584 }} electronic-book {{ISBN|978-94-007-5561-1}} {{issn|1559-0836}} electronic-{{issn|1868-0402}}</ref><ref>{{cite journal|vauthors=Mahan D, Shields R |title=Macro- and micromineral composition of pigs from birth to 145 kilograms of body weight |url=http://jas.fass.org/cgi/reprint/76/2/506 |journal=J Anim Sci |volume=76 |issue=2 |pages=506–12 |year=1998 |pmid=9498359 |url-status=dead |archive-url=https://web.archive.org/web/20110430042613/http://jas.fass.org/cgi/reprint/76/2/506 |archive-date=2011-04-30 |doi=10.2527/1998.762506x |url-access=subscription }}</ref><ref name=Husted>{{cite journal |vauthors=Husted S, Mikkelsen B, Jensen J, Nielsen N |title=Elemental fingerprint analysis of barley (Hordeum vulgare) using inductively coupled plasma mass spectrometry, isotope-ratio mass spectrometry, and multivariate statistics |journal=Anal Bioanal Chem |volume=378 |issue=1 |pages=171–82 |year=2004 |pmid=14551660 |doi=10.1007/s00216-003-2219-0}}</ref> These metals are used as protein [[Cofactor (biochemistry)|cofactors]] and signalling molecules. Many are essential for the activity of enzymes such as [[catalase]] and oxygen-carrier proteins such as [[hemoglobin]].<ref>{{cite journal |vauthors=Finney L, O'Halloran T |s2cid=14863354 |title=Transition metal speciation in the cell: insights from the chemistry of metal ion receptors |journal=Science |volume=300 |issue=5621 |pages=931–6 |year=2003 |pmid=12738850 |doi=10.1126/science.1085049|bibcode = 2003Sci...300..931F }}</ref> 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 [[ferritin]] or [[metallothionein]] when not being used.<ref>{{cite journal |vauthors=Cousins R, Liuzzi J, Lichten L |title=Mammalian zinc transport, trafficking, and signals |journal=J Biol Chem |volume=281 |issue=34 |pages=24085–9 |year=2006 |pmid=16793761 |doi=10.1074/jbc.R600011200|doi-access=free }}</ref><ref>{{cite journal |vauthors=Dunn L, Rahmanto Y, Richardson D |title=Iron uptake and metabolism in the new millennium |journal=Trends Cell Biol |volume=17 |issue=2 |pages=93–100 |year=2007 |pmid=17194590 |doi=10.1016/j.tcb.2006.12.003}}</ref> [[Cobalt]] is essential for the functioning of [[vitamin B12]].<ref>{{cite book 
|last1=Cracan|first1=Valentin |last2=Banerjee|first2=Ruma   
|editor1-first=Lucia|editor1-last=Banci |series=Metal Ions in Life Sciences |volume=12 
|chapter= Cobalt and Corrinoid Transport and Biochemistry
|title=Metallomics and the Cell |year=2013 |pages=333–74 |publisher=Springer |isbn=978-94-007-5560-4|doi=10.1007/978-94-007-5561-1_10 |pmid=23595677 }} electronic-book {{ISBN|978-94-007-5561-1}} {{issn|1559-0836}} electronic-{{issn|1868-0402}}
</ref>

===Main group compounds===
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 [[ester]]s.  Sulfur exists in a variety of oxidation states, ranging from sulfate ({{chem|SO|4|2-}}) down to sulfide (S<sup>2−</sup>).  Selenium is a trace element involved in proteins that are antioxidants. Cadmium is important because of its toxicity.<ref>{{cite book
|last1=Maret
|first1=Wolfgang
|last2=Moulis
|first2=Jean-Marc
|editor=Astrid Sigel, Helmut Sigel and Roland K. O. Sigel
|title=Cadmium: From Toxicology to Essentiality
|series=Metal Ions in Life Sciences
|volume=11
|year=2013
|publisher=Springer
|pages=1–30
|chapter=Chapter 1. The Bioinorganic Chemistry of Cadmium in the Context of its Toxicity}}
</ref>

== See also ==
* [[Cofactor (biochemistry)|Cofactor]]
* [[Human iron metabolism|Iron metabolism]]
* [[Physiology]]

==References==
{{reflist|30em}}

==Literature==
{{refbegin|2}}
* Heinz-Bernhard Kraatz (editor), Nils Metzler-Nolte (editor), ''Concepts and Models in Bioinorganic Chemistry'', John Wiley and Sons, 2006, {{ISBN|978-3-527-31305-1}}
* Ivano Bertini, Harry B. Gray, Edward I. Stiefel, Joan Selverstone Valentine, ''Biological Inorganic Chemistry'', University Science Books, 2007, {{ISBN|978-1-891389-43-6}}
* Wolfgang Kaim, Brigitte Schwederski "Bioinorganic Chemistry: Inorganic Elements in the Chemistry of Life." John Wiley and Sons, 1994, {{ISBN|978-0-471-94369-3}}
* Rosette M. Roat-Malone,  ''Bioinorganic Chemistry : A Short Course'', [[John Wiley & Sons|Wiley-Interscience]], 2002, {{ISBN|978-0-471-15976-6}}
* 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|978-0-19-850848-9}}
* Lawrence Que, Jr., ed., ''Physical Methods in Bioinorganic Chemistry'', University Science Books, 2000, {{ISBN|978-1-891389-02-3}}
{{refend}}

== External links ==
*[http://www.sbichem.org/ The Society of Biological Inorganic Chemistry (SBIC)'s home page]
*[http://www.frenchbic.cnrs.fr/ The French Bioinorganic Chemistry Society]
*[https://web.archive.org/web/20050204054913/http://www.chem.qmw.ac.uk/iupac/bioinorg/ Glossary of Terms in Bioinorganic Chemistry]
*[https://web.archive.org/web/20140603015531/http://tanna.bch.ed.ac.uk/ Metal Coordination Groups in Proteins by Marjorie Harding]
*[http://www.ebi.ac.uk/ European Bioinformatics Institute]
*[http://metalweb.cerm.unifi.it/ MetalPDB: A database of metal sites in biomolecular structures] {{Webarchive|url=https://web.archive.org/web/20150915055956/http://metalweb.cerm.unifi.it/ |date=2015-09-15 }}

{{Metal metabolism}}
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[[Category:Bioinorganic chemistry| ]]
[[Category:Biochemistry]]
[[Category:Inorganic chemistry]]
[[Category:Medicinal inorganic chemistry]]