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Chemical structure of tris
Preferred IUPAC name
Other names
TRIS, Tris, Tris base, Tris buffer, Trizma, Trisamine, THAM, Tromethamine, Trometamol, Tromethane, Trisaminol
3D model (JSmol)
ECHA InfoCard 100.000.969 Edit this at Wikidata
EC Number
  • 201-064-4
RTECS number
  • TY2900000
  • InChI=1S/C4H11NO3/c5-4(1-6,2-7)3-8/h6-8H,1-3,5H2 checkY
  • InChI=1/C4H11NO3/c5-4(1-6,2-7)3-8/h6-8H,1-3,5H2
  • OCC(N)(CO)CO
Molar mass 121.136 g·mol−1
Appearance White crystalline powder
Density 1.328g/cm3
Melting point >175-176 °C (448-449 K)
Boiling point 219 °C (426 °F; 492 K)
~50 g/100 mL (25 °C)
Acidity (pKa) 8.07 (conjugate acid)
B05BB03 (WHO) B05XX02 (WHO)
Occupational safety and health (OHS/OSH):
Main hazards
GHS labelling:
GHS07: Exclamation mark
H315, H319, H335
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P332+P313, P362, P403+P233, P405
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 2: Intense or continued but not chronic exposure could cause temporary incapacitation or possible residual injury. E.g. chloroformFlammability (red): no hazard codeInstability (yellow): no hazard codeSpecial hazards (white): no code
Flash point Non-flammable
Safety data sheet (SDS) External MSDS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Tris, or tris(hydroxymethyl)aminomethane, or known during medical use as tromethamine or THAM, is an organic compound with the formula (HOCH2)3CNH2, one of the twenty Good's buffers. It is extensively used in biochemistry and molecular biology as a component of buffer solutions[2] such as in TAE and TBE buffers, especially for solutions of nucleic acids. It contains a primary amine and thus undergoes the reactions associated with typical amines, e.g., condensations with aldehydes. Tris also complexes with metal ions in solution.[3] 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 in specific circumstances.[4][5] Some medications are formulated as the "tromethamine salt" including Hemabate (carboprost as trometamol salt), and "ketorolac trometamol".[6] While Good's buffers should be inert, in 2023 a strain of Pseudomonas hunanensis was found to be able to degrade TRIS buffer.[7]

Buffering features[edit]

The conjugate acid of tris has a pKa of 8.07 at 25 °C, which implies that the buffer has an effective pH range between 7.1 and 9.1 (pKa ± 1) at room temperature.

Buffer details[edit]

  • 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.[8]
  • In general, a 10-fold increase in tris buffer concentration will lead to a 0.05 unit increase in pH and vice versa.[8]
  • Silver-containing single-junction pH electrodes (e.g., silver chloride electrodes) 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[edit]

  • Tris inhibits a number of enzymes,[9][10] and therefore should be used with care when studying proteins.
  • Tris can also inhibit enzyme activity via chelation of metal ions.[3]


Tris is prepared industrially by the exhaustive condensation of nitromethane with formaldehyde under basic conditions (i.e. repeated Henry reactions) to produce the intermediate (HOCH2)3CNO2, which is subsequently hydrogenated to give the final product.[11]


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 to standardize acid solutions for chemical analysis.

Tris is used to increase permeability of cell membranes.[12] It is a component of the Moderna COVID-19 vaccine[13] and the Pfizer-BioNTech COVID-19 vaccine for use in children 5 through 11 years of age.[14]


Tris (usually known as THAM in this context) is used as alternative to sodium bicarbonate in the treatment of metabolic acidosis.[15][16]

See also[edit]


