Iron nicotinatoascorbate: synthesis, toxicity, application prospects

In this work, the effect of a triple chelate iron-containing complex on laboratory animals was investigated. To synthesize the triple chelate iron-containing complex, vitamin B₃ was mixed with ascorbic acid in a molar ratio of 1:1. The synthesis was carried out by a mechanochemical method from a ferrous sulfate precursor. Quantum-chemical modeling of the interaction of iron with vitamins C and B₃ was carried out using the QChem program. As a result, it was found that the optimal interaction is the iron atom with vitamin B₃ through the carboxyl group and tertiary amino group in the pyridine ring, and with vitamin C through a pair of hydroxyl groups attached to the C₅ and C₆ atoms of vitamin C (E = -2372.470 kcal/mol, η = 0.153 eV). Then, a study was carried out on the effect of the developed complex on the hematological parameters of laboratory animals. When studying the acute toxicity of ferrous nicotinate ascorbate, behavioral reactions, food and water consumption, and respiratory rate in all animals of the experimental groups remained within the normal range and did not differ from the control. It was found that toxic doses exceed the maximum possible concentrations and maximum possible volumes with intragastric administration of the drug LD50 > 5000 mg/kg, therefore the developed compound belongs to low-hazard substances. Then, the subacute toxicity of ferrous nicotinate ascorbate was studied with intragastric administration. It was found that repeated use of the drug in the tested doses did not cause significant changes in the clinical condition of white rats. The rats retained motor activity comparable to that of the control animals. All changes that were found in the hematological picture of the blood of the experimental rats corresponded to the reference values for this type of animal.

1. Kodentsova V.M., Vrzhesinskaya O.A., Risnik D.V., Nikityuk D.B., Tutelyan V.A. Micronutrient status of population of the Russian Federation and possibility of its correction. state of the problem. Problems of nutrition. 2017; 86(4): 113–124 (in Russian). https://www.elibrary.ru/zftklt

2. Kasymov S.K., Rebezov M.B. Development of functional foods for ecologically unfavorable regions. Bulletin of the South Ural State University. Series: Food and Biotechnology. 2015; 3(3): 83–91 (in Russian). https://elibrary.ru/uhajfx

3. Bril Yu.A. Zone of personal responsibility. StatusPraesens. Ginekologiya, akusherstvo, besplodnyy brak. 2017; (3): 79–90 (in Russian). https://www.elibrary.ru/vsekth

4. Skalny A.V. Microelements: Vigor, Health, Longevity. 4th ed. Moscow: Pero. 2019; 294 (in Russian). ISBN 978-5-00150-066-7

5. Sorokina A. Anemia in pregnant women. Vrach. 2015; (5): 65–70 (in Russian). https://www.elibrary.ru/twmwjz

6. Mayurnikova L.A., Koksharov A.A., Krapiva T.V., Novoselov S.V. Food Fortification as a Preventive Factor of Micronutrient Deficiency. Food Processing: Techniques and Technology. 2020; 50(1): 124–139 (in Russian). https://doi.org/10.21603/2074-9414-2020-1-124-139

7. Saidova G.T., Sayfullayeva. S.G., Boriboyev U.F. Biological significance of important microelements, such as zinc, iodine, iron, in the human body. Research Journal of Trauma and Disability Studies. 2024; 3(2): 433–435. (in Russian)

8. Ostapenko V.A. Iron and its role in the human body. Fundamental and applied research in the context of geopolitical instability. Proceedings of the XXIII All-Russian Scientific and Practical Conference. Rostov-on-Don: Manuskript. 2023; 180–184 (in Russian). https://www.elibrary.ru/mjzmrp

9. Stuklov N.I., Kovalchuk M.S., Gurkina A.A., Kislyi N.D. Epidemiology of iron deficiency in Russia: serum ferritin values depending on sex and age. Clinical Medicine (Russian Journal). 2023; 101(6): 308–314 (in Russian). https://doi.org/10.30629/0023-2149-2023-101-6-308-314

10. Lytkina K.A. Iron deficiency and immunity: what’s new in the third decade of the 21st century? The unique capabilities of ferrocerone. Practitioner. 2022; (5–6): 70–76 (in Russian). https://doi.org/10.51793/OS.2022.25.6.013

