TY - JOUR T1 - Synthesis, Characterization and Radical Scavenging Activities of 1,3-Disubstituted Benzimidazolium Salts AU - Demir Düşünceli, Serpil AU - Karatepe, Buket AU - Keser, Serhat PY - 2025 DA - June Y2 - 2025 DO - 10.54565/jphcfum.1712592 JF - Journal of Physical Chemistry and Functional Materials PB - Niyazi BULUT WT - DergiPark SN - 2651-3080 SP - 91 EP - 102 VL - 8 IS - 1 LA - en AB - The reaction of N-substituted benzimidazole and alkyl halides (benzyl bromoacetate and trifluoromethoxybenzyl bromide) gave a series of 1,3-disubstituted benzimidazolium salts. The structure of synthesized compounds was confirmed by various spectroscopic techniques such as 1H, 13C and 19F NMR spectroscopy, FT-IR and elemental analysis. Biological efficiency of these compounds was evaluated by antioxidant activities like ABTS, OH and DPPH radical scavenging activity. KW - Benzimidazolium salt KW - trifluoromethoxy KW - ester group KW - antioxidant activity CR - [1] Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., Bitto, A., 2017. Oxidative Stress: Harms and Benefits for Human Health, Oxid. Med. Cell Longev. 1, 1-13. CR - [2] Rajendran, P., Nandakumar, N., Rengarajan, T., Palaniswami R., Gnanadhas, E. N., Lakshminarasaiah, U., Gopas, J., Nishigaki, I., 2014. Antioxidants and human diseases, Clinica Chimica Acta 436, 332-347. CR - [3] Wu, J. Q., Kosten, T. R., Zhang, X. Y., 2013. Free radicals, antioxidant defense system, and schizophrenia, Prog. Neuro-Psychopharmacol. Biol. Psychiatry 46, 200-206. CR - [4] Taniyama, Y., Griendling, K. K., 2003. Reactive oxygen species in the vasculature, Hyper-tension 42, 1075-1081. CR - [5] Al-Gubory, K. H., Garrel, C., Faure, P., Sugino,N., 2012. Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress, Reproductive Biomedicine Online 25, 551-560. CR - [6] Saffrané, L. M., DellaPenna, D., 2010. Biosynthesis, regulation and functions of tocochromanols in plants, Plant Physiol. Biochem. 48, 301-309. CR - [7] Pandey, A. K., 2007. Anti-staphylococcal activity of a pan-tropical aggressive and ob-noxious weed Pariheniumhisterophorus: an in vitro study, Natl. Acad. Sci. Lett. 30, 383-386. CR - [8] Carr, A., Frei, B., 1999. Does vitamin C act as pro-oxidant under physiological conditions?, FASEB Journal 13, 1007-1024 . CR - [9] Prochazkova, D., Bousova, I., Wilhelmova, N., 2011. Antioxidant and prooxidant properties of flavonoids, Fitoterapia 82, 513-523. CR - [10] Alagöz, Z. A., Buyukbingol, I., 2001. Synthesis of some novel tetrahydronaphthalene benzimidazole derivatives, Heterocycl Commun. 7, 455-460. CR - [11] Alagöz, Z. A., Kuş, C., Çoban, T., 2005. Synthesis and antioxidant properties of novel benzimidazoles containing substituted indole or 1,1,4,4-tetramethyl1,2,3,4-tetrahydro-naphthalene fragments,” J. Enzy. Inhib. Med. Chem. 20:4, 325-331. CR - [12] Kılcıgil, G. A., Kuş, C., Özdamar, E. D., Eke, B. C., İşcan, M., 2007. Synthesis and Antioxidant Capacities of Some New Benzimidazole Derivatives, Arch Pharm Chem. Life Sci. 340, 607-611. CR - [13] Kuş¸ C., Kılcıgil, G. A., Eke, B C., İşcan, M., 2004. