بررسی اتصال به DNA تیموس گوساله و فعالیت پاداکسیدانی کمپلکس جدید Zn(II) با لیگاندهای الکتروندهنده نیتروژنی و اکسیژنی: مطالعه¬های طیفسنجی و الکتروشیمیایی
محورهای موضوعی : شیمی معدنیآمنه حیدری 1 , پیمان میرزایی 2 , زهرا داورنیا 3
1 - استادیار شیمی معدنی، گروه شیمی، دانشگاه زابل، زابل، ایران.
2 - استادیار شیمی معدنی، گروه شیمی، دانشگاه زابل، زابل، ایران.
3 - دانشجوی کارشناسی گروه شیمی، دانشگاه زابل، زابل، ایران.
کلید واژه: کمپلکس روی, پاداکسنده, برهم¬کنش با DNA, طیفسنجی فلوئورسانس.,
چکیده مقاله :
در این مطالعه کمپلکس جدیدی از روی [Zn(DAP)(SSA)] (DAP: 4،3-دیآمینوبنزوفنون و SSA: گروه سولفوسالسیلیک اسید) طراحی و سنتز شد. سپس، با روشهای طیفسنجی فروسرخ تبدیل فوریه (FTIR)، طیفسنجی مرئی-فرابنفش (UV-Vis)، طیفسنجی تشدید مغناطیسی هسته (¹H-NMR) و تجزیه عنصری شناسایی شد. فعالیت پاداکسندگی این کمپلکس با رادیکال آزاد 2و2-دیفنیل-1-پیکریلهیدرازیل (DPPH) بررسی شد. برپایه نتیجههای بهدستآمده، مشخص شد که فعالیت پاداکسیدانی کمپلکس سنتزشده قابل مقایسه با نمونه استاندارد (ویتامین C) بود. برهمکنش این کمپلکس با DNA تیموس گوساله با روشهای متفاوتی مطالعه شد. مطالعههای انجامشده در این کار نشان داد که برهمکنش بین این کمپلکس و DNA تیموس گوساله بهصورت شیاری انجام میشود، ولی نقش برهمکنشهای الکترواستاتیک نیز بهدلیل وجود گروههای باردار بر حلقه آروماتیک بیتاثیر نیست. نتیجههای بهدستآمده از اندازهگیری گرانروی و مطالعههای الکتروشیمیایی و فلوئورسانس این یافته را تایید کردند. مطالعههای فلوئورسانس نشان داد که سازوکار پیشنهادی برای خاموشی فلورسانس از نوع خاموشی ایستا بود. عاملهای ترمودینامیکی (تغییرهای آنتالپی و آنتروپی) نشان داد که برهمکنش کمپلکس با DNA از راه نیروهای آبگریز رخ میدهد. همچنین، مقدار بهدستآمده برای تغییرهای انرژی آزاد گیبس نمایانگر انجام خودبهخودی این برهمکنش بود.
In this study, a novel Zn(II) complex, [Zn(DAP)(SSA)] (DAP: 3,4-diaminobenzophenone ligand and SSA: sulfosalicylic acid group) was designed and synthesized. Its characterization was carried out using Fourier transform infrared (FTIR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, proton nuclear magnetic resonance (¹H-NMR), and elemental analysis. The antioxidant activity of the complex was investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. This experiment revealed that the antioxidant activity of the synthesized complex was comparable to that of standard vitamin C. The interaction of this complex with CT-DNA was studied by various methods. The studies conducted in this work indicated that the interaction between this complex and CT-DNA occurred via groove binding, but the role of electrostatic interactions was also not negligible due to the presence of charged groups on the aromatic ring. The results obtained from viscosity measurements, electrochemical studies, and fluorescence studies confirmed this finding. Fluorescence studies showed that the proposed mechanism for fluorescence quenching was static quenching. Thermodynamic parameters (enthalpy and entropy changes) indicated that the interaction of the complex with DNA occurred through hydrophobic forces. Furthermore, the obtained value for the Gibbs free energy change signified the spontaneous nature of this interaction.
