CID 5819

C₁₅H₁₁I₄NO₄

Thyroxine

C 15
H 11
I 4
N 1
O 4

Ball-and-stick Stick Space-filling

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35 atoms, 36 bonds.

IUPAC name: (2S)-2-amino-3-[4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodophenyl]propanoic acid
Molar mass: 776.856(77) g/mol
Atoms: 35
SMILES: C1=C(C=C(C(=C1I)OC2=CC(=C(C(=C2)I)O)I)I)CC(C(=O)O)N
InChIKey: XUIIKFGFIJCVMT-LBPRGKRZSA-N
PubChem CID: 5819

Made of

C H I N O

Structural formula of thyroxine. Each unlabelled corner is a carbon atom, and the seven hydrogens on carbon are not drawn. Wedges come toward you, hashes go back. It shows which atoms are joined to which, not the shape. The model above shows the shape.

About 65 per cent of the mass of a thyroxine molecule is iodine. Thyroxine is the main hormone the thyroid gland makes, shortened to T₄, MedlinePlus says. The US National Cancer Institute (NCI) describes it speeding up chemical reactions in cells and helping to control growth and development. The medicine levothyroxine is the same molecule made in a laboratory, and NIDDK, the US institute for diabetes, digestive and kidney diseases, calls it identical to the natural hormone.

Thyroxine’s 35 atoms are carbon, hydrogen, iodine, nitrogen and oxygen, in the formula C₁₅H₁₁I₄NO₄, at 776.86 g/mol. The US Environmental Protection Agency (EPA) lists it as an L-tyrosine: that amino acid with two iodine atoms on its ring and a second, iodine-bearing ring on its oxygen. The Hazardous Substances Data Bank (HSDB) records crystals that dissolve slightly in water and decompose at 235–236 °C.

Structure and bonding

Thyroxine’s four iodine atoms are divided evenly, two on each of its rings. Both rings are flat carbon hexagons, bridged by one oxygen atom. In Ball-and-stick, one pair flanks the bridging oxygen on the inner ring and the other flanks the O–H group that ends the outer ring. Labels marks each of the four with an I. Their C–I bonds, 2.092 Å in this computed model, are the longest drawn.

The model sets the ring planes at right angles: with one hexagon face-on, the other is edge-on. Space-filling makes the iodine atoms the four largest spheres. From the inner ring’s far corner a CH₂ carbon leads to a carbon holding –NH₂, –COOH and one hydrogen: the amino-acid end, in its L form.

Each ring is a benzene ring, drawn with alternating single and double bonds. In benzene the double bonds’ electrons are spread around the whole ring, and all twelve ring bonds here measure 1.384 to 1.395 Å. The model also shows the uncharged molecule. ChEBI, the Chemical Entities of Biological Interest database, lists a zwitterion form as well, the kind set out on the glycine page.

Where it turns up

Thyroxine begins as part of a protein. Medical Subject Headings (MeSH) describes it forming where diiodotyrosine units, tyrosines carrying two iodine atoms each, are coupled inside thyroglobulin. HSDB describes the hormone as made and stored in the gland as part of that protein’s chain. It stays there until the protein is cut up (proteolysis) and the freed thyroxine enters the blood. The iodine page tells how iodine reaches the tyrosine units.

In blood it travels bound to plasma proteins, and HSDB lists thyroxine-binding globulin and albumin among them. MedlinePlus Genetics describes transthyretin carrying thyroxine only as a tetramer, four copies of the protein joined together.

The first medicines for an underactive thyroid were animal thyroid products, in use since the late nineteenth century, says the US Food and Drug Administration (FDA). They came from cow, sheep or pig glands, and most now come from pigs. HSDB also records veterinary levothyroxine labelled for horses and dogs.

