Painting with rubber

While exploring my creativity, trying to prove I can reinvent myself and find a lost connection with a free-spirited self, I just couldn’t kick the chemistry habit. I was coming up with all sorts of questions like ‘What is this pigment made of?’ ‘Does the state of California actually have something against ultramarine blue? Is it going to follow the faith of cinnabar vermilion and lead white?’ And inevitably, ‘How does paint dry?’

Oil paints have been used for centuries, which explains why so much is known about how they work. I refer you to this 36-page review covering in detail how oil paint dries. Reading about the curing of oil paints led to another mystery; ‘But how do acrylic paints cure?’

First, let’s cover some terms:

Monomer is a small molecule which can be used to build a bigger one like links in a chain.

Polymer is the chain: a big molecule formed from many little ones.

Acrylic refers to a molecule derived from acrylic acid. It contains an alkene double bond and a carboxylic acid. These are important for two reasons: the alkene is used to connect the monomers amongst them, the carboxylic acid is useful because it allows to easily add extra features to our molecules.

Emulsion is a mixture of two liquids which cannot form a solution; instead, one is dispersed as small droplets throughout the other. An emulsion of acrylic monomers in water is used to prepare acrylic polymers – ready suspended in water – by a process called emulsion-polymerisation. Britannica have a very good explanation here.

Glass phase transition is the point at which an amorphous solid (i.e. its molecules are disordered) such as a polymer transitions between the glass and rubber phases. In the glass phase, below the glass phase transition temperature (Tg), the long polymer molecules can’t change shape: the solid is a glass, rigid and brittle. In the rubber phase, above the glass phase transition temperature (Tg), the long polymer molecules can change shape: the solid is rubbery, elastic. Here is a good summary.

Crosslinking is forming chemical bonds across from one molecule to another, linking them together.

Covalent bond is the strongest kind of chemical bond.

Think of rubber: if it’s too cold it becomes stiff and it’s not stretchy anymore, because the molecules can’t change shape and move past each other. Bring it back to the rubber state by warming up and you can stretch and bend it. But only to a certain extent. If you put too much force, it will eventually tear. The molecules come apart and the material with it. That is why rubber gets vulcanised. Vulcanisation is a form of crosslinking by which actual bonds are made between the rubber molecules. Some of the stretchiness is lost, but the rubber is much harder to break apart. The molecules can’t move as freely, but they are much harder to pull apart.

Introduction to polymers over (and me refreshing my memory), let’s discuss acrylic paint and how it dries (I get curious about the strangest things). The compulsory Google search yielded some pretty good and consistent results: acrylic paint drying is a physical process. Some resources here and here. Let’s compare oil paints and acrylic paints for perspective. In oil paints monomer molecules crosslink (bond) under the influence of air, light and additives to form a paint film held together by covalent bonds. Acrylic paints don’t contain monomers. They contain polymers held apart in emulsion form. As water and other solvents evaporate after the paint is applied, the polymer molecules in the emulsion move from their droplet form to come together and form a solid. Sounds simple.

However, I didn’t find this explanation enough. If there is no reaction taking place and no bonds are formed between the polymer molecules, how can the film formed be so strong?

I strayed outside of my comfort zone and into the fearsome field of polymer chemistry. Lucky for me, I found this research article: Acrylic Paints: An Atomistic View of Polymer Structure and Effects of Environmental Pollutants, published by Aysenur Iscen, Nancy C. Forero-Martinez and Omar Valsson, headed by Kurt Kremer. They were looking from the same angle I wanted to approach this: from the atom scale. Theirs is a thorough computational investigation, but let’s see what the main learnings are.

  • Acrylic paints are mostly composed from pigment (colour, <10%), binder (the acrylic polymer, ~30%) and carrier (water, ~40%). When the paint dries, the polymer content goes up to ~60-70% because of water loss
  • The binders used are P(MMA-co-EA) and P(MMA-co-nBA). MMA, EA and nBA are the monomers. The P stands for polymer, and the parentheses tell us what monomers go into making the polymer
Image reproduced from The Journal of Physical Chemistry B 2021 125 (38), 10854-10865
DOI: 10.1021/acs.jpcb.1c05188 under a CC-BY-4.0 licence
  • The glass transition temperature (Tg) for the polymers used in acrylic paints is around room temperature. This means the paint has a good compromise of qualities under normal usage conditions: it is flexible enough so it won’t crack easily, but is not too sticky and will hold its shape
  • The polymer molecules are pretty much stuck in one place at room temperature. They can wriggle but can’t move easily to another location
  • nBA is used more than EA nowadays because it makes the paints soft and rubbery, so they are easier to work with. nBA lowers the glass transition temperature and makes the polymer molecules more mobile. This is essentially because the bigger nBA is more demanding in terms of space, preventing polymer molecules coming together and staying together
  • Using the bigger nBA has another effect: it stretches out the polymers. Each polymer chain has many nBA fragments, and they can’t bump into each other. The polymer has to stretch out to give them space. This stretching actually makes the material weaker and leaves gaps in which water or other molecules can travel

Let’s summarise all this. There are two microscopic properties we care about: how easily individual polymer molecules change shape and how easily polymer molecules move past each other. There are two macroscopic properties we care about: how flexible our material is (i.e. is it more like rubber or more like glass?) and how tough it is (i.e. how much force can I put on it before it breaks?). Keep in mind ‘breaking’ means different things. Glass will shatter by breaking cleanly into sharp pieces, rubber will tear into shredded pieces.

