Research into complexes of triethanolamine with ZnCl₂ and CdCl₂ using NMR Spectroscopy and Quantum Chemistry methods

Complexes of triethanolamin with ZnCl₂ and CdCl₂ were studied using the methods of quantum chemistry and NMR spectroscopy. Triethanolamine complexes are prone to ligand exchange, which make them suitable as metal transporters. Therefore, research into the biological action of such compounds is of particular importance. ¹H and ¹³C NMR spectra were recorded using a Bruker DPX250 pulsed spectrometer operated at 298 K. Non-empirical quantum-chemical calculations were performed by the B3LYP method using the Gaussian 09 software package. Changes in the chemical shifts and spin-spin coupling constants during the formation of triethanolamine complexes with heavy metals were studied. The obtained experimental data indicate that changes in the NMR spectrum shifts are accompanied by an increase in the spinspin coupling constants, with the ¹J(C, H) constants of the methylene group associated with nitrogen being the most significant. On the basis of the conducted NMR spectrum analysis, the authors propose a scheme for describing the structure and intermolecular dynamics of the complexes under study. In order to elucidate the observed changes in the NMR spectra of triethanolamine in the process of complex formation, a series of quantum-chemical calculations was carried out. Three states corresponding to mono-, bi- and tricyclic structures were taken into account. According to the obtained theoretical and experimental results, the complexes under study are characterized by intermolecular metabolic processes that lead to the averaging of NMR signals from various compounds existing in the solution. For triethanolamine complexes with CdCl₂, the existence of bi- and tricyclic forms is equally probable. For triethanolamine complexes with ZnCl₂, the tricyclic form seems to be more beneficial.

1. Pinkert A, Ang KL, Marsh KN, Pang S. Density, viscosity and electrical conductivity of protic alkanolammonium ionic liquids. Physical Chemistry Chemical Physics. 2011;13(11):5136-5143. https://doi.org/10/1039/c0cp02222e

2. Mirskova AN, Mirskov RG, Adamovich SN, Voronkov MG. 2-Hydroxyethylammonium salts of organylsulphanyl(sylphonyl)acetic acids as new pharmacologically active compounds. Khimiya v interesakh ustoichivogo razvitiya = Chemistry for Sustainable Development. 2011;19(5):467-478. (In Russian)

3. Oberlis D, Harland B, Rocky A. Biological role of macro- and micronutrients in humans andani-mals. St. Petersburg: Nauka; 2008. 248 p. (In Russian)

4. Naiini АА, Young V, Verkade JG. New complexes of thriethanolamine (Tea): Novel structural features of [Y(TEA)2](ClO4)3-3C5H5N and [Cd(TEA)2](NO3)2. Polyhedron. 1995;14(3):393-400. https://doi.org/10.1016/0277-5387(95)93020-2

5. Rasulov MM, Voronkov MG, Nurbekov MK, Mirskova AN, Adamovich SN, Mirskov RG. Complex bis-2-(methylphenoxyacetate) zinc with tris-2-(hydroxythyl) amine - activator of synthesis of total tryptophanyl-tRNA-synthetase. Doklady Akademii nauk. 2012;444(2):219-220. (In Russian)

6. Kolesnikova OP, Mirskova AN, Adamovich SN, Kuznetsova GA, Kudaeva OT, Goldina IA, et al. Screening of immunoactive and antitumor properties of triethanolamine complex with salts of biotrace elements. Byulleten' Sibirskogo otdeleniya Rossii-skoi akademii meditsinskih nauk. 2009;6:73-79. (In Russian)

7. Adamovich SN, Mirskova AN, Kolestenkov OP. Antineoplastic agent. Patent RF, no. 2623034; 2016. (In Russian)

8. Ushakov IA, Voronov VK, Grishmanovskii DS, Adamovich SN, Mirskov RG, Mirskova AN. NMR spectra of metallated alkanolammonium ionic liquids. Russian Chemical Bulletin. 2015;64(1):58-61. https://doi.org/10.1007/s11172-015-0821-x

9. Panyushkin VT, Chernysh YE, Volynkin VA, Borodkin GS, Borodkina IG. Nuclear magnetic resonance in structural studies. Moscow: CRASAND; 2016. 352 p. (In Russian)

10. Voronov VK, Ushakov IA. Structure and intramolecular dynamics of biologically active compounds: analysis of NMR spectra transformed by spin labels. Applications of NMR Spectroscopy. 2016;5:3-62. https://doi.org/10.2174/97816810826751160500006

11. Ushakov IA, Voronov VK, Adamovich SN, Mirskov RG, Mirskova AN. The NMR study of biologically active metallated alkanol ammoinium ionic liquids. Journal of Molecular Structure. 2016;1103:125-131. https://doi.org/10.1016/j.molstruc.2015.08.074

12. Naqi HA, Woodman TJ, Husbands SM, Blagbrough IS. 19F and 1H quantitative-NMR spectroscopic analysis of fluorinated third-generation synthetic cannabinoids. Analytical Methods. 2019;11(24):3090-3100. https://doi.org/10.1039/c9ay00814d

13. Chernyak AV, Slesarenko NA, Volkov VI. Complexes based on calix[4]arene sulfonic acid with acetic acid and Its derivatives: NMR analysis. Applied Magnetic Resonance. 2019;50(1-3):199-209. https://doi.org/10.1007/s00723-018-1063-5

14. Voronov VK. Use of high-resolution NMR spectra transformed by paramagnetic complexes for studying molecular structure. Izvestiya Vuzov. Priklad-naya Khimiya i Biotekhnologiya = Proceedings of Universities. Applied Chemistry and Biotechnology. 2019;9(2)183-193. (In Russian) https://doi.org/10.21285/2227-2925-2019-9-2-183-193

15. Waudby CA, Ouvry M, Davis B, Christodou-lou J. Two-dimensional NMR lineshape analysis of single, multiple, zero and double quantum correlation experiments. Journal of Biomolecular NMR. 2020;74(55):95-109. https://doi.org/10.1007/s10858-019-00297-7

16. Selivanov SI, Wang S, Filatov AS, Stepakov AV. NMR study of spatial structure and internal dynamic of adducts of ninhydrin-derived azomethine ylide with cyclopropenes. Applied Magnetic Resonance . 2020;51(2):165-182. https://doi.org/10.1007/s00723-019-01178-w

17. Krivdin LB, Sauer SPA, Peralta JE, Contreras RH. Non-empirical calculation of NMR indirect carboncarbon coupling constants: 1. Three-membered rings. Magnetic Resonance in Chemistry. 2002;40(3):187-194. https://doi.org/10.1002/MRC.989

18. Rusakov YuYu, Krivdin LB. Modern quantum chemical methods for calculating spin-spin coupling constants: theoretical basis and structural applications in chemistry. Russian Chemical Reviews. 2013;82(2):99-130. https://doi.org/10.1070/RC2013v082n02ABEH004350

19. Krivdin LB. Carbon-carbon spin-spin coupling constants: Practical applications of theoretical calculations. Progress in Nuclear Magnetic Resonance Spectroscopy. 2018;105:54-99. https://doi.org/10.1016/j.pnmrs.2018.03.001