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver,” Arch Pharm Res. 27, 156-163. CR - [14] Elimam, D. M., Elgazar, A. A., El-Senduny, F. F., El-Domany, R. A., Badria, F. A., Eldehna, W. M., 2022. Natural inspired piperine-based ureas and amides as novel antitumor agents towards breast cancer, J. Enzyme Inhib. Med. Chem. 37, 39-50. CR - [15] Ozkay, Y., Tunali, Y., Karaca, H., Işıkdağ, İ., 2010. Antimicrobial activity and a SAR study of some novel benzimidazole derivatives bearing hydrazone moiety, Eur. J. Med. Chem. 45, 3293-3298. CR - [16] Sreena, K., Ratheesh, R., Rachana, M., Poornima, M., Shyni, C., 2009. Synthesis and anthelmintic activity of benzimidazole derivatives, Hygeia 1, 21-22 . CR - [17] Matiadis, D., Sagnou, M., 2020. Pyrazoline hybrids as promising anticancer agents: an up-to-date overview, Int. J. Mol. Sci. 21 (2020): 5507. CR - [18] Lien, J. C., Chung, C.-L., Huang, T.‐F., Chang, T.‐C., Chen, K.‐C., Gao, G.‐Y., Hsu, M.‐J., Huang, S. W., 2019. A novel 2-aminobenzimidazole-based compound Jzu 17 exhibits anti-angiogenesis effects by targeting VEGFR-2 signalling, Br. J. Pharmacol. 176, 4034-4049. CR - [19] Kusanur, R. A, Kulkarni, M. W., 2014. A novel route for the synthesis of recemic 4-(coumaryl) alanines and their antimicrobial activity, Asian J. Chem. 4, 1077-1080. CR - [20] Akhtar, M. J., Yar, M. S., Sharma, V. K., Khan, A. A., Ali, Z., Haider, M. R., Pathak, A., 2020. Recent progress of benzimidazole hybrids for anticancer potential, Curr. Med. Chem. 27, 5970-6014. CR - [21] Haque, R. A., Iqbal, M. A., Asekunowo, P., Majid, A.M.S.A., Ahamed, M.B.K., Umar, M. I., Al-Rawi, S. S., Al-Suede, F. S. R., 2013. Synthesis, structure, anticancer, and antioxidant activity of para-xylyl linked bis-benzimidazolium salts and respective dinuclear Ag(I) N-heterocyclic carbene complexes (Part-II), Med. Chem. Res. 22, 4663-4676. CR - [22] Bal, S., Demirci, Ö., Şen, B., Taslimi, P., Aktaş, A., Gök, Y., Aygün, M., Gülçin, İ., 2021. Synthesis, characterization, crystal structure, α-glycosidase, and acetylcholinesterase inhibitory properties of 1,3-disubstituted benzimidazolium salts, Arch. Pharm. 354,: e2000422. CR - [23] Kazancı, A., Gök, Y., Kaya, R., Aktaş, A., Taslimi, P., Gülçin,İ., 2021. Synthesis, characterization and bioactivities of dative donor ligand N-heterocyclic carbene (NHC) precursors and their Ag(I)NHC coordination compounds, Polyhedron 193, 114866. CR - [24] Atyam, V. S.S.S.G., Raidu, C. S., Nannapaneni, D. T., Reddy, M. I., 2010. Synthesis, characterization, and biological evaluation of benzimidazole derivatives as potential anxiolytics, J. Young Pharm. 2, 273-279. CR - [25] Meanwell, N. A., 2018. Fluorine and fluorinated motifs in the design and application of bioisosteres for drug design, J. Med. Chem., 61, 5822-5880. CR - [26] Gillis, E. P., Eastman, K. J., Hill, M. D., Donnelly, D. J., Meanwell, N. A., 2015. Applications of fluorine in medicinal chemistry, J. Med. Chem., 58, 8315-8359. CR - [27] Gök, Y., Kaya, G., Demir,Y., Karabıyık, H., Tok, T. T., M. İzmirli, Aktaş, A., Gülçin, İ., 2025. Benzimidazolium salts bearing ester group: Synthesis characterization, crystal structure, molecular docking studies, and inhibitory properties against metabolic enzymes, J.Mol.Struc. 