The most studied small molecule in human history

SOL

I would be interested to hear peoples ideas for what this could be:

Just to put in some criteria, by small I mean between 100-500 ish molecular weight, so not water or ethanol.

My candidate is Quinine, so if people have opinions for and against this and other suggestions, this might be an interesting discussion...

stealinhorses

Lysergic acid diethylamide? 323.43 g/mol.

Lbeard

stealinhorses wrote: »

Lysergic acid diethylamide? 323.43 g/mol.

Funnily, that could be true, in the sense the op intended.


First quinine. As quinine was essential for the European conquest of the malarial zones of the world. It's supply effected the balance of world power. It would be impossible to either invade or hold a malarial country without it. Everyone was funding a race for its' synthesis.

As the story goes plucky young William Perkins, was experimenting in his mothers garden shed, trying to make quinine, when he stumbled purely by chance on the colour mauve. (other accounts I've read, state that wasn't exactly true, and he knew what he was doing. Applying modern chemistry to 'a little bit of this, a little bit of that' recipes - he had a lucky head start being Von Hoffmann's student) Perkin's chemical; aniline. Could be a candidate for the most researched chemical as it's had so many uses in everything from colouring to medicine.


But. It could be LSD.

Ergotamine, it has a number of uses. One is it's the only known remedy for migraine. LSD-25 being the most effective ergotamine derivative for migraine. The obvious "problem", if you think these things are "problems", is that it's also the famous Acid that melted a million minds, and launched Jimi Hendrixs, a nondescript shy backing rhythm guitarist, into outer-inner-and-extra-stellar space and beyond.

A lot of time, money and effort has been applied into finding a highless derivative of Ergotamine, that's as effective as, but isn't, LSD-25. It would be a block buster drug. It's not that a lot of people are working on it, but they've been working on it a very long time. There are other things that are really interesting about LSD-25. It only takes a few micro-grams to have a profound effect. If it was fully understood how it does that, it could open up a whole new family of psychiatric drugs.

SOL

I'd say LSD definitely is up there for the most studied molecule by intelligence agencies, project MK-ultra is definitely worth reading about, the believe it would act as a truth serum and carried out many experiments without subjects consent with (unsurprisingly) unfortunate results. I'm not sure it would be overall the most studied though since it is only a late 20th century discovery... but it is an interesting one...

Maybe I should rename this, famous and interesting small molecules.

Also, I should give a history of quinine.


As you say, Perkins studies of quinine lead to Mauve, though I don't think it was in his garden shed. At the time though, they had figure out the molecular formula for quinine and his methodology was to try and react things which would add to the same formula. Obviously from a modern viewpoint this is total nonsense but at the time it was the most rational thing to try. This is how he discovered his formula.
An account of Perkins studies with his mentor Hoffmann actually makes interesting reading. (It is unfortunately behind a pay wall. You can see the abstract with that link, if you want a full copy PM me, (written in 1895 so it's out of copyright).

Interestingly though, Perkins discovery of Mauve was really important to chemistry. Politically at the time research into chemistry was losing appeal since it hadn't produced anything useful and the academic discoveries weren't very exciting.All science depended on funding of the gentry through the royal societies back then so chemistry would have suffered badly if not for this exciting, practical discovery which was also immensely lucrative.

Back to quinine though. Quinine (as cinchona bark) was brought to Europe in the 17th century, the only known cure for malaria, which at the time was endemic to southern Europe, making it an extremely valuable commodity. Studies trying to figure out what the active ingredient in the bark was began soon after. I wasn't until 1820 that this was actually achieved, by P. J. Pelletier and J. B. Caventou. (Part of the difficulty in isolating the material was because it isn't stable in acidic aqueous solutions and it isn't soluble in basic ones).

From there attempts at total synthesis started, leading to Perkins and many that followed. This took until the 1940's till Woodward and Doering published the first "Formal synthesis" however, they never completed their synthesis instead creating a molecule that had previously been transformed into quinine. This later lead to disputes as the veracity of the earlier paper on which their claim relied was questioned.

In 2001 a full total synthesis of quinine was published by Stork et al., and they claimed this as the first synthesis (leading to subsequent discussion).


In the meantime, back in 1853, Louis Pasteur identified a concept called Chirality. He realised that quinine was a useful molecule for separating out mixtures of this kind. Thus quinine became a popular molecule within chemistry. Since then (again within the field of chemistry), it has also been used for lots of other things like ligands for asymmetric reactions and a catalyst in its own right. An it has continued to be very popular in organic chemistry for over 100 years.

Interestingly though, it is still far easier to grow quinine in a tree than it is to make it artificially in a lab, and about 7,000 tons of Cinchona bark are harvested for this purpose annually, most though ends up in food as a flavouring.

Finally, the last aspect of quinine has been its medical used, which as Lbeard pointed out has been really important to mankind.
The advent of quinine essentially resulted in the colonisation of Africa, before quinine malaria made travel in Africa too deadly. Obviously quinine was thus important to national security and the efforts to steal quinine from south America are definitely worth reading about if you have time (but not for now).
Quinine production moved from South America to southeast asia, largely as a result of Dutch efforts AFAIK. During world war 2, this resulted in loss of control of the quinine supply to the Japanese, which resulted in the deaths of tens of thousands of allied troops. In fact in many theatres the level of malarial deaths was greater than combat casualties! The Japenese however, didn't make full use of the quinine they now possessed as they gave insufficient quinine supplies to their soldiers meaning that they also suffered tremendous casualties due to malaria in the south pacific.

Anyways, that is a few quick points about quinine, I'd love if anyone can share some history of any other molecules.

stealinhorses

Very interesting!

DaithiMC

I would put forward aspirin aka salicylic acid. If has stood the test of time in terms of its use as an anti inflammatory, has found other use as a cardio vascular medication and related use in the prevention of deep vein thrombosis during air travel. It's not as old as quinine but it arrived on the scene when chemistry was practiced by many more people so could have easily caught up in terms of man hours of research.

Capt'n Midnight

I still can't get over that ethlyene is a hormone with just 6 atoms