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Before the mid-1930s, the ceremony speech for Domagk's prize recalls, attempts to treat bacterial infections with chemicals had mostly ended in disappointment. The first class of such drugs came not from a mould, as penicillin did, but from a dye factory. This post covers how Gerhard Domagk found it, the chemistry of why it works, and a short calculation that shows how closely the drug imitates a nutrient bacteria need.
Who was Gerhard Domagk?
His Nobel facts page says he was born on 30 October 1895 in Lagow, then in Germany and now in Poland, and died on 24 April 1964. He received the 1939 Nobel Prize in Physiology or Medicine "for the discovery of the antibacterial effects of prontosil". The page adds that he "was caused by the authorities of his country to decline the award but he later received the diploma and the medal".
His Nobel biography says he was a medical student when the First World War began, was wounded in December 1914, and later served in cholera hospitals in Russia, where he saw how helpless doctors were against infection. After qualifying he became a pathologist, and from 1927 he did research in the laboratories of the chemical company I.G. Farbenindustrie in Wuppertal.
What did the 1932 experiment show?
The 1939 award ceremony speech describes it. Domagk planned animal tests while two chemists, Mietzsch and Klarer, made compounds. Mice were injected with 10 times the lethal dose of a haemolytic streptococcus taken from a patient with blood poisoning. About half were then given a red dye later named Prontosil, an hour and a half after infection. The experiment began on 20 December 1932. On 24 December all the untreated mice were dead, and all the treated mice were alive.
Domagk did not publish until February 1935, in a paper in Deutsche Medizinische Wochenschrift. His biography records that his own daughter became seriously ill with a streptococcal infection and recovered after he gave her Prontosil, but he left this out of his report and waited for results from doctors testing the drug on patients.
How does a sulfa drug work?
Researchers in France soon found, the ceremony speech notes, that Prontosil's effect came mainly from its sulphonamide part. The Nobel biography describes Prontosil as a derivative of sulphanilamide, a compound first made in 1908, and sulphanilamide became the parent of the sulfa drugs.
A 2021 review in Antibiotics explains the mechanism. Sulfonamides have a structure like para-aminobenzoic acid (PABA). Bacteria use PABA as a raw material to make folate, which they need to build DNA and RNA. A sulfonamide sits in the active site of the enzyme dihydropteroate synthase in place of PABA, a case of competitive inhibition, so folate is not made and the bacteria stop growing.
Worked example: how alike are PABA and sulphanilamide?
Both are a benzene ring with an NH₂ group on one side and a second group directly opposite (the para position).
PABA, H₂N–C₆H₄–COOH, formula C₇H₇NO₂. Molar mass = 7(12.01) + 7(1.008) + 14.01 + 2(16.00) = 84.07 + 7.06 + 14.01 + 32.00 = 137.1 g/mol.
Sulphanilamide, H₂N–C₆H₄–SO₂NH₂, formula C₆H₈N₂O₂S. Molar mass = 6(12.01) + 8(1.008) + 2(14.01) + 2(16.00) + 32.07 = 72.06 + 8.06 + 28.02 + 32.00 + 32.07 = 172.2 g/mol.
The only change is –COOH swapped for –SO₂NH₂. The shape and the amino group are close enough to fit the enzyme's PABA pocket, but the molecule cannot be used to make folate.
Is a sulfa drug an antibiotic?
It depends on the definition. The NCERT Class 12 chapter Microbes in Human Welfare defines antibiotics as chemicals "produced by some microbes" that kill or slow other microbes, and names penicillin the first antibiotic discovered. Sulfonamides are made by chemists, not microbes, so by NCERT's definition they are synthetic antibacterial drugs. Use your textbook's definition in exams. Read about penicillin in our post on Alexander Fleming.
Why could he not accept the Nobel Prize?
The facts page says the German authorities made him decline it. The ceremony speech, given when he finally received his medal and diploma in 1947, notes that during the eight years since the award, sulfonamides had "introduced a new era in the treatment of infectious diseases". His biography adds that he went on to work on drugs against tuberculosis.
What can a student take from Domagk's way of working?
Test in a living system. Many compounds kill bacteria in a dish; he tested whether a compound cured infected animals.
Keep controls. The untreated mice, all dead by day four, made the result impossible to ignore.
Separate a story from evidence. He kept his daughter's recovery out of the paper and waited for clinical data.
For the idea Domagk was building on, read about Paul Ehrlich's magic bullet. If molar mass sums slip under time pressure, the Fermi Problem Library has worked problems with a step-by-step solver that explains the reasoning rather than printing an answer.
Try it now: calculate the percentage of sulphur by mass in sulphanilamide.
