Do drugs have "left and right hands"? The mysterious mystery of chirality

The internationally renowned journal "Journal of Nanoscience" recently published an online paper titled "Chiral skyrmions interact with chiral flowers", pointing out that the chiral properties of active substances play an important role in the dynamics of the interaction between active substances and chiral structures. The internationally renowned journal "Nature" also announced the 125 most challenging scientific problems, and the question "Why does life need chirality" is among them, which shows the importance of chirality.

What is chirality?

Humans have two treasures, hands and brains. Hands are part of the body. Do we have enough knowledge about them? Have we ever considered such a simple question: Can our left hand and right hand overlap? The answer is no. Our left hand and right hand are the relationship between the real object and the mirror image. They have the same appearance, but they cannot overlap. Interestingly, this feature of hands is also widely found in other substances in nature. Therefore, we figuratively call the feature that a certain substance and its mirror image cannot overlap as chirality or chirality.

Chirality exists at every level of matter, from microscopic molecules to the macroscopic universe. Simply put, molecules with chiral characteristics are called chiral molecules. Chiral molecules have a most basic property, which is optical activity, while molecules without chirality are called achiral molecules, which have no optical activity.

If a molecule is chiral due to the asymmetric arrangement of its atoms or groups around a certain point, then we call this point a chiral center. For example, if the three hydrogen atoms in the methane molecule are replaced by alkyl, hydroxyl and carboxyl groups respectively, a lactic acid molecule showing optical activity is obtained. Here, we can call the carbon atom connected to four different groups an asymmetric carbon atom or a chiral carbon atom.

Twin brothers: Enantiomers

Each chiral molecule has two different spatial configurations, and these two molecules with different spatial configurations are enantiomers. The atoms and functional groups of enantiomers are the same, and they only differ in spatial arrangement. Therefore, their physical and chemical properties in non-chiral environments are basically the same, such as melting point, boiling point, solubility, etc. Here we compare highly similar enantiomers to twin brothers. Enantiomers are real objects and mirror images of each other, but they cannot overlap.

Chiral drugs have different effects

It should be noted that the properties of enantiomers in chiral environments are different. In organisms, various enzymes and substrates are chiral, so enantiomers show great differences in physiological effects and pharmacological activities. In the 1960s, a large number of deformed babies with abnormal hands and feet were born across Europe. Investigations revealed that the mothers had taken a chiral drug, thalidomide, during pregnancy.

If a pair of enantiomers are mixed together in equal amounts, a composition with zero optical rotation can be obtained, which we call a racemate. Thalidomide is the racemate of the chiral drug thalidomide. R-thalidomide has the effects of relieving pregnancy reactions, stopping vomiting and sedation, while S-thalidomide has strong teratogenicity. Therefore, the drug thalidomide formed by mixing R-thalidomide and S-thalidomide will cause fetal malformation.

In the field of chemistry, chiral molecules have many important applications, especially in the field of medicine. Drug molecules are usually chiral. The enantiomers of chiral drugs may have different bioavailability and metabolic rates in the body, and the therapeutic effects and toxicity of drugs may vary significantly due to the different chiral isomers. Currently, more than 50% of drugs on the market are chiral drugs.

Recent progress in chirality-related research

At present, the international frontiers of chirality research are mainly divided into the following aspects: First, the synthesis and separation technology of chiral substances. Since chiral drugs have different efficacy and toxicity, there are very high requirements for the synthesis and separation technology of drugs. At present, researchers mainly rely on chiral separation technology and asymmetric synthesis technology to solve this problem. The Nobel Prize in Chemistry in 2001 and 2021 were both awarded in the field of chiral asymmetric synthesis.

Secondly, chirality inspires us to rethink the origin of life on Earth and even the universe. Why does life need chirality? The mechanism of action of chiral compounds in living organisms has always been a hot topic pursued by researchers.

As an important natural property, chirality has penetrated into many fields such as chemistry, life sciences, and materials science, and its research is also developing in depth. Mastering some basic knowledge of chirality will help us correctly understand and view chiral drugs in life and deeply understand chiral phenomena in nature.

(The first author is a professor and doctoral supervisor at Northwest Normal University, and the second author is a master's student at Northwest Normal University)