Fluoride

Fluoride is the anion F−, the reduced form of fluorine when as an ion and when bonded to another element. Both organofluorine compounds and inorganic fluorine containing compounds are called fluorides. Fluoride, like other halides, is a monovalent ion (−1 charge). Its compounds often have properties that are distinct relative to other halides. Structurally, and to some extent chemically, the fluoride ion resembles the hydroxide ion. Fluorine-containing compounds range from potent toxins such as sarin to life-saving pharmaceuticals such as efavirenz, and from inert materials such as sulfur hexafluoride to the highly reactive chlorine trifluoride. The range of fluorine-containing compounds is vast because fluorine is capable of forming compounds with all the elements except helium and neon.

Occurrence
Solutions of inorganic fluorides in water contain F− and bifluoride HF2−. Few inorganic fluorides are soluble in water without undergoing significant hydrolysis. In terms of its reactivity, fluoride differs significantly from chloride and other halides, and is more strongly solvated due to its smaller radius/charge ratio. Its closest chemical relative is hydroxide. When relatively unsolvated, fluoride anions are called "naked". Naked fluoride is very strong base. The presence of fluoride and its compounds can be detected by 19F NMR spectroscopy.

Natural occurrence
Many fluoride minerals are known, but of paramount commercial importance are fluorite and fluorapatite.

Fluoride is usually found naturally in low concentration in drinking water and foods. The concentration in seawater averages 1.3 parts per million (ppm). Fresh water supplies generally contain between 0.01–0.3 ppm, whereas the ocean contains between 1.2 and 1.5 ppm. In some locations, the fresh water contains dangerously high levels of fluoride, leading to serious health problems.

Applications
Fluorides are pervasive in modern technology. Hydrofluoric acid is the fluoride synthesized on the largest scale. It is produced by treating fluoride minerals with sulfuric acid. Hydrofluoric acid and its anhydrous form hydrogen fluoride are used in the production of fluorocarbons and aluminium fluorides. Hydrofluoric acid has a variety of specialized applications, including its ability to dissolve glass.

Pesticides
Sulfuryl fluoride is used as a pesticide and fumigant on agricultural crops. In 2010, the United States Environmental Protection Agency proposed to withdraw the use of sulfuryl fluoride on food. Sulfuryl fluoride releases fluoride when metabolized. Cryolite is a pesticide that can leave fluoride on agricultural commodities.

Organic synthesis
Fluoride reagents are significant in synthetic organic chemistry. Due to the affinity of silicon for fluoride, and the ability of silicon to expand its coordination number, silyl ether protecting groups can be easily removed by the fluoride sources such as sodium fluoride and tetra-n-butylammonium fluoride (TBAF). The Si-F linkage is one of the strongest single bonds. In contrast, other silyl halides are easily hydrolyzed.

Inorganic fluorides
Sulfur hexafluoride is an inert, nontoxic insulator that is used in electrical transformers. Uranium hexafluoride is used in the separation of isotopes of uranium between the fissile isotope U-235 and the non-fissile isotope U-238 in preparation of nuclear reactor fuel and atomic bombs. The volatility of fluorides of uranium and other elements may also be used for nuclear fuel reprocessing.



Fluoropolymers
Fluoropolymers such as polytetrafluoroethylene, Teflon, are used as chemically inert and biocompatible materials for a variety of applications, including as surgical implants such as coronary bypass grafts, and a replacement for soft tissue in cosmetic and reconstructive surgery. These compounds are also commonly used as non-stick surfaces in cookware and bakeware, and the fluoropolymer fabric Gore-Tex used in breathable garments for outdoor use.

Cavity prevention
Fluoride-containing compounds are used in topical and systemic fluoride therapy for preventing tooth decay. They are used for water fluoridation and in many products associated with oral hygiene. Originally, sodium fluoride was used to fluoridate water; hexafluorosilicic acid (H2SiF6) and its salt sodium hexafluorosilicate (Na2SiF6) are more commonly used additives, especially in the United States. The fluoridation of water is known to prevent tooth decay and is considered by the U.S. Centers for Disease Control and Prevention as "one of 10 great public health achievements of the 20th century". In some countries where large, centralized water systems are uncommon, fluoride is delivered to the populace by fluoridating table salt. Fluoridation of water has its critics (see Water fluoridation controversy).



Biomedical applications
Positron emission tomography is commonly carried out using fluoride-containing pharmaceuticals such as fluorodeoxyglucose, which is labelled with the radioactive isotope fluorine-18, which emits positrons when it decays into 18O.

Numerous drugs contain fluorine including antipsychotics such as fluphenazine, HIV protease inhibitors such as tipranavir, antibiotics such as ofloxacin and trovafloxacin, and anesthetics such as halothane. Fluorine is incorporated in the drug structures to reduce drug metabolism, as the strong C-F bond resists deactivation in the liver by cytochrome P450 oxidases.

Fluoride salts are commonly used to inhibit the activity of phosphatases, such as serine/threonine phosphatases. Fluoride mimics the nucleophilic hydroxyl ion in these enzymes' active sites. Beryllium fluoride and aluminium fluoride are also used as phosphatase inhibitors, since these compounds are structural mimics of the phosphate group and can act as analogues of the transition state of the reaction.

Toxicology
Fluoride-containing compounds are so diverse that it is not possible to generalize on their toxicity, which depends on their reactivity and structure, and in the case of salts, their solubility and ability to release fluoride ions.

Soluble fluoride salts, of which sodium fluoride is the most common, are mildly toxic but have resulted in both accidental and suicidal deaths from acute poisoning. While the minimum fatal dose in humans is not known, the lethal dose for most adult humans is estimated at 5 to 10 g (which is equivalent to 32 to 64 mg/kg elemental fluoride/kg body weight). However, a case of a fatal poisoning of an adult with 4 grams of sodium fluoride is documented, while a dose of 120 g sodium fluoride has been survived. A toxic dose that may lead to adverse health effects is estimated at 3 to 5 mg/kg of elemental fluoride. For Sodium fluorosilicate (Na2SiF6), the median lethal dose (LD50) orally in rats is 0.125 g/kg, corresponding to 12.5 g for a 100 kg adult. The fatal period ranges from 5 min to 12 hours. The mechanism of toxicity involves the combination of the fluoride anion with the calcium ions in the blood to form insoluble calcium fluoride, resulting in hypocalcemia; calcium is indispensable for the function of the nervous system, and the condition can be fatal. Treatment may involve oral administration of dilute calcium hydroxide or calcium chloride to prevent further absorption, and injection of calcium gluconate to increase the calcium levels in the blood. Hydrogen fluoride is more dangerous than salts such as NaF because it is corrosive and volatile, and can result in fatal exposure through inhalation or upon contact with the skin; calcium gluconate gel is the usual antidote.

In the higher doses used to treat osteoporosis, sodium fluoride can cause pain in the legs and incomplete stress fractures when the doses are too high; it also irritates the stomach, sometimes so severely as to cause ulcers. Slow-release and enteric-coated versions of sodium fluoride do not have gastric side effects in any significant way, and have milder and less frequent complications in the bones. In the lower doses used for water fluoridation, the only clear adverse effect is dental fluorosis, which can alter the appearance of children's teeth during tooth development; this is mostly mild and is unlikely to represent any real effect on aesthetic appearance or on public health.