How easily polymer molecules change shape determines how flexible the material is. How easily polymer molecules move past each other determines strength.

So far we covered in quite a lot of detail how changing the polymer changes its flexibility (and that of the material it comprises). But what about its strength, i.e. how well it holds together? This has to do with entanglement. Steven Abbott has a great explanation on his website. In summary, long polymer molecules, like the ones used in commercial products, become tangled. And as you’ve probably noticed with any tangled mess (rope, cooked spaghetti, cables, Christmas lights) simply grabbing on to it and pulling will not bring the components apart. The more strands you have and the longer they are, the harder it is to untangle the mess.

Engineering the polymers and paint composition to make the paint work is tricky business. One composition change can impact more than one property. It can improve one feature, but be detrimental to another (flexibility vs strength). Balancing everything is key to optimising properties.

To wrap up, how strong is artist’s acrylic paint anyway? I realised I didn’t really have a feeling for this. I started by believing it’s really strong with the way it creates a film on the painting surface. After writing this article I wonder, is it not more like rubber?

I came up with a little test. I used my white acrylic paint and made a little circle. The thickness was between 4 and 6 mm. I then left it to dry for 3 weeks (but didn’t watch) and removed it from the support. I was left with a little rubbery creation that is really stretchy and strong.

Check out the video below.

Bricks and clay

I set to build myself anew,
I tore old walls apart to trade
Crumbling brick for moving clay 
And shape honest to the core. 

I shaped myself a shallow bowl,
I erred to craft a solid plate.
I passed success and took 
Such a mangled clump apart. 

I tried to shape one, 
but no better than another,
Oh! to stand tall. 
But now it stands to fall. 

Wicked devils eager work
Lump to cut with string. 
Pieces come apart a brick,
Shapes all to drown in slip. 

But what is worth 
in making after all?

It’s been a while since I felt like writing anything creative. Lately I’ve felt like doing nothing much, I missed direction, occupation and enthusiasm. It’s a terrible state in which I desperately need something to do, but don’t feel like doing anything. It’s a vicious circle with boredom and apathy feeding each other.

Today I am happy to have written this poem. I’m happy with it now, so here it is.

Bitter is the coffee

Many of us don’t go through the day without having at least one cup of coffee, and some hardcore enthusiasts I’ve met spend the whole day drinking coffee instead of water, only to finish strong with a 9pm espresso. No later so it won’t affect their sleep.

Our dependence on coffee is partially due to the functional addiction caffeine induces: once it leaves the body, we feel more tired than before, and we crave more. We believe we can’t function without it and see it as our means of coping with constant demands for performance.

To a large extent, however, we drink coffee because we have a lifestyle dependence on it. It fills many gaps in our often boring days and we like it for its taste and flavour, and for its bitterness. This latter liking is acquired, and many drown out the bitter taste with sugar and dairy products. But if you’re a true fan of coffee, you probably want the bitterness and appreciate the additives for the new experience they create.

I was intrigued when I found that in 2016 a US company called Senomyx claimed in patent number US 9.247,759 B2 a way to reduce consistently the perceived bitterness of coffee. The food and pharmaceutical industries have been masking out bitter tastes for a long time. The additives used are trivial – sugar, salt – or already widely used and derived from natural sources: gluconate, carboxymethylcellulose or beta-cyclodextrin. But early in the 2000s companies started looking at ways to block the taste, rather than just mask it. Some potential uses appeared sensible, for example to make very bitter drugs more palatable to patients.

Tasting bitter

We can taste many different compounds as bitter, but can’t tell them apart based on taste, i.e. we can’t discern different kinds of bitter. The intensity of the sensation determines how we react: coffee and tonic water earn our liking, but intensely bitter substances, such as denatonium benzoate, make us so strongly averse that they are used as deterrents to prevent accidental poisoning. Little was known about the molecular basis of our tasting bitter before a team of scientists (Elliot Adler, Mark Hoon, Ken Mueller, Jayaram Chandrashekar, Nicholas Ryba, Charles Szuker, Luxin Feng and Wei Guo) reported in the year 2000 the discovery of a type of taste receptor called T2R (Taste receptor type 2, also abbreviated as TAS2R) responsible for bitter taste detection in mammals.

