In collaboration with Payame Noor University and Iranian Chemical Science and Technologies Association

Document Type : Full research article


1 Department of Chemistry, Payame Noor University, P. O. Box 19395-4697 Tehran, Iran

2 Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran


Chelation therapy has been used to remove toxic metals from the body for a long time. Flavonoids such as quercetin (QUR), a well-known protective antioxidant and free radical scavenger, can bind to metal cations and protect our bodies from toxic metals. In the current study, we used UV–Vis, 1HNMR, IR, and fluorescence spectroscopic techniques as well as viscosity measurements to investigate the synthesis, characterization, and interaction between Bi(III)-QUR complex and calf thymus DNA (ctDNA) in physiological buffer. The antioxidant activity of the complex was assessed utilizing DPPH and ABTS free radical scavenging, and ferric reducing potential. After chelation of the Bi(III) cation, the antioxidant potential of QUR was reduced. In the presence of ctDNA, the absorption spectrum of Bi(III)-QUR complex was raised, and the fluorescence intensity of Bi(III)-QUR complex was increased. With the addition of the Bi(III)-QUR complex, the relative viscosity of ctDNA rose. These findings indicate that the Bi(III)-QUR complex interacts with ctDNA in a groove-binding mode. The thermodynamic parameters (ΔH, ΔS, and ΔG) of the Bi(III)-QUR complex with ctDNA, as well as well as association constant, Ka, and number of binding sites (n), were assessed from the fluorescence data, indicating that the binding of Bi(III)-QUR complex to ctDNA was primarily driven by hydrophobic interactions.


