Synthesis, characterization, and investigation of antibacterial and antifungal properties of salt and metal complexes of 2-amino-5-chloropyridine and 2,6-pyridinedicarboxylic acid

Abstract

In this study, the salt (3) of 2-amino-5-chloropyridine (1) and 2,6-pyridinedicarboxylic acid (2) and the complexes of the salt (H1)x[M(2)2].nH2O, M = Fe (III), x = 1, n = 3 (4); M = Co(II), x = 2, n = 4 (5); M = Ni(II), x = 2, n = 5 (6); M = Cu(II), x = 2, n = 4 (7)} were synthesized. The structures of 3-7 were suggested by NMR, AAS, IR, UV, magnetic susceptibility and molar conductivity methods. As a result of spectroscopic analysis, it was observed that all metal complexes had an ionic and octahedral structure. All substances were susceptible to Candida albicans (yeast), Escherichia coli, Bacillus subtilis, Enterococcus faecalis, Pseudomonas aeruginosa, Listeria monocytogenes and Staphylococcus aureus bacteria were examined. Antimicrobial activity results were compared with Fluconazole, Ketoconazole, Chloramphenicol, Levofloxacin, Vancomycin and Cefepime. In the activity results, the best values were observed 3, 5 and 7 in S. aureus bacteria, 1 and 5 in E. coli bacteria, 1, 3 and 7 in P. aeruginoa bacteria, all compounds in L. monocytogenes bacteria, all compounds (except 4) in E. faecalis bacteria, 1 and 3-5 in B. subtilis bacteria and 3, 4 and 7 in C. albicans yeast.

Keywords

• 2-Amino-5-chloropyridine
• 2,6-pyridinedicarboxylic acid
• salt
• metal complex
• antimicrobial activity.

References

1. [1] M. Marinescu, “2-Aminopyridine - a classic and trendy pharmacophore,” Int. J. Pharma Bio. Sci., vol. 8, no. 2, pp. 338-355, 2017, doi: 10.22376/ijpbs.2017.8.2.p338-355.
2. [2] R. N. Rao and K. Chanda “2-Aminopyridine – an unsung hero in drug discovery,” Chem. Commun., vol. 58, pp. 343-382, 2022, doi: 10.1039/D1CC04602K.
3. [3] K. J. Orie, R. U. Duru and R. I. Ngochindo “Syntheses, complexation and biological activity of aminopyridines: a mini-review,” Am. J. Het. Chem., vol. 7, no. 2, pp. 11-25, 2021, doi: 10.11648/j.ajhc.20210702.11.
4. [4] P. Sharma and P. Sinha, “Recent advancements in multicomponent reactions of substituted 2- aminopyridines synthesis: a decade review,” vol. 3, e061223224235, pp. 18, 2023, doi: 10.2174/0126660016267259231012105113.
5. [5] C. Yenikaya, M. Poyraz, M. Sarı, F. Demirci, H. İlkimen and O. Büyükgüngör, “Synthesis, characterization and biological evaluation of a novel Cu(II) complex with the mixed ligands 2,6-pyridinedicarboxylicacid and 2-aminopyridine,” Polyhedron, vol. 28, no. 16, pp. 3526-3532, 2009, doi: 10.1016/j.poly.2009.05.079.
6. [6] C. Yenikaya, N. Büyükkıdan, M. Sarı, R. Keşli, H. İlkimen, M. Bülbül and O. Büyükgüngör, “Synthesis, characterization and biological evaluation of novel Cu(II) complexes with proton transfer salt of 2,6-pyridinedicarboxylic acid and 2-amino-4-methylpyridine,” J. Coord. Chem., vol. 64, no. 19, pp. 3353-3365, 2011, doi: 10.1080/00958972.2011.620608.
7. [7] Centers for Disease Control and Prevention Facts about Antibiotic Resistance and Antibiotic Prescribing: Attitudes, Behaviors, Trends, and Cost. [(accessed on 21 April 2022)]; Available online: http://www.cdc.gov/getsmart/community/about/fast-facts.html
8. [8] M. M. Khalil and A. E. Attia, “Potentiometric studies on the binary and ternary complexes of copper(II) containing dipicolinic acid and amino acids,” J. Chem. Eng. Data, vol. 44, no. 2, pp. 180-184, 1999, doi: 10.1021/je980185d.