The biology

Taste receptor cells are found on taste buds covering the surface of the tongue, and in other areas of the mouth. You can see an illustration of a taste bud here. Receptor cells contain structures which allow for interaction with a tastant (a chemical entity eliciting the sensation of taste). Sour and salty are detected by channels in the cell membrane, but sweet, bitter and umami are detected by TRs (type 1 deals with sweet and umami). Adler et al. showed that taste cells contain T2Rs and proved they function as bitter taste receptors. Some only responded to a single compound, like mT2R5 (m for mouse strain) which reacted to cycloheximide, while others were not so selective. Using cell experiments the researchers explained why mice with mutations in T2R5 were about 8 times less sensitive to the repulsive cycloheximide.

Adler’s team showed how a bitter compound can be detected by one or more receptors, and that by blocking those receptors it should be possible to reduce the sensation of bitterness experienced. They also predicted from genome analysis the existence of 40 to 80 different T2Rs in humans.

The chemistry

A study published in 2010 (by Wolfgang Meyerhof, Claudia Batram, Christina Kuhn, Anne Brockhoff, Elke Chudoba, Bernd Bufe, Giovanni Appendino and Maik Behrens) investigated the detection range of human T2Rs (25 known at the time) against a selection of 104 compounds from natural and synthetic sources. A complex picture emerged with most T2Rs detecting multiple compounds – hT2R14 (h for human) was the least selective in this study and responded to 33 compounds – and more than half of the compounds activating up to 3 receptors, with one (diphenidol) found to activate 15 different hT2Rs. This complex detection pattern probably emerged from the evolutionary process which shaped it into a sophisticated means of preventing poisoning. For example, the studies of Meyerhof et al. showed how hT2R46 detected the toxic compound strychnine and the very similar, but about 100-200 times less toxic, brucine. The sensitivity for strychnine over brucine was just about as high as the toxicity factor and orders of magnitude higher than required to detect the poison in food.

It is no surprise that with so many receptors responding to so many different compounds, we end up finding bitter things that are not toxic to us today. Caffeine itself is bitter, but not dangerous in the amount we usually ingest.

Senomyx reported that compound C (below) can be used in taste tests to reduce consistently the perceived bitterness of a coffee fraction (i.e. instant coffee, medium roast or medium-dark roast) to which it had been added. The receptors targeted were hT2R8 and hT2R14, found to respond to bitter compounds in coffee. Compound C was also found to block to different extents the response of 19 other T2Rs, indicating it could be used broadly to reduce the bitterness of products.

Reported synthesis of compound C by Senomyx.

The chemistry for making compound C is nothing to write home about. It’s a simple three step procedure. The sulfonyl chloride starting material is reacted with 4-methoxybenzyl amine to form a sulfonamide, which is then N-alkylated with benzyl bromide under basic conditions. This results in the carboxylic acid being benzylated as well, so the final step involves a base hydrolysis of the benzyl ester to give compound C.

Bitter is the coffee

Animals have developed complicated systems to detect bitter chemicals as a means to avoid poisoning. Although we are now far less reliant on these defense systems, should we try to block them out? I agree there is value in applying this strategy to medical products, especially if intended for children who are more sensitive to bitter taste than adults. But what about foods and drinks?

What got me thinking was the structure of compound C and others Senomyx exemplified. They look to me more like drug molecules than food additives. The compounds chosen would have to be approved by regulatory agencies, so I don’t think there is any real danger there, as far as the science is concerned.

My question regards the principle. Cheating your own senses to avoid disagreeable sensations covers a range from necessity to indulgence. Taking painkillers is a valid improvement to our quality of life made possible by modern science. It is necessary if we are to function normally. Numbing our tongues to eliminate disagreeable taste from a drink we consume for enjoyment is luxury.

Where do we draw the line between necessity and luxury? Is it wrong to make use of any opportunity to increase our satisfaction and make life as enjoyable as possible? No, if it doesn’t contravene legal and moral principles. Is there value in denying ourselves this then? I think the value is in pushing ourselves to pursue more elevated means of satisfaction. Rather than spend time and energy fixing every nuissance, we could be thinking of better ways to find joy in our lives. Or how to acquire a liking for the bitter things.

Turning red into gold

Quinacridone gold, also known as PO49, Pigment Orange 49, was a golden pigment used in the automotive and artist’s paint industries until 2001, when production reportedly stopped. The pigment had gathered somewhat of a following within the artists’ community. Artists such as Jane Blundell explored alternatives on the market, and others like Sandrine Maugy bemoaned the last supply of pigment having been used to mix lesser colours.

Quinacridone gold appears to have been special even by the standards of the quinacridone family of pigments, which Bruce MacEvoy at handprint described as follows: “Among the miracles of modern industrial chemistry […] one must include the discovery and development of the quinacridones.”

Quinacridone gold PO49 is described at The Color of Art Pigment Database as “a mixed crystal phase of Quinacridone & Quinacridonequinone; C.I.Pigment Violet 19 (C.I. 73900) and C.I.Pigment Red 206 (C.I. 73920) co-precipitated. The exact derivative has not been disclosed.” Bruce MacEvoy at handprint claims “PO49 is another mixed crystal form of PV19 alpha and beta.”

