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Application of Ru(II) Polypyridyl complexes in Metallopharmaceuticals and Material science

Sravani Gudikandula, Aruna Kodipaka, Navaneetha Nambigari


A series of three mononuclear ruthenium(II) polypyridyl complexes of the type [Ru(A)2qpd] (ClO4)2.2H2O, where qpd = N, N1-(8,9-Quinoxalinediylidene)-1,10-phenanthroline-5,6-diamine and A = (phen = 1,10 Phenanthroline (1), bpy = bipyridyl (2), tbz= 2-(1H-Pyrrol-2-yl)-1H-indole (3), were synthesized and characterized by several spectroscopic studies. The study focuses on DNA binding affinities, structural, nonlinear optical (NLO) properties, and docking interactions (with ds DNA) by both experimental (Biophysical methods – UV Absorption, Fluorescence, quenching, and viscosity) and computational (Density functional theory) methods.

The research shows that binding constant (Kb) values are in the order 1> 2 > 3 for the Ru (II) polypyridyl complexes 1 to 3. The findings suggest that the phen and bpy complex has a stronger ability to bind with DNA than the tbz ligand, highlighting the importance of the auxiliary ligand. For molecular geometry (Ground State) and electronic characteristics using DFT calculations at B3LYP/LanL2DZ level. All complexes show an intense band due to metal to ligand CT band, n →π* transition (HOMO to LUMO gap, Eg). The Eg gap of phen complex is most minor (2.0865 eV) compared to the Intercalator (2.5327eV). Among the three complexes, the phen complex has the most extended Intercalator length 15.8812 Å, and paramount optical properties. Further molecular docking predicted a DNA-binding preference for guanine, indicating a correlation with the experimental binding constant. 

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M.J. Clark, Ruthenium metallopharmaceuticals, Coordination Chemistry Reviews, 2003, 236, 209-33.

R.W. Sun, D.L. Ma, E.L. Wong, C.M. Che, Some uses of transition metal complexes as anticancer and anti-HIV agents, Dalton Transactions, 2007, 43, 4884-4892.

M. Poursharifi, M.T. Wlodarczyk, A.J. Mieszawska, Nano-based systems and biomacromolecules as carriers for metallodrugs in anticancer therapy, Inorganics, 2018, 7, 1-19.

B.K. Keppler, Metal Complexes in Cancer Chemotherapy, Weinheim, Germany: VCH, 1993,187-202.

E. Thomas, K. Franz, M. Stefan, D. Dimić,I. Morgan, M. Saoud, D. Milenković, Z. Marković,T. Rüffer, J.D. Marković, N. Kaluđerović, Synthesis, Crystallographic Structure, Theoretical Analysis, Molecular Docking Studies, and Biological Activity Evaluation of Binuclear Ru(II)-1-Naphthylhydrazine Complex, Int. J. Mol. Sci., 2023, 24, 689.

N.G. García-Peña, A.M. Caminade, A. Ouali, R. Redón, C.O. Turrin, Solventless synthesis of Ru (0) composites stabilized with polyphosphorhydrazone (PPH) Dendron’s and their use in catalysis, RSC advances, 2016, 6, 64557-64567.

R. Hudson, V. Chazelle,M.Bateman, R. Roy, C.J. Li, A. Moores, Sustainable synthesis of magnetic ruthenium-coated iron nanoparticles and application in the catalytic transfer hydrogenation of ketones, ACS Sustainable Chemistry & Engineering, 2015, 4, 814-820.

S. Santoro, V. Sebastian, A.J. Moro, C.A. Portugal, J.C. Lima, I.M. Coelhoso, Development of fluorescent thermoresponsive nanoparticles for temperature monitoring on membrane surfaces, Journal of Colloid and Interface Science, 2017, 15, 144-1452.

R.A. Krause, Synthesis of ruthenium (II) complexes of aromatic chelating heterocycles: Towards the design of luminescent compounds, Coordination Compounds: Synthesis and Medical Application, 2005, 67, 1-52.

D.R. Casimiro, J.H. Richards, J.R. Winkler, H.B. Gray, Electron transfer in ruthenium-modified cytochromes c sigma.-tunneling pathways through aromatic residues, The Journal of Physical Chemistry, 1993, 97, 13073-13077.