  1. ^ "Tromethamine".
  2. ^ Gomori, G., Preparation of Buffers for Use in Enzyme Studies. Methods Enzymology., 1, 138-146 (1955).
  3. ^ a b FISCHER, Beda E.; HARING, Ulrich K.; TRIBOLET, Roger; SIGEL, Helmut (1979). "Metal Ion/Buffer Interactions. Stability of Binary and Ternary Complexes Containing 2-Amino-2(hydroxymethyl)-1,3-propanediol (Tris) and Adenosine 5'-Triphosphate (ATP)". European Journal of Biochemistry. Wiley. 94 (2): 523–530. doi:10.1111/j.1432-1033.1979.tb12921.x. ISSN 0014-2956. PMID 428398.
  4. ^ Stanley, David; Tunnicliffe, William (June 2008). "Management of life-threatening asthma in adults". Continuing Education in Anaesthesia, Critical Care & Pain. 8 (3): 95–99. doi:10.1093/bjaceaccp/mkn012. Retrieved 21 July 2017.
  5. ^ Hoste, Eric A.; Colpaert, Kirsten; Vanholder, Raymond C.; Lameire, Norbert H.; De Waele, Jan J.; Blot, Stijn I.; Colardyn, Francis A. (May 2005). "Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis". Journal of Nephrology. 18 (3): 303–307. ISSN 1121-8428. PMID 16013019.
  6. ^ BNF 73 March-September 2017. British Medical Association,, Royal Pharmaceutical Society of Great Britain. London. 21 March 2017. ISBN 978-0857112767. OCLC 988086079.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  7. ^ Holert, Johannes; Borker, Aron; Nuebel, Laura Lucia; Daniel, Rolf; Poehlein, Anja; Philipp, Bodo (August 1, 2023). "A patchwork pathway of apparently recent origin enables degradation of the synthetic buffer compound TRIS in bacteria". bioRxiv. bioRxiv 10.1101/2023.08.01.551466. doi:10.1101/2023.08.01.551466. S2CID 260442300.
  8. ^ a b "Sigma tris(hydroxymethyl)aminomethane; Tris Technical Bulletin No. 106B" (PDF). Sigma-Aldrich. Retrieved 2020-06-04.
  9. ^ Desmarais, WT; et al. (2002). "The 1.20 Å resolution crystal structure of the aminopeptidase from Aeromonas proteolytica complexed with tris: A tale of buffer inhibition". Structure. 10 (8): 1063–1072. doi:10.1016/S0969-2126(02)00810-9. PMID 12176384.
  10. ^ Ghalanbor, Z; et al. (2008). "Binding of tris to Bacillus licheniformis alpha-amylase can affect its starch hydrolysis activity". Protein Pept. Lett. 15 (2): 212–214. doi:10.2174/092986608783489616. PMID 18289113.
  11. ^ Markofsky, Sheldon, B. (15 October 2011). "Nitro Compounds, Aliphatic". Ullmann's Encyclopedia of Industrial Chemistry. Vol. 24. p. 296. doi:10.1002/14356007.a17_401.pub2. ISBN 978-3527306732.{{cite book}}: CS1 maint: multiple names: authors list (link)
  12. ^ Irvin, R.T.; MacAlister, T.J.; Costerton, J.W. (1981). "Tris(hydroxymethyl)aminomethane Buffer Modification of Escherichia coli Outer Membrane Permeability". J. Bacteriol. 145 (3): 1397–1403. doi:10.1128/JB.145.3.1397-1403.1981. PMC 217144. PMID 7009585.
  13. ^[bare URL PDF]
  14. ^[bare URL PDF]
  15. ^ Kallet, RH; Jasmer RM; Luce JM; et al. (2000). "The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM)". American Journal of Respiratory and Critical Care Medicine. 161 (4): 1149–1153. doi:10.1164/ajrccm.161.4.9906031. PMID 10764304.
  16. ^ Hoste, EA; Colpaert, K; Vanholder, RC; Lameire, NH; De Waele, JJ; Blot, SI; Colardyn, FA (2005). "Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis". Journal of Nephrology. 18 (3): 303–7. PMID 16013019.