Asymmetric autocatalysis describes a chemical reaction where the product itself catalyzes more of its own production, creating a runaway effect that follows a sigmoid curve over time, similar to how the Krebs and Calvin cycles work in biology. Kenso Soai's lab found a chiral molecule, a 5-pyrimidyl alkanol, that could catalyze its own formation: a 1995 Nature paper showed it amplifying a 2% enantiomeric excess up to 87%, and a 2003 paper described the full Soai reaction, where a starting imbalance of about one part in two million grew to roughly 57% after one round, about 99% after a second round, and above 99.5% after a third. The hosts frame this as a laboratory demonstration of how a tiny chance asymmetry can be amplified into an overwhelming one-handed outcome, not as proof of how biological chirality actually originated.
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The reaction type is an organozinc addition to an aldehyde, with dimethyl zinc adding to a chiral ligand to produce an alcohol product structurally similar to the catalyst itself.
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Before Soai's work, chemists knew of autocatalytic reactions but none that were asymmetric, meaning none that favored one molecular hand over the other.
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The hosts describe the 2003 result as the first lab demonstration of generating high chirality starting from non-chiral combinations of molecules.
1,430 words · auto-generated from the episode video
42:20So yeah. Okay, so with that said, we now have the nonlinear part of this 2026 chemistry Nobel. The next word in the Nobel description is autocatalysis. How do we get there? Yes, this is where we get into autocatalysis. The idea of autocatalysis is that the product participates in catalyzing the reaction that produces more of the product, that then catalyzes more of the reaction, that produces more of the product. So as the product accumulates, you get this runaway reaction. And a signature of this type of reaction in reaction kinetics is as time goes on, you get kind of a sigmoid, where the first half is like exponential because the more and more products you
43:04get, you start blowing up. But as you start running out of the reactants, you reach a baseline where all of the reactants are finally taken care of, right? Life has a bunch of these type of autocatalysis. For example, there's several cycles that we have in life where you create a particular product, and then that particular product feeds back into the cycle itself. The Krebs cycle in mitochondria is a great one. The Calvin cycle in photosynthesis is a great one. So life does this all the time, right? And you can imagine, like, kind of makes sense, right? If you've got a workshop that builds tools, and then the tools build themselves, then
43:47you've got this thing going. This is not recursive self-improvement, and we're not talking about AI. Yeah, we're not talking about AI, although that is also a runaway effect that we should be certainly concerned about. In any case, so Soai and his collaborators, they start exploring reactions in which organozinc reagents add to aldehydes to make alcohols. Let's take this particular reaction here. This is an asymmetric catalytic addition of dimethyl zinc, which is the Me2Zn, Me is the methyl, so dimethyl group. This is being attached to a chiral ligand on the left-hand side, the pH is a phenyl group,
44:29that's a C6H5, okay? When you scrutinize this thing, look at the product. The product also has a phenyl with OH. It's a bit different from the reactant, but it's also kind of similar to the thing that is catalyzing the reaction at the very top, because it's got a phenyl group, an OH group, an extra carbon, and the carbon, if you can somehow attach it to the N-benzene ferridine, the NBN over there, then perhaps you could make more of this stuff, okay? So this is kind of a, like, you know, maybe there's something here. This sparks an idea, right? Perhaps you can design a reaction where the catalyst forms itself.
45:09Now, at this time, early 1990s, there's several known examples of auto catalytic reactions, but none that are asymmetric, okay? There's several reactions of this thing doing it, but we need something that prefers one hand over the other, right? And by experimenting with many different molecules, Soai succeeds in finding a chiral substance called 5-pyramidal alkenol. I almost said alcohol, and chemists with their, dude, I remember organic chemistry. Like, if you put down alcohol and not alkenol, which by the way, the H kind of looks like an N, like you get a zero. So, oh my God, I hate it, Orgo.