D.P. Rillema, G. Allen, T.J. Meyer, D. Conrad, Redox properties of ruthenium (II) tris chelate complexes containing the ligands 2, 2’-bipyrazine, 2, 2’-bipyridine, and 2, 2’-bipyrimidine, Inorganic Chemistry, 1983, 22, 1617-1622.

C.K. Prier, D.A. Rankic, D.W. MacMillan, Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis, Chemical Reviews, 2013, 10, 5322-5363.

E. Tfouni, Photochemical reactions of ammineruthenium (II) complexes, Coordination Chemistry Reviews, 2000, 1, 281- 305.

S. Wolfgang, T.C. Strekas, H.D. Gafney, R.A. Krause, K. Krause, Spectral and photophysical properties of ruthenium (II) 2-(phenylazo) pyridine complexes, Inorganic Chemistry, 1984, 23,


F. Millett, B. Durham, Design of photoactive ruthenium complexes to study interprotein electron transfer, Biochemistry. 2002,41, 11315-11324.

Y. Qin, Q. Peng, Ruthenium sensitizers and their applications in dye-sensitized solar cells, International Journal of Photoenergy, 2012, 2012, 1-21.

M.K. Nazeeruddin, F. De Angelis, S. Fantacci, A. Selloni, G. Viscardi, P. Liska, Combined experimental and DFT-TDDFT computational study of photoelectrochemical cell ruthenium sensitizers, Journal of the American Chemical Society, 2005, 127,16835-16847.

L. Zeng, Y. Chen, H. Huang, J. Wang, Cyclometalated Ruthenium (II) Anthraquinone complexes exhibit strong anticancer activity in hypoxic tumor cells, Chemistry, 2015, 21,15308–15319.

F.E. Poynton, S.A. Bright, S. Blasco, D.C. Williams, The development of Ruthenium (II) Polypyridyl complexes and conjugates for invitro cellular and invivo applications, Che.Soc. Rev., 2017, 4, 7706–7756.

A. Juris, V. Balzani, F. Barigelletti, S. Campagna, P. Belser, A. von Zelewsky, Ru(II) Polypyridine Complexes: Photophysics, Photochemistry, Electrochemistry, and Chemiluminescence, Coordination Chemistry Reviews, 1988, 84, 285-277.

F. Diederich, M. Gómez-López, Supramolecular fullerene chemistry, Chem. Soc. ReV., 1999, 28, 263-277.

M.D. Meijer, G.P.M. van Klink, G. van Koten, Metal-chelating capacities attached to fullerenes, Coordination Chemistry Reviews, 2022, 230, 141–163.

F. D’Souza, O. Ito, H. R. Nalwa, Handbook Org. Elec. Phot, American Scientific Publishers, 2008, 1, 485-521.

R. Chitta, F. D’Souza, Self-assembled tetrapyrrole–fullerene and tetrapyrrole– carbon nanotube donor–acceptor hybrids for light induced electron transfer applications, J. Mater. Chem., 2008, 18, 1440-1447.

D.M. Guldi, T. Da Ros, P. Braiuca, M. Prato, E. Alessio,C60 in the box. A supramolecular C60–porphyrin assembly, J. Mater. Chem., 2002, 12, 2001-2008.

A.F. Collings, C. Critchley, Artificial Photosynthesis: From Basic Biology to Industrial Application; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2005.

V. Balzani, M. Clemente-Leo´n, A. Credi, B. Ferrer, M. Venturi, A.H. Flood, J.F. Stoddart, Autonomous artificial nanomotor powered by sunlight Proc, Natl. Acad. Sci., 2006, 103, 1178-1183.

M. Yamada, Y. Tanaka, Y. Yoshimoto, S. Kuroda, I. Shimao, Synthesis and Properties of Diamino-Substituted Dipyrido [3,2-a: 2′,3′-c]phenazine, Bull. Chem. Soc. Jpn., 1992, 65, 1006.

B.P. Sullivan, D.J. Salmon, T. Meyer, Mixed phosphine 2,2'-bipyridine complexes of ruthenium, Inorg. Chem., 1987, 17, 3334.

N. Navaneetha, K. Aruna, V. Ravi Kumar, A. Praveen Kumar, S. Satyanarayana, A Biophysical Study of Ru(II) Polypyridyl Complex, Properties and its Interaction with DNA, Journal of Fluorescence, 2022, 32, 1211-1228.

