Selenium

Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium,. It rarely occurs in its elemental state in nature, but instead is obtained as a side-product in the refining of other elements.

Selenium is found in sulfide ores such as pyrite, where it partially replaces the sulfur. Minerals that are selenide or selenate compounds are also known, but are rare. The chief commercial uses for selenium today are in glassmaking and in pigments. Uses in electronics, once important, have been supplanted by silicon semiconductor devices. It is a semiconductor with the unusual property of conducting electricity better in the light than in the dark, and is used in photocells.

Selenium salts are toxic in large amounts, but trace amounts are necessary for cellular function in many organisms. It is a component of the enzymes glutathione peroxidase and thioredoxin reductase (which indirectly reduce certain oxidized molecules in animals and some plants). It is also found in three deiodinase enzymes, which convert one thyroid hormone to another. Selenium requirements in plants differ by species, with some plants, it seems, requiring none.

Physical
The most stable allotrope of selenium is a dense purplish-gray solid. In terms of structure, it adopts a helical polymeric chain. The Se-Se distance is 2.37 Å and the Se-Se-Se angle is 103°. It is a semiconductor with the unusual property of conducting electricity better in the light than in the dark, and is used in photocells. Gray selenium resists oxidation by air and is not attacked by non-oxidizing acids. With strong reducing agents, it forms polyselenides.

Red Se and related molecular allotropes
The second major allotrope of Se is red selenium. The solid consists of individual molecules of eight-membered ring molecules, like its lighter cousin sulfur. The Se-Se distance is 2.34 Å and the Se-Se-Se angle is 106°. Unlike sulfur, however, the red form converts to the gray polymeric allotrope with heat. Other rings with the formula Sen are also known.

Elemental selenium produced in chemical reactions invariably appears as the amorphous red form: an insoluble, brick-red powder. When this form is rapidly melted, it forms the black, vitreous form, which is usually sold industrially as beads. The red allotrope crystallises in three habits. Selenium does not exhibit the unusual changes in viscosity that sulfur undergoes when gradually heated.

Isotopes
Selenium has six naturally occurring isotopes, five of which are stable: 74Se, 76Se, 77Se, 78Se, and 80Se. The last three also occur as fission products, along with 79Se, which has a half-life of 327,000 years. The final naturally occurring isotope, 82Se, has a very long half-life (~1020 yr, decaying via double beta decay to 82Kr), which, for practical purposes, can be considered to be stable. Twenty-three other unstable isotopes have been characterized.

See also Selenium-79 for more information on recent changes in the measured half-life of this long-lived fission product, important for the dose calculations performed in the frame of the geological disposal of long-lived radioactive waste.

Occurrence


Native selenium is a rare mineral, which does not usually form good crystals, but, when it does, they are steep rhombohedrons or tiny acicular (hair-like) crystals. Isolation of selenium is often complicated by the presence of other compounds and elements. Selenium occurs naturally in a number of inorganic forms, including selenide-, selenate-, and selenite-containing minerals.

In living systems, selenium is found in the amino acids selenomethionine, selenocysteine, and methylselenocysteine. In these compounds, selenium plays a role analogous to that of sulfur. Another naturally occurring organoselenium compounds is dimethyl selenide.

Certain solids are selenium-rich, and selenium can be bioconcentrated by certain plants. In soils, selenium most often occurs in soluble forms such as selenate (analogous to sulfate), which are leached into rivers very easily by runoff.

Anthropogenic sources of selenium include coal burning and the mining and smelting of sulfide ores.

Production
Selenium is most commonly produced from selenide in many sulfide ores, such as those of copper, silver, or lead. It is obtained as a byproduct of the processing of these ores, e.g., from the anode mud of copper refineries and the mud from the lead chambers of sulfuric acid plants. These muds can be processed by a number of means to obtain selenium. Specifically, most elemental selenium comes as a byproduct of refining copper or producing sulfuric acid.

Industrial production of selenium often involves the extraction of selenium dioxide from residues obtained during the purification of copper. Common production begins by oxidation with sodium carbonate to produce selenium dioxide. The selenium dioxide is then mixed with water and the solution is acidified to form selenous acid (oxidation step). Selenous acid is bubbled with sulfur dioxide (reduction step) to give elemental selenium.

