Biyoaktif Yeni Benzimidazol Aren Rutenyum Organometalik Bileşiğinin Sentezi ve Karakterizasyonu

Bu çalışmada [(η6-p-simen)Ru(L2)Cl]CI genel formülüne sahip olan biyoaktif benzimidazol aren rutenyum organometalik bileşiği, salisilaldehitin 2-(aminometil)benzimidazol dihidroklorür(ambm2.2HCI) bileşiği ile reaksiyona sokulmasının ardından, [Ru(p-simen)klorür]2 eklenmesi ile hazırlandı. Biyoaktif benzimidazol aren rutenyum organometalik bileşiği UV-VIS, IR, ESI-MS, 1H NMR, 13C NMR spektroskopisi teknikleriyle karakterize edildi. Bileşiğin, Diferansiyel termal analiz (DTA) ve Termogravimetrik analiz (TGA) teknikleri ile ölçümleri yapıldı, ölçüm verileri incelendi.

Anahtar Kelimeler:

Aren rutenyum, Benzimidazol, Organometalik kimya, Termal bozunma, Biyoaktif, Sentez

Synthesis and Characterization of Bioactive New Benzimidazole Arene Ruthenium Organometallic Compound

In this study, [(η6-p-cymene)Ru(L2)Cl]CI bioactive benzimidazole arene ruthenium organometallic compound, reacting Salicylaldehyde with 2-(Aminomethyl)benzimidazole dihydrochloride, followed by the addition of the corresponding [Ru(p-cymene)chloride]2. The bioactive benzimidazole arene ruthenium organometallic compound was characterized by standard techniques including UV-VIS, IR, ESI-MS, 1H NMR, 13C NMR spectroscopy. Thermal decomposition measurement data of arene ruthenium compound were examined. These measurements were made by Differential thermal analysis (DTA) and Thermogravimetric analysis (TGA) techniques.

Keywords:

Arene ruthenium, Benzimidazole, Organometallic chemistry, Thermal decomposition, Bioactive, Synthesis,