  • Ndagi, N. Mhlongo, and M.E. Soliman, Metal complexes in cancer therapy – an update from drug design perspective, Drug Des. Devel. Ther. 11 (2017) 599–616.
  • H. Thompson and C. Orvig, Metal complexes in medicinal chemistry: new vistas and challenges in drug design, Dalton Trans. 6 (2006) 761–764.
  • CA Bruijnincx and P.J. Sadler, New trends for metal complexes with anticancer activity, Curr. Opin. Chem. Biol. 12 (2008)197–206.
  • L. Heras, A. Amesty, A. Estevez-Braun and S. Hortelano, Metal complexes of natural product like-compounds with antitumoral activity, AntiCancer Agents Med. Chem. 19 (2019) 48-65.
  • Khater, D. Ravishankar, F. Greco and H. MI Osborn, Metal complexes of flavonoids: their synthesis, characterization and enhanced antioxidant and anticancer activities, Future Med. Chem. 11 (2019), 2845–2867.
  • Shaghaghi, S. Rashtbari, S. Vejdani, G. Dehghan, A. Jouyban and R. Yekta, Exploring the interactions of a Tb(III)-quercetin complex with serum albumins (HSA and BSA): spectroscopic and molecular docking studies, Luminescence 35 (2020) 512-524.
  • Wang, Y. Huang, J.S. Zhang and X.B. Yang, Synthesis, characterization, DNA interaction, and antitumor activities of La(III) complex with Schiff base ligand derived from kaempferol and diethylenetriamine, Bioinorg. Chem. Appl. 2014 (2014) 1-9.
  • E.A. Ikeda, E.M. Novak, D.A. Maria, A.S. Velosa, and R.M.S. Pereira, Synthesis, characterization and biological evaluation of Rutin–zinc(II) flavonoid -metal complex, Chem.-Biol. Interact. 239 (2015) 184–191.
  • B. Bukhari, S. Memon, M. Mahroof-Tahir and M.I. Bhanger, Synthesis, characterization and antioxidant activity copper–quercetin complex, Spectrochim. Acta A 71 (2009) 1901–1906.
  • P. Qadeer, and S. Memon, Synthesis of Cr(III)-morin complex: characterization and antioxidant Study, Sci. World J. 2014 (2014) 1-8.
  • M.S. Pereira, N.E.D. Andrades, N. Paulino, A.C.H.F. Sawaya, M.N. Eberlin, M.C. Marcucci, G.M. Favero, E.M. Novak, and S.P. Bydlowski, Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, anti-inflammatory and tumor cell cytotoxicity, Molecules 12 (2007) 1352-1366.
  • A. Farhan, Study on the interaction of copper (II) complex of morin and its antimicrobial effect, Int. J. Chem. Sci. 11(2013) 1247-1255.
  • Zhang, J. Guo, N. Zha, and J. Wang, Study of interaction between kaempferol–Eu3+ complex and DNA with the use of the neutral red dye as a fluorescence probe, Sens. Actuators B Chem. 144 (2010) 239–246.
  • Liu, and M. Guo, Studies on transition metal-quercetin complexes using electrospray ionization tandem mass spectrometry, Molecules 20 (2015) 8583-8594.
  • Zhang, J. Guo, J. Pan, X. Chen and J. Wang, Spectroscopic studies on the interaction of morin–Eu(III) complex with calf thymus DNA, J. Mol. Struct. 923 (2009) 114–119.
  • M. Kasprzak, A. Erxleben and J. Ochocki, Properties and applications of flavonoid metal Complexes, J. Name. 00, 1-3 (2013) 1-23.
  • Ezzati Nazhad Dolatabadi, A. Mokhtarzadeh, S.M. Ghareghoran, and G. Dehghan, Synthesis, characterization, and antioxidant property of quercetin-Tb(III) complex, Adv. Pharm. Bull. 4 (2014) 101-104.
  • M. Bothwell, S.W. Krabbe, and R.S. Mohan, Applications of bismuth(III) compound in organic synthesis. Chemical Society Reviews, 40, 4649-4707.
  • Pannequin, S. Kovact, J.P. Tantiongco, R.S. Norton, A. Shulkes, K.J. Barnham, and G.S. Baldwin, A novel effect of Bismuth ions: selective inhibition of the biological activity of glycine-extended gastrin. J. Biol. Chem. 279 (2004) 2453–2460.
  • J. Sadler, H. Li, and H. Sun, Coordination chemistry of metals in medicine: target sites for bismuth. Coord. Chem. Rev. 185-186 (1999) 689-709.
  • Wang, X. Zhang, J. Lin, J. Chen, Q. Xu, and Z. Guo, DNA-binding property and antitumor activity of bismuth(III) complex with 1,4,7,10-tetrakis(2-pyridylmethyl)-1,4,7,10 tetraazacyclododecane, Dalton Trans. 12 (2003) 2379-2380.
  • S. Prasad, L.S. Kumar, S. Chandan, R.M. Naveen Kumar, and H.D. Revanasiddappa, Palladium(II) complexes as biologically potent metallo-drugs: Synthesis, spectral characterization, DNA interaction studies, and antibacterial activity, Spectrochim. Acta A Mol. Biomol. Spectrosc. 107 (2013) 108–116.
  • ShaghaghiG. DehghanA. JouybanP. Sistani and M. Arvin, Studies of interaction between terbium(III)-deferasirox and double-helix DNA by spectral and electrochemical methods, Spectrochim. Acta A Mol. Biomol. Spectrosc. 120 (2014) 467-472.
  • Hanifeh Ahagh, G. Dehghan, M. Mahdavi, M.A. Hosseinpour Feizia, R. Teimuri-Mofrad, E. Payami, M. Mehdipour, and S. Rashtbari, DNA binding ability and cytotoxicity, cell cycle arrest and apoptosis-inducing properties of a benzochromene derivative against K562 human leukemia cells, against K562 human leukemia cells, Nucleos. Nucleot. Nucl. 2021,40, 732-753.
