SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITIES OF 3-(2-HYDROXYETHYL)-1-(3-AMINOPROPYL)-1H-IMIDAZOLE-3-IUM BROMIDE

Yıl 2017, Cilt: 18 Sayı: 1, 49 - 54, 22.05.2017

Gühergül Uluçam

https://doi.org/10.23902/trkjnat.291076

Öz

3-(2-hydroxyethyl)-1-(3-aminopropyl)-1H-imidazole-3-ium bromide as an N-heterocyclic carbene salt was synthesized by
the reaction of 3-(1H-imidazole-1-yl
)propane -1-amine with 2-bromoethanol.
The salt can
also be named as imidazole salt which is one of the most stable group of
N-heterocyclic carbenes.  The molecular
structure of the product was elucidated by FTIR, ¹H NMR, ¹³C
NMR, GS-MS and elemental analysis. The antimicrobial, antifungal and anticancer
activities of the imidazole salt were also examined. The probit analysis
revealed that IC₅₀ values on HeLa and HepG2 cell lines were 155.955μM and 76.769μM, respectively, at the end of 24
hours treatment. It also was determined that the product has no harmful effect
on healthy mouse
embryonic fibroblasts
(MEF) cells. Significant antimicrobial and antifungal activities of the salt on
Escherichia coli (Migula, 1895) O157:H7 and Listeria
monocytogenes (Pirie, 1940) ATCC 19115 bacteria and the yeast Candida albicans (Berhout,
1923) ATCC
10231 were determined at a concentration value of 32μM.

Anahtar Kelimeler

Imidazole, carbene, antibacterial activity, antifungal activity, anticancer activity

3-(2-HİDROKSİETİL)-1-(3-AMİNOPROPİL)-1H-İMİDAZOL-3-İUM BROMİD SENTEZİ, KARAKTERİZASYONU VE BİYOLOJİK AKTİVİTELERİ

Öz

Bir N-heterohalka karben
tuzu olarak, 3-(2-hidroksietil)-1-(3-aminopropil)-1H-imidazol-3-ium bromid,
3-(1H-imidazol-1-il)propan-1-amin ile 2-bromoetanol’ün reaksiyonu sonucunda sentezlenmiştir.
Tuz, N-heterohalka karbenlerin en kararlı gruplarından biri olan imidazol tuzu
olarak da isimlendirilebilir. Ürünün moleküler yapısı FTIR, ¹HNMR, ¹³C NMR, GS-MS, elemental analiz yöntemleri ile
aydınlatılmıştır. Ayrıca, antimikrobiyal, antifungal ve antikanser aktiviteleri
incelenmiştir. Probit analizi yapılarak,
HeLa ve HepG2 kanser hücre serileri üzerinde 24 saatlik uygulama sonrası IC₅₀
değerlerinin sırasıyla 155,955µM ve 76,769µM olduğu saptanmıştır. Sentezlenen
maddenin sağlıklı fare embriyonik fibroblast
(MEF) hücreleri üzerinde zararlı bir etkisine rastlanmamıştır. Escherichia coli (Migula, 1895) O157:H7,
Listeria monocytogenes (Pirie, 1940)
ATCC 19115 bakterileri ve Candida
albicans (Berhout, 1923) ATCC 10231 mayası
üzerinde ise 32µM’lık konsantrasyonda kayda değer antimikrobiyal ve antifungal
aktivitesinin de olduğu belirlenmiştir.

