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- Secrets of selenium: scientists accelerate the development of drugs and contrast agents for MRI
Secrets of selenium: scientists accelerate the development of drugs and contrast agents for MRI
Russian scientists have significantly accelerated the development of new medicines and agrochemicals based on selenium. It plays an important role in biology and medicine, as it is part of enzymes that protect cells from oxidative stress, for example, and promising anticancer drugs. In addition, the developed method promises revolutionary changes in diagnostic medicine, where it will be possible to create new highly sensitive contrast agents for MRI, the scientists told Izvestia.
What is nuclear magnetic resonance?
Scientists from the International Tomographic Center of the Siberian Branch of the Russian Academy of Sciences (Novosibirsk), the R.E. Alekseev Nizhny Novgorod State Technical University (Nizhny Novgorod) and the A.N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences (Moscow) have found a way to accelerate the search for selenium-containing molecules. They play an important role in medicine due to their antioxidant and immunomodulatory properties, as well as their involvement in hormonal metabolism, especially in the thyroid gland.
The nuclear magnetic resonance (NMR) method is used to study the molecules. As part of this approach, a molecule is placed in a magnetic field, under the influence of which the intrinsic magnetic moments (spins) of its nuclei are oriented in the direction of an external magnetic field. As a result, the nuclei absorb or emit certain radio frequency signals specific to different elements, which can be used to determine the chemical composition and molecular structure of the compounds. However, the spins of not all nuclei react strongly enough to the magnetic field, which is why the signal from them is too weak.
The signal deficiency is especially pronounced in the case of rare isotopes, variants of the same atom with different masses.
One of them, selenium—77, plays an important role in biology and medicine, as it is a part of enzymes, for example, protecting cells from oxidative stress, and promising anticancer drugs. Therefore, to detect it in molecules, it is necessary to use methods that enhance the signal, but they are expensive, require complex equipment and extremely low temperatures, and therefore difficult to implement.
A selenediazole molecule polarized with hydrogen vapor
As part of the new approach, the substance under study is placed in a magnetic field along with an iridium catalyst, the scientists said. Then hydrogen vapor is passed through the solution, a form of a hydrogen molecule in which the magnetic moments (spins) of the nuclei are oriented in opposite directions. Such a compound is "invisible" to the detecting device, so its presence does not distort the analysis results.
— The proposed technology is promising in several fields of science at once. In the pharmaceutical industry, it can significantly accelerate the development of new medicines and agrochemicals," Alexey Kiryutin, project manager and senior researcher at the Laboratory of Photochemical Radical Reactions at the International Tomographic Center of the Siberian Branch of the Russian Academy of Sciences, told Izvestia.
Magnetic resonance imaging
According to him, biomedical research opens up unique opportunities for monitoring biochemical processes involving selenium.
"In addition, the method promises revolutionary changes in diagnostic medicine, and it will be possible to create new highly sensitive contrast agents for magnetic resonance imaging," the scientist noted.
How to use selenium-77
The authors applied the proposed method to analyze a selenium-containing organic compound with potential antimicrobial and antitumor activity. With the help of a new approach, scientists in 12 thousand The signal from selenium nuclei was amplified once and rare molecules with two nuclear isotopes in their composition, selenium—77 and nitrogen-15, were detected in the sample, the proportion of which was only 0.028% of the total number of studied molecules.
The developed method will be especially valuable in the study of promising selenium—containing drugs, in particular, compounds of the selenediazole class, which demonstrate pronounced antitumor and antimicrobial activity, the experts noted.
— Scientists have significantly increased the sensitivity of the analysis, which facilitates the process of creating a dosage form and allows us to develop convenient methods for studying the distribution of a drug in the body, pharmacokinetics and pharmacodynamics, and the entire range of biopharmaceutical research. In addition, it allows us to develop convenient, fast methods for drug quality control, if any," Andrei Kritchenkov, professor at the Patrice Lumumba Peoples' Friendship University of Russia and head of the Laboratory of Sonochemistry at the Institute of Technical Acoustics of the National Academy of Sciences of Belarus, told Izvestia.
Employees of the ITC SB RAS at the NMR spectrometer with magnetic field switching. From left to right: Alexey Kiryutin, Alexandra Yurkovskaya, Danil Markelov
The proposed method can be used to analyze complex mixtures of organoselenium compounds even at very low concentrations, said Alexander Tskhovrebov, a leading researcher at the Joint Institute of Chemical Research of the Rudn University.
"Due to such a significant signal amplification, the new method significantly expands the capabilities of NMR spectroscopy in the study of selenium compounds," he stressed.
Selenium-77 is especially valuable in areas where high accuracy and safety are needed: it is not radioactive, but it gives a clear signal in NMR, which makes it an ideal tool for developing personalized medicine and next-generation selenium drugs, said Sergey Kharitonov, a molecular biologist and researcher at the Faculty of Soil Science at Lomonosov Moscow State University..
The results of the study, supported by a grant from the Russian Science Foundation (RSF), are published in the Journal of the American Chemical Society.
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