Over the past several years, the Nobel Prize in Chemistry has often gone to researchers who work in the space where chemistry bleeds into biology, which occasionally elicited some grumbles from the more chemically inclined. They'll have nothing to complain about this year, as a trio of chemists, Richard F. Heck, Ei-ichi Negishi, and Akira Suzuki, have been honored for their work in developing palladium-based catalysts that are now used for the synthesis of many complex molecules. That's not to say that their work hasn't had significant impact on biology, however, as the primary uses of the techniques are for the production of drugs and the synthesis of natural products.

Via evolution, many species have handily come out ahead of humans when it comes to the synthesis of large and complicated organic molecules. In recent decades, scientists have become increasingly aware of the potential value of many of these compounds, which are often used in the biological warfare that goes on in the natural world. If we've identified a pest we'd like to kill, chances are some other species has too, and many of these produce chemicals that successfully do so. In addition, some of these compounds—the chemotherapy drug taxol is a classic example—have unexpected uses that make them candidates for drug development.

But the organisms that produce these chemicals via enzymes often produce very little, or the organism itself is very rare. This can create a huge bottleneck when it comes to ensuring a supply that's sufficient to even start testing, never mind full-scale commercial production. In some cases, we've had to wait years until the enzymes required for the synthesis have been identified and cloned into bacteria. In others, promising drug leads identified by other methods have had a complex structure that made them difficult to synthesize.

Unfortunately, as molecules grow larger and more complex, this synthesis gets increasingly problematic. If a compound has a handful of double bonds in its carbon backbone, modifying the right one can be a nightmare. The same applies to challenges like adding the right side chain in the right location, or even building a large carbon backbone in the first place.

Starting in about 1970, this trio of scientists made everybody's life a bit easier by figuring out a way to specifically link carbon atoms together through a process that was so mild that it rarely produced unwanted side products.

Previously, the common methods of linking carbon atoms into longer molecules generally involved highly reactive intermediates in which the carbon was linked to common metals like magnesium. These reactions tended to produce many unwanted products, leaving chemists to separate out a small fraction of the desired molecule from a complicated soup of related chemicals. Try to combine a few too many of these reactions, and there was no reasonable way to get sufficient end product once all the inefficiencies came into play.

Shortly before Heck began his work in the 1960s, however, palladium, a less reactive rare earth metal, saw its first use in an industrial synthesis process, catalyzing the oxidation of a simple organic molecule. Heck helped develop the first general way to use palladium to create a general method of building longer chains of carbon. The trick to this process is the fact that palladium can displace other chemicals attached to a carbon chain, forming bonds with the carbon itself. When two separate carbon molecules are bound to the atom's surface at once, their proximity will cause them to react with each other, linking them together.

The schematics of a Heck reaction are shown below. The palladium (red) can react with both the double bond of a small carbon molecule, and displace the bromine from a benzene ring. The carbon-containing intermediates will then react with each other. Because the placement of bromine and double bonds can be controlled, the reaction is remarkably specific.

Negishi and Suzuki are credited with refining the reaction, creating variants that were more flexible, and even less likely to react in unexpected ways. Negishi is credited with replacing the double bond used in the Heck reaction with zinc, which meant that a far larger array of additional carbon chains could be attached via the palladium. Suzuki swapped out the zinc for a boron, which is even less reactive. Nevertheless, in the presence of palladium, these reactions were even more efficient and specific. Since boron compounds are generally nontoxic, this approach has been widely adopted.

The first three laureates this year all hailed from the UK, but chemistry has ended this trend. Heck is from the US; Negishi was born in Japan, but has been working in the US since he got his PhD here; Suzuki has remained in Japan for his entire career.

David Kroll notes that Heck's award is especially poignant. His work is often called the Mizoroki-Heck reaction because of the work of another investigator who also helped develop the approach. Chemist David Kroll notes that Tsutomu Mizoroki wasn't eligible to receive the prize, since he died less than a decade after the breakthrough. Heck himself dropped out of science over a decade ago after he had difficulty getting funding for his work. He'll apparently have to travel from his retirement home in the Philippines to receive his award.

Listing image by Nobel Prize website