Many compounds which are necessary to sustain life on Earth can exist in two forms. These are so-called enantiomers which, despite having the same chemical formula, are characterised by varied optical activity and, thereby, completely different biological effects. Nowadays, more and more medicinal products contain only selected enantiomers of substances that were used earlier. This makes it possible to not only improve their therapeutic efficacy, but also to reduce the risk of adverse reactions. Polish scientists have made an important discovery in the field of enantiomer research, and its results have been published in the prestigious Angewandte Chemie International Edition journal.
A group of scientists from the Faculty of Chemistry, Jagiellonian University, working closely with researchers from the Institute of Organic Chemistry, Polish Academy of Sciences in Warsaw, and the Institute of Plant Biology and Biotechnology, University of Agriculture in Kraków, demonstrated the origin of the optical activity of biological macromolecules. “We have shown that the molecules which are not optically active can, under certain conditions, create optically active systems, and the process takes place in nature,” said Prof. dr hab. Małgorzata Barańska from the Department of Chemical Physics at the Faculty of Chemistry, Jagiellonian University. “What spurred out research was the observation of a high optical activity of carotene crystals that naturally occur in the carrot. The crystals are 95 percent composed of optically inactive beta-carotene and only 5 percent of optically active alpha-carotene. We first observed this phenomenon in the model system, i.e. in carrot tissue cultures obtained at the laboratory of the Institute of Plant Biology and Biotechnology, University of Agriculture in Krakow. However, as we found out in further research, the crystals which accumulate naturally in carrot root cells also display this property,” added Prof. Barańska.
The mystery of chirality
As a result, the researchers proposed a hypothesis that the optical properties of carotene crystals are the result of inducing so-called chirality. A property of molecules, chirality is responsible for their optical activity and entails structural asymmetry which makes the mirror image of the molecule dissimilar to the original molecule. In other words, these two molecules – the original and the mirror image – are not superimposable, and that’s what makes them enantiomers. This is the case, for example, with human hands, where the left and right are the mirror images of each other, yet it is not possible to superimpose one on the other. There are many naturally occurring chiral compounds. The majority of constituents making up living organisms has a chiral structure, including amino acids, sugars, nucleic acids, and proteins. This is why unveiling the mystery of chirality is so important.
“In our research into the induction of chirality in carotene crystals, we used, in addition to natural crystals isolated in carrots, model systems created in the laboratories of the Institute of Organic Chemistry, Polish Academy of Sciences, which contain deuterium, a hydrogen isotope. Through this modification, we were able to precisely track the history and behaviour of individual molecules,” explained Prof. Barańska. Scientists have proven that the induction of chirality in carotene systems follows the “sergeants and soldiers” principle. A chiral (optically active) compound, which is relatively sparse in terms of quantity (alpha-carotene), serves as a sergeant controlling achiral (optically inactive) and much more numerous soldier molecules (beta-carotene). “We have demonstrated that this system, despite consisting mostly of achiral beta-carotene, exhibits strong optical activity determined by the presence of chiral alpha-carotene in small quantities. We could achieve such surprising results thanks to using the cutting-edge equipment of the Raman spectroscopy laboratory at the Jagiellonian Centre for Experimental Therapeutics, recording the Raman Optical Activity of the tested carotene systems. Since it turned out that the ROA of the studied carotene crystals can be enhanced through resonance, we were able to analyse carotene aggregates which occur naturally in very small, micro-mole concentrations,” highlighted Prof. Barańska.
Discovering the phenomenon of chirality induction was possible owing to scientific cooperation of three research groups, encompassing teams financed by the FNP with the Smart Growth Operational Programme (SG OP) funds. Among these is the team led by Prof. Jacek Młynarski from the Institute of Organic Chemistry, Polish Academy of Sciences, which is implementing a grant within the TEAM programme.
photo: Krzysztof Sordyl