Chemical compounds
Selenium compounds commonly exist in oxidation states -II, +II, +IV, and +VI.

Chalcogen compounds
Selenium forms two stable oxides: selenium dioxide and selenium trioxide. Selenium dioxide is formed by the reaction of elemental selenium with oxygen:
 * + 8 → 8

It is a polymeric solid that forms monomeric molecules in the gas phase. It dissolves in water to form selenous acid,. Selenous acid can also be made directly by oxidising elemental selenium with nitric acid:


 * 3 Se + 4 → 3  + 4 NO

Unlike sulfur, which forms a stable trioxide, selenium trioxide is unstable and decomposes to the dioxide above 185 °C:


 * 2 → 2  +   (ΔH = −54 kJ/mol)

Salts of selenous acid are called selenites. These include silver selenite and sodium selenite.

Hydrogen sulfide reacts with aqueous selenous acid to produce selenium disulfide:
 * + 2 →  + 3

Selenium disulfide consists of 8-membered rings of a nearly statistical distribution of sulfur and selenium atoms. It has an approximate composition of, with individual rings varying in composition, such as and. Selenium disulfide has been use in shampoo as an anti-dandruff agent, an inhibitor in polymer chemistry, a glass dye, and a reducing agent in fireworks.

Selenium trioxide may be synthesized by dehydrating selenic acid,, which is itself produced by the oxidation of selenium dioxide with hydrogen peroxide:

Hot, concentrated selenic acid is capable of dissolving gold, forming gold(III) selenate.

Halogen compounds
Iodides of selenium are not well known. The only stable chloride is Se2Cl2; the corresponding bromide is also known. These species are structurally analogous to the corresponding disulfur dichloride. Selenium dichloride is an important reagent in the preparation of selenium compounds (e.g. the preparation of Se7). It is prepared by treating selenium with sulfuryl chloride. Selenium reacts with fluorine to form selenium hexafluoride:
 * + 24 → 8

In comparison with its sulfur counterpart (sulfur hexafluoride), is more reactive and is toxic pulmonary irritant. Some of the selenium oxyhalides, such as and selenium oxychloride have been used as specialty solvents.

Selenides
Analogous to the behavior of other chalcogens, selenium forms a dihydride. It is a strongly odiferous, toxic, and colourless gas. It is more acidic than. In solution it ionizes to HSe-. The selenide dianion Se2- forms a variety of compounds, including the minerals from which selenium is obtained commercially. Illustrative selenides include mercury selenide (HgSe), lead selenide (PbSe), zinc selenide (ZnSe), and copper indium gallium diselenide. These materials are semiconductors. With highly electropositive metals, such as aluminium, these selenides are prone to hydrolysis:
 * + 6 H2O → 8  +  H2Se

Alkali metal selenides react with selenium to form polyselenides, Sex2-, which exist as chains.

Other compounds
Tetraselenium tetranitride,, is an explosive orange compound analogous to tetrasulfur tetranitride. It can be synthesized by the reaction of with.

Selenium reacts with cyanides to yield selenocyanates:
 * 8 KCN + → 8 KSeCN

Organoselenium compounds
Selenium, especially in the II oxidation state, forms stable bonds to carbon. Typical compounds include selenols with the formula RSeH (e.g., benzeneselenol), selenides with the formula RSeR (e.g., diphenylselenide), and diselenides, with the formula RSeSeR (e.g., diphenyldiselenide). Selenoxides, with the formula RSe(O)R, and selenyl chlorides, with the formula RSeCl, are useful intermediates in organic chemistry.

History and global demand
Selenium (Greek σελήνη selene meaning "Moon") was discovered in 1817 by Jöns Jakob Berzelius, who found the element associated with tellurium (named for the Earth). It was discovered as a byproduct of sulfuric acid production.

