The study of the optical activity of some S-derivatives 4-R-5-((((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1, 2,4-triazole-3-thiols
DOI:
https://doi.org/10.14739/2409-2932.2022.2.255791Keywords:
1,2,4-triazole, optical activity, polarimetry, enantiomersAbstract
About half of the drugs currently produced are chiral compounds, and about 90 % of these compounds are sold as racemates, consisting of an equimolar mixture of two enantiomers. Although they have the same chemical structure, most of the optical isomers of chiral substances show marked differences in biological activity. It is known that the presence of a single asymmetric atom has become almost an integral part of advanced drug design.
The aim of this work was to determine the angle of rotation of the polarization plane of solutions of some S-derivatives of 4-R-5-((((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl))-4H-1,2,4-triazole-3-thiols and the establishment of regularities between the structure of the studied molecules and their optical activity.
Materials and methods. The subject of the study was 2-[5-R1-4R2-1,2,4-triazole-3-ylthio]-1-aryletanols. The study of the angle of rotation of the plane of polarization of solutions of newly synthesized compounds was carried out using an Atago AP-300 polarimeter and the DFU 2.2.7 physical-chemical analysis method “Optical rotation”.
Results. The results of the physical-chemical analysis were carried out that the studied compounds exhibit optical activity. The compound 1-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)-2-phenylethan-1-ol (+43° [deg∙g/cm3∙dm]). The only levorotatory substance was 1-(4-fluorophenyl)-2-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl)thio))methyl)-4H-1,2,4-triazole-3-yl)thio)ethan-1-ol with specific rotation [α]D20 = -43° [deg∙g/cm3∙dm].
Conclusions. Studies had shown that 1-(4-fluorophenyl)-2-((4-methyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl))thio)methyl)-4H-1,2,4-triazole-3-yl)thio)ethan-1-ol was able to rotate the light polarization plane to the left, which was evidence of the advantage of the S-enantiomer in the racemic mixture, and therefore this compound was considerable interest for further preclinical research. Also, all other analyzed compounds behave as optical isomers.
References
Browne, W. R., Hesek, D., Gallagher, J. F., O'Connor, C. M., Killeen, J. S., Aoki, F., Ishida, H., Inoue, Y., Villani, C., & Vos, J. G. (2003). Structural and photophysical characterisation of coordination and optical isomers of mononuclear ruthenium (II) polypyridyl 1,2,4-triazole complexes. Dalton Transactions, (12), 2597-2602. https://doi.org/10.1039/b301961f
Willia, K., & Lee, E. (1985). Importance of Drug Enantiomers in Clinical Pharmacology. Drugs, 30(4), 333-354. https://doi.org/10.2165/00003495-198530040-00003
Hambuchen, M. D., Hendrickson, H. P., Gunnell, M. G., McClenahan, S. J., Ewing, L. E., Gibson, D. M., Berquist, M. D., & Owens, S. M. (2017). The pharmacokinetics of racemic MDPV and its (R) and (S) enantiomers in female and male rats. Drug and alcohol dependence, 179, 347-354. https://doi.org/10.1016/j.drugalcdep.2017.07.011
Jiang, L., Dziedzic, P., Spacil, Z., Zhao, G. L., Nilsson, L., Ilag, L. L., & Córdova, A. (2014). Abiotic synthesis of amino acids and self-crystallization under prebiotic conditions. Scientific reports, 4, 6769. https://doi.org/10.1038/srep06769
Valimaña-Traverso, J., Amariei, G., Boltes, K., García, M. Á., & Marina, M. L. (2019). Enantiomer stability and combined toxicity of duloxetine and econazole on Daphnia magna using real concentrations determined by capillary electrophoresis. The Science of the total environment, 670, 770-778. https://doi.org/10.1016/j.scitotenv.2019.03.208
Rikken, G. L. J. A., & Raupach, E. (1997). Observation of magneto-chiral dichroism. Nature, 390(6659), 493-494. https://doi.org/10.1038/37323
Purdie, N., & Swallows, K. A. (1989). Analytical applications of polarimetry, optical rotatory dispersion, and circular dichroism. Analytical chemistry, 61(2), 77A-89A. https://doi.org/10.1021/ac00177a001
Karpun, Y., Parchenko, V., Fotina, T., Demianenko, D., Fotin, A., Nahornyi, V., & Nahorna, N. (2021). The investigation of antimicrobial activity of some s-substituted bis-1,2l4-triazole-3-thiones. Pharmacia, 68(4), 797-804. https://doi.org/10.3897/pharmacia.68.e65761
Klebe, G. (2013). Optical Activity and Biological Effect. In G. Klebe (Ed.), Drug Design: Methodology, concepts, and mode-of-action (pp. 89-109). Springer. https://doi.org/10.1007/978-3-642-17907-5_5
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
