Palladium Nobel Prize in Chemistry
Anton Chugunov, "Biomolecule", based on the official press release of the Nobel Committee.
Nature is the most talented chemist – substances with a fantastic range of unique properties are found in natural sources, many of which humanity would not refuse to put at its service. However, natural compounds are much more complicated than modern organic synthesis can create. The Nobel Prize in Chemistry was awarded in 2010 for the development of palladium catalysis techniques that allow very accurately (with a minimum of by-products) to "stitch" carbon atoms, which is necessary for the construction of substances that approach natural molecules in their structure and properties.
Palladium– a noble metal from the platinum group, was isolated from platinum ore in 1803. Interestingly, it is not named directly after Pallas Athena, but was named after the Pallas asteroid, discovered shortly before the first metal samples were obtained (in 1802), and this asteroid was just named after Athena. The market price of palladium is 500-600 dollars per troy ounce (the unit of mass measurement is 31.1034768 g – it is used in banking and jewelry to measure the weight of precious metals, and in other areas – for example, in cosmetics – to measure the weight of particularly valuable ingredients).
Humanity is dependent on the chemicals that it produces – these are medicines, plastics, rubber, and much more. The need for new molecules is constantly growing, and new generations of artificial molecules are distinguished by a more complex and elegant structure than the previous ones. But according to this parameter, "man-made" compounds are far from nature, in which there are molecules of a very complex configuration, which cannot be synthesized by modern chemistry. (We are not talking about proteins or nucleic acids, which consist of relatively simple "building blocks".) If we compare the elemental composition of natural "organics" and industrial substances, it turns out that the former consist almost entirely of carbon, hydrogen, oxygen and nitrogen, while the latter contain large amounts of halogens, sulfur, phosphorus. But on the other hand, natural compounds are distinguished by the impressive complexity of the carbon "framework" with the presence of many asymmetric (chiral) atoms, which people have not yet learned to control chemical reactions with the participation of which in most cases.
At the same time, natural molecules of high complexity often have an impressive set of biological qualities – for example, they can prevent the development of cancer. So, at the end of the 1980s, from a depth of 33 meters, the Discodermia dissoluta sponge was caught from the bottom of the Caribbean Sea, defending itself from its enemies solely by producing complex organic toxins of a non-protein nature. (By the way, toxic molecules of biological origin, regardless of their specific chemical nature, are fantastically diverse) Researchers have found that many of the substances produced by this sponge have antimicrobial, antiviral or anti-inflammatory properties. One of the first identified compounds, discodermolide, slowed the development of cancer cells in vitro and is currently being tested as an agent for chemotherapy.
Studies have shown that discodermolide acts similarly to one of the most common drugs prescribed for various forms of cancer, Paclitaxel, by suppressing the synthesis of microtubules and preventing cancer cells from dividing. However, those microscopic amounts of the substance that can be obtained from the depths of the Caribbean Sea with the help of divers (discodermolide decomposes under the influence of light, so you can't get it on the shallows) are not enough even for detailed studies, let alone for cancer drugs.
The story with discodermolide would have ended there if not for the achievements noted this year by the Nobel Prize in Chemistry – the complete synthesis of this substance was still completed using palladium catalysis, which was developed by the American Richard Heck and the Japanese Eiichi Nagishi and Akira Suzuki (Akira Suzuki).
Palladium: the place of "stitching" cannot be changedIn order to synthesize a complex organic molecule, one must be able to "stitch" various fragments together with unprecedented precision according to clearly defined carbon atoms – since organic chemistry is by definition the chemistry of carbon compounds, then the "backbone" of most organic molecules is carbon.
The "classic" way to make a carbon atom that already occupies its place in an organic molecule react with something is the use of special substances (for example, Grignard reagent) that "activate" carbon (releasing its valence). However, the problem with these methods is that carbon begins to react with literally everything in a row, forming a mass of by-products, reducing the yield of the required substance and making the task of separating the chemical mixture almost impossible.
The main feature of palladium catalysis, which put this method in an honorable place in organic synthesis, is the ability to conduct reactions by "crosslinking" carbon atoms with the highest selectivity and under fairly mild conditions. This is extremely important for multi-stage synthesis (such as the synthesis of discodermolide), which is practically impossible in the case of a large number of by-products. The chemistry of palladium catalysis is based on the fact that two carbon atoms are located next to the same palladium atom and, "activated", they connect with each other, and not with any other atoms. Palladium in this reaction, as befits a catalyst, is not consumed.
