Tris, or tris(hydroxymethyl)aminomethane, or known during medical use as tromethamine or THAM, is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

with the formula (HOCH₂)₃CNH₂. It is extensively used in

biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...

and

molecular biology Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...

as a component of

buffer solution A buffer solution is a solution where the pH does not change significantly on dilution or if an acid or base is added at constant temperature. Its pH changes very little when a small amount of strong acid or base is added to it. Buffer solution ...

s such as in TAE and

TBE buffer TBE or Tris/Borate/EDTA, is a buffer solution containing a mixture of Tris base, boric acid and EDTA. In molecular biology, TBE and TAE buffers are often used in procedures involving nucleic acids, the most common being electrophoresis. Tris-aci ...

s, especially for solutions of

nucleic acid Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a pentose, 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nuclei ...

s. It contains a

primary amine In chemistry, amines (, ) are organic compounds that contain carbon-nitrogen bonds. Amines are formed when one or more hydrogen atoms in ammonia are replaced by alkyl or aryl groups. The nitrogen atom in an amine possesses a lone pair of elec ...

and thus undergoes the reactions associated with typical amines, e.g., condensations with

aldehydes In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

. Tris also complexes with metal ions in solution. In medicine, tromethamine is occasionally used as a drug, given in intensive care for its properties as a buffer for the treatment of severe

metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidn ...

in specific circumstances. Some medications are formulated as the "tromethamine salt" including Hemabate (

carboprost Carboprost (International Nonproprietary Name, INN, trade names for the tromethamine salts Hemabate, Tham) is a synthetic prostaglandin analogue of Prostaglandin F2alpha, PGF2α (specifically, it is 15-methyl-PGF2α) with oxytocic properties. Ca ...

as trometamol salt), and "

ketorolac Ketorolac, sold under the brand name Toradol, Acular and Sprix, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain. Specifically it is recommended for moderate to severe pain. Recommended duration of treatment is l ...

trometamol". In 2023 a strain of ''

Pseudomonas ''Pseudomonas'' is a genus of Gram-negative bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 348 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a ...

hunanensis'' was found to be able to degrade TRIS buffer. Since Tris' pKa is more strongly temperature dependent, its use is not recommended in biochemical applications requiring consistent pH over a range of temperatures. Moreover, the temperature dependance of the pKa (and in turn buffer solution pH) makes pH adjustment difficult. (E.g., the 'room temperature' pH adjustment would not translate to 'measurement conditions' pH, unless care is taken to calculate the effect of temperature, see below.)

Buffering features

The

conjugate acid A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid gives a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as it loses a hydrogen ion in the rever ...

of tris has a p''K''_a of 8.07 at 25 °C, which implies that the buffer has an effective pH range between 7.1 and 9.1 (p''K''_a ± 1) at room temperature.

Buffer details

*In general, as temperature decreases from 25 °C to 5 °C the pH of a tris buffer will increase an average of 0.03 units per degree. As temperature rises from 25 °C to 37 °C, the pH of a tris buffer will decrease an average of 0.025 units per degree. *In general, a 10-fold increase in tris buffer concentration will lead to a 0.05 unit increase in pH and vice versa. *

Silver Silver is a chemical element; it has Symbol (chemistry), symbol Ag () and atomic number 47. A soft, whitish-gray, lustrous transition metal, it exhibits the highest electrical conductivity, thermal conductivity, and reflectivity of any metal. ...

-containing single-junction pH electrodes (e.g.,

silver chloride electrode A silver chloride electrode is a type of reference electrode, commonly used in Electrochemistry, electrochemical measurements. For environmental reasons it has widely replaced the saturated calomel electrode. For example, it is usually the intern ...

s) are incompatible with tris since an Ag-tris precipitate forms which clogs the junction. Double-junction electrodes are resistant to this problem, and non-silver containing electrodes are immune.

Buffer inhibition

*Tris inhibits a number of enzymes, and therefore should be used with care when studying proteins. *Tris can also inhibit enzyme activity via

chelation Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

of metal ions.

Preparation

Tris is prepared industrially by the exhaustive condensation of

nitromethane Nitromethane, sometimes shortened to simply "nitro", is an organic compound with the chemical formula . It is the simplest organic nitro compound. It is a polar liquid commonly used as a solvent in a variety of industrial applications such as in ...

with

formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...

under basic conditions (i.e. repeated

Henry reaction The Henry reaction is a classic carbon–carbon bond formation reaction in organic chemistry. Discovered in 1895 by the Belgian chemist Louis Henry (1834–1913), it is the combination of a nitroalkane and an aldehyde or ketone in the presence ...

s) to produce the intermediate (HOCH₂)₃CNO₂, which is subsequently

hydrogenated Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organi ...

to give the final product.

Uses

The useful buffer range for tris (pH 7–9) coincides with the physiological pH typical of most living organisms. This, and its low cost, make tris one of the most common buffers in the biology/biochemistry laboratory. Tris is also used as a

primary standard A primary standard in metrology is a standard that is sufficiently accurate such that it is not calibrated by or subordinate to other standards. Primary standards are defined via other quantities like length, mass and time. Primary standards are ...

to standardize acid solutions for chemical analysis. Tris is used to increase permeability of cell membranes. It is a component of the

Moderna COVID-19 vaccine The Moderna COVID19 vaccine, sold under the brand name Spikevax, is a COVID-19 vaccine developed by the American company Moderna, the United States National Institute of Allergy and Infectious Diseases (NIAID), and the Biomedical Advanced ...

and the Pfizer-BioNTech COVID-19 vaccine for use in children 5 through 11 years of age.

Medical

Tris (usually known as THAM in this context) is used as alternative to

sodium bicarbonate Sodium bicarbonate ( IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda (or simply “bicarb” especially in the UK) is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cat ...

in the treatment of

References

{{reflist, 2 Polyols Amines Buffer solutions