NMR-spectral and structural characteristics of new pyridoxine derivatives

A.S. Tarasov^*, I.Z. Rakhmatullin^**, Yu.G. Shtyrlin^***, V.V. Klochkov^****

Kazan Federal University, Kazan, 420008 Russia

E-mail: ^*tarasov_as2010@mail.ru, ^**IZRahmatullin@kpfu.ru@mail.ru, ^***Yurii.Shtyrlin@kpfu.ru, 

^****Vladimir.Klochkov@kpfu.ru

Received February 22, 2019

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DOI: 10.26907/2542-064X.2019.2.231-244

For citation: Tarasov A.S., Rakhmatullin I.Z., Shtyrlin Yu.G., Klochkov V.V. NMR-spectral and structural characteristics of new pyridoxine derivatives. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2019, vol. 161, no. 2, pp. 231–244. doi: 10.26907/2542-064X.2019.2.231-244. (In Russian)

Abstract

The relevance of the study is determined by the fact that in the last decade pyridoxine derivatives have been widely used for the synthesis of molecules with important biological and physical properties. However, synthesis of the compounds with desirable biochemical or physical properties often requires information about their spatial structure and conformational mobility. NMR spectroscopy is a powerful tool for conformational analysis of biologically important samples, such as pyridoxine derivatives, in solution.

Two new pyridoxine derivatives were studied using high-resolution nuclear magnetic resonance (NMR) spectroscopy: one-dimensional ¹H NMR spectroscopy, two-dimensional ¹H-¹H COSY NMR techniques, dynamic ¹H NMR. The lineshape analysis of obtained spectra was carried out and the values of rate constants of the exchange of assumed conformational processes were calculated in the WinDNMR computer program. The thermodynamic parameters characterizing the transitions between the observed conformers and the types of conformational processes are determined.

Based on the results of the study, the following conclusions were made. The studied compounds are involved into two types of conformational exchange processes: restricted rotations of the dinitrophenyl fragment around the C₁₂–O bond and twist-twist interconversions of the seven-membered ring (for compound 1). Comparison of the obtained results shows that the dynamics of neighboring conformational processes have a significant effect on each other. It was established that the influence of the “twist” process in compound 1 leads to a decrease in the rotation barrier by 10 kJ/mol. This observation can be explained by the increased steric hindrance of the substituents raising the energy of the ground state, and thus lowering the activation energy barrier.

Keywords: pyridoxine, dynamic NMR, conformation, medicine, chemical exchange

Acknowledgments. The study was supported by the Russian Science Foundation (project no. 18-73-10088) and funded in part by the subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities (project no. 3.5283.2017/6.7).

Figure Captions

Fig. 1. The structural formulas of pyridoxine derivatives: a) compound 1; b) compound 2.

Fig. 2. ¹H NMR spectrum of compound 1 in acetone solution at a temperature of 300 K, * – signals from the solvent and impurities.

Fig. 3. ¹H NMR spectrum of compound 2 in an acetone solution at a temperature of 300 K, * – signals from the solvent and impurities.

Fig. 4. The fragments of ¹H NMR spectra of compound 1 (signals CH – 17, 19, 9, 20) at temperatures of –80 ?C…+30 ?C.

Fig. 5. The fragments of ¹H NMR spectra of compound 1 (signals CH₂ – 4, 7, CH₃-13, CH₂ – 8, 24, 21, 23, 22) at temperatures of –80 ?C…+30 ?C.

Fig. 6. The fragments of ¹H NMR spectra of compound 2 (signals CH –17, 19, 9, 20, 2, CH₂ – 4, 7) at temperatures of –80 ?C…+30 ?C.

Fig. 7. The lineshape analysis of the signals CH₃-13 of compounds 1 and 2 and exchange rate constants (k) at various temperatures.

Fig. 8. The dependences of exchange rate constants on temperatures for signals CH₃-13 of compounds 1 and 2.

Fig. 9. Schematic representation of the intramolecular conformational processes and the activation energy of the process of rotation of the dinitrophenyl fragment around the C–O bond in compounds 1 and 2.

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