[1] Anjomshoa M, Fatemi SJ, Torkzadeh-Mahani M, Hadadzadeh H. DNA-and BSA-binding studies and anticancer activity against human breast cancer cells (MCF-7) of the zinc (II) complex coordinated by 5, 6-diphenyl-3-(2-pyridyl)-1, 2, 4-triazine. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2014;127:511-20. doi: org/10.1016/j.saa.2014.02.048
[2] Gao C-Y, Qiao X, Ma Z-Y, Wang Z-G, Lu J, Tian J-L, et al. Synthesis, characterization, DNA binding and cleavage, BSA interaction and anticancer activity of dinuclear zinc complexes. Dalton Transactions. 2012;41(39):12220-32. doi: org/10.1039/C2DT31306E
[3] Tarushi A, Raptopoulou CP, Psycharis V, Terzis A, Psomas G, Kessissoglou DP. Zinc (II) complexes of the second-generation quinolone antibacterial drug enrofloxacin: structure and DNA or albumin interaction. Bioorganic & medicinal chemistry. 2010;18(7):2678-85 doi: org/10.1016/j.bmc.2010.02.021
[4] Zhang H, Liu C-S, Bu X-H, Yang M. Synthesis, crystal structure, cytotoxic activity and DNA-binding properties of the copper (II) and zinc (II) complexes with 1-[3-(2-pyridyl) pyrazol-1-ylmethyl] naphthalene. Journal of Inorganic Biochemistry. 2005;99(5):1119-25. doi: org/10.1016/j.jinorgbio.2005.02.005
[5] Silvestri A, Barone G, Ruisi G, Anselmo D, Riela S, Liveri VT. The interaction of native DNA with Zn (II) and Cu (II) complexes of 5-triethyl ammonium methyl salicylidene orto-phenylendiimine. Journal of inorganic biochemistry. 2007;101(5):841-8. doi: org/10.1016/j.jinorgbio.2007.01.017
[6] Dorafshan Tabatabai AS, Dehghanian E, Mansouri-Torshizi H. In-silico and in-detail experimental interaction studies of new antitumor Zn (II) complex with CT-DNA and serum albumin. Journal of Biomolecular Structure and Dynamics. 2023;41(19):9614-31. doi: org/10.1080/07391102.2022.2144459
[7] Shao J, Ma Z-Y, Li A, Liu Y-H, Xie C-Z, Qiang Z-Y, Xu J-Y. Thiosemicarbazone Cu (II) and Zn (II) complexes as potential anticancer agents: Syntheses, crystal structure, DNA cleavage, cytotoxicity and apoptosis induction activity. Journal of Inorganic Biochemistry. 2014;136:13-23. doi: org/10.1016/j.jinorgbio.2014.03.004
[8] Kelland L. The resurgence of platinum-based cancer chemotherapy. Nature Reviews Cancer. 2007;7(8):573-84. doi: org/10.1038/nrc2167
[9] Mendiguchia BS, Aiello I, Crispini A. Zn (II) and Cu (II) complexes containing bioactive O, O-chelated ligands: Homoleptic and heteroleptic metal-based biomolecules. Dalton Transactions. 2015;44(20):9321-34. doi: org/10.1039/C5DT00817D
[10] Guo Q, Li L, Dong J, Liu H, Xu T, Li J. Synthesis, crystal structure and interaction of l-valine Schiff base divanadium (V) complex containing a V2O3 core with DNA and BSA. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2013;106:155-62. doi: org/10.1016/j.saa.2012.12.089
[11] Misirlic-Dencic S, Poljarevic J, Isakovic AM, Sabo T, Markovic I, Trajkovic V. Current development of metal complexes with diamine ligands as potential anticancer agents. Current Medicinal Chemistry. 2020;27(3):380-410. doi: org/10.2174/0929867325666181031114306
[12] Jamil W, Solangi S, Ali M, Khan KM, Taha M, Khuhawar MY. Syntheses, characterization, in vitro antiglycation and DPPH radical scavenging activities of isatin salicylhydrazidehydrazone and its Mn (II), Co (II), Ni (II), Cu (II), and Zn (II) metal complexes. Arabian Journal of Chemistry. 2019;12(8):2262-9. doi: org/10.1016/j.arabjc.2015.02.015
[13] Özdemir Ö. Bis-azo-linkage Schiff bases—Part (II): Synthesis, characterization, photoluminescence and DPPH radical scavenging properties of their novel luminescent mononuclear Zn (II) complexes. Journal of Photochemistry and Photobiology A: Chemistry. 2020;392:112356. doi: org/10.1016/j.jphotochem.2020.112356
