Nobel Prize History
The Nobel Prize is the most prestigious award in the scientific world. It was created according to Mr. Alfred Nobel’s will to give a prize “to those who, during the preceding year, have conferred the greatest benefit to humankind” in physics, chemistry, physiology or medicine, literature, and peace.
A sixth prize would be later on created for economic sciences by the Swedish central bank, officially called the Prize in Economic Sciences, often better known as the Nobel Prize in Economics.
The decision of who to attribute the prize to belongs to multiple Swedish academic institutions.
Legacy Concerns
The decision to create the Nobel Prize came to Alfred Nobel after he read his own obituary, following a mistake by a French newspaper that misunderstood the news of his brother’s death. Titled “The Merchant of Death Is Dead”, the French article hammered Nobel for his invention of smokeless explosives, of which dynamite was the most famous one.
His inventions were very influential in shaping modern warfare, and Nobel purchased a massive iron and steel mill to turn it into a major armaments manufacturer. As he was first a chemist, engineer, and inventor, Nobel realized that he did not want his legacy to be one of a man remembered to have made a fortune over war and the death of others.
Nobel Prize
These days, Nobel’s Fortune is stored in a fund invested to generate income to finance the Nobel Foundation and the gold-plated green gold medal, diploma, and monetary award of 11 million SEK (around $1M) attributed to the winners.
Source: Britannica
Often, the Nobel Prize money is divided between several winners, especially in scientific fields where it is common for 2 or 3 leading figures to contribute together or in parallel to a groundbreaking discovery.
Over the years, the Nobel Prize became THE scientific prize, trying to strike a balance between theoretical and very practical discoveries. It has rewarded achievements that built the foundations of the modern world, like radioactivity, antibiotics, X-rays, or PCR, as well as fundamental science like the power source of the sun, the electron charge, atomic structure, or superfluidity.
The Quest For More Catalysts
From the early era of chemistry, scientists have looked at ways to speed up chemical reactions or make molecules react in unusual ways. Sometimes, it can be achieved by changing the physical conditions, like using heat or pressure. However, for other chemical reactions, special products called catalysts are needed.
Catalysts are usually boosting the chance of a chemical reaction to happen, therefore increasing its speed and/or its efficiency.
What makes catalysts unique is that while they are involved in the chemical reaction, they are left unchanged at the end of it – the only “facilitate” the reaction.
This makes catalysts an often forgotten keystone of the modern world and absolutely essential in the manufacturing of everyday goods like refined oil, plastics, air filters, water purification, pharmaceuticals, perfume, flavoring, foodstuff, etc.
Altogether, catalysts contribute in one way or another to the production of as much as 35% of the world’s GDP.
Many Types Of Catalysts
The first catalytic activity to be discovered was from metals like silver, nickel, platinum, palladium, etc. However, these catalysts are expensive. Metal catalysts also have a low selectivity, meaning that they can catalyze many different reactions.
While this can sometimes be an advantage, it is not the case when only one precise reaction is desired, like in the production of pharmaceuticals.
Another type of catalyst is enzymes. These proteins are able to accelerate very specific chemical reactions and are essentially the gears and machines powering life itself.
The preparation of pure enzymes was a significant scientific breakthrough and was awarded a Nobel Prize in 1946. Today, enzymes are routinely used in countless chemical processes.
The limit of enzymes is that they were designed by nature to perform specific tasks in living cells. So when the catalysis required is for something unrelated to biology, such as the production of plastics, it can be rather hard or even impossible to find a matching enzyme for the task.
Enzymes can also be fragile and not work in conditions of extreme acidity, for example. So, there was a strong need for non-metallic, custom-designed catalysts. This is where organocatalysts enter the scene. They are made of ordinary carbon, hydrogen, nitrogen, sulphur, and phosphorus but no metals.
Organocatalysts
In 2021, the Nobel Prize in Chemistry was attributed to Benjamin List and David W.C. MacMillan, for the development of asymmetric organocatalysis.
As explained, organocatalysts are made of cheap and abundant elements forming the basis of organic chemistry (centered around carbon). The “asymmetric” part is important, as for most chemical and biological processes, molecules can display different versions, depending on their symmetry.
Such changes in the molecule orientation, also called “chirality”, have often important consequences for its functionality. For example, the same molecule of limonene will smell differently depending on which side it is oriented.
Source: Nobel Prize
List & MacMillan were not the first to discover organocatalysts. Some were found by accident as early as 1912 with quinine catalysis of cyanohydrins production. Later on, a quinine-derived catalyst would be used to perform asymmetric catalysis.