Not surprising that the formula was proprietary, but still, what is it? And what is PV19?

The discovery

PV19 stands for Pigment Violet 19 and is one of the forms of the original quinacridone, patented in parallel as alpha (bluish red), beta (violet) and gamma (bluish red) forms by DuPont in the 1950s.

Chemical structure of linear quinacridone

Let’s look at our glossary of terms before discussing further.

Polymorphism describes the existence of a solid compound (containing more than one type of atom) in different crystalline forms differing in the way molecules are arranged in the solid. Polymorphs have different properties, which is why controlling their formation is crucial in pigment manufacture. Polymorphs are often referred to as crystal phases.

Crystal phase refers to a form of a solid in which the comprising atoms or molecules are arranged in an orderly fashion throughout. The crystal is said to have long range order, i.e. it is possible to predict with a high certainty what atom will be found at a specified position.

Powder X-Ray diffraction pattern is a graphical representation of the crystal phase features still distinguishable in the powder, i.e. after the crystal has been ground up, or if only a collection of minute crystals is available. X-rays are diffracted through a crystal like visible light is diffracted through a prism. The X-ray diffraction experiment records where the light ends up and how intense it is.

Solid solution describes a homogeneous mixture with structure and properties different to those obtained by simply mixing the components in the same ratio. It shows an X-ray diffraction pattern different to the sum of the patterns of its components.

First (amusing) bit of information is the mention how better red pigments were needed in the 1950s due to it having recently become a popular colour for cars.

The alpha, beta and gamma crystal phases of quinacridone and the method for controlling their formation represents the scope of the three DuPont patents, together with the characteristic X-ray diffraction patterns each phase exhibits.

The crude quinacridone formed by oxidation of dihydroquinacridone (more on this later) is subjected to a milling process under defined conditions which generates a material fine enough to use as pigment, and with control over the crystal phase. The process looks deceptively simple: quinacridone is mixed with salt, mill balls or cylpebs (little cylinders) and nails (the latter to prevent caking), and the mixture rotated until the pigment particles are fine enough. The material is then washed with dilute sulfuric acid to remove the salt and any metal contamination introduced by the milling process. The quinacridone can then be used as a paste, or washed with methanol (to remove water) and xylene (to remove methanol) before drying to obtain the powder.

The chemistry

The control over phase formation is achieved using solvents. Milling without DMF (dimethylformamide) or xylene converts quinacridone to the alpha form. Adding 25% xylene with respect to quinacridone during milling results in the beta phase forming. Adding DMF during milling or stirring quinacridone in DMF either prevents the gamma phase from turning to alpha, or turns other phases to gamma. Long story short, the gamma phase is the most stable and will form (predominantly) when sparingly soluble quinacridone crystallises from solution.

Such crystallisation also occurs in the high temperature oxidation of dihydroquinacridone with nitrobenzene-m-sodium sulfonate under alkaline conditions in a water/alcohol mixture. DuPont patented their way of making dihydroquinacridone.

DuPont synthesis of dihydroquinacridone in Dowtherm A

The condensation of diethyl succinate was performed in Dowtherm A (23.5% biphenyl and 76.5% diphenylether) and after a quick water wash, the resulting diethyl succinyl succinate (name which I find terribly confusing) solution was treated with aniline and catalytic anyline hydrochloride and heated under vacuum (no further detail here). Another quick wash to get rid of the catalyst, a distillation to remove aniline and the resulting substituted dihydroterephthalate can be used as a suspension in Dowtherm. The discovery here is the closing of the quinacridone ring system by heating the dihydroterephthlate at a high temperature (which is why Dowtherm is used) in the absence of oxygen to give dihydroquinacridone. The last step is an oxidation to remove the extra two hydrogen atoms, which is preferably achieved using the soluble oxidant meta-nitrobenzenesodium sulfonate. The great thing about the (dihydro)quinacridones is they are so insoluble, and isolation by filtration provides pure products.

The background and chemistry covered, let’s return to the question of PO49.

Turning red into gold

A number of other developments made by DuPont over the following decade resulted in what is most likely PO49. This patent from 1964 describes a number of inventions which allowed for extending the range of colours quinacridone pigments can attain. First of them is the incorporation of a derivative of quinacridone called quinacridonequinone, which can be formed by extending the reaction time in the oxidation of dihydroquinacridone described above. This sounds like a cost effective solution – tweaking a known process rather than having to develop a whole new one.

Quinacridonequinone

A mixture of quinacridone and quinacridonequinone can be processed to form an intimate mixture either by milling or by co-precipitation from concentrated sulfuric acid in water (known as drowning). This mixture, on solvent treatment (DMF) converts to a solid solution. Solid solutions, having properties different to that of a simple mixture, can have a colour different to that of their components. A solid solution containing quinacridone and quinacridonequinone is reported to have a maroon colour, quite different to the reds that quinacridone alone can generate. By varying amounts of components and their nature (various other quinacridones) a whole range of colours shifting towards yellow or blue was reported. But no gold.