It came to medical notice later because of its toxicity to humans working in industry. It was also recognized as an important veterinary toxin, seen in animals eating high-selenium plants. In 1954, the first hints of specific biological functions of selenium were discovered in microorganisms. Its essentiality for mammalian life was discovered in 1957. In the 1970s, it was shown to be present in two independent sets of enzymes. This was followed by the discovery of selenocysteine in proteins. During the 1980s, it was shown that selenocysteine is encoded by the codon TGA. The recoding mechanism was worked out first in bacteria and then in mammals (see SECIS element).

Health effects and nutrition
Although it is toxic in large doses, selenium is an essential micronutrient for animals. In plants, it occurs as a bystander mineral, sometimes in toxic proportions in forage (some plants may accumulate selenium as a defense against being eaten by animals, but other plants such as locoweed require selenium, and their growth indicates the presence of selenium in soil). See more on plant nutrition below.

Selenium is a component of the unusual amino acids selenocysteine and selenomethionine. In humans, selenium is a trace element nutrient that functions as cofactor for reduction of antioxidant enzymes, such as glutathione peroxidases and certain forms of thioredoxin reductase found in animals and some plants (this enzyme occurs in all living organisms, but not all forms of it in plants require selenium).

The glutathione peroxidase family of enzymes (GSH-Px) catalyze certain reactions that remove reactive oxygen species such as hydrogen peroxide and organic hydroperoxides:


 * 2 GSH + H2O2GSH-Px → GSSG + 2 H2O

Selenium also plays a role in the functioning of the thyroid gland and in every cell that uses thyroid hormone, by participating as a cofactor for the three known thyroid hormone deiodinases, which activate and then deactivate various thyroid hormones and their metabolites. It may inhibit Hashimotos's disease, in which the body's own thyroid cells are attacked as alien. A reduction of 21% on TPO antibodies was reported with the dietary intake of 0.2 mg of selenium.

Dietary sources of Se
Dietary selenium comes from nuts, cereals, meat, mushrooms, fish, and eggs. Brazil nuts are the richest ordinary dietary source (though this is soil-dependent, since the Brazil nut does not require high levels of the element for its own needs). In descending order of concentration, high levels are also found in kidney, tuna, crab, and lobster.

The human body's content of selenium is believed to be in the 13-20 milligram range.

Indicator plants
Certain species of plants are considered indicators of high selenium content of the soil, since they require high levels of selenium to thrive. The main selenium indicator plants are Astragalus species (including some locoweeds), prince's plume (Stanleya sp.), woody asters (Xylorhiza sp.), and false goldenweed (Oonopsis sp.)

Toxicity
Although selenium is an essential trace element, it is toxic if taken in excess. Exceeding the Tolerable Upper Intake Level of 400 micrograms per day can lead to selenosis. This 400 microgram (µg) Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow up study on the same five people in 1992. The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to not only avoid toxicity, but also to avoid creating an imbalance of nutrients in the diet and to account for data from other countries. In China, people who ingested corn grown in extremely selenium-rich stony coal (carbonaceous shale) have suffered from selenium toxicity. This coal was shown to have selenium content as high as 9.1%, the highest concentration in coal ever recorded in literature.

Symptoms of selenosis include a garlic odor on the breath, gastrointestinal disorders, hair loss, sloughing of nails, fatigue, irritability, and neurological damage. Extreme cases of selenosis can result in cirrhosis of the liver, pulmonary edema, and death. Elemental selenium and most metallic selenides have relatively low toxicities because of their low bioavailability. By contrast, selenates and selenites are very toxic, having an oxidant mode of action similar to that of arsenic trioxide. The chronic toxic dose of selenite for humans is about 2400 to 3000 micrograms of selenium per day for a long time. Hydrogen selenide is an extremely toxic, corrosive gas. Selenium also occurs in organic compounds, such as dimethyl selenide, selenomethionine, selenocysteine and methylselenocysteine, all of which have high bioavailability and are toxic in large doses.

