Creating mirror images of molecules

Many molecules have a right and a left form, like shoes. In pharmaceuticals, it is important that the correct form of the molecule is used. Researchers at the University of Gothenburg, Sweden, have been able to produce a mirror image using crystals with special properties.

Photo credit: Susanne Olsson.

Molecules that are the same but mirror images are called chiral molecules. The mirror image forms of chiral molecules have identical properties except when they interact with other chiral molecules - like the left shoe fitting the left foot better than the right shoe.

Our bodies contain chiral molecules such as amino acids in proteins and sugar molecules in our genetic material. But in all living organisms, only one of the two mirror image forms is used.

“Why it is like this is a mystery to the scientific community, but this is of major significance, to the production of pharmaceuticals for instance,” said Susanne Olsson of Gothenburg’s Department for Chemistry and Molecular Biology.

The mirror images can have different effects in our bodies where one can provide the desired effect while the other, in the worst-case scenario, can give rise to serious side effects.

“Today, all new pharmaceuticals must contain only the mirror image form with the desired effect. But when a chiral molecule is produced in a laboratory, equal amounts of the two mirror images are obtained,” said Olsson.

Creating the active mirror image form is a difficult process. It is produced by adding a mirror image form of another substance - a substance which must then be separated from the pharmaceutical.

So Olsson set out to produce the desired mirror image form without having to add mirror image forms of other substances.

“The generation of optical activity from achiral or racemic precursors - absolute asymmetric synthesis - is … often (incorrectly) regarded as being impossible,” she said.

“One approach to absolute asymmetric synthesis is the use of compounds that form chiral crystals. If the compounds are also stereochemically labile in solution, all crystals in a batch may crystallise as the same enantiomer via total spontaneous resolution.”

Thus, by using compounds where the mirror image molecules switched between the right and left forms, she succeeded in getting all crystals to contain only the one mirror image - without using any other substance.

She noted that the method is industrially usable since crystallisation is a process that is good for large-scale production.

“The rare occurrence of conglomerates means that it is advantageous if the optical activity generated during the crystallisation can be transferred via stereoselective reactions to produce several enantiopure products from a single conglomerate phase,” she said. “For this purpose, organometallic reagents and coordination compounds are well suited, since they combine stereochemical lability in solution with high reactivity.”

Olsson’s dissertation on the subject can be accessed at http://hdl.handle.net/2077/32316.