Synthesis, Characterization and Investigation of Antimicrobial Activities of Salts and Complexes Containing 2-Amino-5-Bromopyridine and Dipicolinic Acid

Abstract

The salt {(H2a5Brp)(Hpka), 1} of 2-amino-5-bromopyridine (2a5Brp) and dipicolinic acid (H2pka) and metal complexes of salt (1) {(H2a5Brp)[Fe(pka)2].2H2O (2), (H2a5Brp)2[Co(pka)2].4H2O (3), (H2a5Brp)2[Ni(pka)2].3H2O (4), (H2a5Brp)2[Cu(pka)2].2H2O (5)} were synthesized. Elements analysis, NMR, AAS, IR, UV, molar conductivity magnetic, and susceptibility procedures all showed the structures of 1–5. Spectroscopic investigation showed that every metal compound had an octahedral and ionic structure. All substances were tested for their antimicrobial properties against the following microorganisms: Candida albicans (ATCC 14053) (yeast), Bacillus subtilis, Listeria monocytogenes (ATCC 7644), Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 29212), and Staphylococcus aureus (NRRL-B 767) bacteria. Results Of Antimicrobial Activity Were Contrasted With Those Of Ketoconazole, Fluconazole, Vancomycin, Cefepime, Chloramphenicol, and Levofloxacin. The findings of the activity indicated that the highest values were found 3 in C. albicans yeast, all compounds in E. coli bacteria, 1 and 2 in S. aureus bacteria, 2 in L. monocytogenes bacteria, 1 in B. subtilis bacteria, 2a5Brp, 1 and 2 in P. aeruginoa bacteria and all compounds (except 4 and 5) in E. faecalis bacteria.

Keywords

• Dipicolinic acid
• 2-Amino-5-bromopyridine
• Salt
• Metal complex
• Antimicrobial activity.

2 Amino 5 bromopiridin ile Dipikolinik Asit İçeren Tuz ve Komplekslerinin Sentezi, Karakterizasyonu ve Antimikrobiyal Aktivitelerinin Araştırılması

Abstract

2-Amino-5-bromopiridin (ap) ile dipikolinik asitin (H2pka) tuzu {(Hap)(Hpka), 1) ve tuzun metal kompleksleri {(Hap [Fe(pka)2].2H2O (2), (Hap)2[Co(pka)2].4H2O (3), (Hap)2[Ni(pka)2].3H2O (4), (Hap)2[Cu(pka)2].2H2O (5)} sentezlenmiştir. 1-5'in yapıları elementel analiz, NMR, AAS, IR, UV, molar iletkenlik ve manyetik duyarlılık yöntemleri ile önerilmiştir. Spektroskopik analiz sonucunda tüm metal komplekslerinin iyonik ve oktahedral yapıya sahip olduğu görülmüştür. Çalışmada kullanılan ve sentezlenen bileşiklerin Candida albicans (ATCC 14053) mayasına karşı antifungal, Bacillus subtilis, Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 29212), Listeria monocytogenes (ATCC 7644) ve Staphylococcus aureus (NRRL-B 767) bakterilerine karşı antibakteriyel aktiviteleri incelenmiştir. Antifungal aktivite sonuçları Ketokonazol ve Flukonazol ile karşılaştırılırken, antibakteriyel aktiviteler Levofloksasin, Vankomisin, Kloramfenikol ve Sefepim ile karşılaştırılmıştır. Aktivite sonuçlarında en iyi değerler C. albicans mayasında 3, E. coli bakterisinde tüm bileşikler, S. aureus bakterisinde 1 ve 2, L. monocytogenes bakterisinde 2, B. subtilis bakterisinde 1, ap, P. aeruginoa bakterisinde 1 ve 2 ve E. faecalis bakterisinde ise tüm bileşiklerde (4 ve 5 hariç) gözlenmiştir.

Keywords

• Dipikolinik asit
• 2-amino-5-bromopiridin
• Tuz
• Metal kompleksi
• Antimikrobiyal aktivite.

