Courtesy of Cornell University

Prof. Tristan Lambert, chemistry, above, was a former colleague of David MacMillan and contributed to his discoveries that led to the 2021 Nobel Prize.

November 2, 2021

Contribution From Cornell Prof. Catalyzes the Nobel Prize in Chemistry

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In 1998, Prof. Tristan Lambert, chemistry, then a first-year Ph.D. student at UC Berkeley, was stuck on a reaction mechanism. 

When his research adviser Prof. David MacMillan, chemistry, Princeton University, walked by, Lambert asked: “Why is it that this works … Why doesn’t it do this other thing?” unknowing that his simple question would lead MacMillan on his way to win the Nobel Prize in Chemistry 2021. 

The 2021 Nobel Prize in Chemistry was awarded to David MacMillan and Benjamin List, who are credited for developing asymmetric organocatalysis — a way of catalyzing reactions using organic molecules to form specific copies of a compound. This tool increases the capabilities of medicinal chemistry. MacMillan and List, director at the Max Planck Institute for Coal Research, came across the concept simultaneously yet an ocean apart in the late 1990s. 

According to Lambert, chemical reactions can be understood through an analogy of people going across a mountain — they can either go up one side and down the other, or tunnel through. 

“The catalyst is basically tunneling through the mountain to give a much easier pathway, a much lower energy [is needed],” Lambert said. 

While catalysis is a common tool used in chemical reactions, “asymmetry” is what makes MacMillan’s and List’s findings stand apart.

In organic chemistry, many organic molecules have an “asymmetric” property of chirality, when two molecules are mirror images of one another, according to Lambert. A classic example of chirality, or handedness, is the relationship between a person’s left and right hand — while a glove can match either the left or right hand, it will only align with the hand that it is created for.

“You can’t put your right hand in the left hand [of] the glove, right? So they’re identical, except that they are not superimposable,” Lambert said. 

Asymmetric organocatalysis allows the correct mirror image of a molecule to be produced using organic materials. The molecule can then be used to catalyze specific reactions, according to Lambert.

In the pharmaceutical industry, enzymes must be made to fit the correct glove. If the right hand went into the wrong glove, the drug could be inefficient or detrimental to health. 

For example, thalidomide, a drug that was prescribed to women in the 1950s to treat morning sickness, only worked if it had the correct mirror image. The wrong version of the molecule led to horrific birth defects, and even death, for thousands of babies. 

MacMillan’s development of asymmetric organocatalysis “provided new and nontoxic ways to do this type of catalysis” and achieve selectivity between mirror image molecules, Lambert said. 

Lambert explained that this tool has profound potential, such as leading to the development of new heart medications or drugs to treat cancer, which is thrilling for medicinal chemistry, the pharmaceutical industry and people worldwide.

Organic chemistry has been transformed by MacMillan — so when Lambert woke up to get his morning coffee on Oct. 7, and his wife greeted him with “Dave won the Nobel,” Lambert said he was “thrilled.” 

However, MacMillan’s award was not a surprise to Lambert and his wife who expected MacMillan to win the prize, based on their knowledge of the drastic impacts asymmetric organocatalysis could have.

“[It’s] a pretty cool feeling to know anybody who won a Nobel, and especially to know him before he became so famous,” Lambert said. 

Interestingly, MacMillan’s more recent research in other areas of organic chemistry has been popular among scientists, prompting Lambert to believe MacMillan would win the Nobel for those findings instead. 

“He actually didn’t win it for the chemistry that everyone thought he was going to win it for. It is actually the stuff that he’s done more recently… [that’s] arguably more impactful,” Lambert said. “He’s helped initiate two revolutions in organic chemistry in his career.  And I think many people, myself included, thought that the Nobel might go for this more recent work.” 

Because of the impact of these more recent findings, Lambert said the 2021 Nobel is likely not the last time MacMillan will be recognized for his groundbreaking work in organic chemistry.

“He and his group completely transform the way that people go about making molecules, and it’s been really stunning to watch that develop over the last quarter century,” Lambert said. “I expect he’s going to win a second [Nobel Prize]… Most people kind of think that’s probably going to happen soon.” 

Lambert initially became interested in organic chemistry in an introductory course at the University of Wisconsin at Platteville. He later decided to apply to graduate programs, and learning UC Berkeley was ranked number one in chemistry, he applied and was accepted. 

The choice to attend led Lambert to not only his Ph.D., but also a small contribution in this year’s Nobel Prize in Chemistry. 

In the early 2000s, the MacMillan group moved to the California Institute of Technology, where Lambert earned his Ph.D. after receiving a masters from UC Berkeley. Thereafter, Lambert and his wife have stayed close with MacMillan, and regard him as both a friend and colleague.