1322, 140342. CR - [28] Sheppard, W. A., 1964. α-Fluorinated ethers. I. Aryl fluoroalkyl ethers1, J. Org. Chem. 29, 1-11. CR - [29] Aldrich, P.E., Sheppard, W. A., 1964. α-Fluorinated ethers. II. Alkyl fluoroalkyl ethers1 , J. Org. Chem. 29, 11-15. CR - [30] Muniz, S.C., Anthony, R., Niemann, S., Alffenear, J. W. C., 2017. “New approaches and therapeutic options for mycobacterium tuberculosis in a dormant state, Clin. Microbiol. Rev. 31, 1-13. CR - [31] Skripconoka, V., Danilovits, M., Pehme, L., Tomson, T., Skenders, G., Kummik, T., Cirule, A., Leimane, V., Kurve, A., Levina, K., Geiter, L. J., Manissereo, D., Wells, C. D., 2013. Delamanid improves outcomes and reduces mortality in multidrugresistant tuberculosis, Eur. Respir. J. 41, 1393-1400. CR - [32] Mathew, S. J., Manji, H. K., Charney, D. S., 2008. Novel drugs and therapeutic targets for severe mood disorders, Neuropsychopharmacology 33, 2080-2092. CR - [33] Blumberg, D., Doron, S., Bitton, S., 1985. Effect of triflumuron on two species of nitidulid beetles, Carpophilus hemipterus and Urophorus humeralis, Phytoparasitica 13, 9-19. CR - [34] Chen, Y., Zhang, A. F., Wang, W. X., Zhang Y., Gao, T. C., 2012. Baseline sensitivity and efficacy of thifluzamide in Rhizoctonia solani, Ann. Appl. Biol. 161, 247-254. CR - [35] Whipker, B. E., McCall, I., Gibson, J. L., Cavins, T. J., 2002, Efficacy of flurprimidol (Topflor) on bedding plants, Acta Hortic. 624, 413-418. CR - [36] Cueva, C., Arribas,M. V. M., Alvarez, P. J. M., Bills, G., Vicente, M. F., Basilio, A., Rivas, C. L., Requena, T., Rodrıguez, J. M., Bartolome, B., 2010. Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria, Res. Microbiol. 161, 372-382. CR - [37] Chong, K. P., Rossall,S., Atong, M., 2009. In vitro antimicrobial activity and fungitoxicity of syringic acid, cafeic acid and 4-hydroxybenzoic acid against Ganoderma Boninense,” J. Agric. Sci. 1, 15-20. CR - [38] Kosová, M., Hrádková, I., Mátlová, V., Kadlec, D., Smidrkal, J., Filip, V., 2015. Antimicrobial efect of 4-hydroxybenzoic acid ester with glycerol, J. Clin. Pharm. Ther. 40, 436-440. CR - [39] Özçelik, H., Kartal, M., Orhan, I., 2011. Cytotoxicity, antiviral and antimicrobial activities of alkaloids, favonoids, and phenolic acids, Pharm. Biol. 49, 396-402. CR - [40] Flausino, O. A., Dufau, L., Regasini, L. O., Petronio, M. S., Silva, D. H. S., Rose, T., Bolzani, V. S., Ravaux, M. R., 2012. Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization, Curr. Med. Chem. 19, 4534-4540. CR - [41] Manuja, R., Sachdeva, S., Jain, A., Chaudhary, J., 2013. A comprehensive review on biological activities of P-hydroxy benzoic acid and its derivatives, Int. J. Pharm. Sci. Rev. Res. 22, 109-115. CR - [42] Patchett, A. A., 1984. The chemistry of enalapril, Br. J. Clin. Pharmacol. 