Chemistry Nobel goes to reactions like those that gave life a hand

Life is remarkably selective. Life relies on many molecules with what is termed “handedness”—they’re chemically identical but are mirror images of each other. Most chemical reactions will make a 50-50 mix of the left- and right-handed forms of a chemical, but life uses only one of them. In fact, because of the differences between left- and right-handed chemicals, most of the key enzymes used by organisms will fail to work if they’re presented with chemicals that have the wrong handedness.

That poses a bit of a challenge for origin-of-life research, as we’re forced to explain how a world that may have started with an even mix of left- and right-handed chemicals produced organisms that only used one of them.

Today’s Nobel Prize in Chemistry goes to two individuals, Henri Kagan and Kenso Soai, who discovered chemical reactions could be biased, producing large excesses of one of the two forms of a chemical.

Chirality and life

The technical term for molecular handedness is “chirality,” and scientists replace left and right with dextro (D) and levo (L). But the ideas are largely the same. Your hands have all the same components—fingers and thumbs—organized in the same way. Yet if you point your thumb upward, the fingers curl in opposite directions, making one the mirror image of the other. Depending on the arrangements of the chemical bonds, many molecules can form similar mirror-image forms, with all the same parts oriented slightly differently in space.

(For the geekier among the readership: carbon atoms have four potential sites that can form bonds, spread evenly across the surface of the atom’s sphere. If each of those sites is linked to a different chemical, then swapping the chemicals located in any two of them can potentially change the way it’s arranged in 3D space.)

Amino acids come in both D and L forms, but all of life relies on just one of those.

This can really matter when it comes to enzymes, which typically latch onto chemicals using binding sites that are sculpted by evolution to fit only that chemical and its close relatives. Try to feed the enzyme the mirror-image version of that same chemical, and it will often fail to fit the binding site. Since life uses nothing but the D form of sugars, all of its enzymes are optimized to latch onto those, and many cannot interact at all with the L form.

There are two ways this could have happened. The first life may not have been as picky about the reactions it catalyzed and only evolved chirality preferences slowly. Or life could have evolved in an environment where one chiral form dominated. Or there was some combination of the two. But either of the latter two cases simply pushes the question back a bit: How could chemistry create an environment where one chiral form dominates?

From theory to practice

Over the years, there have been a number of ideas about how this might occur. Several of those trace back to a physicist, Frederick Charles Frank, who addressed this issue in a data-free, theory-focused paper. (It’s clear from the Nobel Prize Committee’s writing that, were Frank still alive, he might have shared in this award.) One option is that a catalyst with only a slight preference for forming a D or L molecule could, over time, produce a large excess of that form. Another is that a chiral reaction product could itself serve as a catalyst for forming more of the same form. Or the chiral reaction product could inhibit the formation of its mirrored form.

Many chemical reactions reach an equilibrium, finding a point where forward and reverse reactions occur at similar rates. If the reverse reaction is indifferent to chirality, but the forward one is influenced by one of the factors above, then time would allow this to create a large excess of one chiral form.

All of these were hypotheticals, however, until the researchers being honored got to work. Henri Kagan of the University of Paris-Sud also approached his work very theoretically, describing the factors that would be needed to drive reactions that favored a single chirality. But in several cases, he was able to go out and find actual chemical reactions that demonstrated his ideas mattered in the real world.

Kagan worked with a catalyst that was itself chiral. He found that, in a mix of L and D versions of his catalyst, one of the forms was much more active than the other. While the forms might be present at the same level, most of the actual catalysis was performed by just one of them. And, if it was used to catalyze a reaction that produced a chiral product, this difference could lead to much higher levels of a single chirality.

By the mid-1960s, Kagan had found three different reactions that could produce an excess of a single chiral form. Other researchers who followed up on his ideas showed that chiral catalysts could also be selectively activated or inhibited by the addition of non-chiral chemicals, allowing a finer degree of control that found its way into the production of pharmaceuticals.

Self catalysis

About a decade later, Tokyo University’s Kenzo Soai was working on reactions where one of the products of the reaction acted as a catalyst to boost the same reaction. Eventually, he found one that selected for chirality; one form of the reaction product would catalyze the formation of more molecules of the same chirality. He started the reaction with a slight excess of one form of catalyst and found that, after a single round of reactions, the excess in the catalyst had risen to 55 percent. Using that as a catalyst for a new round of reactions would enhance the excess further; after several rounds, 90 percent of the products were a single chirality.

Eventually, Soai found conditions where one product would not only catalyze the formation of more of the same form, but inhibit the formation of the opposite chirality. This allowed him to start with a tiny excess of a single chiral form (0.00005 percent more) and, after a few rounds of reactions, bring the excess to over 99 percent.

Others later found conditions where a similar reaction that reached an equilibrium of forward and back reactions would gradually lead to a single chiral form dominating.

There are three different aspects of this work that are worth celebrating. One is that it’s simply great science; people reasoned through the ways that an excess of one chiral form could emerge, and then others found ways to demonstrate that the behavior took place in the real world. A second is that it has immense practical applications. Many of our drugs work because they interact with proteins, where chirality often matters. And there are many examples of drugs where the wrong chiral form can be inactive or positively harmful. So finding new ways to catalyze the production of specific chiral forms has a lot of utility.

But the final thing comes back to the origin of life. None of these reactions were demonstrated with anything closely related to a biomolecule, so it’s not obvious that this particular work is directly relevant to the origin of life. But it does show that small excesses of some chiral forms—smaller than the 90 percent seen in this work, but still significant—may be common in the natural world.

The current thinking is that those small differences weren’t decisive, but did help push the emergence of life along a pathway that ultimately led to the exclusive chemistry we see now.

John is Ars Technica's science editor. He has a Bachelor of Arts in Biochemistry from Columbia University, and a Ph.D. in Molecular and Cell Biology from the University of California, Berkeley. When physically separated from his keyboard, he tends to seek out a bicycle, or a scenic location for communing with his hiking boots.