Ruthenium complexes present two states of oxidation that are Ru(II) and Ru(III). Both are assumed to present cytotoxic activity at ground state. On the purpose of highlighting their differences, DFT, TD-DFT and NBO have been performed at both Wb97xd/Lanl2dz and B3lyp/Lanl2dz levels. NBO program shows that both groups of ruthenium complexes present almost the same charge of Ru atom. Moreover, they display nearly the same structure of valence orbitals of the ruthenium. However, when it comes to compare their frontier orbitals HOMO and LUMO, we notice that the chloride atom has a great influence on their energy. The lack of Chloride atoms reduces the energy of frontier orbitals regardless of the functional. And the more the number of chloride atoms, the higher the energy. Also, RuCl3Terpy and α-RuCl2(Azpy)2 have been discovered to display the best energy suitable for reaction as cytotoxic agents. Yet, both are from groups different. Thus, at ground state, there is practically no difference between both groups. However, regarding TDDFT prediction with the determination of vertical electronic affinity VEA and vertical ionization potential VIP both at ground state S and at exciting T1 state, we notice that Ru(II) complexes are not active either in the presence or absence of 3O2 molecule. Here, only Ru(III) complexes are able to react on Guanine through their radical cations or by generating the superoxide radical anion . Therefore, the Ru(III) complexes are assumed to be active both at a fundamental state and under the effect of light for photodynamic therapy. We come to conclude that Ru(II) complexes are not active by excitation as their valence electrons are paired thereby making these complexes more stable. Besides, ？, a Ru(II) molecule that is not active at ground state owing certainly to its C3 symmetry or Azpy ligand presents all the same a difficult activity on generating . For the coming paper, we intend to check whether Ru(II) complex can be active under the effect of light if it is in a triplet charge state.
References
[1]
Clarke, M.J., Zhu, F. and Frasca, D.R. (1999) Non-Platinum Chemotherapeutic Metallopharmaceuticals. Chemical Reviews, 99, 2511-2534. https://doi.org/10.1021/cr9804238
[2]
Chen, H.M. Parkinson, J.A., Parson, S., Coxall, R.A., Grould, R.O. and Sadler, P.J. (2002) Organometallic Ruthenium(II) Diamine Anticancer Complexes: Arene- Nucleobase Stacking and Stereospecific Hydrogen-Bonding in Guanine Adducts. Journal of the American Chemical Society, 124, 3064-3082. https://doi.org/10.1021/ja017482e
[3]
Urruticoechea, A., Alemany, R., Balart, J., Villanueva, A., Viñals, F. and Capellá, G. (2010) Recent Advances in Cancer Therapy: An Overview. Current Pharmaceutical Design, 16, 3-10. https://doi.org/10.2174/138161210789941847
[4]
Pieter, P. and Lippard, S.J. (1997) Cisplatin and Related Drugs. Encyclopedia of Cancer, 1, 525-543.
