Sains Malaysiana 51(11)(2022): 3689-3702

http://doi.org/10.17576/jsm-2022-5111-14

Sintesis dan Pencirian Kompleks Fenolbenzimidazol dan Kajian Interaksi terhadap CT-DNA

(Synthesis and Characterization of Phenolbenzimidazole Complexes and Interaction Studies with CT-DNA)

NOR FALAHIAH ISMAIL, NUR AQILAH ZAHIRAH NORAZMI & NURUL HUDA ABD KARIM^*

Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

Received: 30 March 2022/Accepted: 12 July 2022

Abstrak

Kompleks fenolbenzimidazol berjaya disintesis dan dicirikan menggunakan spektroskopi resonans magnet nukleus (RMN), spektroskopi inframerah transformasi Fourier (FTIR), penentuan julat takat lebur, analisis ultralembayung-boleh nampak (UL-BN), analisis unsur (CHNS), kerentanan magnet dan Kristalografi Sinar-X. Mod pengikatan interaksi antara kompleks fenolbenzimidazol dengan DNA timus anak lembu (CT-DNA) dikaji dengan kaedah pentitratan DNA menggunakan serapan elektronik UL-BN dan kajian nisbah kepekatan DNA menggunakan analisis pendarfluor. Berdasarkan spektrum UL-BN, anjakan hipokromism dan batokromism diperhatikan apabila kompleks fenolbenzimidazol dititratkan dengan CT-DNA dan menunjukkan pembentukan kompleks baru. Kompleks fenolbenzimidazol berinteraksi dengan CT-DNA secara pengikatan interkalasi dengan pemalar pengikatan, K_b (1.68 ± 1.4) × 10⁵ - (1.02 ± 0.1) × 10⁷ M^-1. Kajian pendarfluor dijalankan untuk memerhati sifat optik kompleks fenolbenzimidazol terhadap CT-DNA. Keputusan kajian ini sangat bernilai dan berpotensi dalam menjadikan kompleks fenolbenzimidazol sebagai prob DNA sensor optik.

Kata kunci: DNA timus; interkalasi; kompleks fenolbenzimidazol

Abstract

Phenolbenzimidazole complexes were successfully synthesized, and characterizations were carried out using Nuclear Magnetic Resonance Spectroscopy (NMR), Infrared Spectroscopy (FTIR), melting point range determination, ultraviolet-visible (UV-Vis) analysis, elemental analysis CHNS, magnetic susceptibility and X-ray crystallography.  The binding modes of interaction between phenolbenzimidazole complexes and calf thymus (CT-DNA) were determined by UV-Vis titration and fluorescence using distinct ratios. Based on UV-Vis spectra, hypochromism and bathochromism (red-shift) were observed upon titration of the complexes with CT-DNA which suggested formation of new complexes. Phenolbenzimidazole complexes interact with CT-DNA by intercalation binding mode with the binding constant, K_b (1.68 ± 1.4) × 10⁵ - (1.02 ± 0.1) × 10⁷ M^-1. Fluorescence study was performed to observe the optical properties of phenolbenzimidazole complexes against CT-DNA. These findings will be valuable for the potential use of phenolbenzimidazole complex as a probe in optical sensor DNA.  

Keywords: Intercalation; phenolbenzimidazole complexes; thymus DNA

REFERENCES

Aida Mastura, B.M.Y. & Nurul Huda, A.K. 2014. Interaction of Bis-Zn(II) salphen complex with calf thymus-DNA. AIP Conference Proceedings 1614: 386-392.

Al-Zaqri, N., Salih, K.S.M., Awwadi, F.F., Alsalme, A., Alharthi, F.A., Alsyahi, A., Al Ali, A., Zarrouk, A., Aljohani, M., Chetouni, A. & Warad, I. 2020. Synthesis, physicochemical, thermal, and XRD/HSA interactions of mixed [Cu(Bipy)(Dipn)](X)2 complexes: DNA binding and molecular docking evaluation. Journal of Coordination Chemistry 73(23): 3236-3248.

Arola-Arnal, A., Benet-Buchholz, J., Neidle, S. & Vilar, R. 2008. Effects of metal coordination geometry on stabilization of human telomeric quadruplex DNA by square-planar and square-pyramidal metal complexes. Inorganic Chemistry 47(24): 11910-11919.

Campbell, N.H., Karim, N.H.A., Parkinson, G.N., Gunaratnam, M., Petrucci, V., Todd, A.K., Vilar, R. & Neidle, S. 2012. Molecular basis of structure-activity relationships between salphen metal complexes and human telomeric DNA quadruplexes. Journal of Medicinal Chemistry 55(1): 209-222.

Chandrasekar, T., Arunadevi, A. & Raman, N. 2021. Synthesis, spectral characterization, DNA-binding and antimicrobial profile of biological active mixed ligand Schiff base metal(II) complexes incorporating 1,8-diaminonaphthalene. Journal of Coordination Chemistry 74(4-6): 804-822.

Dey, S., Sarkar, S., Paul, H., Zangrando, E. & Chattopadhyay, P. 2010. Copper(II) complex with tridentate N donor ligand: Synthesis, crystal structure, reactivity and DNA binding study. Polyhedron 29(6): 1583-1587.

Eda Yuhana, A., Lee, Y.H., Tan, L.L. & Nurul Huda, A.B. 2018. Sintesis dan pencirian kompleks nikel ( II ) salfen dengan rantai sisi piperidina dan kajian interaksi dengan DNA denggi. Sains Malaysiana 47(6): 1139-1146.