N. Navaneetha, K. Aruna, V. Ravi Kumar, A. Praveen Kumar, S. Satyanarayana, Binding and Photocleavage studies of Ru (II) Polypyridyl Complexes with DNA: An In Silico and Antibacterial activity, Analytical Chemistry Letters, 2022, 12, 266–282.

L.H. Han, C.R. Zhang, J.W. Zhe, N.Z. Jin, Y.L. Shen, W. Wang, J.J. Gong, Y.H. Chen, Z.J. Liu, Understanding the electronic structures and absorption properties of porphyrin sensitizers YD2 and YD2-o-C8 for dye-sensitized solar cells, Int. J. Mol. Sci., 2013, 14, 20171-20188.

T. Mihaylov, N. Trendafilova, I. Kostova, I. Georgieva, G. Bauer, DFT modeling and spectroscopic study of metal-ligand bonding in La(III) complex of coumarin-3-carboxylic acid, Chem. Phys., 2006, 327, 209-219.

M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G.A. Petersson, Gaussian 09, Revision D. 01, Gaussian Inc, Wallingford, 2009.

R.E. Stratmann, G.E. Scuseria, M.J. Frisch, An efficient implementation of time-dependent density-functional theory for the calculation of excitation energies of large molecules, J. Chem. Phys., 1998, 109, 8218–8224.

R.G. Parr, Density Functional Theory, Annual Review of Physical Chemistry, 1983, 34, 631-656.

C. Lee, W. Yang, R.G. Parr, Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Physical Review B, 1988, 37, 785-789.

A.B. Punnarao, K. Gulati, N. Joshi, D.K. Deb, D. Rambabu, W. Kaminsky, K.M. Poluri, M.R. Kollipara, Molecular structure, spectroscopic investigation and quantum chemical calculations of Ruthenium (II) complex of isoniazid ligand, Inorg Chim Acta, 2017, 1693, 30488.

N.A. Ogorodnikova, On invariance of the Mulliken substituent-induced charge changes in quantum-chemical calculations of different levels, J. Mol. Struct., 2009, 894, 41–49.

A.N. El-Ghamaz, M.A. Diab, A.A. El-Bindary, Geometrical structure and optical properties of antipyrine Schiff base derivatives, Mater Sci Semicond Process, 2014, 27, 521–531.

A.Z. El-Sonbati, M.A. Diab, A.A. El-Bindary, S.M. Morgan, Supramolecular spectroscopic and thermal studies of azodye complexes, Spectrochim Acta Part A Mol Biomol Spectrosc, 2014, 127, 310–328.

A.Z. El-Sonbati, M.A. Diab, A.A. El-Bindary, Molecular docking, DNA binding, thermal studies and antimicrobial activities of Schiff base complexes. J. Mol. Liq., 2016, 218, 434–456.

V.M. Geskin, C, Lambert, J.L. Bredas, Origin of High Second- and Third-Order Nonlinear Optical Response in Ammonio/Borato Diphenylpolyene Zwitterions: the Remarkable Role of Polarized Aromatic Groups, J Am Chem Soc., 2003, 125, 15651.

V. Barone, M. Cossi, J. Thomasi, Geometry optimization of molecular structures in solution by the polarizable continuum model, J ComputChem., 1998, 19, 404-417.

N.A. Ogorodnikova, On invariance of the Mulliken substituent-induced charge changes in quantum-chemical calculations of different levels, J. Mol. Struct., 2009, 894, 41–49.

D. Schneidman-Duhovny, Y. Inbar, R. Nussinov, H.J. Wolfson, PatchDock and SymmDock: servers for rigid and symmetric docking, Nucleic Acids Res., 2005, 33, W363–W367.

T.P. James, M. Matshwele , O. Sebusi, D. Mapolelo, M. Leteane, G. Lebogang, D. Julius, O. Nkwe, and F. Nareetsile, Antibacterial Activity of 2-Picolyl-polypyridyl-Based Ruthenium (II/III) Complexes on Non-Drug-Resistant and Drug-Resistant Bacteria, Bioinorganic Chemistry and Applications, 2021, 2021, 5563209.

A.D. Allen, C.V. Senoff, Preparation and infrared spectra of some ammine complexes of ruthenium(II) and ruthenium(III), Can. J. Chem., 1967, 45, 1337-1341.

