Penicillin G

C 16
H 18
N 2
O 4
S 1

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41 atoms, 43 bonds.

IUPAC name: (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Molar mass: 334.390(62) g/mol
Atoms: 41
SMILES: CC1(C(N2C(S1)C(C2=O)NC(=O)CC3=CC=CC=C3)C(=O)O)C
InChIKey: JGSARLDLIJGVTE-MBNYWOFBSA-N
PubChem CID: 5904

Made of

C H N O S

Structural formula of penicillin G. Each unlabelled corner is a carbon atom, and the 10 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.

Penicillin G, also called benzylpenicillin, is an antibiotic that a mould makes, and it kills bacteria by disabling enzymes they need to finish their cell walls. The NCI Thesaurus, the National Cancer Institute’s reference vocabulary, describes it as a naturally occurring penicillin of the beta-lactam type. The US Food and Drug Administration (FDA) classes it as a penicillin-class antibacterial.

FDA has approved it for certain serious bacterial infections, among them pneumonia, meningitis, gonorrhoea and syphilis, according to the Clinicalinfo.hiv.gov drug database. The ChEMBL drug database records it as prescription-only, first approved in 1947. Benzylpenicillin is the name the World Health Organization (WHO) uses. Its Model List of Essential Medicines carries the drug for uses that include syphilis, syphilis in newborns, bacterial meningitis and severe pneumonia in children.

Structure and bonding

Penicillin G is built on two fused rings: a four-membered beta-lactam ring of three carbon atoms and one nitrogen, and a five-membered ring closed by a sulfur atom. Ball-and-stick shows the small ring’s bonds meeting at 86 to 96° on PubChem’s computed geometry, near a square’s corners. One of its carbons holds a doubly bonded oxygen, and the next carries the side chain.

Labels traces that chain: N–H, C=O, a bare CH₂, then a phenyl ring whose five free corners each hold a hydrogen. Three of the ring’s six bonds are drawn double, yet all six measure 1.39 to 1.40 Å in the model. The ring’s electrons in fact spread round it, above and below its plane, as in benzene. Space-filling packs the fused rings into a compact head, the phenyl ring held out on the chain.

At the other end, the model shows a neutral COOH, the carboxyl group of an organic acid. ChEBI, the Chemical Entities of Biological Interest database, names its conjugate base, the molecule less one proton, benzylpenicillin(1−).

Where it turns up

Outside the clinic, penicillin G has been found in Sarocladium strictum and Hohenbuehelia grisea, among other organisms, according to the LOTUS natural-products database. The US Department of Agriculture (USDA) tells of a mouldy cantaloupe from a Peoria market whose penicillium strain made the most penicillin of those studied at its Peoria centre. At the centre, mould grown submerged in deep vats, rather than on a surface, grew faster and gave larger amounts of penicillin.

Veterinary medicine uses it too: FDA’s new animal drug listings cover dogs, cats, cattle, sheep, swine, horses and turkeys. A joint expert committee of WHO and the Food and Agriculture Organization classes it as a veterinary antimicrobial drug. Laboratories have found a use for it outside infection. MeSH describes it as an experimental convulsant, a substance used in research to bring on convulsions, because of its actions on nerve signalling carried by gamma-aminobutyric acid (GABA).

Why it matters

Penicillin G kills bacteria outright: the Hazardous Substances Data Bank (HSDB) calls it bactericidal and says it blocks the building of the bacterial cell wall. Its targets are the penicillin-binding proteins (PBPs), enzymes at work in the final stages of putting that wall together. The NCI Thesaurus describes the drug binding to these proteins and inactivating them. That disrupts the cross-linking of the wall’s peptidoglycan chains, which gives the wall its strength and rigidity. Weakened, the wall eventually gives way and the cell bursts, a process called lysis.

Alexander Fleming discovered penicillin in 1928 at St Mary’s Hospital in London. Intensive research began only in 1939, when an Oxford University group showed that it could kill infectious bacteria. Work at Peoria began in July 1941. After clinical trials in 1943, penicillin was available in quantity for Allied soldiers wounded on D-Day. As production rose its price fell, and three of the British group received the Nobel Prize.

Properties

Properties of penicillin G Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 5904.
Property	Value	Unit	Source
Molecular formula (Hill order)	C₁₆H₁₈N₂O₄S
Molar mass	334.390(62) g/mol	g/mol	IUPAC/CIAAW 2024
Carbon atoms	16
Hydrogen atoms	18
Nitrogen atoms	2
Oxygen atoms	4
Sulfur atoms	1
Bonds	43
Single bonds	37
Double bonds	6
PubChem molecular weight	334.4 g/mol	g/mol	PubChem

Safety

From 1945 the Penicillin Amendment required FDA to test every penicillin product and certify it safe and effective. Later amendments widened that control to all antibiotics, and in 1983 it was judged unnecessary and abolished. The pure substance carries the signal word Danger, and every one of 75 company reports to the European Chemicals Agency says it may cause an allergic skin reaction. About half add that inhaling it may bring on allergy or asthma symptoms or breathing difficulties, as the PubChem Laboratory Chemical Safety Summary sets out.

Questions

Where is the beta-lactam ring in penicillin G?

It is the small four-membered ring at the centre of the molecule, three carbons and one nitrogen, with an oxygen double-bonded to one of those carbons. In the 3D model it is fused to a five-membered ring holding the sulfur atom. ChEBI, a database of chemicals of biological interest, defines penicillin G as the penicillin whose penam ring carries a phenylacetamido group at position 6: a side chain of N–H, C=O, CH₂ and a six-carbon ring.

What causes penicillin allergy?

The Hazardous Substances Data Bank (HSDB) calls the penicillins and the products the body breaks them into potent immunogens, substances that provoke an immune response. They do so because they combine with proteins and act as haptens, small molecules the immune system targets once bound to a protein. Most often the link forms once the beta-lactam ring opens, at the amide group. ChEBI lists drug allergen among the roles of penicillin G.

Which form of penicillin G do medicines contain?

Commonly a salt. MeSH, the National Library of Medicine's subject headings, notes that penicillin G is commonly supplied as its sodium or potassium salt, while the 3D model draws the neutral acid with its COOH group intact. HSDB lists official preparations of the potassium, sodium, procaine and benzathine salts. The forms behave differently in water: HSDB calls the acid sparingly soluble, the sodium salt very soluble and the potassium salt freely soluble.

How is penicillin G made?

A living mould makes it. In HSDB's outline of manufacture, the mould is grown in a nutrient solution and releases penicillin into that liquid, from which the drug is extracted and purified by countercurrent extraction. The broth also decides which penicillin comes out: adding suitable precursors to the nutrient solution makes the mould produce different varieties.

Made of the same elements

C₁₆H₁₉N₃O₅S Amoxicillin 44 atoms, 46 bonds.
C₃H₇NO₂S Cysteine 14 atoms, 13 bonds.