El-Sayed, Y.S., Gaber, M. & El-Nahass, M.N. 2021. Structural elucidation, spectroscopic, and metalochromic studies of 2-(2-hydroxy phenyl)-1-H–benzimidazole complexes: Metal ions sensing, DNA binding, and antimicrobial activity evaluation. Journal of Molecular Structure 1229: 129809.

Faheem, M., Rathaur, A., Pandey, A., Kumar Singh, V. & Tiwari, A.K. 2020. A review on the modern synthetic approach of benzimidazole candidate. ChemistrySelect 5(13): 3981-3994.

Ghosh, K., Kumar, P., Tyagi, N., Singh, U.P., Aggarwal, V. & Baratto, M.C. 2010. Synthesis and reactivity studies on new copper(II) complexes: DNA binding, generation of phenoxyl radical, SOD and nuclease activities. European Journal of Medicinal Chemistry 45(9): 3770-3779.

Kaushal, R., Thakur, S. & Nehra, K. 2016. ct-DNA binding and antibacterial activity of octahedral titanium (IV) heteroleptic (benzoylacetone and hydroxamic acids) complexes. International Journal of Medicinal Chemistry 2016: 2361214.

Liu, H.K. & Sadler, P.J. 2011. Metal complexes as DNA intercalators. Accounts of Chemical Research 44(5): 349-359.

Mahmood, K., Hashmi, W., Ismail, H., Mirza, B., Twamley, B., Akhter, Z., Rozas, I. & Baker, R.J. 2019. Synthesis, DNA binding and antibacterial activity of metal(II) complexes of a benzimidazole Schiff base. Polyhedron 157: 326-334.

Mann, J., Baron, A., Opoku-Boahen, Y., Johansson, E., Parkinson, G., Kelland, L. & Neidle, S. 2001. A new class of symmetric bisbenzimidazole-based DNA minor groove-binding agents showing antitumor activity. Journal of Medicine 44(2): 138-144.

Mohd Sukri, S.A., Lee, Y.H. & Abd Karim, N.H. 2017. Synthesis, characterization and DNA-binding studies of hydroxyl functionalized platinum(II) salphen complexes. Journal of Fluorescence 27(3): 1009-1023.

Munawar, K.S., Ali, S., Tahir, M.N., Khalid, N., Abbas, Q., Qureshi, I.Z., Hussain, S. & Ashfaq, M. 2020. Synthesis, spectroscopic characterization, X-ray crystal structure, antimicrobial, DNA-binding, alkaline phosphatase and insulin-mimetic studies of oxidovanadium(IV) complexes of azomethine precursors. Journal of Coordination Chemistry 73(16): 2275-2300.

Norhidayah, S., Lee, Y., Nurul Izzaty, H. & Nurul Huda, A. 2016. Synthesis and characterization of 6,6’-Bis (2-Hydroxyphenyl)-2,2’-Bipyridyl Ligand and its platinum complex for the interaction with Ct-DNA. Journal of Analytical Sciences 20(1): 111-120.

Paul, K., Bindal, S. & Luxami, V. 2013. Synthesis of new conjugated coumarin – Benzimidazole hybrids and their anticancer activity. Bioorganic & Medicinal Chemistry 23(12): 3667-3672.

Roshatiara, S., Muhammad Ameerullah, S., Nur Hasyareeda, H. & Nurul Huda, A. 2017. Interaction of n,n’-bis[4-[1-(2-hydroxyethoxy)] salicylidene]-phenyldiamine-nickel(II) and copper(II) complexes with G-quadruplex DNA. Malaysian Journal of Analytical Science 21(3): 544-551.

Sahudin, M.A., Su’ait, M.S., Tan, L.L., Lee, Y.H. & Abd Karim, N.H. 2019. Zinc(II) salphen complex-based fluorescence optical sensor for biogenic amine detection. Analytical and Bioanalytical Chemistry 411(24): 6449-6461.

Shahabadi, N. & Mohammadi, S. 2012. Synthesis characterization and DNA interaction studies of a new ZN(II) complex containing different dinitrogen aromatic ligands. Bioinorganic Chemistry and Applications 2012: 571913.

Singla, P., Luxami, V. & Paul, K. 2014. Benzimidazole-biologically attractive scaffold for protein kinase inhibitors. RSC Advances 4(24): 12422-12440.

Sirajuddin, M., Ali, S. & Badshah, A. 2013. Drug-DNA interactions and their study by UV-Visible, fluorescence spectroscopies and cyclic voltametry. Journal of Photochemistry and Photobiology B: Biology 124: 1-19.

Topala, T., Andreea, B., Oprean, L. & Oprean, R. 2014. Experimental techniques employed in the study of metal complexes-DNA – Interactions. Farmacia 62(6): 1049-1061.

Veerasamy, R., Roy, A., Karunakaran, R. & Rajak, H. 2021. Structure–activity relationship analysis of benzimidazoles as emerging anti-inflammatory agents: An overview. Pharmaceuticals 14(7): 663.

Wu, H., Kou, F., Jia, F., Liu, B., Yuan, J. & Bai, Y. 2011. Synthesis and characterization of the ligand based on benzimidazole and its copper complex: DNA binding and antioxidant activity. Bioinorganic Chemistry and Applications 2011: 105431.

Xu, H., Xu, Z.F., Yue, Z.Y., Yan, P.F., Wang, B., Jia, L.W., Li, G.M., Sun, W.B. & Zhang, J.W. 2008. A novel deep blue-emitting ZnII complex based on carbazole-modified 2-(2-hydroxyphenyl)benzimidazole: Synthesis, bright electroluminescence, and substitution effect on photoluminescent, thermal, and electrochemical properties. Journal of Physical Chemistry C 112(39): 15517-15525.

^*Corresponding author; email: nurulhuda@ukm.edu.my