Why it matters

Thyroid hormones control how the body uses energy, so nearly every organ feels their effect, the beating heart included, NIDDK says. Too little slows many of the body’s functions; too much speeds them up. The pituitary gland makes more thyroid-stimulating hormone (TSH) when thyroxine runs low, pushing the thyroid to work harder, and stops when thyroxine runs high. In peripheral tissues thyroxine is de-iodinated, losing iodine, to give triiodothyronine, T₃. The NCI Thesaurus describes T₃ binding receptors in the cell nucleus and triggering gene expression.

Hypothyroidism, too little thyroid hormone for the body’s needs, affects nearly 5 in 100 Americans aged 12 and over, by NIDDK’s count. Its most common cause in the United States, NIDDK adds, is Hashimoto’s disease, in which antibodies made by the immune system attack the gland. Levothyroxine is the usual replacement: of the 24 million patients on thyroid hormone replacement in 2024, FDA counts about 94 per cent as prescribed it. In Graves’ disease an antibody called thyroid-stimulating immunoglobulin attaches to thyroid cells and drives the gland into overproduction, hyperthyroidism.

Properties

Properties of thyroxine Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 5819.
Property	Value	Unit	Source
Molecular formula (Hill order)	C₁₅H₁₁I₄NO₄
Molar mass	776.856(77) g/mol	g/mol	IUPAC/CIAAW 2024
Carbon atoms	15
Hydrogen atoms	11
Iodine atoms	4
Nitrogen atoms	1
Oxygen atoms	4
Bonds	36
Single bonds	29
Double bonds	7
PubChem molecular weight	776.87 g/mol	g/mol	PubChem

Safety

As levothyroxine, thyroxine is a prescription-only medicine whose amount a doctor sets. FDA describes thyroid hormone replacement as having a narrow therapeutic index, meaning the amount must be tightly regulated. NIDDK lists atrial fibrillation and osteoporosis among the serious problems too much medicine can cause. The PubChem Laboratory Chemical Safety Summary for thyroxine lists the pure substance’s classifications, among them harmful if swallowed and suspected of harming fertility or the unborn child.

Questions

How many iodine atoms does thyroxine have?

Four. The formula is C₁₅H₁₁I₄NO₄, and the 3D model places two iodine atoms on each ring: either side of the bridging oxygen on the inner ring, and either side of the O–H group on the outer one. At 126.9 g/mol apiece they come to 507.6 of the 776.86 g/mol, about 65 per cent of the mass.

What is levothyroxine?

Levothyroxine is thyroxine made as a medicine. NIDDK calls it identical to the natural hormone, and HSDB notes that the synthetic compound cannot be told apart from what the gland secretes. The medicine holds its sodium salt, levothyroxine sodium in the NCI Drug Dictionary, where the model draws the acid. It is prescription-only, sits on the World Health Organization's Model List of Essential Medicines, and comes as a pill, a liquid or a soft gel capsule.

How does thyroxine become T₃?

By losing iodine. The NCI Thesaurus describes thyroxine being de-iodinated in peripheral tissues to form triiodothyronine, T₃, and the NCI Drug Dictionary names the enzyme that does it, 5'-deiodinase. T₃ is cleared faster: HSDB gives usual plasma half-lives of 6 to 7 days for thyroxine and about 1 to 2 days for T₃. It puts the difference partly down to carrier proteins binding thyroxine more strongly.

What is free T₄?

Free T₄ is thyroxine that is not attached to a carrier protein. In blood, the hormone binds to proteins that stop it entering the body's tissues, and MedlinePlus describes that bound share as a backup supply, kept in the bloodstream until tissues need it. Free T₄ is the form that enters tissues. In HSDB's words, only unbound hormone is metabolically active.

Why are newborns tested for thyroid hormone?

Some babies are born with an underactive thyroid, congenital hypothyroidism. Left untreated it can cause growth failure and intellectual disability, NIDDK says, and early treatment can prevent both, so most babies born in the United States are tested. NICHD, one of the US National Institutes of Health, describes a screening technique that measures thyroid hormone and thyroid-stimulating hormone, its two main markers, and every state screens newborns for it.