Finally, a technical improvement on the precipitation step from sulfuric acid afforded “a bright gold pigment.” This invention adds the sulfuric acid solution to a high velocity flow of water to form very fine particles, which is believed to favour solid solution formation. The resulting slurry is then heated to convert the solid mixture into the solid solution. There is no need for any solvent treatments, which makes the process even more attractive.

I would say the story of PO49 going out of production sounds plausible. For whatever reason, the automotive industry didn’t want PO49 anymore. No demand – I would imagine the amount of pigment used by industry is far greater than what artists go through – means no supply, even if to the outsider chemist the gold pigment does not stand out as anymore of a challenge than red. Quinacridones are still being produced, and since PO49 does not appear to have any special challenges associated, its demise really might be due to gold falling out of favour while red is still going strong. Perhaps PO49 was superseded; chemists are always mixing something up.

The value of trying and failing

I tried working a copywriter job. I wasn’t good enough, so I was let go. It was a positive experience because it was the first time I could accept rejection. My qualities were acknowledged alongside my failings. It was a balanced evaluation, it was based on evidence, and that is why I accepted it.

This was the first time I got sacked, but not the first time I failed. In the past I interviewed for patent attorney and consultant jobs. I didn’t even get hired. Some other things I interviewed for, got rejected and was very bitter over: undergrad student accommodation supervisor (or something along those lines), prestigious PhD studentship working on cancer research, posh doctoral training programme. There’s also all the things I applied for and never heard back, or only much later. If you send me a rejection email after two months without any other contact, I wasn’t really holding my breath at that point really. But thanks, better late than never.

I think this is good proof on the value of honest feedback. Not the ‘we’ve had a very strong selection of candidates.’ Not the ‘you’re good, but not good enough.’ Empty encouragement is wasting people’s time. Telling them what they can and cannot do right now will set them on the right track.

Looking at my puzzle of experience and its missing piece finally found I can write these three lessons:

  1. I like chemistry the way a nerd does, not like a professor or like an entrepeneur.
  2. I don’t care for lofty ideals. I care about a job well done.
  3. I’m not good at saying what needs saying, the way it needs saying. It’s bad for me whenever I do it.

I’m happy I tried doing all the things that are not for me, I failed with, I stopped caring for, or never cared for at all. I have a better idea what is for me, what I can do and what I like.

I am a bit more confident. Maybe I can make some better choices.

Squeezing a Mannich reaction in Haloperidol synthesis

I recently learned about the life of Dr Paul Adriaan Jan Janssen, the Belgian physician who founded Janssen Pharmaceutical Companies and contributed, directly or otherwise, to the development of 80 medications, 18 of which are on the WHO List of Essential Medicines.

I want to discuss one of his company’s early breakthrough discoveries: Haloperidol. The drug is used for its antipsychotic properties, and is prescribed for treating various conditions.

Haloperidol

Bernard Granger and Simona Albu discuss the story of the discovery in this article: The Story of Haloperidol, Ann. Clin. Psychiatry 2005; 17(3): 137-40. The compound is reported to have been synthesised in February 1958 during an intense screening campaign, not unlike those used in today’s medicinal chemistry.

One of the investigators’ early compounds R 951 is presented as follows: “. . . a Mannich base of meperidine would be much more active. The synthesis of such a product is achieved very easily by using meperidine, acetophenone and formalin, and takes 30 minutes. The Mannich base of meperidine, known as propiophenone, was synthesized under the code name R 951”

R 951 does certainly look like it could have been made by the Mannich reaction, but not from meperidine which is N-methylated. R 951 is a substituted propiophenone, but not propiophenone proper.

Top left: meperidine. Top right: propiophenone. Bottom: R 951.

The article does not indicate how haloperidol R 1625 might have been made. I went in search of the original procedure.

Paul Janssen reported the discovery in the Journal of Medicinal and Pharmaceutical Chemistry, but unfortunately I don’t have access to this article. I found the synthesis in this patent granted by the United States Patent Office.

It turns out to be a nice bit of chemistry many chemists have probably seen, most likely on an exam question, yet never knew where it originated. A Friedel-Crafts acylation of fluorobenzene generates intermediate A, which is used to alkylate the piperidine B to form Haloperidol. Three days at 120 °C, a real struggle with that chloride.

Two-step synthesis of Haloperidol

One thing caught my attention: of the two reported ways to make amine B one does involve conditions similar to a Mannich reaction: formaldehyde solution and ammonium chloride.