References

1. [1] M. Marinescu, “2-Aminopyridine – a classic and trendy pharmacophore”. Inter. J. Pharm. Bio Sci., vol. 8, no. 2, pp. 338-335, 2017.
2. [2] C. Yenikaya, M. Poyraz, M. Sarı, F. Demirci, H. İlkimen and O. Büyükgüngör, “Synthesis, characteriza-tion 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.
3. [3] C. Yenikaya et al. “Synthesis, characterization and biological evaluation of novel Cu(II) complexes with proton transfer salt of dipicolinic acid and 2-amino-4-methylpyridine” J. Coord. Chem., vol. 64, no. 19, pp. 3353-3365, 2011.
4. [4] 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.
5. [5] 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, no. 2, pp. 57-67, 2015.
6. [6] 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, 732-754, 2013.
7. [7] 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, 506-512, 2007.
8. [8] M. Hakimi, E. Motieiyan, F. Bertolotti, D. Marabello, R. Nunes and H. Vitor, “Three new bismuth(III) pyridine-2,6-dicarboxylate compounds: Synthesis, characterization and crystalstructures”. J. Mol. Struct., vol. 1099, pp. 523-533, 2015.

9. [9] G. Sharma and A.K. Narula, “Synthesis and optoelectronic properties of three Eu(III)-dipicolinate comp-lexes based on a-picolinic acid, 2-aminopyridine and 2-hydroxypyridine as secondary ligands”. J. Mat. Sci.: Mat. Elect., vol. 26, no. 2, pp. 1009-1017, 2015.
10. [10] M. Mirzaei, et al. “Crystal engineering with coordination compounds of NiII, CoII, and CrIII bearing di-picolinic acid driven by the nature of the noncovalent interactions”. CrystEngComm, vol. 16, no. 24, pp. 5352-5363, 2014.
11. [11] S. Sheshmani, M. Ghadermazi, E. Motieiyan, A. Shokrollahi, Z. Malekhosseini and M.A. Fashapoyeh, “Potentiometric and structural studies of MIIA(Ca, Sr, Ba)-pyridine-2,6-dicarboxylic acid-2-aminopyridine adduct”. J. Coord. Chem., vol. 66, no. 22, pp. 3949-3969, 2013.
12. [12] S. Mistri, E. Zangrando and S.C. Manna, “Cu(II) complexes of pyridine-2,6-dicarboxylate and N-donor neutral ligands: Synthesis, crystal structure, thermal behavior, DFT calculation and effect of aromatic compounds on their fluorescence”. Inorg. Chim. Acta, vol. 405, pp. 331-338, 2013.
13. [13] M. Mirzaei, H. Eshtiagh-Hosseini and J.T. Mague, “2-Aminopyridinium bis(pyridine-2,6-dicarboxylato)ferrate(III)”. Acta Cryst., vol. E68, no. 2, pp. m174-m174, 2012.
14. [14] M. Trivedi, R. Nagarajan, A. Kumar and N.P. Rath, “A new single pot synthesis of m-bis(oxido)bis{oxidovanadium(V)} dipicolinato complex with 2-aminopyridinium as counter cation: Spectroscopic, structural, catalytic and theoretical studies”. J. Organomet. Chem., vol. 695, no. 12-13, pp. 1722-1728, 2010.
15. [15] S. Pramanik, et al. “Investigation of electrical conductance properties, non-covalent interactions and TDDFT calculation of a newly synthesized copper(II) metal complex”. J. Mol. Struct., vol. 1206, 127663, 2020.
16. [16] M. Zohrevandi, et al. “Synthesis, characterization, crystallographic structure, theoretical studies, and in vitro cytotoxicity assessment of two Gd(III) and Ce(IV) complexes containing pyridine-2,6-dicarboxylate”. Polyhedron, vol. 211, 115561, 2022.
17. [17] H. İlkimen, S.G. Salün, A. Gulbandilar and M. Sari, “The new salt of 2-amino-3-methylpyridine with di-picolinic acid and its metal complexes: Synthesis, characterization and antimicrobial activity studies”. J. Mol. Struct., vol. 1270, 133961, 2022.
