Trifluoroacetic acid (TFA): identity and role in peptide work

Last updated: 2026-10-10 · Research use only. Not for human or veterinary use.

Short answer

Trifluoroacetic acid (TFA, 2,2,2-trifluoroacetic acid, C2HF3O2, 114.02 g/mol, PubChem CID 6422) is a strong, volatile carboxylic acid. In peptide chemistry it cleaves peptides from the resin in Fmoc SPPS, acts as an ion-pairing modifier in RP-HPLC, and remains as the trifluoroacetate counter-ion in many lyophilised peptides. [1]

At a glance

Term	Definition / specification
IUPAC name	2,2,2-trifluoroacetic acid
Formula	C2HF3O2
Molecular weight	114.02 g/mol
PubChem CID	6422
Uses in peptide work	Resin cleavage, HPLC ion pairing, salt counter-ion
Trifluoroacetate anion	CF3COO−, ~113 Da, counted in salt formula weight

Ion pairing

At a typical literature level of about 0.1% in HPLC mobile phases [2], TFA protonates basic groups and pairs with them, sharpening peaks.

Residual counter-ion

Because the anion binds to positively charged residues, it persists through lyophilisation and contributes to gross weight; it can be exchanged for acetate.

FAQ

Is TFA the same as trifluoroacetate?

TFA is the acid; trifluoroacetate is its anion, the form bound in peptide salts.

Can residual TFA be removed?

Largely, by counter-ion exchange; see /ref/tfa-vs-acetate-salts.

Related reference pages

Sources

Roux S et al. Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: a critical evaluation of different approaches. J Pept Sci. 2008. PMID: 18035848
Hansen PR et al. Fmoc Solid-Phase Peptide Synthesis. Methods Mol Biol. 2015. PMID: 26424261
PubChem. Trifluoroacetic acid (C2HF3O2, 114.02 g/mol). CID 6422

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Plain

Sable Peptides. (2026). trifluoroacetic-acid. UK Research Peptide Reference. Retrieved 11 October 2026, from https://www.sablepeptides.co.uk/ref/trifluoroacetic-acid

APA

Sable Peptides. (2026, October 11). *trifluoroacetic-acid*. UK Research Peptide Reference. https://www.sablepeptides.co.uk/ref/trifluoroacetic-acid

BibTeX

@misc{sable_trifluoroacetic-acid_2026,
  author = {{Sable Peptides}},
  title = {{trifluoroacetic-acid}},
  year = {2026},
  howpublished = {\url{https://www.sablepeptides.co.uk/ref/trifluoroacetic-acid}},
  note = {Accessed 11 October 2026. CC BY 4.0}
}

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Date modified: 2026-10-16