Tetraethylammonium (TEA) is a

quaternary ammonium cation In organic chemistry, quaternary ammonium cations, also known as quats, are positively-charged polyatomic ions of the structure , where R is an alkyl group, an aryl group or organyl group. Unlike the ammonium ion () and the primary, secondary, ...

with the

chemical formula A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as pare ...

, consisting of four

ethyl group In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry The International Union of Pure and Applied ...

s (, denoted Et) attached to a central

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

atom. It is a

counterion 160px, cation-exchange_resin.html" ;"title="Polystyrene sulfonate, a cation-exchange resin">Polystyrene sulfonate, a cation-exchange resin, is typically supplied with as the counterion. In chemistry, a counterion (sometimes written as "counter ...

used in the research laboratory to prepare

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

salts of inorganic anions. It is used similarly to

tetrabutylammonium Tetrabutylammonium is a quaternary ammonium cation with the formula , also denoted (where Bu = butyl group). It is used in the research laboratory to prepare lipophilic salts of inorganic anions. Relative to tetraethylammonium derivatives, tetr ...

, the difference being that its salts are less lipophilic, more easily crystallized and more

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

Preparation

The halide salt is prepared by the reaction of

triethylamine Triethylamine is the chemical compound with the formula N(CH2CH3)3, commonly abbreviated Et3N. Like triethanolamine and the tetraethylammonium ion, it is often abbreviated TEA. It is a colourless volatile liquid with a strong fishy odor remini ...

and an ethyl halide: : This method works well for the preparation of tetraethylammonium iodide (where X = I). Most tetraethylammonium salts are prepared by

salt metathesis A salt metathesis reaction (also called a double displacement reaction, double replacement reaction, or double decomposition) is a type of chemical reaction in which two ionic compounds in aqueous solution exchange their component ions to form two ...

reactions. For example, the synthesis of tetraethylammonium perchlorate, a salt that has been useful as a supporting electrolyte for polarographic studies in non-

aqueous An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, also known as sodium chloride (NaCl), in wat ...

solvents, is carried out by mixing the water-soluble salts

tetraethylammonium bromide Tetraethylammonium bromide (TEAB) is a quaternary ammonium compound with the chemical formula C8H20N+Br−, often written as "Et4N+Br−" in the chemical literature. It has been used as the source of tetraethylammonium ions in pharmacological and ...

and sodium perchlorate in water, from which the water-insoluble tetraethylammonium perchlorate

precipitate In an aqueous solution, precipitation is the "sedimentation of a solid material (a precipitate) from a liquid solution". The solid formed is called the precipitate. In case of an inorganic chemical reaction leading to precipitation, the chemic ...

s: : Other examples include

tetraethylammonium cyanide Tetraethylammonium cyanide is the organic compound with the formula . It is a " quat salt" of hydrogen cyanide. It consists of tetraethylammonium cations and cyanide anions . This salt is a colorless, deliquescent solid that is soluble in polar ...

(), and trichlorostannate (). In some cases, salts are produced of anions that cannot be generated in water, such as the tetrahedral salt.

Uses

The principal chemical characteristic of tetraethylammonium salts is their ability to engage in processes involving phase-transfer, such as phase-transfer catalysis. Typically, the four ethyl groups surrounding the nitrogen are too small to facilitate efficient ion transfer between aqueous and organic phases, but tetraethylammonium salts have been found to be effective in a number of such applications, and these are exemplified under the headings of the individual salts. TEA salts such as tetraethylammonium tetrafluoroborate and tetraethylammonium methylsulfonate are used in

supercapacitor alt=Supercapacitor, upright=1.5, Schematic illustration of a supercapacitor upright=1.5, A diagram that shows a hierarchical classification of supercapacitors and capacitors of related types A supercapacitor (SC), also called an ultracapacitor, ...

s as organic

electrolyte An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...

s. TEA halide and its hydroxide are used for the synthesis of high-silica

zeolite Zeolites are a group of several microporous, crystalline aluminosilicate minerals commonly used as commercial adsorbents and catalysts. They mainly consist of silicon, aluminium, oxygen, and have the general formula ･y where is either a meta ...

, especially for the zeolite beta. TEA can act as a template for micropore of zeolites under hydrothermal conditions during crystallization processes.

Properties

The effective radius of the tetraethylammonium ion is reported as ~0.45 nm, which is comparable in size to that of the hydrated ion.C. M. Armstrong (1971). "Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons." ''J. Gen. Physiol.'' 58 413-437. The

ionic radius Ionic radius, ''r''ion, is the radius of a monatomic ion in an ionic crystal structure. Although neither atoms nor ions have sharp boundaries, they are treated as if they were hard spheres with radii such that the sum of ionic radii of the cati ...

for TEA is given as 0.385 nm; several thermodynamic parameters for the TEA ion are also recorded. The octanol-water partition coefficient of TEA iodide, ''P''_o-w was determined experimentally to be (or ).

Biology

Pharmacology

The literature dealing with the pharmacologically-related properties of tetraethylammonium is vast, and research continues. It is clear that TEA blocks autonomic

ganglia A ganglion (: ganglia) is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system, this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system, there a ...

