CID 896
C13H16N2O2
Melatonin
- C 13
- H 16
- N 2
- O 2
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- IUPAC name
- N-[2-(5-methoxy-1H-indol-3-yl)ethyl]acetamide
- Molar mass
- 232.283(33) g/mol
- Atoms
- 33
- SMILES
- CC(=O)NCCC1=CNC2=C1C=C(C=C2)OC
- InChIKey
- DRLFMBDRBRZALE-UHFFFAOYSA-N
- PubChem CID
- 896
Darkness is the cue for melatonin. The brain makes this hormone in response to it, as NCCIH, the US National Center for Complementary and Integrative Health, describes. Most of it comes from the pineal gland, a tiny organ near the middle of the brain. Melatonin’s IUPAC name builds the molecule from three parts: acetamide, a two-carbon ethyl link and a 5-methoxy-1H-indol-3-yl group. Acetamide is an N–H holding C(=O)CH3; indole is two fused rings, here carrying a methoxy group, O–CH3. The 33 atoms are thirteen carbon, sixteen hydrogen, two nitrogen and two oxygen, for a molar mass of 232.28 g/mol.
The body builds it from serotonin in two steps, each run by its own enzyme. Melatonin itself is a white-cream to yellowish crystalline powder that melts at 116–118 °C, according to the Hazardous Substances Data Bank (HSDB). A litre of water dissolves 2 g of it at 20 °C and 5 g at 50 °C.
Structure and bonding
Both ends of the melatonin molecule are capped. A methoxy group, O–CH3, sits on the six-membered ring of the indole group, a fused pair of rings. A two-carbon chain leaves the five-membered ring and ends in an acetamide, an N–H holding C(=O)CH3. Neither oxygen carries a hydrogen and each nitrogen carries one, as the Labels button shows: no O–H, no NH2.
In Space-filling, the ring end of PubChem’s computed model is a flat slab: the nine ring atoms and the methoxy oxygen and carbon share one plane. The chain’s acetamide end stands out of it. In the model, four ring bonds are drawn double, C=C, with single bonds between them. Those double bonds’ electrons are really spread around the rings, as the tryptophan page explains for the same group. The six-membered ring’s bonds all measure 1.39–1.41 Å in the model, drawn single or double.
In Ball-and-stick, each nitrogen’s three bonds lie flat, and the acetamide’s C–N bond measures 1.39 Å against 1.44 Å for the neighbouring N–CH2 bond. HSDB lists melatonin as uncharged across the entire pH range, and the model shows that neutral molecule.
Where it turns up
The pineal gland is not its only maker: the US National Cancer Institute’s thesaurus adds the retina. MeSH, the US National Library of Medicine’s subject headings, records melatonin in animals and plants. The NIH Catalyst, a National Institutes of Health publication, reports that production climbs at night in all vertebrates. Most of what circulates is inactivated in the liver, where HSDB has it oxidised first to 6-hydroxymelatonin.
Shops sell it as tablets, capsules, liquids and gummies. NCCIH notes that supplement melatonin is most often synthetic, though it can come from animals or microorganisms. Cosmetics use it as an antioxidant. A US Food and Drug Administration (FDA) rule covers a melatonin implant for mink, used to speed up the fur priming cycle.
NASA’s lighting guidance for spacecraft puts blue light in the crew’s morning, to help wake them, and red light before bed, to help melatonin production along.
Why it matters
The human master clock is the suprachiasmatic nucleus, a cluster of nerve cells. It sets melatonin production by how much light the eyes take in, according to NIGMS, the US National Institute of General Medical Sciences. The hormone acts by binding and activating its own receptors. NCCIH credits it with helping to time circadian rhythms, the body’s 24-hour clock, and with sleep.
Nightfall reaches the pineal gland through nerves that release norepinephrine onto its cells. According to HSDB, the norepinephrine makes stored serotonin available for conversion and activates the enzymes that convert it. A team at NICHD, the US child-health institute, attributes the night-time increase in production to a large rise in the activity of one enzyme, arylalkylamine N-acetyltransferase (AA-NAT).
As a supplement, NCCIH says, melatonin may help with jet lag, anxiety around surgery, delayed sleep-wake phase disorder and some sleep disorders in children. Studies of whether it helps shift workers, by its account, were mostly small or inconclusive.
Properties
| Property | Value | Unit | Source |
|---|---|---|---|
| Molecular formula (Hill order) | C13H16N2O2 | ||
| Molar mass | 232.283(33) g/mol | g/mol | IUPAC/CIAAW 2024 |
| Carbon atoms | 13 | ||
| Hydrogen atoms | 16 | ||
| Nitrogen atoms | 2 | ||
| Oxygen atoms | 2 | ||
| Bonds | 34 | ||
| Single bonds | 29 | ||
| Double bonds | 5 | ||
| PubChem molecular weight | 232.28 g/mol | g/mol | PubChem |
Safety
As a chemical, melatonin is essentially harmless. It met no GHS (Globally Harmonized System) hazard criteria in 139 of 144 reports, as the PubChem Laboratory Chemical Safety Summary for melatonin records. LiverTox, the liver-injury database of NIDDK and NLM, states that it has not been implicated in liver injury. Of supplements, NCCIH reports that short-term use appears safe for most people, that long-term safety information is lacking, and that children and teenagers might risk overdose.