18. [18] A. Hejrani-Dalir, M. Tabatabaee and A. Sheibani, “Synthesis and crystal structure of 2-amino-3-hydroxypyridinium dioxido(pyridine-2,6-dicarboxylato-κ3O2,N,O6)vanadate(V) and its conversion to na-nostructured V2O5”. Acta Cryst., vol. C71, no. 2, pp. 89-92, 2015.
19. [19] M.A. Sharif, M. Tabatabaee, M. Adinehloo and H. Aghabozorg, “2-Amino-4-methylpyridinium 6-carboxypyridine-2-carboxylate sesquihydrate”. Acta Cryst., vol. 66, no. 12, pp. o3232-o3232, 2010.
20. [20] H. Aghabozorg, A.M. Rouchi, M. Mirzaei and B. Notash, “2-Amino-4-methylpyridinium 6-carboxypyridine-2-carboxylate methanol monosolvate”. Acta Cryst., vol. E67, no. 1, pp. o54-o54, 2011.
21. [21] M. Cai and J. Chen, “A new ultrasonic synthetic method for proton transfer compound of dipicolinic acid and 2,6-pyridinediamine”. Youji Huaxue, vol. 30, no. 7, pp. 1076-1079, 2010.
22. [22] H. Aghabozorg, M.A. Rouchi, B. Notash and M. Mirzaei, “Bis(2-amino-4-methylpyridinium) bis(pyridine-2,6 dicarboxylato)cuprate(II)” Acta Cryst., vol. E67, no. 2, pp. m189-m189, 2011.
23. [23] M. Mirzaei et al. “Syntheses, crystal, molecular structures, and solution studies of Cu(II), Co(II) and Zn(II) coordination compounds containing pyridine-2,6-dicarboxylic acid and 1,4-pyrazine-2,3-dicarboxylic acid: comparative computational studies of Cu(II) and Zn(II) complexes”. Structural Che-mistry, vol. 22, no. 6, pp. 1365-1377, 2011.
24. [24] H. Eshtiagh-Hosseini et al. “Diversity in coordination behavior of dipicolinic acid with lead(II), cal-cium(II) and nickel(II) in the presence of pyrazine and 2-amino-4-methylpyridine spacers in construction of three supramolecular architectures”. J. Mol. Struct., vol. 973, no. 1-3, pp. 180-189, 2010.
25. [25] E. Movahedi et al., “A novel Cu(II)-based DNA-intercalating agent: Structural and biological insights using biophysical and in silico techniques”. Spectrochim. Acta, Part A: Mol. Biomol. Spec., vol. 293, 122438, 2023.
26. [26] 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).
27. [27] A. Polat, H. İlkimen, B. Yılmaz, E. Yurt and A. Gülbandılar “Synthesis, characterization, and investiga-tion of antibacterial and antifungal properties of salt and metal complexes of 2-amino-5-chloropyridine and dipicolinic acid”. J. Sci. Rep. A, vol. 057, pp. 110-120, 2024.
28. [28] M. Mirzaei et al., “Synthesis, structure and DFT study of a chelidamic acid based Cu coordination poly-mer: On the importance of π-π interactions and hexameric water clusters”. J. Mol. Struct., vol. 1080, pp. 30-36, 2015.
29. [29] H. Pasdar, A. Ebdam, H. Aghabozorg and B. Notash, “Bis(2-amino-6-methylpyridinium) tris(pyridine-2,6-dicarboxylato)zirconate(IV) dihydrate”. Acta Cryst., vol. 67, no. 3, pp. m294, Sm294/1-Sm294/11, 2011.
30. [30] H. Eshtiagh-Hosseini, Z. Yousefi, M. Shafiee and M. Mirzaei, “Fe(III) and cobalt(II) coordination com-pounds of 5-bromo-6-methyl-2-morpholinepyrimidinium-4-amine pyridine-2,6-dicarboxylate”, J. Coord. Chem., vol. 63, no. 18, pp. 3187-3197, 2010.
31. [31] Z.A. Kaplancikli, G. Turan-Zitouni, G. Revial and K. Guven, “Synthesis and study of antibacterial and antifungal activities of novel 2-[[(benzoxazole/benzimidazole-2-yl) sulfanyl] acetylamino] thiazoles”. Arch. Pharm. Res., vol. 27, pp. 1081-1085, 2004.