[5]
Zhang, C.X. and Lippard, S.J. (2003) New Metal Complexes as Potential Therapeutics, Current Opinion in Chemical Biology, 7, 481-489. https://doi.org/10.1016/S1367-5931(03)00081-4
[6]
Wong, E. and Giandomenico, C.M. (1999) Current Status of Platinum-Based Antitumor Drugs. Chemical Reviews, 99, 2451-2466. https://doi.org/10.1021/cr980420v
[7]
Lebwohl, D. and Canetta, R. (1998) Clinical Development of Platinum Complexes in Cancer Therapy: An Historical Perspective and an Update. European Journal of Cancer, 34, 1522-1534. https://doi.org/10.1016/S0959-8049(98)00224-X
[8]
Wang, D. and Lippard, S.J. (2005) Cellular Processing of Platinum Anticancer Drugs. Nature Review Drug Discovery, 4, 307-320. https://doi.org/10.1038/nrd1691
[9]
Galanski, M., Jakupec, M.A. and Keppler, B.K. (2005) Update of the Preclinical Situation of Anticancer Platinum Complexes: Novel Design Strategies and Innovative Analytical Approaches. Current Medicinal Chemistry, 12, 2075-2094. https://doi.org/10.2174/0929867054637626
[10]
Garazd, Y., Garazd, M. and Lesyk, R. (2017) Synthesis and Evaluation of Anticancer Activity of 6-Pyrazolinylcoumarin Derivatives. Saudi Pharmaceutical Journal, 25, 214-223. https://doi.org/10.1016/j.jsps.2016.05.005
[11]
Morsy, S.A., Farahat, A.A., Nasr, M.N.A. and Tantawy, A.S. (2017) Synthesis, Molecular Modeling and Anticancer Activity of New Coumarin Containing Compounds. Saudi Pharmaceutical Journal, 25, 873-883. https://doi.org/10.1016/j.jsps.2017.02.003
[12]
Jamieson, E. and Lippard, S. (1999) Structure, Recognition, and Processing of Cisplatin-DNA Adducts. Chemical Reviews, 99, 2467-2498. https://doi.org/10.1021/cr980421n
[13]
Antonarakis, E.S. and Emadi, A. (2010) Ruthenium-Based Chemotherapeutics: Are They Ready for Prime Time? Cancer Chemotherapy and Pharmacology, 66, 1-9. https://doi.org/10.1021/cr9804238
[14]
Clarke, M.J., Zhu, F. and Frasca, D.R. (1999) Non-Platinum Chemotherapeutic Metallopharmaceuticals. Chemical Reviews, 99, 2511-2534.
[15]
Chen, J.C., Li, J.L., Qian, L. and Zheng, K.C. (2005) Electronic Structures and SARs of the Isomeric Complexes α-, β-, γ-[Ru(mazpy)2Cl2] with Different Antitumor Activities. Journal of Molecular Structure: THEOCHEM, 728, 93-101. https://doi.org/10.1016/j.theochem.2005.05.005
[16]
Notaro, A. and Gasser, G. (2017) Monomeric and Dimeric Coordinatively Saturated and Substitutionally Inert Ru(II) Polypyridyl Complexes as Anticancer Drug Candidates. Chemical Society Reviews, 46, 7317-7337. https://doi.org/10.1039/C7CS00356K
[17]
Zhu, B.-Z., Chao, X.-J., Huang, C.-H. and Li, Y. (2016) Delivering the Cell-Impermeable DNA “Light-Switching” Ru(ii) Complexes Preferentially into Live-Cell Nucleus via an Unprecedented Ion-Pairing Method. Chemical Science, 7, 4016-4023. https://doi.org/10.1039/C5SC03796D
[18]
Jenkins, Y., Friedman, A.E., Turro, N.J. and Barton, J.K. (1992) Characterization of Dipyridophenazine Complexes of Ruthenium(II): The Light Switch Effect as a Function of Nucleic Acid Sequence and Conformation. Biochemistry, 31, 10809-10816. https://doi.org/10.1021/bi00159a023
[19]
Liu, J.-G., Ye, B.-H., Li, H., Zhen, Q.-X., Ji, L.-N. and Fu, Y.-H. (1999) Polypyridyl Ruthenium(II) Complexes Containing Intramolecular Hydrogen-Bond Ligand: Syntheses, Characterization, and DNA-Binding Properties. Journal of Inorganic Biochemistry, 76, 265-271. https://doi.org/10.1016/S0162-0134(99)00154-3