[14] Tarpey P, Parnau J, Blow M, Woffendin H, Bignell G, Cox C, et al. Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. The American Journal of Human Genetics. 2004;75(2):318-24. doi: 10.1086/422703
[15] Ravanat J-L, Sauvaigo S, Caillat S, Martinez GR, Medeiros MH, Mascio PD, et al. Singlet oxygen-mediated damage to cellular DNA determined by the comet assay associated with DNA repair enzymes. Biological Chemistry. 2004;385(1):17-20. doi: org/10.1515/BC.2004.003
[16] Shahraki K, Shahraki S, Nezami ZS, Delarami HS. New acetohydrazide-based Schiff base complexes with the ability to enhance catalase activity. Inorganic Chemistry Communications. 2024;163:112318. doi: org/10.1016/j.inoche.2024.112318
[17] Keikha Oveisi A, Shahraki S, Dehghanian E, Mansouri-Torshizi H. Effect of central metal ion on some pharmacological properties of new Schiff base complexes. Anticancer, antioxidant, kinetic/thermodynamic and computational studies. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2025;325:125034. doi: org/10.1016/j.saa.2024.125034
[18] Revathi N, Sankarganesh M, Dhaveethu Raja J, Vinoth Kumar GG, Sakthivel A, Rajasekaran R. Bio-active mixed ligand Cu (II) and Zn (II) complexes of pyrimidine derivative Schiff base: DFT calculation, antimicrobial, antioxidant, DNA binding, anticancer and molecular docking studies. Journal of Biomolecular Structure and Dynamics. 2021;39(8):3012-24. doi: org/10.1080/07391102.2020.1759454
[19] Brand-Williams W, Cuvelier M-E, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT-Food science and Technology. 1995;28(1):25-30. doi: org/10.1016/S0023-6438(95)80008-
[20] Mohammadi F, Mansouri-Torshizi H. Five novel palladium (II) complexes of 8-hydroxyquinoline and amino acids with hydrophobic side chains: Synthesis, characterization, cytotoxicity, DNA-and BSA-interaction studies. Journal of Biomolecular Structure and Dynamics. 2020;38(10):3059-73. doi: org/10.1080/07391102.2019.1651219
[21] Dustkami M, Mansouri-Torshizi H. Refolding and unfolding of CT-DNA by newly designed Pd (II) complexes. Their synthesis, characterization and antitumor effects. International journal of biological macromolecules. 2017;99:319-34. doi: org/10.1016/j.ijbiomac.2017.02.063
[22] Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958;181(4617):1199-200. doi:org/10.1038/1811199a0
[23] Shahraki S, Majd MH, Heydari A. Novel tetradentate Schiff base zinc (II) complex as a potential antioxidant and cancer chemotherapeutic agent: Insights from the photophysical and computational approach. Journal of Molecular Structure. 2019;1177:536-44. doi: org/10.1016/j.molstruc.2018.10.005
[24] Koetsier G, Cantor E. A practical guide to analyzing nucleic acid concentration and purity with microvolume spectrophotometers. USA: New England Biolabs Inc.; 2019.
[25] Benesi HA, Hildebrand J. A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. Journal of the American Chemical Society. 1949;71(8):2703-7. doi: org/10.1021/ja01176a030
[26] Heidari A, Mansouri-Torshizi H, Saeidifar M, Abdi K. Experimental and computational studies on the interaction between DNA and BSA with a couple of isomeric [Pd(daf)(Leu)]+, and [Pd(daf)(Ile)]+ antitumor complexes, their synthesis and spectral characterization. Bulletin of the Chemical Society of Japan. 2021;94(11):2678-94. doi: org/10.1246/bcsj.20210221
[27] Lakowicz JR, Lakowicz JR. Energy transfer. Principles of fluorescence spectroscopy. 1999;36:7-94. doi: org/10.1007/978-0-387-46312-4_2
[28] Feng X-Z, Lin Z, Yang L-J, Wang C, Bai C-l. Investigation of the interaction between acridine orange and bovine serum albumin. Talanta. 1998;47(5):1223-9. doi: org/10.1016/S0039-9140(98)00198-