9. [9] S. Xiang, D. X. Bao, J. Wang, Y.C. Li and X.Q. Zhao, “Luminescent lanthanide coordination compounds with pyridine-2,6-dicarboxylicacid,” J. Lumin., vol. 186, pp. 273–282, 2017, doi: 10.1016/j.jlumin.2017.02.037
10. [10] M. J. Celestine, J.L. Bullock, S. Boodram, V. H. Rambaran and A.A. Holder, “Interesting properties of p-, d-, and f-block elements when coordinated with dipicolinic acid and its derivatives as ligands: their use as inorganic pharmaceuticals,” Rev. Inorg. Chem., vol. 35, vol. 2, pp. 57-67, 2015, doi: 10.1515/revic-2014-0004
11. [11] A. M. Kirillov and G. B. Shul’pin, “Pyrazinecarboxylic acid and analogs: highly efficient co-catalysts in the metal-complex-catalyzed oxidation of organic compounds,” Coord. Chem. Rev., vol. 257, pp. 732-754, 2013, doi: 10.1016/j.ccr.2012.09.012
12. [12] M. V. Kirillova, M. F. C. Guedes da Silva, A. M. Kirillov, J. J. R. Frausto da Silva and A. J. L. Pombeiro, “3D hydrogen bonded heteronuclear CoII, NiII, CuII and ZnII aqua complexes derived from dipicolinic acid,” Inorg. Chim. Acta, vol. 360, pp. 506-512, 2007, doi: 10.1016/j.ica.2006.07.087.
13. [13] N. Büyükkıdan, “Proton transfer salts and their complexes and mixed-ligand complexes of pyridine dicarboxylic acids and piperazines: a short review,” J. Sci. Rep. A, vol. 49, pp. 198-235, 2022.
14. [14] H. Aghabozorg, F. Manteghi and S. Sheshmani, “A brief review on structural concepts of novel supramolecular proton transfer compounds and their metal complexes,” J. Iran. Chem. Soc., vol. 5, pp. 184-227, 2008, doi: 10.1007/BF03246111.
15. [15] H. İlkimen, S. G. Salün, A. Gülbandılar and M. Sarı, “The new salt of 2-amino-3-methylpyridine with dipicolinic acid and its metal complexes: Synthesis, characterization and antimicrobial activity studies,” J. Mol. Struct., vol. 1270, pp. 133961, 2022, doi: 10.1016/j.molstruc.2022.133961.
16. [16] H. İlkimen, S. G. Salün, A. Gülbandılar and M. Sarı, “Synthesis, characterization, antimicrobial activity studies of a novel salt of dipicolinic acid with 2-amino-5-methylpyridine and their metal complexes,” Pharm. Chem. J., 2024, (in press).
17. [17] H. İlkimen and A. Gülbandılar, “Synthesis, characterization, anti-microbial activity studies of salicylic acid and 2-aminopyridine derivatives salts and their Cu(II) complexes,” J. Sci. Rep. A, vol. 56, pp. 94-104, 2024.
18. [18] H. İlkimen, C. Yenikaya and A. Gülbandılar, “Investigation of the antimicrobial activities of proton transfer salts of 5-sulfosalicylic acid and 2-aminopyridine derivatives,” 3rd International Conference on Innovative Academic Studies, September 26-28, 2023, Konya, Türkiye, pp. 779-783. ISBN: 978-625-6530-66-9.
19. [19] H. İlkimen, N. Türken and A. Gülbandılar, “Synthesis, characterization, antimicrobial and antifungal activity of studies of two novel aminopyridine-sulfamoylbenzoic acid salts and their Cu(II) complexes,” J. Iranian Chem. Soc., vol. 18, no. 9, pp. 1941-1946, 2021, doi: 10.1007/s13738-021-02157-4.
20. [20] H. İlkimen and A. Gülbandılar, “Synthesis, characterization, anti-microbial activity studies of 2-methoxy-5-sulfamoylbenzoic acid and 2-amino-5/6-picoline salts and their Cu(II) complexes,” Uşak Univ. J. Sci. Nat. Sci., 2024, (in press).
21. [21] H. İlkimen, C. Yenikaya and A. Gülbandılar, “Synthesis, characterization and investigation of antimicrobial activities of salts of 2- aminopyridine derivatives and 2-methoxy-5-sulfamoylbenzoic acid,” Selcuk Univ. J. Sci. Fac., vol. 49, no. 2, pp. 53-63, 2023, doi: 10.35238/sufefd.1315568.