On 19 April 2009, twenty-one polo ponies began to die shortly before a match in the United States Polo Open. Three days later, a pharmacy released a statement explaining that the horses had received an incorrect dose of one of the ingredients used in a vitamin/mineral supplement compound, with which the horses had been injected. Such nutrient injections are common to promote recovery after a match, but this mixture had been compounded by a compounding pharmacy not familiar with it. Analysis of blood levels of inorganic compounds in the supplement indicated the selenium concentrations were ten to fifteen times higher than normal in the horses' blood samples, and 15 to 20 times higher than normal in their liver samples. It was later confirmed that selenium was the ingredient in question. Selenium is active in only tiny amounts, and has a history of causing accidental poisonings in supplements when the dose that is supposed to be in micrograms is given by mistake in milligrams (1000 times as much).

Selenium poisoning of water systems may result whenever new agricultural runoff courses through normally dry, undeveloped lands. This process leaches natural soluble selenium compounds (such as selenates) into the water, which may then be concentrated in new "wetlands" as the water evaporates. High selenium levels produced in this fashion have been found to have caused certain congenital disorders in wetland birds.

Deficiency
Selenium deficiency is rare in healthy, well-nourished individuals. It can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, and in those of advanced age (over 90). Also, people dependent on food grown from selenium-deficient soil are at risk. Although New Zealand has low levels of selenium in its soil, adverse health effects have not been detected.

Selenium deficiency may only occur when a low selenium status is linked with an additional stress, such as chemical exposure or increased oxidant stress due to vitamin E deficiency.

There are interactions between selenium and other nutrients, such as iodine and vitamin E. The interaction is observed in the etiology of many deficiency diseases in animals and pure selenium deficiency is rare. The effect of selenium deficiency on health remains uncertain, particularly in relation to Kashin-Beck disease.

Controversial health effects

 * Cancer

Several studies have suggested a possible link between cancer and selenium deficiency. One study, known as the NPC, was conducted to test the effect of selenium supplementation on the recurrence of skin cancers on selenium-deficient men. It did not demonstrate a reduced rate of recurrence of skin cancers, but did show a reduced occurrence of total cancers, particularly for lung, colorectal and prostate cancers (Relative Risk 0.63). There was also a significant reduction in total cancer mortality (-50 %), although without a statistically significant change in overall mortality. The preventative effect observed in the NPC was greatest in those with the lowest baseline selenium levels. In 2009, the 5.5 year SELECT study reported selenium and vitamin E supplementation, both alone and together, did not significantly reduce the incidence of prostate cancer in 35,000 men who "generally were replete in selenium at baseline". The SELECT trial reported vitamin E did not reduce prostate cancer as it had in the alpha-tocopherol, beta carotene (ATBC) study, but the ATBC had a large percentage of smokers, while the SELECT trial did not. There was a slight trend toward more prostate cancer in the SELECT trial, but in the vitamin E only arm of the trial, where no selenium was given.

Dietary selenium prevents chemically induced carcinogenesis in many rodent studies. It has been proposed that selenium may help prevent cancer by acting as an antioxidant or by enhancing immune activity. Not all studies agree on the cancer-fighting effects of selenium. One study of naturally occurring levels of selenium in over 60,000 participants did not show a significant correlation between those levels and cancer. The SU.VI.MAX study concluded low-dose supplementation (with 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 µg of selenium, and 20 mg of zinc) resulted in a 30% reduction in the incidence of cancer and a 37% reduction in all-cause mortality in males, but did not get a significant result for females. A Cochrane review of studies concluded that there is no convincing evidence that individuals, particularly those who are adequately nourished, will benefit from selenium supplementation with regard to their cancer risk. However, there is evidence selenium can help chemotherapy treatment by enhancing the efficacy of the treatment, reducing the toxicity of chemotherapeutic drugs, and preventing the body's resistance to the drugs. Studies of cancer cells in vitro showed that chemotherapeutic drugs, such as taxol and Adriamycin, were more toxic to strains of cancer cells when selenium was added.

In March 2009, vitamin E (400 IU) and selenium (200 micrograms) supplements were reported to affect gene expression and can act as a tumor suppressor. Eric Klein, MD from the Glickman Urological and Kidney Institute in Ohio said the new study “lend[s] credence to the previous evidence that selenium and vitamin E might be active as cancer preventatives”. In an attempt to rationalize the differences between epidemiological and in vitro studies and randomized trials like SELECT, Klein said randomized controlled trials “do not always validate what we believe biology indicates and that our model systems are imperfect measures of clinical outcomes in the real world”.