[20]
Bamba, K., Leger, J.-M., Garnier, E., Bachmann, C., Servat, K. and Kokoh, K.B. (2005) Selective Electro-Oxidation of D-Glucose by RuCl2(azpy)2 Complexes as Electrochemical Mediators. Electrochimica Acta, 50, 3341-3346. https://doi.org/10.1016/j.electacta.2004.12.007
[21]
De Sousa, K., Chagas, M., dos Santos, J., Galvão, A., de Moraes, F., Ribeiro, A., Fortaleza, D., da Encarnação Amorim, K. and dos Santos, W. (2018) Theoretical and Comparative Study of the Complex [RuCl3(H2O)2(Gly)] by Density Functional Theory. Open Journal of Inorganic Chemistry, 8, 43-53. https://doi.org/10.4236/ojic.2018.81004
[22]
Vlan Vliet, P.M., Toekimin, S.M.S., Haasnoot, J.G., Reedijk, J., Novakova, O. and Brabec, V. (1995) mer-[Ru(terpy)Cl3] (terpy = 2,2':6',2\"-terpyridine) Shows Biological Activity, Forms Interstrand Cross-Links in DNA and Binds Two Guanine Derivatives in a Trans Configuration. Inorganica Chimica Acta, 231, 57-64. https://doi.org/10.1016/0020-1693(94)04320-U
[23]
Sava, G., Bergamo, A., Zorzet, S., Gava, B., Casarsa, C., Cocchietto, M., Furlani, A., Scarcia, V., Serli, B., Iengo, E., Alessio, E. and Mestroni, G. (2002) Influence of Chemical Stability on the Activity of the Antimetastasis Ruthenium Compound NAMI-A. European Journal of Cancer, 38, 427-435. https://doi.org/10.1016/S0959-8049(01)00389-6
[24]
Chen, T., Liu, Y., Zheng, W.J., Liu, J. and Wong, Y.S. (2010) Ruthenium Polypyridyl Complexes that Induce Mitochondria-Mediated Apoptosis in Cancer Cells. Inorganic Chemistry, 49, 6366-6368. https://doi.org/10.1021/ic100277w
[25]
Tan, C., Lai, S., Wu, S., Hu, S., Zhou, L., Chen, Y., Wang, M., Zhu, Y., Lian, W., Peng, W., Ji, L. and Xu, A. (2010) Nuclear Permeable Ruthenium(II) β-Carboline Complexes Induce Autophagy To Antagonize Mitochondrial-Mediated Apoptosis. Journal of Medicinal Chemistry, 53, 7613-7624. https://doi.org/10.1021/jm1009296
[26]
Chagas, M.A.S., Galvão, A.D., de Moraes, F.T., Ribeiro, A.T.B.N., de Siqueira, A.B., de Assis Salama, I.C.C., Arrais-Silva, W.W., de Sousa, K.M.D., de Sousa Pereira, C.C. and dos Santos, W.B. (2017) Synthesis, Characterization and Analysis of Leishmanicide Ability of the Compound [Ru(Cl)3(H2O)2(gly)]. Open Journal of Inorganic Chemistry, 7, 89-101. https://doi.org/10.4236/ojic.2017.74006
[27]
N’guessan, K.N., Guy-Richard Koné, M., Bamba, K., Wawohinlin Patrice, O. and Ziao, N. (2017) Quantitative Structure Anti-Cancer Activity Relationship (QSAR) of a Series of Ruthenium Complex Azopyridine by the Density Functional Theory (DFT) Method. Computational Molecular Bioscience, 7, 19-31. https://doi.org/10.4236/cmb.2017.72002
[28]
Velders, A.H., Van der Schilden, K., Hoste, A.C.G., Reedijk, J., Kooijman, H. and Speck, A.L. (2004) Dichlorobis(2-phenylazopyridine)ruthenium(II) Complexes: Characterization, Spectroscopic and Structural Properties of Four Isomers. Dalton transactions, 3, 448-455. https://doi.org/10.1039/B313182C
[29]
Hotze, A.C.G., Velders, A.H., Ugozzoli, F., Biagini-Cingi, M., Manotti-Lanfredi, A.M., Haasnoot, J.G. and Reedijk, J. (2000) Synthesis, Characterization, and Crystal Structure of α-[Ru(azpy)2(NO3)2] (azpy = 2-(Phenylazo)pyridine) and the Products of Its Reactions with Guanine Derivatives. Inorganic Chemistry, 39, 3838-3844. https://doi.org/10.1021/ic000066v
