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Scientists from St. Petersburg State University, together with researchers from the St. Petersburg Federal Research Center of the Russian Academy of Sciences and the Research Center for Environmental Safety of the Russian Academy of Sciences, have developed a new organic compound, the biological activity of which is increased under the influence of a laser. The created phosphonate will allow a more accurate and safer effect on the cells of the body.
The problem of the controlled effect of drugs on the human body is being actively studied today in photopharmacology - the field of pharmaceuticals that studies substances that change their activity under the influence of light. Chemists at St. Petersburg State University have developed a new phosphonate capable of being controlled by light, that is, increasing its biological activity, for example, when the substance reaches the area of ​​inflammation.
Typically, photopharmacological agents consist of a drug and a photoactive switch that activates it. However, scientists have obtained a compound that performs both functions at the same time - these are phosphorylated arylaminomalonates. Under the influence of a laser, a part of the molecule of a substance (phosphonate group) literally turns, thus changing the shape and structure of the entire molecule in space, which leads to an increase in biological properties.
The substance obtained by chemists can find its use in ophthalmology, the treatment of neurodegenerative diseases (for example, Alzheimer's disease) and other fields of medicine, since the synthesized phosphonate is an inhibitor of cholinesterase, an important enzyme of the nervous and other systems of the human body. Already, there are publications explaining how the leveling of cholinesterase is involved in the treatment of skin diseases - you can apply a drug to the skin, illuminate it, and thus “turn it on” or “turn it off”.
Earlier, a research group of scientists from St. Petersburg State University and St. Petersburg Federal Research Center of the Russian Academy of Sciences - NCEB RAS developed a substance, the biological activity of which decreases under the influence of light. The new phosphonate has the opposite effect: a directed laser beam with a wavelength of 266 or 325 nanometers changes the absorption spectrum and enhances the biological activity of the substance. This result is achieved at once at two wavelengths (one of them - 266 nanometers - previously allowed researchers to "turn off" the activity of the substance).
As noted by the author of the study, Professor of the Department of Laser Chemistry and Laser Materials Science of St. Petersburg State University, Doctor of Chemical Sciences Alina Manshina, the substances created by scientists belong to the same group, but respond differently to optical effects: one is "turned on" and the other is "turned off." In the future, these compounds may be able to be used together, controlling both "on" and "off", but this requires additional research.
“Our main merit is that we were the first to discover such a reaction of phosphonates to optical radiation - no one has previously studied the change in the properties of phosphonates using a light beam. It is also important that the substances we have created do not just somehow react to light, they change their shape under the influence of a laser, that is, they significantly change their biological activity. Such a find is a kind of accident, which is often found in science, but we managed to experimentally verify and describe it, ”Alina Manshina said about the study.

“It is also important that the substances we have created do not just somehow react to light, they change their shape under the influence of a laser, that is, they significantly change their biological activity. Such a find is a kind of accident, which is often found in science, but we managed to experimentally verify and describe it, ”Alina Manshina said about the study.
In addition, scientists have noticed that the biological properties of phosphonates are also influenced by the substituent substances that make up the compound. In the structure of the resulting substance there is a so-called phenyl ring, to which different elements can be attached: fluorine, bromine, chlorine, hydrogen or a methyl group CH3. Thus, one and the same substance - phosphonate - will eventually be endowed with different biological properties, since different substituents will react differently to laser exposure.
For some substances, the biological activity increases very slightly, while for others the activity increases to 90–95% - this is a very large increase, which indicates the effect of the substituent substance in the structure of the molecule. Thus, the biological activity after irradiation increases in the order PhAM-F> PhAM-Cl> PhAM-Br. The greatest increase in inhibitory ability is observed in fluorine-substituted phosphonate - 6.5 times.
An experimental study of the effect of optical radiation on the biological properties of phosphonates was carried out at the Resource Center "Optical and Laser Methods for Investigating Matter" of the Science Park of St. Petersburg State University. The work on the part of the St. Petersburg Federal Research Center of the Russian Academy of Sciences was carried out within the framework of the state assignment of the Ministry of Education and Science of the Russian Federation for 2019–2021 (No. АААА-А19-119020190099-1) with the support of the Center of Excellence Photonics Center, funded by the Ministry of Science and higher education of the Russian Federation (contract No. 075-15-2020-906).
“Potentially, this can be used to solve the problems of personalized medicine, which takes into account the characteristics of each person and selects the optimal doses and duration of exposure to the substance,” explained Alina Manshina.
In the future, the researchers want to study in more detail how the developed chemicals affect the body and whether they are capable of causing damage to tissue cells. Testing for cytoxicity will allow you to more accurately determine the field of application and begin clinical trials, and then use in real practice.
“We are well aware that the path from a substance that we synthesized in a test tube and the results of experiments to the production of a specific drug and its launch on the market is very long. But we are also interested in finding that key moment that determines whether a substance will react to optical radiation or whether this phosphonate will be insensitive to laser action, we will devote new research to finding answers to these questions, ”said Alina Manshina.
Article published in the New Journal of Chemistry
PHOTO: Mechanism of rotation of a part of a molecule under the influence of a laser © Press Service of St. Petersburg State University
Source: Press Service of St. Petersburg State University, sci-dig.ru