 * HIV/AIDS

Some research has indicated a geographical link between regions of selenium-deficient soils and peak incidences of HIV/AIDS infection. For example, much of sub-Saharan Africa is low in selenium. However, Senegal is not, and also has a significantly lower level of AIDS infection than the rest of the continent. AIDS appears to involve a slow and progressive decline in levels of selenium in the body. Whether this decline in selenium levels is a direct result of the replication of HIV or related more generally to the overall malabsorption of nutrients by AIDS patients remains debated.

Low selenium levels in AIDS patients have been directly correlated with decreased immune cell count and increased disease progression and risk of death. Selenium normally acts as an antioxidant, so low levels of it may increase oxidative stress on the immune system, leading to its more rapid decline. Others have argued T-cell-associated genes encode selenoproteins similar to human glutathione peroxidase. Depleted selenium levels in turn lead to a decline in CD4 helper T-cells, further weakening the immune system.

Regardless of the cause of depleted selenium levels in AIDS patients, studies have shown selenium deficiency does strongly correlate with the progression of the disease and the risk of death.


 * Tuberculosis

Some research has suggested selenium supplementation, along with other nutrients, can help prevent the recurrence of tuberculosis.


 * Diabetes

A well-controlled study showed selenium levels are positively correlated with the risk of having type 2 diabetes. Because high serum selenium levels are positively associated with the prevalence of diabetes, and because selenium deficiency is rare, supplementation is not recommended in well-nourished populations, such as the U.S. More recent studies, however, have indicated selenium may help inhibit the development of type 2 diabetes in men, though the mechanism for the possible preventative effect is not known.

Applications
The demand for Se was around 2300 tonnes/y in the years 1989-1991.

Glass production
The largest commercial use of Se, accounting for about 50% of consumption, is for the production of glass. Se compounds confer a red colour to glass. This colour cancels out the green or yellow tints that arise from iron impurities that are typical for most glass. For this purpose various salts of selenite and selenate are added. For other application, the red colour is desirable, in which case mixtures of CdSe and CdS are added.

Rubber industry
Small amounts of organoselenium compounds are used to modify the vulcanization catalysts used in the production of rubber.

Uses in the laboratory
Selenium is a catalyst in some chemical reactions but it is not widely used because of issues with toxicity. In X-ray crystallography, incorporation of one or more Se atoms helps with MAD and SAD phasing.

Alloys
Selenium is used with bismuth in brasses to replace more toxic lead.

Electronics
The demand for Se by the electronics industry is declining, despite a number of continuing applications. Because of its photovoltaic and photoconductive properties, selenium is used in photocopying, photocells, light meters and solar cells. Its use as a photoconductor in plain-paper copiers once was a leading application but in the 1980s, the photoconductor application declined (although it was still a large end-use) as more and more copiers switched to the use of organic photoconductors. It was once widely used in selenium rectifiers. These uses have mostly been replaced by silicon-based devices or are in the process of being replaced. The most notable exception is in power DC surge protection, where the superior energy capabilities of selenium suppressors make them more desirable than metal oxide varistors.

Sheets of amorphous selenium convert x-ray images to patterns of charge in xeroradiography and in solid-state, flat-panel x-ray cameras.

Zinc selenide is used in blue and white LEDs.

Photography
Selenium is used in the toning of photographic prints, and it is sold as a toner by numerous photographic manufacturers including Kodak and Fotospeed. Its use intensifies and extends the tonal range of black-and-white photographic images as well as improving the permanence of prints.

Early photographic light meters used selenium, but this application is now obsolete.

Medical use
The substance loosely called selenium sulfide (approximate formula SeS2) is the active ingredient in some anti-dandruff shampoos. The selenium compound kills the scalp fungus Malassezia, which causes shedding of dry skin fragments. The ingredient is also used in body lotions to treat Tinea versicolor due to infection by a different species of Malassezia fungus.

Nutrition
Selenium is used widely in vitamin preparations and other dietary supplements, in small doses (typically 50 to 200 micrograms per day for adult humans). Some livestock feeds are fortified with selenium as well.