[30]
Bamba, K., Ouattara, W.P., N’Guessan, K.N. and Ziao, N. (2016) SARs Investigation of α-, β-, γ-, δ-, ε -RuCl2(Azpy)2 Complexes as Antitumor Drugs. Computational Chemistry, 4, 1-10. https://doi.org/10.4236/cc.2016.41001
[31]
Novakova, O., Kasparkova, J., Vrana, O., Van Vliet, P.M., Reedijk, J. and Brabec, V. (1995) Correlation between Cytotoxicity and DNA Binding of Polypyridyl Ruthenium Complexes. Biochemistry, 34, 12369-12378. https://doi.org/10.1021/bi00038a034
[32]
Sava, G., Capozzi, I., Clerici, K., Gagliardi, G., Alessio, E. and Mestroni, G. (1998) Pharmacological Control of Lung Metastases of Solid Tumours by a Novel Ruthenium Complex. Clinical & Experimental Metastasis, 16, 371-379. https://doi.org/10.1023/A:1006521715400
[33]
Lentz, F., Drescher, A., Lindauer, A., Henke, M., Hilger, R.A., Hartinger, C.G., Scheulen, M.E., Dittrich, C., Keppler, B.K. and Jaehde, U. (2009) Pharmacokinetics of a Novel Anticancer Ruthenium Complex (KP1019, FFC14A) in a Phase I Dose-Escalation Study. Anti-Cancer Drugs, 20, 97-103. https://doi.org/10.1097/CAD.0b013e328322fbc5
[34]
Trondl, R., Heffeter, P., Kowol, C.R., Jakupec, M.A., Berger, W. and Keppler, B.K. (2014) NKP-1339, the First Ruthenium-Based Anticancer Drug on the Edge to Clinical Application. Chemical Science, 5, 2925-2932. https://doi.org/10.1039/C3SC53243G
[35]
Hartinger, C.G., Zorbas-Seifried, S., Jakupec, M.A., Kynast, B., Zorbas, H. and Keppler, B.K. (2006) From Bench to Bedside—Preclinical and Early Clinical Development of the Anticancer Agent Indazolium Trans-[tetrachlorobis(1H-indazole) ruthenate(III)] (KP1019 or FFC14A). Journal of Inorganic Biochemistry, 100, 891-904. https://doi.org/10.1016/j.jinorgbio.2006.02.013
[36]
Hotze, A.C.G., van der Geer, E.P.L., Kooijman, H., Spek, A.L., Haasnoot, J.G. and Reedijk, J. (2005) Characterization by NMR Spectroscopy, X-Ray Analysis an Cytotoxic Activity of Ruthenium (II) Compound Ru(L3) (PF6)2, (L) 2-Phenylazopyridine or o-Tolylazopyridine and Ru(L’2L’’) (PF6)2 (L’, L’’=2-Phenylazopyrine or 2,2’bipyridine). European Journal of Inorganic Chemistry, 2005, 2648-2657. https://doi.org/10.1002/ejic.200500110
[37]
Das, C., Saha, A., Hung, C.-H., Lee, G.-H., Peng, S.-M. and Goswami, S. (2003) Ruthenium Complexes of 2-[(4-(Arylamino)phenyl)azo]pyridine Formed via Regioselective Phenyl Ring Amination of Coordinated 2-(Phenylazo)pyridine:Isolation of Products, X-ray Structure, and Redox and Optical Properties. Inorganic Chemistry, 42, 198-204. https://doi.org/10.1021/ic0203724
[38]
Liu, J., Zou, X.-H., Zhang, Q.-L., Mei, W.-J., Liu, J.-Z. and Ji, L.-N. (2000) Synthesis, Characterization and Antitumor Activity of a Series of Polypyridyl Complexes. Metal-Based Drugs, 7, Article ID: 427618. https://doi.org/10.1155/MBD.2000.343
[39]
Dwyer, F.P., Gyarfas, E.C., Rogers, W.P. and Koch, J.H. (1952) Biological Activity of Complex Ions. Nature, 170, 190-191. https://doi.org/10.1038/170190a0
[40]
Allardyce, C.S. and Dyson, P.J. (2001) Ruthenium in Medicine: Current Clinical Uses and Future Prospects. Platinum Metals Review, 45, 62-69.