[29] Zhang L-W, Wang K, Zhang X-X. Study of the interactions between fluoroquinolones and human serum albumin by affinity capillary electrophoresis and fluorescence method. Analytica chimica acta. 2007;603(1):101-10. doi: org/10.1016/S0039-9140(98)00198-
[30] Zhang X, Li S, Yang L, Fan C. Synthesis, characterization of Ag (I), Pd (II) and Pt (II) complexes of a triazine-3-thione and their interactions with bovine serum albumin. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2007;68(3):763-70. doi: org/10.1016/j.saa.2006.12.058
[31] Chaveerach U, Meenongwa A, Trongpanich Y, Soikum C, Chaveerach P. DNA binding and cleavage behaviors of copper (II) complexes with amidino-O-methylurea and N-methylphenyl-amidino-O-methylurea, and their antibacterial activities. Polyhedron. 2010;29(2):731-8. doi: org/10.1016/j.poly.2009.10.031
[32] Ramachandran E, Raja DS, Bhuvanesh NS, Natarajan K. Mixed ligand palladium (II) complexes of 6-methoxy-2-oxo-1,2-dihydroquinoline-3-carbaldehyde 4 N-substituted thiosemicarbazones with triphenylphosphine co-ligand: synthesis, crystal structure and biological properties. Dalton Transactions. 2012;41(43):13308-23. doi: org/10.1039/C2DT31079A
[33] Eslami Moghadam M, Saidifar M, Divsalar A, Mansouri-Torshizi H, Saboury AA, Farhangian H, et al. Rich spectroscopic and molecular dynamic studies on the interaction of cytotoxic Pt (II) and Pd (II) complexes of glycine derivatives with calf thymus DNA. Journal of Biomolecular Structure and Dynamics. 2016;34(1):206-22. doi: org/10.1080/07391102.2015.1015056
[34] Biju A, Rajasekharan M, Bhat SS, Khan AA, Kumbhar AS. Synthesis, crystal structure and cytotoxicity studies of cis-dichloro (4, 5-diazafluoren-9-one) platinum (II). Inorganica Chimica Acta. 2014;423:93-7. doi.: org/10.1016/j.ica.2014.09.007
[35] Abdel-Rahman LH, El-Khatib RM, Nassr LA, Abu-Dief AM, Ismael M, Seleem AA. Metal based pharmacologically active agents: Synthesis, structural characterization, molecular modeling, CT-DNA binding studies and in vitro antimicrobial screening of iron (II) bromosalicylidene amino acid chelates. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2014;117:366-78. doi: org/10.1016/j.saa.2013.07.056
[36] Saeidifar M, Mansouri-Torshizi H, Palizdar Y, Eslami-Moghaddam M, Divsalar A, Saboury AA. Synthesis, characterization, cytotoxicity and DNA binding studies of a novel anionic organopalladium (II) complex. Acta Chimica Slovenica. 2014;61(1):126-36.
[37] Reddy PR, Shilpa A, Raju N, Raghavaiah P. Synthesis, structure, DNA binding and cleavage properties of ternary amino acid Schiff base-phen/bipy Cu (II) complexes. Journal of Inorganic Biochemistry. 2011;105(12):1603-12. doi: org/10.1016/j.jinorgbio.2011.08.022
[38] Quintal SM, Félix V, Drew MG, Nogueira HI. Coordination modes of 3-aminosalicylic and 3-hydroxyanthranilic acids in palladium (II), platinum (II) and rhenium (V) complexes. The crystal structure of cis-[Pt(HsalNH)(PPh3)2]·0.25 C2H5OH. Polyhedron. 2006;25(3):753-8. doi: org/10.1016/j.poly.2005.07.034
[39] Heydari A, Mansouri-Torshizi H. Design, synthesis, characterization, cytotoxicity, molecular docking and analysis of binding interactions of novel acetylacetonatopalladium (II) alanine and valine complexes with CT-DNA and BSA. RSC advances. 2016;6(98):96121-37. doi: org/10.1039/C6RA18803F
[40] Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. The lancet. 2000;356(9237):1255-9. doi: 10.1016/S0140-6736(00)02799-
[41] Alam MM, Abul Qais F, Ahmad I, Alam P, Hasan Khan R, Naseem I. Multi-spectroscopic and molecular modelling approach to investigate the interaction of riboflavin with human serum albumin. Journal of Biomolecular Structure and Dynamics. 2018;36(3):795-809. doi: org/10.1080/07391102.2017.1298470
