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Neem has been used against insects in Indian homes and fields for generations, but knowing which molecule does the work, and why, took modern chemistry. T. R. Govindachari spent more than six decades working out the structures of plant compounds, and from his sixties into his eighties he turned to neem. His team grew the first crystals of azadirachtin-A, neem's best-known insect deterrent, and tested which parts of such molecules matter. This post covers his career, the neem work, a short calculation with the molecule, and what students can learn from how he worked.
Who was T. R. Govindachari?
The fullest account is a tribute by his first PhD student, K. Nagarajan, in ARKIVOC (2001), written for an issue in his honour. It records that Tuticorin Raghavachari Govindachari, known to colleagues as TRG, was born in Madras on 30 July 1915. He joined Presidency College, Madras, in 1932 and stayed connected with it for thirty years. He did his PhD with Prof. B. B. Dey, including wartime work on making dye and drug intermediates by electrolysis.
In 1946 he went to the University of Illinois as a Government of Madras scholar and spent three years with the organic chemist Roger Adams, studying Senecio alkaloids. He returned to Presidency College in 1950, became Chief Professor in 1952 and Principal in 1961.
What did he do before neem?
At Presidency College he built a research group on Indian medicinal plants that produced 25 PhDs. The tribute lists the structures they solved, from alkaloids such as tylophorine and carpaine to terpenes and oxygen heterocycles. For many years, Nagarajan writes, a manually operated Beckman DU spectrophotometer "was the sole instrument available". He received the Shanti Swarup Bhatnagar Award for Chemical Sciences in 1960.
In 1963 he became the first Director of the new CIBA Research Centre in Bombay. Under him, the tribute says, the centre screened more than 10,000 new compounds and plant extracts, took twenty into clinical trials and won marketing approval for five drugs. His work over his career ran to about 330 publications.
Our profile of T. R. Seshadri covers another founder of Indian natural-products chemistry, whose focus was plant pigments.
Why did neem become his late-career project?
After retiring from CIBA-Geigy in 1975, he set up research at the Madras company Amrutanjan (1977 to 1986) and started a sustained programme on neem, Azadirachta indica. His group at Presidency College had done some neem work around 1957. The programme then moved to the Centre for Agrochemical Research he set up for SPIC in Madras, which he guided from 1987 to 2001.
The prize was azadirachtin-A. His team's 1994 paper in Current Science explains why. It is the most abundant of the azadirachtins A to K in neem kernels, and earlier work had found that it inhibits moulting in more than two hundred insect species at 1 ppm and stops feeding at 10 to 20 ppm. J. H. Butterworth and E. D. Morgan isolated it in 1968 and found its molecular formula, C35H44O16, but the correct structure took nearly twenty years of work, mostly by NMR.
How did his team crystallise azadirachtin-A?
Crystals matter because X-ray diffraction of a single crystal shows directly where every atom sits. Azadirachtin-A had been reported as a microcrystalline powder, so earlier X-ray work had to use a modified derivative.
The 1994 paper describes the trial and error. From boiling carbon tetrachloride, the purified compound gave long needles, but the crystals trapped solvent in varying amounts, so they "cannot be termed 'pure'". Crystallising from ethyl acetate and hexane gave needles good enough for X-ray work. A companion paper, Crystal and molecular structure of Azadirachtin-A, reported the structure from a crystal measuring 0.5 × 0.05 × 0.1 mm.
The first paper ends with a generous thought: "In retrospect, it appears fortunate that Azadirachtin-A was not obtained in crystalline condition earlier", because otherwise the extensive NMR studies might never have been done. He dedicated it to his teacher B. B. Dey, "who loved crystals greatly".
Which parts of the molecule deter insects?
In a 1995 study in the Journal of Chemical Ecology, his group tested 22 limonoids, the family azadirachtin belongs to, on larvae of the tobacco cutworm Spodoptera litura. The azadirachtins as a group were the most effective, while intact limonoids such as cedrelone were the least. The abstract links antifeedant activity to a cyclohexenone A ring and an α-hydroxy enone group in the B ring.
A 1996 follow-up showed that salannin, another neem compound, also deterred feeding and delayed moulting in two moth species and a grasshopper. The authors stressed that compounds besides azadirachtin-A contribute to the activity of neem oil and seed extracts.
Worked example: reading azadirachtin's formula
Use C = 12.011, H = 1.008, O = 15.999 g/mol.
Molar mass. 35 × 12.011 = 420.385; 44 × 1.008 = 44.352; 16 × 15.999 = 255.984. Total = 720.72 g/mol, matching the Mr of 720.72 in the 1994 X-ray paper.
Degree of unsaturation. For CcHhOo, rings plus π bonds = (2c + 2 − h) ÷ 2. Oxygen does not change it. (2 × 35 + 2 − 44) ÷ 2 = 28 ÷ 2 = 14.
ppm to molarity (sample). Suppose you make a 10 ppm solution in water: 10 mg per litre, or 0.010 g/L. Moles per litre = 0.010 ÷ 720.72 ≈ 1.4 × 10^−5 mol/L.
Common mistakes:
Counting oxygen in the unsaturation formula. Divalent atoms drop out.
Treating ppm as per cent. 1 ppm is 1 part in a million, so 10 ppm is 0.001%, not 10%.
Our guide to purification and chromatography covers the separation methods behind work like this.
What can a student take from his way of working?
Keep going when tools are scarce. Twenty-five PhDs came out of a lab with one key instrument.
Check purity before trusting a result. His team rejected crystals that looked fine but held solvent.
Ask which part of a molecule does the job. Testing 22 related compounds turned "neem works" into specific structural features.
If functional groups or ppm conversions are shaky, the Fermi Concept Library covers every concept in physics, chemistry, biology, mathematics and computing.
Next step: work out the molar mass and degree of unsaturation of salannin, C34H44O9 according to PubChem, the same way.
