MOLECULAR BINDING OF 2-PHENYLETHYLAMINE BY β-CYCLODEXTRIN
Abstract
The paper considers the results of an experimental study of the synthesis of 2-phenylethylamine, a biogenic amine, which is the initial link in natural neurotransmitters and is used in pharmacological practice as an antidepressant and a remedy for the treatment of neurological disorders. The target amine was synthesized by reduction of phenylacetonitrile with lithium borohydride and decarboxylation of the sodium salt of phenylalanine. The reduction reaction proceeds in aqueous ethanol at room temperature, which increases the yield of the product. At the same time, the resulting product quickly passes in air into an insoluble carbonate. Decarboxylation occurs when the sodium salt of phenylalanine is fused with an alkali, which leads to the partial formation of a condensation product, 3,6-dibenzylpiperazine-2,5-dione, at a high temperature. It is shown that both methods lead to the synthesis of the product with yields of about 45%. The inclusion complex of phenylethylamine with β-cyclodextrin, acting as an encapsulator - a container for molecular binding, was obtained by the suspension method. Binding occurs in an aqueous suspension, followed by washing the amine with acetone. The structure of the obtained compounds was proved by the method of nuclear magnetic resonance spectroscopy on 1H nuclei, as well as by thin-layer chromatography. Comparison of the integral intensities of the signals of the protons of the cyclodextrin framework and protons of the amino group of phenylethylamine showed that the process is accompanied by a transition to the bound form of 65% amine at a ratio of cyclodextrin : amine 3:2. It can be expected that such binding can be used in pharmacological practice to increase the stability of the amine, its targeted transport in the body and prevent premature processes of its destruction under the action of the monoamine oxygenase enzyme.
For citation:
Sutyagin A.A., Menshikov V.V., Lisun N.M., Weissman V.O. Molecular binding of 2-phenylethylamine by β-cyclodextrin. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2023. V. 66. N 1. P. 28-33. DOI: 10.6060/ivkkt.20236601.6650.
References
Astakhova A.V., Demina N.B. Modern drug technologies: synthesis, characterization, and use of inclusion complexes between drugs and cyclodextrins (a review). Pharm. Chem. J. 2004. V. 38. N 2. P. 105-108. DOI: 10.1023/B:PHAC.0000032490.04705.ba.
Grachev M.K., Kurochkina G.I., Batalova T.A., Nifantiev E.E. Synthesis and pharmacological tests of some α- and β-cyclodextrins derivatives. Nauka Shkola. 2013. N 3. Р. 179-181 (in Russian).
Kedik S.A., Panov A.V., Tyukova V.S., Zolotareva M.S. Cyclodextrins and their application in pharmaceutical industry (review). Razrab. Registr. Lekarstv. Sredstv. 2016. N 3 (16). P. 68-75 (in Russian).
Metera A., Dłuska E., Markowska-Radomska A., Tudek B., Kosick K. Surface functionalized emulsion for selective drugs transport. ChemChemTech. [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2019. V. 62. N 8. P. 113-119 (in Russian). DOI: 10.6060/ivkkt.20196208.5925.
Sutyagin A.A., Glazyrin A.E., Grachev M.K., Kurochkina,G.I., Nifant'ev E.E. Cyclophosphorylation of tert-butyldimethylsilyl derivatives of cyclodextrins. Rus. J. Gen. Chem. 2001. 71(6). P. 884–887. DOI: 10.1023/A:1012349400638.
Cocchi V., Gasperini S., Hrelia P., Lenzi M., Tirri M., Marti M. Novel psychoactive phenethylamines: impact on genetic material. Int. J. Molec. Sci. 2020. V. 21. N 24. P. 1-17. DOI: 10.3390/ijms21249616.
Levine M., Lovecchio F. New designer drugs. Emerg. Med. Clin. North Am. 2021. V. 39. N 3. P. 677-687. DOI: 10.1016/j.emc.2021.04.013.
Kulinsky V.I., Kolesnichenko L.S. Molecular mechanisms of hormonal activity. I. Receptors. Neuromediators. Systems with second messengers. Biochem. (Moscow). 2005. V. 70. N 1. P. 24-39. DOI: 10.1007/s10541-005-0003-9.
Apryatin S.A., Karpenko M.N., Muruzheva Z.M., Bolshakova M.V., Magazenkova D.N., Klimenko V.M. Neu-rodegenerative and metabolic disorders, mediated by the trace amines and their receptors. Med. Akad. Zurn.. 2020. V. 20. N 1. P. 9-22 (in Russian). DOI: 10.17816/MAJ25746.