18, 201S–207S. CR - [43] Hamide, M. Gök, Y., Demir, Y., Sevinçek, R., Tok, T. T., Tezcan, B., Aktaş, A., Gülçin, İ., Aygün, M. Güzel,B., 2022. Benzimidazolium salts containing trifluoromethoxybezyl: synthesis characterization, crystal structure, molecular docking studies and enzymes inhibitory properties, Chem. Biodiversity. 19, e202200257. CR - [44] Keser, S., Keser, F., Karatepe, M., Kaygili, O., Tekin, S., Turkoglu, I., Demir, E., Yilmaz, O., Kirbag, S., Sandal, S., 2020. Bioactive contents, in vitro antiradical, antimicrobial and cytotoxic properties of rhubarb (Rheum ribes L.) extracts, Natur. Product Res. 34, 3353-3357. CR - [45] Keser, S., Kak, O., 2021. In vitro antimicrobial, antiradical, anticancer evaluation, and phytochemical contents of endemic Scorzonera semicana DC, J. Food Process. Pres. 45, e15971. CR - [46] Shimada, K., Fujikawa, K., Yahara, K., Nakamura, T., 1992. Antioxidant properties of xanthin on autoxidation of soybean oil in cyclodextrin emulsion, J. Agricultur. Food Chem. 40, 945-948. CR - [47] Yu, L., Haley, S., Perret, J., Harris, M., Wilson, J., Qıan, M., 2002. Free radical scavenging properties of wheat extracts, J. Agricultur. Food Chem. 50, 1619-1624. CR - [48] Halliwell, B., Gutteridge, J. M. C., Aruoma, O., 1987. The deoxyribose method: a simple “test tube” assay for determination of rate constants for reactions of hydroxyl radicals, Analytic. Biochem. 165, 215-219. CR - [49] Ebenezer, O., Joshua, F. O., Omotoso, O. D., Shapi, M., 2022. Benzimidazole and its derivatives: Recent Advances (2020–2022), Results in Chem. 5, 100925. CR - [50] El Ouasif, L., Bouyahya, A., Zniber, R., Ghoul, M., Achour, R., Chakchak, H., Talbaoui, A., Boury, H., Dakka, N., Bakri, Y., 2017. Novel 2-mercaptobenzimidazole derivatives: synthesis and evaluation of their antibacterial and antioxidant activities,” Mediterr. J. Chem. 6(3), 77-87. CR - [51] Argirova, M. A., Georgieva, M. K., Avakumova, N. G. H., Vuchev, D. I., Daskalova, G. V. P., Anichina, K. K. Yancheva, D. Y., 2021. New 1H-benzimidazole-2-yl hydrazones with combined antiparasitic and antioxidant activity, RSC Adv. 11, 39848-39868. CR - [52] Khodja, I. A., Bensouici, C., Bouleb, H., 2020. Combined experimental and theoretical studies of the structure antiradical activity relationship of heterocyclic hydrazone compounds, J. Mol. Struct. 1221, 128858. CR - [53] Shatokhin, S. S., Tuskaev, V. A., Gagieva, S. C., Markova, A. A., Pozdnyakov, D. I., Melnikova, E. K., Bulychev, B. M., Oganesyan, E. T., 2022. Synthesis, cytotoxic and antioxidant activities of new n-substituted 3-(benzimidazol-2-yl)-chromones containing 2,6-di-tert-butylphenol fragment, J. Mol. Struct. 1249, 131683. CR - [54] Prakash, S., Somiya, G., Elavarasan, N., Subashini, K., Kanaga, S., Dhandapani, R., Sivanandam, M., Kumaradhas, P., Thirunavukkarasu, C., Sujatha, V., 2021. Synthesis and characterization of novel bioactive azo compounds fused with benzothiazole and their versatile biological applications, J. Mol. Struct. 1224, 129016. UR - https://doi.org/10.54565/jphcfum.1712592 L1 - https://dergipark.org.tr/en/download/article-file/4929383 ER -