Breakthrough in separating left- and right-handed molecules

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In a discovery with broad implications for the specialty chemicals industries like pharmaceuticals, researchers at Rice University and the California Institute of Technology have succeeded in a decades-long quest to make left- and right-handed versions of a molecular sieve, one of the most-used industrial, solid materials.

Molecular sieves that include zeolites are silicate minerals that chemical plants use to make hundreds of millions of tons of diverse products each year, ranging from gasoline and diesel fuel to purified oxygen from air. Despite their ubiquity, molecular sieves today are inherently limited because they do not exhibit “chirality,” or handedness. Just as a person’s right and left hands are mirror opposites, so are some molecules, particularly those produced by living cells.

“Chirality is particularly important in biology,” said biophysicist Michael Deem, co-author of a paper about the breakthrough that will appear online this week in the Proceedings of the National Academy of Sciences Early Edition. “DNA is right-handed. Amino acids are mostly left-handed. Sugars are right-handed, and so on.

“Most industrial and organic chemistry that humans can easily perform synthetically is not chiral,” he said. “When chiral compounds are produced, most often they are made in an equal mix of right- and left-handed versions, or enantiomers. Because the proteins in our bodies are chiral, they can react very differently to a right or left enantiomer of a drug. For example, one enantiomer of thalidomide reduces nausea and the other causes birth defects.”

An industrial example where chirality is paramount is polylactic acid, or PLA, the building block of biodegradable plastic. Lactic acid is a natural compound familiar to any athlete: It’s what causes muscles to “burn” during strenuous workouts. But humans, animals and plants produce left-handed lactic acid, and only this enantiomer is biodegradable. Because the right-handed enantiomer of PLA cannot be digested by bacteria, biodegradable plastic requires enantiomerically pure PLA, a product that today’s industrial chemical methods cannot easily produce.

“Research has been going on for over 30 years to make chiral molecular sieves because it was assumed that chiral molecular sieves would be able to perform chiral catalysis and separation, and allow for new ways to make chiral products in bulk at lower costs,” said Caltech chemical engineer Mark Davis, and corresponding author of the new study.

“We present the first convincing evidence of a chiral molecular sieve, and show that these materials can perform chiral catalysis and separations. With our co-authors at Rice, we have demonstrated a methodology that can in principle produce many different chiral molecular sieves, each with unique properties.”

At a microscopic level, molecular sieves look like Swiss cheese, with interconnected pores. All molecular sieves that are called zeolites are made of silicon, oxygen and aluminum, and their pores can vary in size and shape but are less that 2 nm in size. The pores are what make the solids so useful to chemists, because only molecules of a certain size and shape can pass through. In addition, the pores can act as catalytic reaction chambers to spur the production of specific chemical products.

Deem, the John W. Cox Professor of Bioengineering and professor of physics and astronomy, has worked on computational methods to identify and design zeolites for more than 15 years. His lab has computationally identified the best zeolites for removing carbon dioxide from power plant exhaust and even created a database of about 2.6 million potentially synthesizable zeolites. Deem said the research with Davis’ team on the chiral molecular sieve grew from a 2013 study in which he, Rice visiting research scholar Frits Daeyaert*, and colleagues created a computational procedure to identify small organic molecules that could be used to synthesize zeolites with tailored properties like chirality.

Chiral organic molecules for the new study were designed at Rice by Deem and Daeyaert, with chemical knowledge from Davis and Caltech co-author Joel Schmidt. Davis’ team at Caltech used the chiral organic molecules to direct the synthesis of chiral molecular sieves, and the Caltech team performed adsorption and catalytic tests to confirm the chirality of the molecular sieve samples and the adsorption and catalytic products made with those samples. Deem said the chiral molecular sieve samples were prepared as either the left- or right-handed version of a man-made molecular sieve that had previously been produced only in equal mixtures of right and left versions.

The chiral organic molecule that was designed for the experiments at Caltech was one of about a dozen such candidates that was produced in a yearlong computational analysis at Rice.

“Several of the other candidates may also prove useful, and we’ve begun working with our partners to synthesize some of these other candidates with an eye toward producing additional chiral molecular sieves, each with slightly different properties,” Deem said.
He said chiral molecular sieves and zeolites like the ones found in the new study and the others for which the group is still searching could prove extremely useful for producing biodegradable plastics, enantiomerically pure drugs and other compounds that are troublesome to produce with nonchiral chemistry.

“Right now, there are specialty chemicals that are chiral, but more and more in the future, there will be bulk commodities that will be made from chiral materials,” Deem said. “Chiral synthesis, particularly on hydrocarbon-based chemicals, is one of the things that chiral zeolites could make economically feasible.”

Additional co-authors include Stephen Brand and Marat Orazov, both of Caltech; and Yanhang Ma and Osamu Terasaki, both of ShanghaiTech University. The research was supported by Chevron, the Department of Energy and ShanghaiTech.

Frits Daeyaert is active in the Belgian company Synopsis.

Source: Rice University