Thenoyltrifluoroacetone

Thenoyltrifluoroacetone, C₈H₅F₃O₂S, is a chemical compound used pharmacologically as a chelating agent. It is an inhibitor of cellular respiration by blocking the respiratory chain at complex II.

Thenoyltrifluoroacetone^[1]

Names
Preferred IUPAC name 4,4,4-Trifluoro-1-(thiophen-2-yl)butane-1,3-dione
Other names 2-thenoyltrifluoroacetone
Identifiers
CAS Number	326-91-0 Y
3D model (JSmol)	Interactive image
Abbreviations	TTFA
ChEMBL	ChEMBL1236433
ChemSpider	5399 Y
DrugBank	DB04795 Y
ECHA InfoCard	100.005.743
EC Number	206-316-7
PubChem CID	5601
UNII	MYQ9MNW7NI Y
CompTox Dashboard (EPA)	DTXSID1059812
InChI InChI=1S/C8H5F3O2S/c9-8(10,11)7(13)4-5(12)6-2-1-3-14-6/h1-3H,4H2 Y Key: TXBBUSUXYMIVOS-UHFFFAOYSA-N Y InChI=1/C8H5F3O2S/c9-8(10,11)7(13)4-5(12)6-2-1-3-14-6/h1-3H,4H2 Key: TXBBUSUXYMIVOS-UHFFFAOYAR
SMILES O=C(c1sccc1)CC(=O)C(F)(F)F
Properties
Chemical formula	C8H5F3O2S
Molar mass	222.18 g mol−1
Appearance	fine, slightly yellow crystals
Melting point	40 to 44 °C (104 to 111 °F; 313 to 317 K)
Boiling point	96 to 98 °C (205 to 208 °F; 369 to 371 K) 8 mmHg
Hazards
GHS labelling:
Pictograms
Signal word	Warning
Hazard statements	H315, H319, H335
Flash point	12 °C (54 °F; 285 K) (closed cup)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is YN ?) Infobox references

Perhaps the first report of TTFA as an inhibitor of respiration was by A. L. Tappel in 1960.^[2] Tappel had the (erroneous) idea that inhibitors like antimycin and alkyl hydroxyquinoline-N-oxide might work by chelating iron in the hydrophobic milieu of respiratory membrane proteins, so he tested a series of hydrophobic chelating agents. TTFA was a potent inhibitor, but not because of its chelating ability. TTFA binds at the quinone reduction site in Complex II, preventing ubiquinone from binding. The first x-ray structure of Complex II showing how TTFA binds, 1ZP0, was published in 2005 .^[3]

Thenoyltrifluoroacetone can be made in a Claisen condensation of ethyl trifluoroacetate and 2-acetylthiophene.^[4][5]

References

1. Sigma-Aldrich product page
2. Tappel (July 1960). "Inhibition of electron transport by antimycin A, alkyl hydroxy naphthoquinones and metal coordination compounds". Biochem. Pharmacol. 3 (4): 289–96. doi:10.1016/0006-2952(60)90094-0. PMID 13836892.
3. Sun, Fei; Huo, Xia; Zhai, Yujia; Wang, Aojin; Xu, Jianxing; Su, Dan; Bartlam, Mark; Rao, Zihe (2005). "Crystal Structure of Mitochondrial Respiratory Membrane Protein Complex II". Cell. 121 (7): 1043–1047. doi:10.1016/j.cell.2005.05.025. PMID 15989954. S2CID 16697879.
4. Gergel, Max G. (March 1977). Excuse me sir, would you like to buy a kilo of isopropyl bromide?. Pierce Chemical. p. 130.
5. Taydakov, Ilya V; Kreshchenova, Yuliya M; Dolotova, Ekaterina P (27 December 2018). "A convenient and practical synthesis of β-diketones bearing linear perfluorinated alkyl groups and a 2-thienyl moiety". Beilstein Journal of Organic Chemistry. 14: 3106–3111. doi:10.3762/bjoc.14.290. PMC 6317410. PMID 30643588.