22. [22] H. İlkimen and A. Gülbandılar, “Synthesis, characterization, anti-microbial activity studies of 2-methoxy-5-sulfamoylbenzoic acid and 2-aminopyridine derivatives salts and their Cu(II) complexes,” Pamukkale Univ. J. Eng. Sci., 2024, doi. 10.5505/pajes.2024.48196
23. [23] H. İlkimen, C. Yenikaya and A. Gülbandılar, “Synthesis, characterization, investigation of antimıicrobial properties of proton transfer salt andCu(II) complex of 2-metoxy-5-sulfamoilbenzoic acid and 2,3-diaminopyridine derivatives,” III. Baskent International Conference On Multidisciplinary Studies, September 23-25, 2022, Ankara, Türkiye, pp. 105-119, ISBN - 978-625-8246-04-9.
24. [24] H. İlkimen, C. Yenikaya and A. Gülbandılar, “Synthesis, characterization and investigation of antimicrobial and antifungal activities of 2-methoxy-5-sulfamoylbenzoic acid and 2-aminonitropyridine derivatives,” 3rd International Conference on Innovative Academic Studies, September 26-28, 2023, Konya, Türkiye, pp. 784-793. ISBN: 978-625-6530-66-9.
25. [25] H. İlkimen and A. Gülbandılar, Synthesis, characterization, and investigation of antimicrobial and antifungal activities of 2-Amino-5-substituted epipyridine derivatives and proton transfer salts of 2-methoxy-5-sulfamoylbenzoic acid,” 2nd International Conference on Contemporary Academic Research ICCAR 2023, November 4-5 2023, Konya, Türkiye, pp. 40-47. ISBN: ISBN: 978-625-6530-69-0
26. [26] H. İlkimen, C. Yenikaya and A. Gülbandılar, “2-Amino-6-substitüepiridin türevleri ile 2-metoksi-5-sulfamoyilbenzoik asitin proton transfer tuzlarının sentezi, karakterizasyonu, antimikrobiyal ve antifungal aktivitelerinin incelenmesi,” 2nd International Conference on Contemporary Academic Research ICCAR 2023, November 4-5 2023, Konya, Türkiye, pp. 48-55. ISBN: ISBN: 978-625-6530-69-0.
27. [27] H. İlkimen and A. Gülbandılar, “Synthesis, characterization, antimicrobial and antifungal activity studies of four novel 2-aminopyridine and 2,4-dichloro-5-sulfamoylbenzoic acid salts and their Cu(II) complexes,” Kuwait J. Sci., vol. 50, no. 3A, pp. 1-11, 2023, doi: 10.48129/kjs.19163.
28. [28] H. İlkimen, C. Yenikaya and A. Gülbandılar, “Antimicrobial activity of (E)-3-(4-sulfamoylphenylcarbamoyl)acrylic acid derivatives,” J. Sci. Rep. A, vol. 52, pp. 365-375, 2023, doi: 10.59313/jsr-a.1126888.
29. [29] H. İlkimen, C. Yenikaya and A. Gülbandılar, Synthesis, characterization and investigation of antimicrobial activities of metal complexes of (E)-4-oxo-4-(3-sulfamoylphenyl)amino)but-2-enoic acid,” Bayburt Univ. J. Sci., vol. 6, no. 1, 12-19, 2023, doi: 10.55117/bufbd.1137044.
30. [30] H. İlkimen, C. Yenikaya and A. Gülbandılar, “Antimicrobial activity of proton salts of 3-(sulfamoylphenylcarbamoyl) acrylic acid derivatives with aminopyridine derivatives. J. Sci. Rep. A, vol. 54, no. 2, pp. 264-272, 2023, doi: 10.59313/jsr-a.1311495.
31. [31] D. Cook, “Vibrational spectra of pyridinium salts,” Canadian J. Chem., vol. 39, no. 10, 2009-2024, 1961, doi: 10.1139/v61-271.
32. [32] K. Nakamoto, “Infrared and raman spectra of inorganic and coordination compounds,” 5th ed. NewYork: Wiley-Interscience, pp. 232 (1997).
33. [33] W. J. Geary, “The use of conductivity measurements in organic solvents for the characterisation of coordination compounds,” Coord. Chem. Rev., vol. 7, no. 1, pp. 81-122, 1971, doi: 10.1016/S0010-8545(00)80009-0.