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[1] M. J. Hannon, “Metal-based anticancer drugs: From a past anchored in platinum chemistry to a post-genomic future of diverse chemistry and biology,” Pure and Applied Chemistry, vol. 79, no. 12, pp. 2243–2261, 2007.
[2] S. Ghosh, “Cisplatin: The first metal based anticancer drug,” Bioorganic Chemistry, vol. 88, no. 1295, pp.1-20, 2019.
[3] A. A. Nazarov, C. G. Hartinger and P. J. Dyson, “Opening the lid on piano-stool complexes: An account of ruthenium(II)-arene complexes with medicinal applications,” Journal of Organometallic Chemistry, vol. 751, pp. 251-260, 2014.
[4] L. A. Malley, “Cisplatin,” in Encyclopedia of Toxicology, 3rd ed., vol. 1, National Library of Medicine, Bethesda, USA, 2005, pp. 614-616.
[5] E. Orhan, A. Garci and B. Therrien, “Coordination-driven self-assembly of arene ruthenium metalla-rectangles,” Inorganica Chimica Acta, vol. 461, pp. 78–83, 2017.
[6] E. Orhan, A. Garci, T. Riedel, P. J. Dyson and B. Therrien, “Cytotoxicity of arene ruthenium metalla-rectangles incorporating bis-pyridyl diimide linkers,” Journal of Organometallic Chemistry, vol. 815-816, pp. 53-58, 2016.
[7] A. Grozav, V. Miclaus, O. Vostinaru, S. Ghibu, C. Berce, I. Rotar, C. Mogosan, B. Therrien, F. Loghin and D. Popa, “Acute toxicity evaluation of a thiazolo arene ruthenium (II) complex 2 in rats,” Regulatory Toxicology and Pharmacology, vol. 80, pp. 233-240, 2016.
[8] O. Renier, C. Deacon-Price, J. E. B. Peters, K. Nurekeyeva, C. Russon, S. Dyson, S. Ngubane, J. Baumgartner, P. J. Dyson, T. Riedel, H. Chiririwa and B. Blom, “Synthesis and in vitro (anticancer) evaluation of η6-arene ruthenium complexes bearing stannyl ligands,” Inorganics, vol. 5, no. 4, pp. 1-13, 2017.
[9] W. Kandioller, C. G. Hartinger, A. A. Nazarov, J. Kasser, R. John, M. A. Jakupec, V. B. Arion, P. J. Dyson and B. K. Keppler, “Tuning the anticancer activity of maltol-derived ruthenium complexes by derivatization of the 3-hydroxy-4-pyrone moiety,” Journal of Organometallic Chemistry, vol. 694, no. 6, pp. 922-929, 2009.
[10] N. Mohan, M. K. M. Subarkhan and R. Ramesh, “Synthesis, antiproliferative activity and apoptosis-promoting effects of arene ruthenium(II) complexes with N, O chelating ligands,” Journal of Organometallic Chemistry, vol. 859, pp. 124-131, 2018.
[11] E. Orhan, A. Garci, T. Riedel, M. Saudani, P. J. Dyson and B. Therrien, “Cytotoxic double arene ruthenium metalla-cycles that overcome cisplatin resistance,” Journal of Organometallic Chemistry, vol. 803, pp. 39-44, 2016.
[12] C. S. Allardyce and P. J. Dyson, “Ruthenium in medicine: Current clinical uses and future prospects,” Platin. Met. Rev., vol. 45, no. 2, pp. 62–69, 2001.
[13] I. Kostova, “Ruthenium complexes as anticancer agents,” Curr. Med. Chem., vol. 13, pp. 1085–1107, 2006.
[14] C. S. Allardyce, A. Dorcier, C. Scolaro, and P. J. Dyson, “Development of organometallic (organo-transition metal) pharmaceuticals,” Applied Organometallic Chemistry, vol. 19, pp. 1–10, 2005.
[15] E. Orhan, A. Garci, B. Therrien, “Flexible arene ruthenium metalla-prisms,” Inorganica Chimica Acta, vol. 438, pp. 5–9, 2015.
[16] A. Garci, J. P. Mbakidi, V. Chaleix, V. Sol, E. Orhan and B. Therrien, “Tunable arene ruthenium metallaprisms to transport, shield, and release porphin in cancer cells,” Organometallics, vol. 34, pp. 4138−4146, 2015.
[17] A. Garci, A. A. Dobrov, T. Riedel, E. Orhan, P. J. Dyson, V. B. Arion and B. Therrien, “Strategy to optimize the biological activity of arene ruthenium metalla-assemblies,” Organometallics, vol. 33, pp. 3813−3822, 2014.
[18] U. K. Mazumder, M. Gupta, S. S. Karki, S. Bhattacharya, S. Rathinasamya and T. Sivakumar, “Synthesis and pharmacological activities of some mononuclear Ru(II) complexes,” Bioorganic & Medicinal Chemistry, vol.13, pp. 5766–5773, 2005.
[19] G. R. Jadhav, S. Sinha, M. Chhabra and P. Paira, “Synthesis of novel anticancer ruthenium-arene pyridinylmethylene scaffolds via three-component reaction,” Bioorganic & Medicinal Chemistry, vol. 26, no. 11, pp. 2695-2700, 2016.
[20] G. Süss-Fink, “Water-soluble arene ruthenium complexes: From serendipity to catalysis and drug design,” Journal of Organometallic Chemistry, vol. 751, pp. 2–19, 2014.