P.V. Reddy, M.R. Reddy, S. Satyanarayana, Design, Synthesis, DNA binding affinity, cytotoxicity, apoptosis and cell cycle arrest of Ru(II) polypyridyl complexes, Anal Biochem., 2015, 15, 49-58.

R.K. Gupta, R. Pandey, G. Sharma, DNA Binding and AntiCancer Activity of Redox-Active Heteroleptic Piano-Stool Ru(II), Rh(III), and Ir(III) Complexes Containing 4-(2-Methoxypyridyl) phenyldipyrromethene, Inorg Chem, 2013, 52, 3687–3698.

A.E. Friedman, J.C. Chambron, J.P. Sauvage, N.J. Turro and J.K. Barton, A molecular light switch for DNA: Ru(bpy)2(dppz)2+, J. Am. Chem. Soc., 1990, 112, 4960-4962.

J.B. Lepecq, C. Paoletti, A fluorescent complex between ethidium bromide and nucleic acids. J Mol Biol., 1967, 27, 87–106.

R.K. Vuradi, S. Avudoddi, V.R. Putta, Synthesis, Characterization and Luminescence Sensitivity with Variance in pH, DNA and BSA Binding Studies of Ru(II) Polypyridyl Complexes, J Fluoresc, 2017, 27, 939–952.

J.B. Chaires, Energetics of drug–DNA interactions, Biopolymers, 1997, 44, 201–215.

S. Satyanarayana, J.C. Dabrowiak, J.B. Chaires, Tris(phenanthroline)ruthenium(II) enantiomer interactions with DNA: Mode and specificity of binding, Biochemistry, 1993, 32, 2573–2584.

R.K. Vuradi, V.R. Putta, D. Nancherla, S. Sirasani, Luminescent Behavior of Ru(II) Polypyridyl Morpholine Complexes, Synthesis, Characterization, DNA, Protein Binding, Sensor Effect of Ions/Solvents and Docking Studies, J Fluoresc., 2016, 26, 689–701.

M. Ahmadnezhad, M. Darvish Ganji, M. Rezvani, Theoretical studies on the geometrical and electronic structures of supramolecule bis(2,2ʹbipyridine)-5-amino-1,10-phenanthroline ruthenium(II)/functionalized SWCNT dyads, J Physics and Chemistry of Solids, 2015, 86, 148-154.

R.G. Parr, L. Szentpály, S. Liu, Electrophilicity Index, J Am Chem Soc., 1999, 121, 1922.

N. Choudhary, S. Bee, A. Gupta, P. Tandon, Comparative vibrational spectroscopic studies, HOMO–LUMO and NBO analysis of N-(phenyl)-2,2-dichloroacetamide, N-(2-chloro phenyl)-2,2-dichloroacetamide and N-(4-chloro phenyl)-2,2-dichloroacetamide based on density functional theory, Comp Theor Chem., 2013, 1016, 8-21.

K. Fukui, Role of frontier orbitals in chemical reactions, Science, 1982, 218, 747.

G. Gece, The Use of Quantum Chemical Methods in Corrosion Inhibitor Studies, Corros Sci., 2008, 50, 2981-2992.

L. Sinha, O. Prasad, V. Narayan, S.R. Shukla, Raman, FT-IR spectroscopic analysis and first-order hyperpolarizability of 3-benzoyl-5-chlorouracil by first principles, J Mol Simul., 2011, 37, 153-163.

M. Govindarajan, M. Karabacak, Spectroscopic properties, NLO, HOMO-LUMO and NBO analysis of 2,5-Lutidine, Spectrochim Acta A, 2012, 96, 421.

S. Guidara, A.B. Ahmed, Y. Abid, H. Feki, Molecular structure, vibrational spectra and nonlinear optical properties of 2,5-dimethylanilinium chloride monohydrate: a density functional theory approach, Spectrochim Acta A, 2014, 127, 275-285.

D. F. Eaton, Nonlinear optical materials, Science, 1991, 253, 281-289.

M.N. Drwal, P. Banerjee, M. Dunkel, M.R. Wettig, R. Preissner, ProTox: a web server for the in silico prediction of rodent oral toxicity, Nucleic Acids Res., 2014, 42, W53-W58.



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