Scientists from RUDN University took an active part in the development of a chemical compound that would help to stop convulsions during epileptic seizures. The results of the study were published in Chirality.
Epilepsy is a chronic neuralgic disease which causes convulsive seizures in humans and other animals. The pathogenesis of this disease is paroxysmal - very strong, acute, repetitive - discharges in the nerve cells of the brain that cause convulsions. Anticonvulsants help to stop the epileptic fit. The drug itself is a powder that is dissolved in water and injected into a person who has such a seizure.
In order to obtain such a drug, scientists have developed a compound with a chirality - an asymmetric carbon atom (chiral center) which, with an absolutely identical chemical composition and similar structure, leads to a configuration incompatibility of the left and right forms of the molecule (a good analogy would be left and right hands). Thus, the nearest environment of the chiral center is a tetrahedron - a regular trigonal pyramid in the middle of which there is a chiral carbon atom and at its vertices there are substituents (atoms or groups of atoms replacing hydrogen atoms in hydrocarbon fragments) of various types. The chirality of such a "construction" is that all these four substituents are differently arranged in space relative to each other. In other words, if we isolate individual 3D models of these tetrahedra from the structure of the molecule and try to combine them, they will not coincide.
"One of the most important areas of our scientific research is chemicals that have potential biological activity. In this case, the studied compounds have a specific activity - they are anticonvulsants. This is a common property of compounds of this class, but in order for compounds to show these properties more efficiently, they must be chirally (optically) pure, that is, the asymmetric centers of all molecules in the total substance mass must be of the same configuration. The published paper is devoted to the method of separation of racemic mixtures which contain molecules with various absolute (R or S) configurations of chiral carbon atoms, " said Victor Khrustalev, Doctor of Chemical Sciences, Head of the Department of Inorganic Chemistry of the Faculty of Physics and Mathematics and Natural Sciences of RUDN University.
Scientists synthesized and studied the structure of 3-ethyl-2-phenylpyrrolidin-2-one (EPP) showing anticonvulsant activity. The named compound can exist in three forms: as two chirally pure R / S stereoisomers and a racemate - a mixture of molecules with different R and S configurations of the asymmetric center.
Structure of 3-ethyl-2-phenylpyrrolidin-2-one (EPP). Source: Victor Khrustalev
All three described forms show biological activity to varying degrees. The authors found that the compound effectively helps to stop convulsions only when it is chirally pure, that is, it contains molecules of only one configuration: either R or S. It should be noted that when the compound is produced under normal conditions a racemate is always formed, which makes it difficult to use in medical practice.
In the course of the work scientists synthesized the compound with the desired chemical formula in the form of a racemate, which was confirmed by the methods of NMR and IR spectroscopy. Then, with the use of high-resolution liquid chromatography the authors divided the racemic mixture into optically pure stereoisomers. Thus, the researchers separated the necessary forms of a given chemical compound, which can later serve as a basis for a new drug. The scientists confirmed that there are molecules of only one configuration in the isolated forms after examining them by means of X-ray diffraction analysis.
The work was carried out in collaboration with scientists from the University of Houston (Houston, Texas, USA), Marquette University (Milwaukee, Wisconsin, USA) and New Mexico Highlands University (Las Vegas, New Mexico, USA).
This article has been republished from materials provided by RUDN University. Note: material may have been edited for length and content. For further information, please contact the cited source.
Krivoshein, A. V., Lindeman, S. V., Timofeeva, T. V., & Khrustalev, V. N. (2017). Racemic and enantiopure forms of 3-ethyl-3-phenylpyrrolidin-2-one adopt very different crystal structures. Chirality, 29(10), 623-633. doi:10.1002/chir.22735