Anahtar Kelimeler

Imidazol, karben, antibakterial aktivite, antifungal aktivite, antikanser aktivite

Kaynakça

• 1. Arduengo, A.J., Harlow, R.L. & Kline, M. 1991. A stable crystalline carbene. Journal of the American Chemical Society, 113 (1): 361-363.
• 2. Bhat, S.A., Faizan, M., Alam, M.J. & Ahmad, S. 2016. Vibrational and electronic spectral analysis of 2,3-pyrazinedicarboxylic acid: A combined experimental and theoretical study. Spectroscopy Letters, 49 (7): 449-457.
• 3. Boussessi, R., Dalbouha, S., Timón, V., Komiha, N., Jaïdane, N. & Senent, M.L. 2016. Stability of Van der Waals complexes of the greenhouse effect gases CH4 and SF6 with imidazole in gas mixtures containing CO2. Computational and Theoretical Chemistry, 1094: 82-91.
• 4. Cavell, K.J. & McGuinness, D.S. 2004. Redox processes involving hydrocarbylmetal (N-heterocyclic carbene) complexes and associated imidazolium salts: ramifications for catalysis. Coordination Chemistry Reviews, 248 (7-8): 671-681.
• 5. Danopoulos, A.A., Tsoureas, N., Macgregor, S.A. & Smith, C. 2007. Phosphine- and Pyridine-Functionalized N-Heterocyclic Carbene Methyl and Allyl Complexes of Palladium. Unexpected Regiospecificity of the Protonation Reaction of the Dimethyl Complexes. Organometallics, 26 (2): 253-263.
• 6. Despagnet-Ayoub, E. & Grubbs, R.H. 2005. A Ruthenium Olefin Metathesis Catalyst with a Four-Membered N-Heterocyclic Carbene Ligand. Organometallics, 24 (3): 338-340.
• 7. Elser, I., Frey, W., Wurst, K. & Buchmeiser, M.R. 2016. Molybdenum Imido Alkylidene Complexes Containing N- and C-Chelating N-Heterocyclic Carbenes. Organometallics, 35 (24): 4106-4111.
• 8. Fotakis, G., Cemeli, E., Anderson, D. & Timbrell, J.A. 2005. Cadmium chloride-induced DNA and lysosomal damage in a hepatoma cell line. Toxicology in Vitro, 19 (4): 481-489.
• 9. Hahn, F.E. & Jahnke, M.C. 2008. Heterocyclic carbenes: synthesis and coordination chemistry. Angewandte Chemie International Edition in English, 47 (17): 3122-3172.
• 10. Herrmann, W.A. & Köcher, C. 1997. N-Heterocyclic Carbenes. Angewandte Chemie International Edition in English, 36 (20): 2162-2187.
• 11. Joshi, R.S., Mandhane, P.G., Shaikh, M.U., Kale, R.P. & Gill, C.H. 2010. Potassium dihydrogen phosphate catalyzed one-pot synthesis of 2,4,5-triaryl-1H-imidazoles. Chinese Chemical Letters, 21 (4): 429-432.
• 12. Karabacak, M. & Kurt, M. 2009. The spectroscopic (FT-IR and FT-Raman) and theoretical studies of 5-bromo-salicylic acid. Journal of Molecular Structure, 919 (1–3): 215-222.
• 13. Karatas, M.O., Olgundeniz, B., Gunal, S., Ozdemir, I., Alici, B. & Cetinkaya, E. 2016. Synthesis, characterization and antimicrobial activities of novel silver(I) complexes with coumarin substituted N-heterocyclic carbene ligands. Bioorganic & Medicinal Chemistry, 24 (4): 643-650.
• 14. Kose, E., Atac, A., Karabacak, M., Nagabalasubramanian, P.B., Asiri, A.M. & Periandy, S. 2013. FT-IR and FT-Raman, NMR and UV spectroscopic investigation and hybrid computational (HF and DFT) analysis on the molecular structure of mesitylene. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 116: 622-634.