[42] Zhang Q-L, Liu J-G, Chao H, Xue G-Q, Ji L-N. DNA-binding and photocleavage studies of cobalt (III) polypyridyl complexes: [Co(phen)2IP]3+ and [Co(phen)2PIP]3+. Journal of Inorganic Biochemistry. 2001;83(1):49-55. doi: org/10.1016/S0162-0134(00)00132-
[43] Heidari A, Mansouri-Torshizi H, Saeidifar M, Dehghanian E, Abdi K, Delarami HS. Diverse coordination of dipicolinic acid to Pd (II) ion result antitumor complexes, their interaction with CT-DNA by spectroscopic experiments and computational methods. Journal of Molecular Structure. 2022;1261:132937. doi: org/10.1016/j.molstruc.2022.132937
[44] Yu X, Yao Q, Tao H, Yang Y, Li L, Li X, Zhu S. Spectroscopic studies on the interaction of BSA and 5-spiro-3′-piperidine-2″-spiro-3″-indole-4′,2″-diones. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2013;104:519-26. doi: org/10.1016/j.saa.2012.11.095
[45] Samari F, Hemmateenejad B, Shamsipur M, Rashidi M, Samouei H. Affinity of two novel five-coordinated anticancer Pt (II) complexes to human and bovine serum albumins: A spectroscopic approach. Inorganic chemistry. 2012;51(6):3454-64. doi: org/10.1021/ic202141g
[46] Mansouri-Torshizi H, Zareian-Jahromi S, Ghahghaei A, Shahraki S, Khosravi F, Heidari Majd M. Palladium (II) complexes of biorelevant ligands. Synthesis, structures, cytotoxicity and rich DNA/HSA interaction studies. Journal of Biomolecular Structure and Dynamics. 2018;36(11):2787-806. doi: org/10.1080/07391102.2017.1372309
[47] Saeidifar M, Mansouri-Torshizi H, Palizdar Y, Divsalar A, Saboury AA. Synthesis, characterization, and cytotoxicity studies of a novel palladium (II) complex and evaluation of DNA-binding aspects. Nucleosides, Nucleotides and Nucleic Acids. 2013;32(7)366-88. doi: org/10.1080/15257770.2013.790552
[48] Yang L, Huo D, Hou C, Yang M, Fa H, Luo X. Interaction of monosulfonate tetraphenyl porphyrin (H2TPPS1) with plant-esterase: Determination of the binding mechanism by spectroscopic methods. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2011;78(5):1349-55. doi: org/10.1016/j.saa.2011.01.009
[49] Heidari A, Dehghanian E, Shahraki S, Razmara Z, Majd MH, Ahmar H, et al. Investigating DNA-Interaction and Anticancer Activity of new Cu2+ complex Coordinated with Dipicolinic Acid. Experimental and Computational Studies. 2025;584:122730. doi: org/10.1016/j.ica.2025.122730
[50] Shahabadi N, Mohammadi S, Alizadeh R. DNA interaction studies of a new platinum (II) complex containing different aromatic dinitrogen ligands. Bioinorganic chemistry and applications. 2011;2011(1):429241. doi: org/10.1155/2011/429241
[51] Shoukry AA, Mohamed MS. DNA-binding, spectroscopic and antimicrobial studies of palladium (II) complexes containing 2,2′-bipyridine and 1-phenylpiperazine. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2012;96:586-93. doi: org/10.1016/j.saa.2012.07.012
[52] Abdi K, Hadadzadeh H, Salimi M, Simpson J, Khalaji AD. A mononuclear copper (II) complex based on the polypyridyl ligand 2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz), [Cu(tptz)2]2+: X-ray crystal structure, DNA binding and in vitro cell cytotoxicity. Polyhedron. 2012;44(1):101-12. doi: org/10.1016/j.poly.2012.06.089
[53] Alisufi N, Mansouri-Torshizi H. Preparation, characterization, DNA/BSA interaction and computational binding analyses of a dinuclear, biopotency Pd2+ coordinated with 1,4-phenylenediamine and ethylenediamine as ligands. Journal of the Iranian Chemical Society. 2021;18:1147-66. doi: org/10.1007/s13738-020-02098-4
[54] Qin D-A, Cai X-Q, Miao Q, Wang Z-H, Hu M-L. Cyclic voltammetry and molecular docking study of the interactions of two derivatives of 5-fluorouracil with DNA. International Journal of Electrochemical Science. 2014;9(4):1608-20. doi: org/10.1016/S1452-3981(23)07877-
