When we look at the world at the molecular level, nature turns out to be surprisingly “handed.” Many molecules can exist in two forms that are mirror images of each other, like a left and a right hand. Chemically, these molecules can be very similar, but they often behave very differently in living organisms.

This is why handedness, or chirality, is important in the development of medicines, food products, fragrances, and pesticides. One mirror-image form may produce the desired effect, while the other may be much less effective or have a completely different effect. In nature, enzymes, receptors, and cellular processes can recognize molecules with the correct handedness, much like a hand fitting into the right glove.

But how can this system be created in the laboratory? To distinguish between chiral molecules, the material used to detect them must itself have some form of “handedness.” Researchers from TalTech’s supramolecular chemistry research group led by Riina Aav have found a way to transfer chirality from one molecule to another. To achieve this, they combined two very different types of molecules.

One type was porphyrins—molecules related to compounds found, for example, in hemoglobin and chlorophyll. Their strong optical properties make them well suited for detecting signals, but they cannot distinguish between the handedness of molecules. The second type was hemicucurbiturils—ring-shaped molecules that can be prepared in two mirror-image forms. The researchers found that when an achiral, or “non-handed,” porphyrin binds to a chiral hemicucurbituril, the porphyrin itself begins to behave like a chiral molecule. In other words, handedness can be “taught” to a molecule, and the researchers were able to measure this phenomenon using specialized optical methods.

The study described 31 new molecular structures, showing the many different ways in which porphyrins and hemicucurbiturils can assemble. TalTech doctoral researcher and first author of the paper Marko Šakarašvili comments: “The most surprising finding was that, depending on the components used, the molecules organized into very different structures—isolated complexes, long chains, and even mirror-image helical structures. This shows how flexible this molecular system actually is.”

Binding of porphyrin to a chiral hemicucurbituril leads to the formation of mirror-image chiral structures | Figure: Marko Šakarašvili/TalTech

The results showed that the behavior of the molecules can be directed by choosing relatively simple building blocks. This opens up the possibility of creating a whole “library” of chiral materials with different properties that respond to different molecules. Even more encouraging was the fact that the system worked particularly well in the solid state. In some cases, the chiral signal was up to ten times stronger than in solution. “In nature, the recognition of chiral molecules is highly precise, but it is difficult to replicate this in the laboratory. Our work shows that relatively simple molecules can be used to build a whole range of chiral materials with different properties that could be used in new sensors in the future,” says Šakarašvili.

The practical potential of these materials has been demonstrated in collaboration with researchers at the University of Rome Tor Vergata, where combinations of porphyrins and hemicucurbiturils were used as sensing materials in an electronic nose to distinguish between mirror-image molecules.

Such materials could eventually be used wherever mirror-image molecules need to be distinguished quickly and accurately—for example, in pharmaceutical quality control, food and fragrance analysis, or environmental monitoring. The study shows that achieving complex chiral behavior does not always require complex molecules. Sometimes, it is enough to combine the right building blocks and let them self-organize.

The study was published in the journal Inorganic Chemistry.