Detection in biological fluids
Selenium may be measured in blood, plasma, serum or urine to monitor excessive environmental or occupational exposure, confirm a diagnosis of poisoning in hospitalized victims or to assist in a forensic investigation in a case of fatal overdosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the element. Both organic and inorganic forms of selenium are largely converted to monosaccharide conjugates (selenosugars) in the body prior to being eliminated in the urine. Cancer patients receiving daily oral doses of selenothionine may achieve very high plasma and urine selenium concentrations.

Evolution in biology
Over three billion years ago, blue-green algae were the most primitive oxygenic photosynthetic organisms and are ancestors of multicellular eukaryotic algae. Algae that contain the highest amount of antioxidant selenium, iodide, and peroxidase enzymes were the first living cells to produce poisonous oxygen in the atmosphere. It has been suggested that algal cells required a protective antioxidant action, in which selenium and iodides, through peroxidase enzymes, have had this specific role. Selenium, which acts synergistically with iodine, is a primitive mineral antioxidant, greatly present in the sea and prokaryotic cells, where it is an essential component of the family of glutathione peroxidase (GSH-Px) antioxidant enzymes; seaweeds accumulate high quantity of selenium and iodine. In 2008, a study showed that iodide also scavenges reactive oxygen species (ROS) in algae, and that its biological role is that of an inorganic antioxidant, the first to be described in a living system, active also in an in vitro assay with the blood cells of today’s humans."

From about three billion years ago, prokaryotic selenoprotein families drive selenocysteine evolution. Selenium is incorporated into several prokaryotic selenoprotein families in bacteria, archaea and eukaryotes as selenocysteine, where selenoprotein peroxiredoxins protect bacterial and eukaryotic cells against oxidative damage. Selenoprotein families of GSH-Px and the deiodinases of eukaryotic cells seem to have a bacterial phylogenetic origin. The selenocysteine-containing form occurs in species as diverse as green algae, diatoms, sea urchin, fish and chicken. Selenium enzymes are involved in utilization of the small reducing molecules glutathione and thioredoxin. One family of selenium-containing molecules (the glutathione peroxidases) destroy peroxide and repair damaged peroxidized cell membranes, using glutathione. Another selenium-containing enzyme in some plants and in animals (thioredoxin reductase) generates reduced thioredoxin, a dithiol that serves as an electron source for peroxidases and also the important reducing enzyme ribonucleotide reductase that makes DNA presursors from RNA precursors.

At about 500 Mya, plants and animals began to transfer from the sea to rivers and land, the environmental deficiency of marine mineral antioxidants (as selenium, iodine, etc.) was a challenge to the evolution of terrestrial life. Trace elements involved in GSH-Px and superoxide dismutase enzymes activities, i.e. selenium, vanadium, magnesium, copper, and zinc, may have been lacking in some terrestrial mineral-deficient areas. Marine organisms retained and sometimes expanded their seleno-proteomes, whereas the seleno-proteomes of some terrestrial organisms were reduced or completely lost. These findings suggest that, with the exception of vertebrates, aquatic life supports selenium utilization, whereas terrestrial habitats lead to reduced use of this trace element. Marine fishes and vertebrate thyroid glands have the highest concentration of selenium and iodine. From about 500 Mya, freshwater and terrestrial plants slowly optimized the production of “new” endogenous antioxidants such as ascorbic acid (Vitamin C), polyphenols (including flavonoids), tocopherols, etc. A few of these appeared more recently, in the last 50–200 million years, in fruits and flowers of angiosperm plants. In fact, the angiosperms (the dominant type of plant today) and most of their antioxidant pigments evolved during the late Jurassic period.

The deiodinase isoenzymes constitute another family of eukaryotic selenoproteins with identified enzyme function. Deiodinases are able to extract electrons from iodides, and iodides from iodothyronines. They are, thus, involved in thyroid-hormone regulation, participating in the protection of thyrocytes from damage by H2O2 produced for thyroid-hormone biosynthesis. About 200 Mya, new selenoproteins were developed as mammalian GSH-Px enzymes.