Explainer: What is chirality?

Have you ever put a shoe onto the wrong foot? Usually, you notice straight away that something’s wrong — it doesn’t fit quite right. That’s because your two feet (and your two shoes) have opposite shapes. One is a mirror image of the other.

In chemistry, biology and material science, such mirroring is called chirality. And this mirroring shows up even at the tiniest of scales, among molecules.

“Molecules have shapes,” says Kate Adamala. She’s a synthetic biologist at the University of Minnesota in Minneapolis. A molecule is made up of an assortment of atoms that combine together.

With most simple molecules, such as water (H₂O), there’s only one way for the atoms to combine. They can only make one shape. So water is achiral. It does not have chirality.

But many larger, more complex molecules have atoms that can combine in more than one way. Sometimes, the atoms connect in a different order. Or they may connect in the same order but fold or twist into different 3-D shapes. All these alternate ways for a molecule to form are called isomers.

Chirality is a special feature of some isomers where the same atoms connect in the same order but with mirror-image shapes. Two chiral forms are made from the same stuff, but just like your two feet, their shapes won’t overlap perfectly. The two mirrored versions of the molecule are known as the left- and right-handed forms. 

Spearmint gum or rye bread?

Just as shoes need to fit onto feet to be useful, molecules often need to fit into other molecules to have an effect. An achiral molecule, like water, will react the same way with either form of a chiral molecule. But chiral molecules react very differently with the opposite forms of other chiral molecules.

“Depending on the molecules, the reaction may work well, [or] it may not work as well. It may make different products. And it may not work at all,” says Vincent Maloney. He’s an organic chemist who retired from Purdue University in Fort Wayne, Ind.

Opposite chiral forms can lead to drastically different effects. You can experience a simple example of this with a quick trip to the kitchen.

Sniff a stick of mint gum and a fresh loaf of rye bread. They smell completely different. But these two scents come from the same molecule, called carvone. The scent receptors in your nose are chiral, explains Maloney. So they react differently to the mirror-image forms of carvone. The right-handed version of the molecule occurs naturally in spearmint, which gives chewing gum its minty scent. And the left-handed version is found in caraway, the seeds that flavor rye bread.  

Most of the molecules that make up living things are chiral. But bodies only make one of the two possible chiral forms. DNA always twists to the right. The sugar glucose — the body’s main source of energy — is right-handed, too. Proteins are the workhorses of biology, and these are formed from amino acids. Just one amino acid, glycine, is achiral. The rest of the amino acids our bodies make are all left-handed. 

The chiral shape of a molecule is “incredibly important for all of biology — for all of life on Earth,” says Adamala.

A medical disaster

The body’s reactions to mirror-image molecules are highly important in medicine.

Medicines often work because the shape of a drug molecule fits into a shape on a target. That target may be a problematic enzyme in a person’s body or a disease-causing germ. The drug can disable the enzyme or germ — but only if it has the right shape. And one chiral form of a drug molecule may be the right shape while the other chiral form doesn’t fit.

Making a drug with just one chiral form can be a painstaking process. To make a drug, chemists can trigger a series of chemical reactions to get substances to combine in just the right way. But most known triggers, called catalysts, are achiral. So they produce a hodge-podge mix of both left- and right-handed forms of a desired chiral molecule. The mixture is called a racemate (RAY-suh-mate).

Drug makers often sell a medicine as a racemate, even though only one of the chiral forms in the mixture does the job. The opposite form may do nothing at all inside the body. But in some cases, it can be harmful.

Back in 1957, women in Europe began taking the drug thalidomide for nausea during pregnancy. The drug calmed their symptoms. But it also caused many babies to be born with missing or deformed arms and legs and other serious health problems.

Research eventually revealed that only the right-handed form of the drug eased nausea. The left-handed form harmed developing babies. Plus, the right-handed form could morph inside the body to become the left-handed form. So neither form is a safe medicine for pregnant people.

Drug makers today have to test both forms of a chiral molecule to prove they are each safe. Many drugs are still racemates. But others are carefully crafted to include only the most effective chiral form of a molecule. Or drug makers can carefully filter out one chiral form from a racemate. Both processes can be slow and expensive.

Making a single chiral form “is a pain in the lower back,” says Adamala.

But “we’re getting better and better at it,” says Maloney.

Mirror life

Lab-made, or synthetic, drugs almost always form a racemate. But if the wanted substance is a biomolecule — one that forms naturally — then there’s another option. Chemists can coax living bacteria to make it.

Living things can only make one chiral form of a biomolecule. For example, they make right-handed DNA and proteins formed from left-handed amino acids. This is true of people, animals, plants and even fungi and bacteria.

And, only the natural chiral form of a biomolecule can react with the body’s chemistry. One made from ingredients that twist or bend the wrong way typically won’t interact with body systems. It’s like a stealthy ninja.

This fact is something many drug makers want to take advantage of. Drugs often fail to work well because the body recognizes them as not part of itself. The result can be a drug that fails to work because the stomach digests it. Or there could be problematic side effects because the immune system attacks it. A wrong-handed ninja molecule can reach a target in the body without being detected along the way. And biologists can carefully craft it so it can still fit onto its target. So these kinds of drugs could be safer and more effective.

But, as we learned above, single chiral forms are tough to manufacture. It can take hours to days to make a few micrograms of a mirror version of one of life’s molecules.

Mirror, mirror

All DNA twists to the right, as depicted on the right side of this illustration. A mirrored left-handed form, as shown on the left, doesn’t exist in nature.

To speed things up, scientists once imagined creating something they call mirror life. This would be a bacterium whose DNA and amino acids all twist or branch the opposite way. It would be a new form of life that had never existed before. And it could crank out biomolecules with the opposite chiral form.

Mirror life would be sort of like something from the Upside Down in the TV show Stranger Things. It would look like a normal living thing, but its chemistry would work the opposite way. And it turns out that, just like in the show, the upside-down variety of life could be very dangerous.

A single mirror molecule that twists the wrong way can be useful. But as soon as you make mirror bacteria, they could do what life does and “make more of themselves,” Adamala says. That’s a huge problem because no life on Earth has evolved alongside such organisms. That means “nothing eats them, and nothing makes them sick,” says Adamala. So they could potentially spread out of control. (They’d be able to eat normal, non–mirror life food because bacteria can feed on very simple, achiral molecules.)

Perhaps us normal lifeforms would manage to adapt, and something would evolve to eat or kill the mirror bacteria. But what if that doesn’t happen? Adamala and a large group of other experts around the world have agreed to stop all efforts toward developing mirror life.

While it might be cool to create a new form of life, the risks are too dire. And “responsibility in science is as important as innovation,” says Adamala.

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Materials, with a twist

Chirality is important for more than just biology and medicine. In materials science, chirality can affect properties such as toughness or flexibility. Most plastics form from long chains of molecules. If the molecules are chiral and all line up in the same direction or in a regular pattern, this can make the material harder and tougher. But if the chiral molecules pile together randomly “like spaghetti,” says Maloney, the material will be softer.

In other cases, the molecules that make up a material may not be chiral themselves. But the way these molecules pack together forms structures that twist in a specific way. The way the structures within a material twist can give it special properties. For example, it might react with sound or light differently. Or it might conduct electricity differently.

These and other exciting possibilities inspire new efforts to make mirror molecules. A simple twist can make a world of difference in medicines, materials and more.