[21] H. Küçükbay, R. Durmaz, E. Orhan and S. Günal, “Synthesis, antibacterial and antifungal activities of electron-rich olefins derived benzimidazole compounds,” Farmaco, vol. 58, pp. 431–437, 2003.
[22] H. Küçükbay, S. Günal, E. Orhan and R. Durmaz, “Synthesis and antimicrobial activities of some transition metal benzimidazole complexes,” Asian Journal of Chemistry, vol. 22, pp. 7376–7382, 2010.
[23] T. Lazarevic, A. Rilak, Z. D. Bugarcic, “Platinum, palladium, gold and ruthenium complexes as anticancer agents: Current clinical uses, cytotoxicity studies and future perspectives,” European Journal of Medicinal Chemistry, vol. 142, pp. 8-31, 2017.
[24] Ü. Ergun, “ONO ve ONNO tipindeki schiff bazlarının geçiş metalleri komplekslerinin termal bozunma tepkimelerinde kinetik parametrelerinin belirlenmesi ve bazı koordinasyon bağ enerjilerinin hesaplanması,” Doktora tezi, Kimya Bölümü, Ankara Üniversitesi, Ankara, Türkiye, 2009.
[25] M. A. Bennett and A. K. Smith, “Arene Ruthenium ( II ) Complexes formed by dehydrogenation of cyclo-hexadienes with ruthenium( III) trichloride,” Journal of the Chemical Society, pp. 233–241, 1974.
[26] P. Jogi, KVTS P. Kumar, “Studies on DNA cleavage and antimicrobial screening of transition metal complexes of a schiff base derived from 2-(Aminomethyl)- benzimidazole and p-chloro benzaldehyde,” Journal of Chemical and Pharmaceutical Research, vol. 4, no. 2, pp. 1389-1397, 2012.
[27] G. Kumaravel, N. Raman, “A treatise on benzimidazole based Schiff base metal(II) complexes accentuating their biological efficacy: Spectroscopic evaluation of DNA interactions, DNA cleavage and antimicrobial screening,” Materials Science and Engineering: C, vol. 70, no. 1, pp. 184-194, 2017.
[28] A. Grozav, L. I. Găină, V. Pileczki, O. Crisan, L. Silaghi-Dumitrescu, B. Therrien, V. Zaharia and I. Berindan-Neagoe, “The synthesis and antiproliferative activities of new arylidene-hydrazinyl-thiazole derivatives,” International Journal of Molecular Sciences, vol. 15, pp. 22059-22072, 2014.
[29] A. Grozav, O. Balacescu, L. Balacescu, T. Cheminel, I. Berindan-Neagoe and B. Therrien, “Synthesis, anticancer activity, and genome profiling of thiazolo arene ruthenium complexes,” Journal of Medicinal Chemistry, vol. 58, pp. 8475−8490, 2015.
[30] N.K. Kar, M.K. Singh , R.A. Lal, “Synthesis and spectral studies on monometallic ruthenium (III) complexes of N-(2-hydroxysalicyliden-1-yl)methylenebenzoylhydrazide,” Arabian Journal of Chemistry, vol. 10, pp. 76–80, 2017.
[31] M. U. Rehman, M. Imran, M. Arif, M. Farooq, “Metal-based antimicrobial agents: synthesis, characterization and biological studies of mannich base derivatives of benzimidazole and their metal complexes,” Science Journal of Chemistry, vol. 1, no. 5, pp. 56-66, 2013.
[32] M. Akkurt, S. Öztürk, H. Küçükbay, E. Orhan, O. Büyükgüngör, “1-ethyl-3-(2-phenylethyl) benzimidazole-2-selone,” Acta Cryst., vol. 60, pp. 1263-1265, 2004.
[33] M. Akkurt, S. Öztürk, H. Küçükbay, E. Orhan, O. Büyükgüngör, “1, 3-bis (2-phenylethyl) benzimidazolium-2-dithiocarboxylate,” Acta Cryst., vol. 60, pp. 219-221, 2004.
[34] S. Türktekin, M. Akkurt, E. Orhan, F. Z. Küçükbay, H. Küçükbay, O. Büyükgüngör, “Dichlorobis [1-(2-ethoxyethyl)-1H-benzimidazole-κN3] cobalt (II),” Acta Cryst., vol. 60, pp. 1220-1222, 2004.
[35] M. Akkurt, S. Karaca, H. Küçükbay, E. Orhan, O. Büyükgüngör, “Dichlorobis [1-(2-ethoxyethyl)-1H-benzimidazole-κN3] nickel (II),” Acta Cryst., vol. 61, pp. 41-43, 2005.
[36] S. Ö. Yıldırım, M Akkurt, H Küçükbay, E Orhan, O. Büyükgüngör, “6-Nitro-1-(2-phenylethyl)-1H-benzimidazole,” Acta Cryst., vol. 61, pp. 2038-2039, 2005.
[37] Ş. Pınar, M. Akkurt, H. Küçükbay, E. Orhan, O. Büyükgüngör, “Bis [1-(but-2-enyl)-5-nitro-1H-benzimidazole-κN3] dichlorocobalt (II),” Acta Cryst., vol. 62, pp. 1663-1665, 2006.
[38] M. Akkurt, S. Ö. Yıldırım, E. Orhan, H. Küçükbay, O. Büyükgüngör, “1-methoxyethyl-5-nitrobenzimidazole,” Acta Cryst., vol. 61, pp. 2804-2805, 2005.
[39] M. Akkurt, S. Karaca, H. Küçükbay, E. Orhan, O. Büyükgüngör, “1-benzyl-3-(2-phenethyl) benzimidazolium bromide monohydrate,” Acta Cryst., vol. 61, pp. 2452-2454, 2005.