Aspirin, from willow bark

Section 2 of 4

You have already met aspirin, a benzene ring with a -⁠COOH group and an ester link. Its story starts in the bark of willow trees, and it works by fitting an enzyme.

In 1763 Edward Stone, a clergyman in England, wrote to the Royal Society that powdered willow bark brought down fevers. In 1828 the German chemist Johann Buchner took the active molecule out of the bark as crystals and named it salicin, after Salix, the Latin name for willow. Your body turns salicin into salicylic acid. In 1838 the Italian chemist Raffaele Piria made salicylic acid from salicin in the lab.

Salicin, C₁₃H₁₈O₇The pain-easing molecule in willow bark. A glucose ring joined through an oxygen atom to a benzene ring, which also carries a -CH₂OH group on the next corner.OOOHOHOHOHOH
Salicin, C₁₃H₁₈O₇, from willow bark. A glucose ring (left) is joined through an oxygen atom to a benzene ring.
Salicylic acid, C₇H₆O₃A benzene ring carrying a -COOH group and, on the next corner, an -OH group.OHOHO
Salicylic acid, C₇H₆O₃: a benzene ring with a -⁠COOH group and an -⁠OH group on neighbouring corners.

By the 1870s doctors gave salicylic acid for pain and fever. It worked, and it was hard on the stomach. In 1897 Felix Hoffmann, a chemist at the Bayer company in Germany, made a pure, stable form of acetylsalicylic acid: salicylic acid whose -⁠OH group has joined an ethanoyl group, -⁠COCH₃, the piece of ethanoic acid that ends up in an ester. Charles Gerhardt in France had first made it, less pure, in 1853. Bayer sold it as Aspirin from 1899.

How aspirin eases pain

Your cells make messenger molecules called prostaglandins, which bring on pain, swelling and fever. An enzyme called cyclooxygenase, COX for short, makes them. In 1971 the British pharmacologist John Vane showed that aspirin stops cells making prostaglandins, and he shared the 1982 Nobel Prize in Physiology or Medicine for this work.

Aspirin fits the channel that leads into COX's active site. There, its ester link meets an -⁠OH group on the side group of one of the enzyme's amino acids, serine. The ethanoyl group moves across and joins the enzyme's oxygen, making a new ester, and the rest of the molecule floats away as salicylic acid.

Aspirin passes its ethanoyl group to the enzyme Left: aspirin, a benzene ring with a -COOH group and an ester group, above the enzyme. The ester's ethanoyl piece, an oxygen-carbon double bond and a methyl group, is drawn in amber. Its C=O carbon sits directly above an -OH group on the enzyme, with nothing between them. An arrow points right. Right: the amber ethanoyl piece is now bonded to the enzyme's oxygen, and the molecule left over, salicylic acid, has an -OH group where the ester was. OOHOOOH OOHOHOO aspirin salicylic acid enzyme enzyme
Aspirin passes its ethanoyl group (amber) to an -⁠OH group of the COX enzyme. The group stays on the enzyme and blocks the way into its active site, and salicylic acid is left over.

The ethanoyl group stays bonded to the enzyme and sits across the channel, so the enzyme's own molecule can no longer get in. That COX is blocked for good, and the cell has to build new enzyme to make prostaglandins again. Most medicines let go of their target after a while. Aspirin, and penicillin later in this lesson, make a covalent bond to their enzyme and stay.

Quick check

In the COX enzyme, aspirin hands its ethanoyl group to an -⁠OH group of the enzyme. What is left of the aspirin molecule?