Industry inspiredRichard Heck, who worked for an American chemical company in Delaware, began work on palladium catalysis in the 1960s, when information spread around the world that the German chemical concern Wacker Chemie AG began using palladium for the industrial production of acetaldehyde from ethylene.
In 1968, Heck published a number of papers, in one of which he talked about the addition of an ethylene molecule to the aromatic ring with the participation of a palladium catalyst to produce styrene (Fig. 1) – the starting material for the common polystyrene plastic. Later, the improved reaction was called the Heck reaction; nowadays it is one of the main ways of forming single bonds between carbon atoms.
Figure 1. Synthesis of styrene. Richard Heck using palladium catalysis
he developed a method for attaching a short olefin (ethylene) to an aromatic ring.
When two carbon atoms "meet" near the surface of a palladium atom,
they are already ready to react – with each other, not with arbitrary atoms!
The product of this reaction is styrene, the raw material for the production of polystyrene plastic.Inspired by industry, this reaction itself is now widely used in chemical production, for example, the anti–inflammatory drug naproxen or the asthma drug montelukast.
Precision is the key to molecular designIn 1977, Eiichi Nagishi worked in the same direction, perfecting the Grignard reagent by replacing magnesium ion with zinc and also using palladium.
When using zinc, the degree of carbon activation is lower compared to the "classical" magnesium for the Grignard reaction, but zinc allows carbon to be coordinated on the same palladium atom, which determines the high selectivity of the Oxide reaction (Fig. 2).
Figure 2. Scientists managed to carry out laboratory synthesis of discodermolide,
using a kind of Nagisi reaction with palladium catalysis
formation of a single bond between two carbon atoms.
In the photo at the bottom left is a sponge, from the poison of which discodermolide was isolated.Two years later, Suzuki conducted experiments using boron as an "activating" atom, which is the mildest and least toxic element among the others mentioned, and this is very important in industrial synthesis.
Suzuki's reaction, in particular, is used in industrial production (thousands of tons) of fungicides – substances that protect crops from destruction by fungi.
Currently, the reactions of Hake, Nagishi and Suzuki are widely used in organic synthesis, for example, one of the most complex organic substances, palitoxin, has been synthesized with their help (Fig. 3), a zoontarium found in the venom of six-ray corals and isolated for the first time in 1971 in Hawaii. Palitoxin has a cardiotoxic effect (causes cardiac arrest) and has traditionally been used by aborigines to manufacture poisoned weapons. The synthesis of such a "dinosaur" is a tour de force of organic chemistry, and the successful solution of the problem confirms the enormous progress made by synthetic chemists compared to Grignard (by the way, also a Nobel Prize winner).
Figure 3. Progress in organic chemistry.
One of the first reactions of organic chemistry is the Kolbe reaction (mid–XIX century, above).
A century and a half later, organics synthesize palitoxin (below),
one of the most complex molecules known (gross formula: C 129 O 54 N 3 H 223).
A tool for finding new medicinesReactions using palladium catalysis have already made it possible to carry out complex organic syntheses by reconstructing various natural substances.
However, palladium catalyst is used not only for synthesis, but also for modification of natural molecules. An example is vancomycin, an antibiotic first isolated in 1950 from a sample of Borneo jungle soil. Nowadays, it is used to fight microorganisms that have developed resistance to "conventional" antibiotics (such as penicillin), – methicillin-resistant Staphylococcus aureus (MRSA) and enterococci. Scientists using palladium catalysis are trying to create derivatives of this antibiotic to defeat resistance and give humanity a reliable tool to fight infections in hospitals and in the field.
Finally, it is worth noting that the scope of the palladium catalyst is not limited to the synthesis of toxins and antibiotics – for example, in modern thin displays on organic light-emitting diodes (OLED), blue elements work on the basis of a substance obtained precisely by palladium catalysis.
Yes, and it is also interesting that, compared to last year, when both the prize in physiology and medicine (for telomeres and telomerase) and the prize in chemistry (for ribosome structure) were both actually prizes in biology, this year the prize in medicine is in medicine (for the development of the method of in vitro fertilization), and the prize in chemistry – for one hundred percent chemistry.
Portal "Eternal youth" http://vechnayamolodost.ru07.10.2010