Source: Nobel Prize
However, for a long time, there was no framework to properly analyze organocatalysts, even less custom design new ones.
How Does Catalysis Work?
Most chemical reactions need some level of energy to be reached at the molecule levels, to make the 2 compounds “bump into each other” and react. Catalysts bring the reagents closer together, reducing the energy required and making the reaction quicker and more likely to happen.
Source: Byjus
So while specific metallic elements are able to cause this lowering of energy levels due to their inherent atomic properties, the amino acids of enzymes are able to do it through the combination of their 3D configuration and chemical properties.
Often, it is only a few amino acids that actually perform the catalytic reaction, with the rest of the enzyme providing stability, activation from biochemical signals, or other functions.
Source: Nobel Prize
This was the starting point for Benjamin List, who wanted to investigate if a small number of amino acids, or even just one could perform catalysis the way entire enzymes do.
List Catalysts: Proline & Chirality
List started to work with a single amino acid called proline, which had been demonstrated to be a potential catalyst more than 25 years ago in the 1970s. Not expecting a very strong reaction, but still curious to learn more about it, he ran the experiment to check on it.
Not only did proline work as a catalyst, but it did so very strongly. Looking at the reaction further, List found that the catalysis was asymmetrical, with one of the 2 possible images of the newly formed molecule a lot more likely to be formed.
This would form the base for a new category of catalyst, called by chemists enamine catalysis, or Lewis base catalysis.
In it, a nitrogen atom reduces the energy required, and a carboxylic acid stabilizes the transition state in the intermediary steps of the chemical reaction catalyzed.
Source: Nobel Prize
MacMillan Catalysts: Iminium Ion
MacMillan had been working on metal-based asymmetrical catalysts but realized the conditions for these to work were rarely workable in an industrial setting, causing the discoveries in labs to be rarely useful for chemical production at scale.
Instead, he looked at how to replicate the basic mechanisms these metals use with organic chemistry.
Metal catalysts are especially active thanks to their ability to temporarily provide or accommodate electrons, reducing the barrier for a chemical reaction to occur.
To replicate such ability with organic molecules (made of a carbon backbone), MacMillan guessed from his chemistry knowledge that the perfect one would be an iminium ion.
As a result, this type of organocatalyst would become known as iminium ion catalysis/Lewis acid catalysis.
The idea here is that the nitrogen atom, with an inherent affinity for electrons, can play the role of the metal atom in a metal catalyst. Large chemical groups around the nitrogen atoms force the reaction to be asymmetrical.
Source: Nobel Prize
The Rise Of Organocatalysts
MacMillan and List would publish their parallel findings almost at the same time in 2000, with the word to describe this new class of catalysts coined by MacMillan.
By fully explaining and investigating how they work, the two researchers and their teams opened the way for the systematic development of organocatalysts, where previous works were done more in a piecemeal fashion or through accidental discoveries.
Organocatalysts are now firmly an important component of the chemical industry for a few key reasons:
- Lower cost, especially when replacing metal-base catalysis.
- Asymmetric production is very important for the final product quality.
- In the case of pharmaceuticals, it can be a matter of life or death, with some molecule symmetry useful and some others deadly.
- Potentially more versatile, with further work done by both MacMillan and List to find more types of reactions that enamine and iminium ion can help accelerate.
- More environmentally friendly chemical processes, such as organocatalysts, are most of the time nontoxic and/or easily recycled.
Organocatalysts’ Achievements
One example of how much organocatalysts can improve the chemical industry is the synthesis of strychnine.
The poison molecule (used in rat poison) was first synthesized in 1952 using a process requiring 29 chemical reactions. Only 0.0009% of the initial product turned into the desired strychnine.
In 2011, researchers using organocatalysis managed to reduce this to only 12 steps and achieved a 7,000x more efficient conversion rate.
Mass production of complex organic products currently extracted from plants or deep-sea organisms can also be important, both to increase availability and reduce prices of important pharmaceutical products.
Future Development
Photocatalysis
Nature provided us with a great example of organocatalysts beyond enzymes: photosynthesis. By combining the ability of organic molecules to move electrons with the absorption of light, photosynthesis is the basic source of energy for the entirety of Earth’s biosphere.
Indirectly, photosynthesis is even the source of today’s fossil fuels, the basic blocs used by the petrochemical industry.
With the need to reduce carbon emissions, an ideal situation would be to develop organocatalysts that could use light to produce energy, either in the form of simple sugar or hydrogen.