45:51But in any case, 5-pyramidal alkenol is a chiral substance that Soai finds that can create itself. And in a publication in 1995 in Nature, he describes this revolutionary experiment, asymmetric autocatalysis and the amplification of enantiomeric excess of a chiral molecule. Banger title. For anyone who is in the field, like this is like, oh, you did it, right? And this is literally like the word for word, some of the stuff that the Nobel committee is citing right? Asymmetric autocatalysis. So, great title, 1995. It's not the end of his work because this is kind of halfway there.
46:33It starts with a 2% excess of one enantiomer and ends up with an excess of 87%. That's pretty good, but the reaction is not what life does because in life you start with a little bit of excess and you gotta get to 100%. It's the Riemann hypothesis. We gotta rule out all of the non-trivial zeros. Yeah yeah yeah. Even when you get to 100%. Yeah, a little different. A little different. A little different. But at least this is like some statistical type thing, right? We're getting close. We're getting close. We're getting close, right? So, another eight years, Soai's lab just continues their search and they finally find the ultimate autocatalytic process. In 2003, they published in the American Chemical Society Journal.
47:15This journal, by the way, is just one of the goats for chemistry. In last year's episode, if you look back, a lot of the MOFs, the Metal Organic Framework Papers, came out in the American Chemical Society Journal. So, kind of goes under the radar compared to like nature, science, but this thing-- We see you. Yeah, we see you. We see you. This thing is a heavy hitter. This is the first time that anyone had successfully created chirality from non-chiral combinations of molecules since the dawn of life. This is where he got to 100% chiral. Unbelievable. Okay. This is the dawn of life. Since the dawn of life, this is the first time.
47:56It's called the Soai reaction and it is considered by chemists as the most elegant chemical experiment ever conducted by some chemists. I just wanna note the pronunciation of the last name, Soai, being the one that created this, is also just like a sort of aesthetically interesting naming convention. It's like Soai and I only. No anyway. Yeah, I think that is quite funny. I mean, it's considered one of the most elegant chemical experiments ever conducted, which that is a high bar to me. So here's what's happening. When you start the catalytic process, you've got both enantiomers that are present, but a tiny
48:39excess of just one creates 100% excess of that one. And that's because effectively what's happening is one enantiomer takes over the entire reaction. The left-hand side creates only left-hand catalysts and the right-hand side creates only right-hand catalysts. But if you've got a tiny imbalance, the left-hand sides create way more than the right-hand side, which is gonna then create way more, which is then gonna create way more. So you start out with something like 0.00005%. After the first run, you get all the way to 57%. Unbelievable. After the second run, you get to 99%.
49:20And after the third run, you get to 99.5%. It's a runaway reaction because of autocatalysis. That is the key. The thing is creating itself, which is then creating itself, right? I remember seeing this image in the Nobel materials and without necessarily connecting the dots, understanding, like looking at this runaway in three runs and three rounds with how small your starting point was in terms of the imbalance, clearly was going to be important. Now the connection as to how and why is fascinating. Yeah, and it's like one part in what, 10,000 I think, if I'm doing the math right, one part in
50:0210,000 is leading to in three runs, 99.5%, almost at 100, right? Just one of them is just dominating, just because of the chance beginning asymmetry. And the small scale of that chance asymmetry at the beginning is very small. Yeah yeah. It could have gone the other way, right? And then in which case we would have had a lot of the left-hand side. This is so good. And so now we've kind of gotten to the point where we understand now all of the component parts of the description. Yes exactly. And just to say it one more time, the nonlinear effects, right? That was Kagan.
50:43That was Kagan. Kagan. Kagan yeah sorry. No, no, and then if it's not, you can let us know in the comments. Yeah please. And then autocatalysis, which is what creates this runaway, in asymmetric organic synthesis, which means the inputs have that slight asymmetry. And it doesn't always have to have a slight asymmetry, but it only requires a slight asymmetry in this example. To then create. This 100% runaway. Runaway reaction. And this is fascinating for a lot of reasons. Obviously we made the connection earlier to how, you know, a couple of things, but one of the notes was that
51:23this changes how we make medicines. Yes. Or pharmaceuticals. So how does
Nobel PrizeChemistryBiochemistryChemical origin of lifeSynthetic Biology