Synthesis of piperidine B

A mixture of reagents is prepared at 60 °C, and then the substituted methylstyrene is added. The exothermic reaction is allowed to proceed with cooling until temperature drops to 40 °C. I assume the reaction will be mostly done at this point and methanol is added to prevent the remaining partially alkylated ammonium salt from precipitating. The reaction is allowed to proceed overnight before methanol is removed. I assume this is mostly to prevent uncontrollable boiling in the next step, but perhaps also to prevent addition into the double bond. Speaking of the next step, this involves an intramolecular SN2 displacement of the ammonium leaving group, at 100 °C in concentrated HCl, to close the piperidine-to-be ring. Yes, not mild conditions. HBr gas is passed for 7 h through a solution of the alkene intermediate in acetic acid to form the corresponding bromide, which is easily hydrolysed with sodium hydroxide. It’s not obvious to me why this sequence from alkene to alcohol wasn’t performed as an acid-catalysed hydration. It must have given inferior results.

No yields are reported. I have a feeling that alkylation to form Haloperidol was terrible. The quality of the work is great, however, with purification either by distillation or crystallisation performed for every intermediate.

Chemistry lesson over, I think Granger and Albu’s little mishap discussing chemical structure is not a big deal. They have my appreciation for the effort. Collaboration between disciplines is in high demand today and researchers, motivated by pressure or curiosity, are venturing more often outside the boundaries of their training. Their slips of the tongue should be forgiven but not ignored. This is all the more important when the target audience does not have expertise on the matter. Passing information along in the style of an ‘oral tradition’ can result in some truly flawed statements forming. If you find it easy to roll something off the tongue, maybe take a closer look to see if it’s correct.

How Louis Pasteur discovered racemisation and resolution

You can familiarise yourselves with these terms using the following glossary for non-specialists:

Handedness (or chirality) is the same property describing molecules as describing hands: left and right. You can’t put a left glove on your right hand.

Racemisation is the process of converting a molecule of one handedness (left or right) to the opposite handedness, and it must involve some kind of breaking and putting back together. The result is a racemate, a mixture of equal amounts of molecules with left and right handedness.

Resolution is the process of separating molecules of one handedness from molecules of the other from a mixture of the two.

Stereochemistry is the branch of chemistry dealing with the 3D shape of molecules and their handedness.

Stereochemistry is even for today’s chemists a bit of a headache: organic chemists are familiar with the concepts of molecular chirality, but to a large extent unfamiliar with chirality on the macroscopic scale. Crystallisation scientists and crystallographers on the other hand are comfortable with the latter. It all began in 19th century France.

Ghislaine Vantomme and Jeanne Crassous recently published a good account on the intense activity in the field of stereochemistry that took place in that era. The report (free to read here) focuses on the work of Louis Pasteur in the area of molecular and crystal chirality, viewed from the perspective of the modern chemist.

But at the time it was all discussed in terms of crystalline properties and solution properties. No use of molecular structure. Pasteur uncovered racemisation and resolution 20 years before the tetrahedral structure of carbon was discovered. The story of his discovery is the kind of textbook novelty that gets me excited, but sadly few chemists remember.

I wanted to read Pasteur’s account for myself, so I went on a bit of a quest in search of the original publications. Fortunately, a list of them is available from the Pasteur foundation, together with links to the texts. The only problem is they are in French.

For this reason, I will only endeavour to discuss one of them: Transformation des acides tartriques en acide racémique – Découverte de l’acide tartrique inactif. Nouvelle méthode de séparation de l’acide racémique en acides tartriques droit et gauche C. R. T. 37 (1853) 162-166.

It is worth noting that Pasteur had been working in the area for 5 years, and his (or someone else’s) enthusiasm is obvious in this communication letter: L. Pasteur, dans une Lettre adressée à M. Biot, annonce qu’il est parvenu à transformer l’acide tartrique en acide racémique C. R. T. 36 (1853) 973, where the text is italicised.

Extract from Pasteur’s letter to M. Biot regarding his discovery.

So how does his article sound to the modern chemist? Let’s see. This is technical, so feel free to skip to number 8 on the list. If you’re a French-speaking chemist and disagree with my translation, please let me know in the comments. I’d like to know better!

  1. Chinconine tartrate (the L-(+) natural form) is gradually heated to convert to chinconicine (it looks to me like ring opening by hydride shift) tartrate. Prolonged heating at 170 °C results in the alkaloid decomposing (forming some tarry material called quinoidine), but more importantly results in some of the racemic tartrate being formed. Treating with calcium chloride in the workup allows for isolation of racemic calcium tartrate.
  2. The alkaloid salts are used as the free acid decomposes at such temperature. The transformation also works with a ‘tartrate ether’ which does not have another optically active component beside the tartrate.
  3. The racemic acid isolated has identical physical and chemical properties to an authentic sample, and furthermore can be separated into left and right tartaric acids (only later does he mention how he achieved this).
  4. It follows that the right tartaric acid was converted artificially into the left.
  5. The experiment was repeated with left tartaric acid to give racemic acid under the same conditions. The conclusion is immense: a collection of dissymetric molecules can be converted to their inverse solely under heating; and the racemic is a mixture of the two isomers.
  6. Another product was discovered in the tarry residue: inactive tartaric acid, what we now call meso. Pasteur extended the reaction time, and this time he kept the filtrate after removing the racemic calcium tartrate. After 24 h he had crystallised the inactive calcium tartrate.
  7. Pasteur concluded the meso was formed from the racemic, and like a good scientist, he heated the isolated racemic to prove he could form the meso without starting from optically active materials.
  8. The most exciting part: “le sel double de soude et d’ammoniaque. Les cristaux qui prennet naissance sont de deux sortes; je sépare manuellement ces cristaux d’après le caractère de leur forme hémiédrique : il n’y a rien là de général. Ce dédoublement s’offre ici comme un accident.”
    In my translation: “the double sodium and ammonium salt. The crystals prepared are of two kinds; I separated them manually using the form of their hemihedral shape: this is nothing but particular. This resolution opportunity is an accident.”
  9. And then in the summary he drops another bomb discovery: resolution by crystallisation of diastereomeric salts: he preferentially crystallised left tartrate of cinchonine from the racemate solution.