This way, sunlight is directly used by the catalyst to power the wanted chemical reaction instead of first being absorbed by solar panels, converted into electricity, and then used for processes like electrolysis.
This could drastically cut the costs of biofuels, a requirement if we want them to be economically competitive against fossil fuels.
AI Molecule Design
There are trillions of possible molecule designs, with only a small fraction that has been studied in any form.
The problem in using computers to simulate these molecules is that if relying purely on physics and quantum mechanics, the calculations quickly become absurdly complex for anything with more than 5-10 atoms.
Currently, many AI systems are being designed to “guess” the right answer instead of performing a brute-force calculation.
This can yield new potential molecules and designs that could not have been guessed otherwise. This method is already yielding fruits with for example AlphaFold from Google for protein folding, predictions about new molecule antibiotic activity, or Microsoft’s AI4Science program.
Source: Microsoft
It is likely that many organocatalysts are yet to be discovered, and that AI could speed up radically these innovations, as we discussed in “Changing the Timeline for Discoveries through Use of Artificial Intelligence (AI)”.
Investing In Organocatalysts
Organocatalysts are a key part of the modern chemical industry. It is also a growing market, expected to reach 6.4% CAGR until 2032.
You can invest in organocatalysts companies through many brokers, and you can find here, on securities.io, our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.
If you are not interested in picking specific organocatalysts companies, you can also look into ETFs like the iShares STOXX Europe 600 Chemicals UCITS ETF (EXV7) or the Vanguard Materials ETF (VAW) which will provide a more diversified exposure to capitalize on the chemical industry.
Catalysts Companies
1. BASF (BASFY)
A giant of the chemical industry, BASF employs 110,000+ people across 11 divisions grouped into 6 segments: Chemicals, Materials, Industrial Solutions, Surface Technologies, Nutrition & Care, and Agricultural Solutions.
20%+ of the activity comes from chemicals and plastics and 20%+ from transportation. It also has a strong presence in agriculture and consumer goods.
Source: BASF
BASF’s catalyst division employs 8,000+, with 30 manufacturing sites.
The company invests massively in R&D, with $2B+ annual spending, spread throughout many sectors, but with a strong focus on creating growth in the agricultural sector (pesticides, herbicides, and seed treatment).
Source: BASF
The expertise in plastics and other chemical manufacturing extends to the nanoscale, notably with a leadership position in nanoparticulate surface coating, porous materials, and polymers.
Combined with expertise in catalysts, this is likely going to make BASF a center of the future economy based on innovations in chemicals, batteries, pharmaceuticals, nanotech, biotech, etc.
2. Schrödinger, Inc.
The company specializes in physics-based models to find the best possible molecule for a given goal, balancing out conflicting metrics like potency, solubility, half-life, synthesizability, etc.
It also uses “normal” machine learning, but the addition of a physics-based model allows it to be tested in entirely novel fields for which no data set exists to “train” the AI. This allows Schrödinger to go from 1 billion potential molecules to just 8 solid candidates in a matter of days, exclusively through digital calculation.
Source: Schrodinger
Schrödinger signed with Bayer a 5-year collaboration agreement in 2020 for revenue of $10M. The agreement is to use Schrödinger technology together with Bayer in-silico prediction models.
Another recent partnership is with Lilly in 2022, with up to $425M in total milestone payments for successful discovery.
Past collaborations included Takeda, Sanofi Bristol Myers Squibb, and other smaller pharmaceutical companies.
Overall, Schrödinger is building a growing portfolio, including more and more proprietary and fully-owned molecules. It currently has 8 products in its proprietary pipeline, with 2 in phase I of clinical trials. And 23 products in partnered programs and collaborations, with 5 in phase I and 3 in phase II of clinical trials.
Source: Schrodinger
While not pre-revenue, the company is still not profitable, focusing on expansion and R&D spending to improve its technology. It should not be a serious concern in the short term, as the company has several years of operation worth of cash on its balance sheet.
It is also looking at expanding toward new segments beyond drug discovery, like complex biopharmaceuticals or even materials like chemicals, batteries, or polymers.
Source: Schrodinger
Investors will want to keep an eye on the new collaborations, as they will reflect the advances of Schrödinger’s technology, as assessed by the leaders in the industry from confidential data, as well as possible success in expanding the core technology to new markets.
With organocatalysts and overall organic chemistry taking over a growing role, AI models like Schrödinger’s will play an increasing role in developing new molecules and optimizing often decade-old chemical manufacturing processes.