Lewin A.H., Navarro H.A., Wayne Mascarella S. Structure-activity correlations for β-phenethylamines at human trace amine receptor 1. Bioorg. Med. Chem. 2008. V. 16. N 15. P. 7415-7423. DOI: 10.1016/j.bmc.2008.06.009.
Drogovoz S.M., Lukyanchuk V.D., Sheyman B.S. Antidepressants in the focus of drug toxicology. Meditsina Neotlozh. Sost. 2014. V. 2. N 57. P. 90–94 (in Russian). DOI: 10.22141/2224-0586.2.57.2014.83138.
McCreary A.C., Müller C.P., Filip M. Psychostimulants: basic and clinical pharmacology. Int. Rev. Neurobiol. 2015. V. 120. P. 41-83. DOI: 10.1016/bs.irn.2015.02.008.
Lee Y.-J., Kim H.R., Lee C.Y., Hyun S.-A., Ko M.Y., Ka M., Hwang D.Y., Lee B.-S. 2-Phenylethylamine (pea) ame-liorates corticosterone-induced depression-like phenotype via the bdnf/trkb/creb signaling pathway. Int. J. Molec. Sci. 2020. V. 21. N 23. P. 1-17. DOI: 10.3390/ijms21239103.
Obata Y., Mizuno M., Nemoto T., Kubota-Sakashita M., Kasahara T., Kato T. Phenethylamine is a substrate of monoamine oxidase B in the paraventricular thalamic nucleus. Sci. Rep. 2022. V. 12. N 1. DOI: 10.1038/s41598-021-03885-6.
Gattuso G., Notti A., Parisi M.F., Pisagatti I., Pappalardo S., Patanè S. Encapsulation of monoamine neurotransmitters and trace amines by amphiphilic anionic calix [5] arene micelles. New J. Chem. 2014. V. 38. N 12. P. 5983-5990. DOI: 10.1039/C4NJ01184H.
Sáez J.A., Escuder B., Miravet J.F. Supramolecular hy-drogels for enzymatically triggered self-immolative drug delivery. Tetrahedron. 2010. V. 66. N 14. P. 2614-2618. DOI: 10.1016/J.TET.2010.02.033.
Yakovishyn L.O. The molecular complex of monoammoni-um glycyrrhizinate (glycyram) with β-cyclodextrin. Zhurn. Org. Pharm. Khim. 2012. V. 10. N 4 (40). P. 71-75 (in Russian).
Sumina E.G., Atayan V.Z., Shtykov S.N. Application of cyclodextrin mobile phases in thin-layer chromatography of organic reagents of xanthene and quinoline series. Sorbts Khromatograf. Prots. 2008. V. 8. N 1. P. 83-93 (in Russian).
Nekhoroshev S.V., Moiseeva E.S., Sharko S.P., Moiseeva O.I. Сhromatographic identification of some phenethylamine derivates. Anal. Kontrol. 2014. V. 18. N 2. P. 182–187 (in Russian). DOI: 10.15826/analitika.2014.18.2.007.
Steiman T.J., Liu J., Mengiste A., Doyle A.G. Synthesis of β-phenethylamines via ni/photoredox cross-electrophile coupling of aliphatic aziridines and aryl iodides. J. Am. Chem. Soc. 2020. V. 142. N 16. P. 7598-7605. DOI: 10.1021/jacs.0c01724.
Molander GA, Vargas F. Beta-aminoethyltrifluoroborates: efficient aminoethylations via Suzuki-Miyaura crosscoupling. Org Lett. 2007. N 9(2). P. 203-206. DOI: 10.1021/ol062610v.
Kapustin М.А., Chubarova А.S., Halavatch Т.N., Cigankov V.G., Bondaruk A.M., Kurchenko V.P. Methods of active compounds with cyclic oligosaccharides nano-complexes obtaining, analysis of it physical and chemical properties and use in food production. Tr. Belorus. Gos. Un-ta. Ser. Fiziolog., Biokhim. Molek. Osn. Funkts. Biosistem. 2016. V. 11. N 1. P. 73-100 (in Russian).
Sutyagin A.A., Vaisman V.O. Synthesis and molecular binding of phenylethylamine. Tez. dokl. uch. rep. conf. s internats. uch. "Physico-chemical biology as the basis of mod-ern medicine". Minsk: Belarusian State University. 2020. P. 173-175 (in Russian).