• 15. Liu, Q.-X., Xu, F.-B., Li, Q.-S., Song, H.-B. & Zhang, Z.-Z. 2004. Formation of the Fluorescent Complexes [(carbene)2MII(CN)2] (M = Ni, Pd, Pt) by C−C Bond Cleavage of CH3CN. Organometallics, 23 (3): 610-614.
• 16. Liu, Q.-X., Zhao, X.-J., Wu, X.-M., Guo, J.-H. & Wang, X.-G. 2007. New mercury(II) and silver(I) complexes containing NHC metallacrown ethers with the π–π stacking interactions. Journal of Organometallic Chemistry, 692 (25): 5671-5679.
• 17. Mi, X., Luo, S. & Cheng, J.P. 2005. Ionic liquid-immobilized quinuclidine-catalyzed Morita-Baylis-Hillman reactions. The Journal of Organic Chemistry, 70 (6): 2338-2341.
• 18. Mi, X., Luo, S., Xu, H., Zhang, L. & Cheng, J.-P. 2006. Hydroxyl ionic liquid (HIL)-immobilized quinuclidine for Baylis–Hillman catalysis: synergistic effect of ionic liquids as organocatalyst supports. Tetrahedron, 62 (11): 2537-2544.
• 19. Mohammadi, A.L.I., Keshvari, H., Sandaroos, R., Rouhi, H. & Sepehr, Z. 2012. A novel polymeric catalyst for the one-pot synthesis of 2,4,5-triaryl-1H-imidazoles. Journal of Chemical Sciences, 124 (3): 717-722.
• 20. Mosmann, T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of Immunological Methods, 65 (1-2): 55-63.
• 21. Özdemir, İ., Düşünceli, S.D., Kaloğlu, N., Achard, M. & Bruneau, C. 2015. Synthesis of ruthenium N-heterocyclic carbene complexes and their catalytic activity for β-alkylation of tertiary cyclic amines. Journal of Organometallic Chemistry, 799-800: 311-315.
• 22. Ramasamy, R. 2015. Vibrational spectroscopic studies of imidazole. Armenian Journal of Physics, 8 (1): 51-55.
• 23. Shelke, K.F., Sapkal, S.B., Shitole, N.V., Shingate, B.B. & Shingare, M.S. 2009. Microwave-Assisted Synthesis of 3-Styrylchromones in Alkaline Ionic Liquid. Bulletin of the Korean Chemical Society, 30 (12): 2883-2886.
• 24. Şahin, Z., Gürbüz, N., Özdemir, İ., Şahin, O., Büyükgüngör, O., Achard, M. & Bruneau, C. 2015. N-Alkylation and N,C-Dialkylation of Amines with Alcohols in the Presence of Ruthenium Catalysts with Chelating N-Heterocyclic Carbene Ligands. Organometallics, 34 (11): 2296-2304.
• 25. Wang, L., Woods, K.W., Li, Q., Barr, K.J., McCroskey, R.W., Hannick, S.M., Gherke, L., Credo, R.B., Hui, Y.H., Marsh, K., Warner, R., Lee, J.Y., Zielinski-Mozng, N., Frost, D., Rosenberg, S.H. & Sham, H.L. 2002. Potent, orally active heterocycle-based combretastatin A-4 analogues: synthesis, structure-activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation. Journal of Medicinal Chemistry, 45 (8): 1697-1711.
• 26. Wang, X.Q., Liu, L.X., Li, Y., Sun, C.J., Chen, W., Li, L., Zhang, H.B. & Yang, X.D. 2013. Design, synthesis and biological evaluation of novel hybrid compounds of imidazole scaffold-based 2-benzylbenzofuran as potent anticancer agents. European Journal of Medicinal Chemistry, 62: 111-121.
• 27. Yiğit, B., Yiğit, M., Dağdeviren, Z. & Özdemir, İ. 2016. Synthesis of silver(I) and palladium(II) N-heterocyclic carbene complexes and their use as catalysts for the direct C5 arylation of heteroaromatic compounds. Transition Metal Chemistry, 41 (7): 751-757.
• 28. Zheng, G.-C., Cai, Z.-B., Pan, Y.-L., Bai, L., Zhou, Y.-T., Li, S.-L. & Tian, Y.-P. 2016. Synthesis and two-photon absorption properties of novel 2-substituted-4,5-diphenyl-1H-imidazoles. Tetrahedron, 72 (22): 2988-2996.