  • Khosravifar, G. Dehghan, S.K. Bidoki and M. Mahdavi, DNA-binding activity and cytotoxic and cell-cycle arrest properties of some new coumarin derivatives: a multispectral and computational investigation, Luminescence 35 (2020) 98-106.
  • H. Hegde, S.N. Prashanth, and J. Seetharamappa, Interaction of antioxidant flavonoids with calf thymus DNA analyzed by spectroscopic and electrochemical methods, J. Pharm. Biomed. Anal. 63 (2012) 40–46.
  • Daravath, M.P. Kumar, A. Rambabu, N. Vamsikrishna and G.N. Shivaraj, Design, synthesis, spectral characterization, DNA interaction and biological activity studies of copper(II), cobalt(II) and nickel(II) complexes of 6-amino benzothiazole derivatives, J. Mol. Struct. 1144 (2017) 147-158.
  • Kumar, S. Dasari and A.K. Patra, Ruthenium(II) complexes of saccharin with dipyridoquinoxaline and dipyridophenazine: Structures, biological interactions, and photo induced DNA damage activity, Eur. J. Med. Chem.136 (2017) 52-62.
  • Dehghan, J. Ezzati Nazhad Dolatabadi, A. Jouyban, K. Asadpour Zeynali, S.M. Ahmadi and S. Kashanian, Spectroscopic studies on the interaction of quercetin–Tb(III) complex with calf thymus DNA. DNA. Cell. Biol. 30 (2011) 195–201.
  • M. Ahmadi, G. Dehghan, M.A. Hosseinpour Feizi, J. Ezzati Nazhad Dolatabadi, and S. Kashanian, Preparation, characterization, and DNA binding studies of water-soluble quercetin–molybdenum(VI) complex. DNA. Cell. Biol. 30 (2011) 517-523.
  • Wettasinghe and F. Shahidi, Scavenging of reactive oxygen species and DPPH free radicals by extracts of borage and evening primrose meals. Food Chem. 70 (2000) 17-26.
  • F.F. Benzie and J.J. Strain, Ferric reducing/ antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Meth. Enzymol. 299 (1999) 15–27.
  • C. Pennycooke, S. Cox, and C. Stushnoff, Relationship of cold acclimation, total phenolic content and antioxidant capacity with chilling tolerance in petunia (Petunia x hybrida). Environ. Exp. Bot. 53 (2005) 225-232.
  • Shaghaghi, J.L.Manzoori, and A. Jouyban, Determination of total phenols in tea infusions, tomato, and apple juice by terbium sensitized fluorescence method as an alternative approach to the Folin–Ciocalteu spectrophotometric method, Food Chem. 108 (2008) 695-701.
  • Zhou, L.F. Wang, J.Y. Wang, and N. Tang, Synthesis, characterization, antioxidative and antitumor activities of solid quercetin rare earth(III) complexes. J. Inorg. Biochem. 83 (2001) 41-48.
  • Pekal, M. Biesaga, and K. Pyrzynska, Interaction of quercetin with copper ions: complexation, oxidation, and reactivity towards radicals. Biometals 24 (2011) 41–49.
  • Dehghan, A. Shafiee, M.H. Ghahremani, S.K. Ardestani, and M. Abdollahi, Antioxidant potential of various extracts from ferula szovitsiana in relation to their phenolic contents, Pharm. Biol. 45(2007) 1–9.
  • Kyropoulou, C.P. Raptopoulou, V. Psycharis, and G. Psomas, Ni(II) complexes with non-steroidal anti-inflammatory drug diclofenac: Structure and interaction with DNA and albumins, Polyhedron 61 (2013) 126–136.
  • Karami, Z. Mehri Lighvan, M. Dehdashti Jahromi, J. Lipkowski, and A.A. Momtazi-Borojeni, Synthesis, electronic structure and molecular docking of new organometallic palladium (II) complexes with intercalator ligands: The influence of bridged ligands on enhanced DNA/serum protein binding and in vitro antitumoral activity, J. Organomet. Chem. 827 (2017) 1–14.
  • Rashtbari and G. Dehghan, Biodegradation of malachite green by a novel laccase-mimicking multicopper BSA-Cu complex: Performance optimization, intermediates identification, and artificial neural network modeling, J. Hazard. Mater. 406 (2021), 124340.
  • Bouroumand, F. Marshall, and F. Khazali Determining the Amount of Metronidazole Drug in Blood and Urine Samples with the help of PbS Sensor functionalized with gelatin as a fluorescence-enhanced probe, Iranian Journal of Analytical Chemistry, Iran. J. Anal. Chem.
    7(2020) 47-56.
  • Wolfe, G.H. Shimer Jr and T. Meehan, Polycyclic Aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA. Biochem. 26 (1987) 6392-6396.
  • D. Ross and S. Subramanian, Thermodynamics of protein association reactions: forces contributing to stability. Biochem. 20 (1981) 3096-3102.
  • Aki and M. Yamamoto, Thermodynamics of the binding of phenothiazines to human plasma, human serum albumin and α1-acid glycoprotein: A calorimetric study. J. Pharm. Pharmacol. 41 (1989) 674-679.
  • L. Eichhorn and Y. Ae Shin, Interaction of metal ions with polynucleotides and related compounds. XII. The relative effect of various metal ions on DNA helicity, J. Am. Chem. Soc. 90 (1968) 7323–7328.
  • Liu, K.A. Meadows, and D.R. McMillin, DNA-binding studies of Cu( bcp)2+ and Cu( dmp)2+: DNA elongation without intercalation of Cu(bcp)2+, J. Am. Chem. Soc. 115 (1993) 6699-6704.