Questions
What is melatonin made from?
Serotonin. The conversion takes two steps and happens mainly in the pineal gland, and also in the retina. NICHD, the US child-health institute, names the enzymes: arylalkylamine N-acetyltransferase (AA-NAT), which acetylates serotonin, and hydroxyindole-O-methyltransferase (HIOMT), which carries out the last step. Their names match the two capped ends in the model: an acetyl group, C(=O)CH3, on the chain nitrogen and a methyl group on the ring oxygen.
Why does light at night lower melatonin?
Blue light, or white light that contains it, sets off photoreceptors in the retina, which send a signal that suppresses melatonin, according to NIOSH, the US occupational safety institute. They ignore red light and barely respond to yellow and orange. Fluorescent and LED lamps and back-lit screens emit blue. A National Institutes of Health team reported in 1998 that light cuts the nerve stimulation of the pineal gland, and the enzyme behind the night-time rise is destroyed.
Is melatonin a drug or a dietary supplement?
In the United States it is sold as a dietary supplement, which NCCIH, the US National Center for Complementary and Integrative Health, says the Food and Drug Administration regulates less strictly than drugs. Several other countries class it as a drug, available only on prescription. Because melatonin is a hormone, NCCIH adds, supplements could possibly disturb hormonal development: puberty, menstrual cycles and the overproduction of prolactin, another hormone. That is not known for sure.
Does melatonin make you sleepy?
NIGMS, the US National Institute of General Medical Sciences, describes the body's master clock telling the brain in the evening to make more melatonin, which causes sleepiness. The NIH Catalyst, a National Institutes of Health publication, adds that not all animals sleep at night, so melatonin is not just a signal to sleep but a signal of time, and some species use it for seasonal timing.
Who discovered melatonin?
A team led by the Yale dermatologist Aaron B. Lerner discovered it in 1958. At the US National Institutes of Health (NIH), the neuroscientist Julius Axelrod was already studying how it is made when the neuroendocrinologist David Klein joined in 1969. Klein found that an enzyme, AA-NAT, regulates the daily rhythm of melatonin production, and named it the 'timezyme'. His team's study of how that production is switched off appeared in Science on 27 February 1998.
Made of the same elements
- C12H17NO DEET 31 atoms, 31 bonds.
- C14H18N2O5 Aspartame 39 atoms, 39 bonds.
- C11H12N2O2 Tryptophan 27 atoms, 28 bonds.
- C13H21NO3 Albuterol 38 atoms, 38 bonds.
- C14H22N2O Lidocaine 39 atoms, 39 bonds.
- C10H12N2O Serotonin 25 atoms, 26 bonds.
- C9H13NO3 Epinephrine 26 atoms, 26 bonds.
- C9H11NO2 Phenylalanine 23 atoms, 23 bonds.
All 25 compounds made of carbon, hydrogen, nitrogen and oxygen
- C17H21NO Diphenhydramine 40 atoms, 41 bonds.
- C8H11NO2 Dopamine 22 atoms, 22 bonds.
- C6H13NO2 Isoleucine 22 atoms, 21 bonds.
- C6H13NO2 Leucine 22 atoms, 21 bonds.
- C9H11NO3 Tyrosine 24 atoms, 24 bonds.
- C8H9NO2 Acetaminophen 20 atoms, 20 bonds.
- C8H10N4O2 Caffeine 24 atoms, 25 bonds.
- C20H24N2O2 Quinine 48 atoms, 51 bonds.
- C5H9NO4 Glutamic acid 19 atoms, 18 bonds.
- C5H6N2O2 Thymine 15 atoms, 15 bonds.
- C3H7NO2 Alanine 13 atoms, 12 bonds.
- C4H4N2O2 Uracil 12 atoms, 12 bonds.
- C4H5N3O Cytosine 13 atoms, 13 bonds.
- C2H5NO2 Glycine 10 atoms, 9 bonds.
- C5H5N5O Guanine 16 atoms, 17 bonds.
- C5H4N4O3 Uric acid 16 atoms, 17 bonds.
- CO(NH2)2 Urea 8 atoms, 7 bonds.
Sources
- PubChem CID 896, melatonin
- IUPAC/CIAAW, Abridged Standard Atomic Weights 2024
- PubChem Laboratory Chemical Safety Summary for melatonin (CID 896)
- LiverTox (NIDDK and NLM), via PubChem CID 896: LiverTox Summary for melatonin
- NCCIH, Melatonin: What You Need To Know
- NIGMS (National Institutes of Health), Circadian Rhythms
- National Cancer Institute, NCI Dictionary of Cancer Terms: melatonin
- NICHD (National Institutes of Health), Researchers Discover How Melatonin Production is Switched Off (1998)
- NIOSH Training for Nurses on Shift Work and Long Work Hours, Module 2: The Color of the Light Affects Circadian Rhythms
- NASA Office of the Chief Health and Medical Officer, Technical Brief OCHMO-TB-026, Lighting Design (2023)
- The NIH Catalyst, Sleep, Perchance to Research (2014)
- Stephen Lower, Chem1 General Chemistry, §9.7 The Hybrid Orbital Model II (LibreTexts, CC BY 3.0)