11. Petunina N.A., Martirosian N.S., Truhina L.V. Thyroid dysfunction and hematopoietic system. Clinical and Experimental Thyroidology. 2011; 7(4): 27–31 (in Russian). https://www.elibrary.ru/qzgmzz

12. Gorokhovskaya G.N., Martynov A.I., Yun V.L. Modern possibilities of diagnostics and treatment of anemia of pregnancy. Medical alphabet. 2016; 1(8): 45–51 (in Russian). https://www.elibrary.ru/wmnmjb

13. Vavilina E.D., Nikitina E.V., Makshanova G.P., Fedorova Yu.S. Effects of deficiency of certain trace elements on the child’s body. Integration of Theory and Practice in Medicine: Achievements and Prospects. Collection of scientific articles. Kemerovo: Kemerovo State Medical University. 2024; 82–92 (in Russian).

14. Vorobyov P.A. Anemia syndrome in clinical practice. Moscow: N′yudiamed. 2001; 168 (in Russian). ISBN 5-88107-034-8

15. Shermatov R.M., Kabilova D.K., Rayimova Z.M., Babadjanova Kh.M., Khaydarov N.S. Mild form of iron deficiency anemia and a latent iron deficiency as a border — line state in infants aged under 2 years. BIO Web of Conferences. 2023; 65: 05024. https://doi.org/10.1051/bioconf/20236505024

16. Cherkasov V.S., Nastausheva T.L. On the role of iron and the consequences of its deficiency in young children. Scientific and Medical Bulletin of the Central Black Earth Region. 2024; 25(95): 56–64 (in Russian). https://doi.org/ 10.18499/1990-472X-2024-25-1-56-64 EDN OQOXKF

17. Blinov A.V., Golik A.B., Gvozdenko A.A., Prasolova A.V., Pirogov M.A., Rekhman Z.A. Iron Ascorbate Threonine (II) as a New Chelated Form of Essential Iron for Food Fortification. Food Industry. 2024; 9(1): 82–90 (in Russian). https://doi.org/10.29141/2500-1922-2024-9-1-9

18. Tutelyan V.A., Sukhanov B.P. Modern approaches to the maintenance of quality and safety of biologically active additivies in the Russian Federation. Pacific Medical Journal. 2009; (1): 12–19 (in Russian). https://www.elibrary.ru/kpytgz

19. Sorokina S.V. Chelate compounds of metals in medicine, chelate therapy. Science of the young - the future of Russia. Collection of scientific articles of the 8th International scientific conference of promising developments of young scientists. Kursk: Universitetskaya kniga. 2023; 6: 226–229 (in Russian). https://elibrary.ru/uquvsq

20. Spirichev V.B. Food supplements as a supplementary source of vitamins in the nourishment of the healthy and ill people. Problems of nutrition. 2006; 75(3): 50–58 (in Russian). https://elibrary.ru/htowvv

21. Blinov A.V., Pirogov M.A., Gvozdenko A.A., Golik A.B., Yakovenko A.A., Blinova A.A. Determination of the optimal configuration of triple chelate complexes of the essential trace element zinc with vitamin C and essential amino acids. Modern Science and Innovations. 2022; (4): 93–102 (in Russian). https://doi.org/10.37493/2307-910X.2022.4.9

22. Kostenko K.V., Blinov A.V., Poydun P.A., Pirogov M.A., Serov A.M., Rebezov M.B. A functional drink based on reconstituted whey powder and a triple chelate complex of the essential trace element zinc. Agrarian science. 2024; (12): 158–165 (in Russian). https://doi.org/10.32634/0869-8155-2024-389-12-158-165

23. Grigorieva A.S., Kanakhovich N.F., Shapovalov S.O., Dolgaya M.Н., Uzlenkova N.E. Gemaprotektor and gemostimul of activity of esmin at gemolitic anaemia for rats. Odesa National University Herald. Biology. 2011; 16(18): 82–88 (in Ukrainian). https://www.elibrary.ru/uhtdaz

24. Dolgaya M.Н. Influence of microelement composition on physiology status in the conditions of rats’ organism. The Animal Biology. 2011; 13(1–2): 98–102 (in Ukrainian). https://www.elibrary.ru/rkuvsn