32. [32] Z.A. Kaplancikli, G. Turan-Zitouni, A. Özdemir, G. Revial and K. Guven, “Synthesis and antimicrobial activity of some thiazolyl-pyrazoline derivatives”. Phos. Sulf. Sil. Relat. Elem., vol 182, no. 4, pp. 749-764, 2007.
33. [33] D. Cook, “Vibrational spectra of pyridinium salts” Canadian J. Chem., vol. 39, no. 10, pp. 2009-2024, 1961.
34. [34] K. Nakamoto, “Infrared and raman spectra of inorganic and coordination compounds” 5th ed NewYork: Wiley-Interscience, pp 232, 1997.
35. [35] W.J. Geary, “The use of conductivity measurements in organic solvents for the characterisation of coor-dination compounds”, Coord. Chem. Rev., vol. 7, no. 1, pp. 81-122, 1971.
36. [36] 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.
37. [37] 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.
38. [38] N. Koyama, J. Inokoshi, H. Tomoda, “Anti-ınfectious agents against MRSA”. Molecules, vol. 18, no. 1, pp. 204-224, 2012.
39. [39] V.R. Anderson, C.M. Perry, “Levofloxacin. A review of its use as a high-dose, short-course treatment for bacterial infection”. Drugs, vol. 68, no. 4, pp. 535-565, 2008.
40. [40] T.M. Chapman, C.M. Perry, “Cefepime. A review of its use in the management of hospitalized patients with pneumonia”. Am. J. Respir. Med., vol. 2, no. 1, pp. 75-107, 2003.
41. [41] C.G. Rivera, P.P. Narayanan, R. Patel, L.L. Estes, “Impact of cefepime susceptible-dose-dependent MIC for enterobacteriaceae on reporting and prescribing”. Antimicrob. Agents Chemother. vol. 60, no. 6, pp. 3854-3855, 2016.
42. [42] R. Vince, R.G. Almquist, C.L Ritter, S. Daluge, “Chloramphenicol binding site with analogues of chlo-ramphenicol and puromycin”. Antimicrob. Agents Chemother, vol. 8, pp. 439-443, 1975.
43. [43] S. Pestka, “Inhibitors of ribosome functions”. Annu. Rev. Microbiol., vol. 25, pp. 487-562, 1971.
44. [44] C.E. Green, H.J. Cameron, G.R. Julian, “Recovery of polysome function of T4-infected Escherichia coli after brief treatment with chloramphenicol and rifampin”. Antimicrob. Agents Chemother, vol. 7, pp. 549-554, 1975.
45. [45] C. Spampinato, D. Leonardi, “Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents”. Biomed. Res. Int. vol. 2013, no. 1 pp. 204237, 2013.
46. [46] L.L. Brunton, R. Hilal-Dandan, B.C. Knollmann, eds. Goodman & Gilman's: “The pharmacological basis of therapeutics” (13th ed.). McGraw-Hill Education, 2018.
47. [47] J.H. Van Tyle, “Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug inte-ractions, adverse reactions and therapeutic use”. Pharmacotherapy, vol. 4, no. 6, pp. 343-73, 1984.
48. [48] C. Spampinato, D. Leonardi, “Candida infections, causes, targets, and resistance mechanisms: traditional and alternative antifungal agents”. Biomed. Res. Int., vol. 2013, no. 1, pp. 204237, 2013.
49. [49] B.G. Tweedy, “Synthesis and assessment of antibacterial activities of ruthenium(III) mixed ligand comp-lexes containing 1,10-phenanthroline and guanide”. Phytopath., vol. 55, pp. 910-914, 1964.
50. [50] Z.H. Chohan, M. Arif, M.A. Akhtar, C. Supuran, “Metal-based antibacterial and antifungal agents: synt-hesis, characterization, and in vitro biological evaluation of Co(II), Cu(II), Ni(II), and Zn(II) complexes with amino acid-derived compounds”. Bioinorg. Chem. Appl., vol. 2006, pp. 83131, 2006.
51. [51] N. Raman, S.J. Raja, A. Sakthivel, “Transition metal complexes with Schiff-base ligands: 4-aminoantipyrine based derivatives–a review”. J. Coord. Chem., vol. 62, no. 5, pp. 691-709, 2009.