This was an immense discovery. Pasteur was aware of it, but he was even more aware of how lucky he had been to stumble on just the right compound to provide him with the experimental results to power his logic work.

The lack of experimental detail is shocking by modern standards. In spite of this, the science is solid and many of the same experiments are the foundation for chemical enquiry. Science was an honourable gentlemen’s enterprise, and there was nothing wrong with that. What I loved, however, was how reasoning and emotion (yes, look at all the exclamation marks in the original) were well at home in his scientific writing. Emotion, when existent in today’s scientific writing, is often weak and artificial, and reasoning restrained and implied. And you certainly don’t see many ‘I’s.

As a final note, Vantomme and Crassous reference the discovery of the meso form (entry 6 on my list) to 1858. I don’t have access to this material, but according to my understanding this discovery was reported in 1853.

You are free to do your own digging if you would like, but the important message is this: there is no better reference than the original report. Try and find it!

On and off topic – the disconnect between sodium ammonium tartrate and Gantt charts

Can I talk about chemistry? Can I be nerdy, veer off course and ramble?

Yes, I can. Unfortunately, it took me more than 15 years to learn this. In fact, I only had this revelation about 10 minutes before I started writing this post. The wonderful topic I was investigating was how could I make racemic sodium ammonium tartrate at home, crystallise it and separate the enantiomers the way Louis Pasteur did to make his way into history books in 1848. (Note: the series of reports made by Pasteur started in 1848 and culminated with this discovery in 1853. A list is available here)

My cause is not noble – I just wanted to make a Youtube video. But the flashback I had was of Proust eating his madeleine with jasmine tea proportions. Don’t worry, my prose is far more modest.

I was somewhat of a weirdo even in the chemistry enclave. My interests never lined up with those of others. Scientists, as you expect, tend to be pragmatic and think about the future, the next discovery. This is great, and necessary for their survival in today’s scientific environment. I, on the other hand, have always been inclined towards the past. I got excited about the stories of discovery usually reserved for textbooks and other materials made for the public.

If you’re not a scientist you might be thinking what is wrong with that? We learn from the past – that’s what history tells us. Scientists generally appreciate the teachings and will go searching the literature for information, but they don’t care that much about who did what and how they got there (not beyond the requirements of referencing anyway). And if the information is now common knowledge, any attempts to uncover the murky, distant past are scoffed at. This makes an onerous task a shameful one. Scientists don’t care much for the history of science.

Back to my experience; I remember working on my master’s project thesis. I had an intro that was a bit like a herpetologist touching on the likely anatomy of the biblical snake in the garden of Eden. Needless to say, it wasn’t well received by my supervisor. I had to cut out a lot of the work which made me so proud.

I was heartbroken and furious. That maybe some points were valid (the page count for example) is irrelevant. Always getting our work edited and aligned with the standards and interests of the majority is damaging. Yes, that is how we learn and improve. But in my case, that is how I completely lost direction.

I ended up being unhappy doing what I liked. I hated what I was doing because it was what someone else wanted. I always got told they wanted to help me. I eventually gave up on chemistry and tried doing something else.

I failed so far. I recently got sacked from a new job (not a chemistry one) after two weeks. But I am not bitter about it. I think it was actually the most honourable rejection I’ve ever received. There was objective evidence I couldn’t do it. I got given a chance for what I had to offer and for my dedication. This is opposite to what I had experienced in chemistry where what I had to offer and who I was never mattered. The only thing that mattered was whether I delivered exactly what was expected.

I am obviously being emotional and still bitter about my chemistry past. I can’t think of anything clever to say here to balance this statement. And the only problem is I feel I should. Here it comes (after hours of mulling). Part of being a scientist is seeing black and white at the same time. But no one cares about dull, grey complexities – Not even scientists.

And that’s a shame. I think part of the problem with modern science is that it’s focused on delivering scientific ‘products’ rather than knowledge. It’s focused on the future, on achievement. It’s creating solutions to predicted problems rather than current ones.