- it was the first " ganglionic blocker" drug to be introduced into clinical practice.''Drill's Pharmacology in Medicine, 4th Ed.'' (1971). J. R. DiPalma (Ed.), pp. 723-724, New York: McGraw-Hill.G. K. Moe and W. A. Freyburger (1950). "Ganglionic blocking agents." ''Pharmacol. Rev.'' 2 61-95. However, TEA also produces effects at the

neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

and at sympathetic nerve terminals.V. Ceña, A. G. García, C. Gonzalez-Garcia, and S. M. Kirpekar (1985). "Ion dependence of the release of noradrenaline by tetraethylammonium and 4-aminopyridine from cat splenic slices." ''Br. J. Pharmacol.'' 84 299–308. At the mechanistic level, TEA has long been known to block voltage-dependent K⁺ channels in nerve, and it is thought that this action is involved in the effects of TEA at sympathetic nerve terminals. With respect to activity at the neuromuscular junction, TEA has been found to be a competitive inhibitor at

nicotinic acetylcholine receptors Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ner ...

, although the details of its effect on these receptor proteins are complex. TEA also blocks Ca²⁺ - activated K⁺ channels, such as those found in

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

and

pituitary The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus control much of th ...

cells. It has also been reported that TEA inhibits

aquaporin Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells. The cell membranes of ...

(APQ) channels, but this still seems to be a disputed issue. A partial effect of these voltage-dependent and permeability properties within each system mentioned above is not only due to the aforementioned inhibitory properties of TEA, but also its ability to inhibit Na,K-ATPase. Acting on the extracellular vestibule of the Na,K-ATPase, inhibiting K+ access similar to ouabain, TEA further accentuates the disrupted K, and Na, gradients within each of these systems.

Clinical considerations

Although TEA (sometimes under the name "Etamon") was explored in a number of different clinical applications, including the treatment of

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

, its major use seems to have been as a probe to assess the capacity for

vasodilation Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...

in cases of

peripheral vascular disease Peripheral artery disease (PAD) is a vascular disorder that causes abnormal narrowing of arteries other than those that supply the heart or brain. PAD can happen in any blood vessel, but it is more common in the legs than the arms. When narro ...

.A. J. P. Graham (1950). "Toxic effects in animals and man after tetraethylammonium bromide." ''Br. Med. J.'' 2 321-322. Because of dangerous, even fatal reactions in some patients, as well as inconsistent cardiovascular responses, TEA was soon replaced by other drugs. TEA is not orally active. Typical symptoms produced in humans include the following: dry mouth, suppression of gastric secretion, drastic reduction of gastric motility, paralysis of urinary bladder, and relief of some forms of pain. Most studies with TEA seem to have been performed using either its chloride or bromide salt without comment as to any distinctions in effect, but Birchall and his co-workers preferred the use of TEA chloride in order to avoid the sedative effects of the

bromide A bromide ion is the negatively charged form (Br−) of the element bromine, a member of the halogens group on the periodic table. Most bromides are colorless. Bromides have many practical roles, being found in anticonvulsants, flame-retard ...

ion.R. Birchall et al. (1947). "Clinical studies of the pharmacological effects of tetraethyl ammonium chloride in hypertensive persons made in an attempt to select patients suitable for lumbodorsal sympathectomy and ganglioectomy." ''Am. J. Med. Sci.'' 213 572-578

Toxicology

An extensive study of the toxicology of

tetraethylammonium chloride Tetraethylammonium chloride (TEAC) is a quaternary ammonium compound with the chemical formula , sometimes written as . In appearance, it is a hygroscopic, colorless, crystalline solid. It has been used as the source of tetraethylammonium ions in ...

in mice, rats and dogs was published by Gruhzit and co-workers in 1948. These workers reported the following symptoms in mice and rats receiving toxic parenteral doses: tremors, incoordination, flaccid prostration, and death from respiratory failure within 10–30 minutes; dogs exhibited similar symptoms, including incoordination, flaccid prostration, respiratory and cardiac depression, ptosis, mydriasis, erythema, and death from respiratory paralysis and circulatory collapse. After non-lethal doses, symptoms abated within 15–60 minutes. There was little evidence of toxicity from chronic administration of non-lethal doses. These investigators recorded the following acute toxicities, as LD₅₀s for TEA chloride (error ranges not shown): :Mouse: 65 mg/kg, i.p.; 900 mg/kg, p.o. :Rat: ~56 mg/kg, i.v.; 110 mg/kg, i.m.; 2630 mg/kg, p.o. :Dog: ~36 mg/kg, i.v.; 58 mg/kg, i.m. Another research group, working at about the same time, but using tetraethylammonium bromide, published the following LD₅₀ data:L. O. Randall, W. G. Peterson and G. Lehmann (1949). "The ganglionic blocking actions of thiophanium derivatives." ''J. Pharmacol. Exp. Ther.'' 97 48-57. :Mouse: 38 mg/kg, i.v.; 60 mg/kg, i.p.; >2000 mg/kg, p.o. :Rat: 63 mg/kg, i.v.; 115 mg/kg, i.p. :Dog: 55 mg/kg, i.v. :Rabbit: 72 mg/kg, i.v. Writing in 1950, Graham made some observations on the toxic effects of tetraethylammonium bromide in humans. In one subject, described as a "healthy woman", 300 mg of tetraethylammonium bromide, i.v., produced incapacitating "curariform" (i.e., resembling the effects of

tubocurarine Tubocurarine (also known as ''d''-tubocurarine or DTC) is a toxic benzylisoquinoline alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxat ...

) paralysis of the skeletal muscles, as well as marked drowsiness. These effects were largely dissipated within 2 hours. Citing the work of other investigators, Graham noted that Birchall had also produced "alarming curariform effects" in humans with i.v. doses of 32 mg/kg of tetraethylammonium chloride.

References

{{Potassium channel blockers Neurotoxins Quaternary ammonium compounds Cations