Problems are solved by experimentation, by study, by reflection. Solutions are always serendipitous. Asking scientists to plan their work and their discoveries is absolutely ridiculous. I remember I had to make a Gantt chart at the beginning of my PhD. I hadn’t even heard of one before – which is to say that the study experience doesn’t quite prepare you for this. What is worse, the work was planned around ideas that were already in place for my project. Ideas which were written before I had arrived.

How can you expect young scientists to develop the skill of coming up with ideas, if you waste all their time researching someone else’s ideas? Pasteur is famous for his statement: ‘In the field of observation chance favours only the prepared mind.’ I don’t think Gantt charts was what he had in mind.

Why is this relevant? Because scientists should care about what they are doing. If you kill their interest and their passion, you are losing your biggest asset: the scientist. I cared. I still want to care. It just bothers me seeing how few people care.

I probably can’t change that. I just hope I can find the strength and ability to convince other people how exciting science can be. To make them appreciate the story of sodium ammonium tartrate.

Information makes me quiet

Imagine you believed your entire life the primary colours are red, blue, and yellow. Then you find out they are cyan, magenta, and yellow. There is also red, green, and blue. But you can also create a palette with any three colours you choose. But you might want to include more for a larger space and more accurate reproduction.

Sustained learning makes me unwilling to talk. It also makes me angry.

I am a simple creature, and like all humans, I like to share my thoughts and feelings. I thought until now that the value is in being acknowledged and, hopefully, appreciated. It made me happy, but it also caused me trouble when I didn’t get the response I hoped for. Now I understand why.

Keeping my mind busy with a constant flow of information gives me comfort. It does a good job, but not perfect, of keeping me from feeling lonely. If I feel less lonely, I have less motivation to talk. Being in company does the same thing: I listen and say less. And if a book or person is not talking, I talk to myself.

That is the value of sharing: it sets the scene for others to talk, providing me with the information flow I crave. I am not angry for not sharing what I’ve learned, or what I wanted to share before knowing better. I am angry because an information overflow is followed by a dry spell.

The quality of what I have to say becomes more important to me as I learn more. The problem is, of course, the more I learn I come to realise how nothing I say can possibly be of much value. I then don’t say anything. And I get angry.

So then, why was I seeking approval? I wanted the new information to build on or agree with what I had already learned. Not to disagree. I got angry when I learnt cyan, magenta, yellow are the primary colours. Maybe so did you when you read that.

Frozen fingers – Part of the Little Blue Marbles Series

Winter that year had a strong bite, punishing people by freezing their cars solid and pushing needles in their bones through insulation, feeble house heating, and layers of woollen personal protection. Snow didn’t come. Most in the area had to decide between having a full stomach or feeling their toes and fingers at least once in a while. Freya’s parents made no exception, but unfortunately they were inclined differently: her dad kept warm on cheap beer and her mother plugged in the electric heater whenever he’d fall asleep.

Freya had just turned thirteen the day they opened the pond to skating. She had always loved to skate, but never got any good at it. Having two left feet would have been less of a problem than hers for skating, assuming the ice skates would fit. Her problem was functional rather than conformational as something in her brain stopped her balancing on one leg and pushing with the other. Her ability never improved and she was stuck awkwardly shuffling on the sides with the beginners every time she skated, every year the pond froze.

Her disappointment turned to desolation and, for this particular birthday, to resentment. She went to the pond with her run-of-the-mill skates in her bag, but on the way threw them in the bin. She climbed the small hill found next to the pond, sat on the frozen ground and looked down on the cheerful throng. The sun was setting behind, leaving her observation point in the shadows.

A lilac haze started slowly perspiring from between the frigid blades of grass, oozing like dense droplets out of the hill’s pores. Something started tensing deep within, something which was out of place, vast, much too large for the physical dimensions of the modest relief. For minutes dripping like spoiled honey from a dying hive, this vague curdling of the earth’s marrow was spreading with a precise rate, not so much up, but out. It grew out of the perimeter and started dawdling towards the pond. Immense but somehow lacking will, it was heading that way reluctantly. A sharp gust of wind marked a shift in growth from size to kind. It was now pulsating, ripples spreading from an epicentre of blood drops hitting an impregnable but malleable resin. The earth was losing control, something else was dictating, prescribing evolutionary course. The hill was growing taller, rising, escaping the sedimentary, ancient foundation it used to stand on. It was drawing back from the inchoate creation, yielding to what it seemed to want. The growing darkness was lit by the wispy lilac tendrils surrounding and permeating the frozen pond. They were somehow growing backward in that direction, like an entangled sillage left by the throng of skaters. Time passed slowly. The hill became enormous, a mountain. The pond grew deeper, the ice insubstantial. The air warmer, thicker, heavier. The mass of curious but reluctant tendrils grew so dense it congealed, it became solid, having no choice but to yield to pulsating. Pulsating with no clear purpose or intention.

An hour passed. Freya’s heart was beating with a strong thump, the echo resounding in her painful temples. She was frozen solid, but her fingers were screaming in pain, still alive. It was dark. She then wandered with lilac-glowing embers of hate tucked away between the folds in her mind.