[41]
Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G.A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H.P., Izmaylov, A.F., Bloino, J., Zheng, G., Sonnenberg, J.L., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Vreven, T., Montgomery Jr., J.A., Peralta, J.E., Ogliaro, F., Bearpark, M.J., Heyd, J., Brothers, E.N., Kudin, K.N., Staroverov, V.N., Kobayashi, R., Normand, J., Raghavachari, K., Rendell, A.P., Burant, J.C., Iyengar, S.S., Tomasi, J., Cossi, M., Rega, N., Millam, N.J., Klene, M., Knox, J.E., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Martin, R.L., Morokuma, K., Zakrzewski, V.G., Voth, G.A., Salvador, P., Dannenberg, J.J., Dapprich, S., Daniels, A.D., Farkas, Ö., Foresman, J.B., Ortiz, J.V., Cioslowski, J. and Fox, D.J. (2009) Gaussian 09. Gaussian, Inc. Print, Wallingford.
[42]
Shriver, D.F. and Atkins, P.W. (1999) Inorganic Chemistry. 3rd Edition, De Boeck University, Paris, p. 229.
[43]
Nobel, N.K., Bamba, K., Patrice, O.W. and Ziao, N. (2017) NBO Population Analysis and Electronic Calculation of Four Azopyridine Complexes by DFT Method. Computational Chemistry, 5, 51-64. https://doi.org/10.4236/cc.2017.51005
[44]
Kurita, N. and Kobayashi, K. (2000) Density Functional MO Calculation for Stacked DNA Base-Pairs with Backbones. Computers & Chemistry, 24, 351-357. https://doi.org/10.1016/S0097-8485(99)00071-6
[45]
Velders, A.H., Kooijman, H., Spek, A.L., Haasnoot, J.G., De Vos, D. and Reedijk, J. (2000) Strong Differences in the in Vitro Cytotoxicity of Three Isomeric Dichlorobis(2-phenylazopyridine)ruthenium(II) Complexes. Inorganic Chemistry, 39, 2966- 2967. https://doi.org/10.1021/ic000167t
[46]
Zhao, X., Zheng, Z., Feng, S., Shi, Z. and Chen, D. (2009) A TD-DFT Study on the Photo-Physicochemical Properties of Chrysophanol from Rheum. International Journal of Molecular Sciences, 10, 3186-3193. https://doi.org/10.3390/ijms10073186
[47]
Liu, J., Zhao, Y.W., Zhao, J.Q., Xia, A.D., Jiang, L.J., Wu, S., Ma, L., Dong, Y.Q. and Gu, Y.H. (2002) Two-Photon Excitation Studies of Hypocrellins for Photodynamic Therapy. Journal of Photochemistry and Photobiology B: Biology, 68, 156-164. https://doi.org/10.1016/S1011-1344(02)00379-2
[48]
Wu, W., Shao, X., Zhao, J. and Wu, M. (2017) Controllable Photodynamic Therapy Implemented by Regulating Singlet Oxygen Efficiency. Advanced Science, 4, 1700113. https://doi.org/10.1002/advs.201700113
[49]
Ouattara, W., Bamba, K., Thomas, A., Diarrassouba, F., Ouattara, L., Ouattara, M., N'guessan, K., Kone, M., Kodjo, C. and Ziao, N. (2021) Theoretical Studies of Photodynamic Therapy Properties of Azopyridineδ-OsCl2(Azpy)2 Complex as a Photosensitizer by a TDDFT Method. Computational Chemistry, 9, 64-84. https://doi.org/10.4236/cc.2021.91004
[50]
Rodica-Mariana, I. (2007) Photodynamic Therapy (PDT): A Photochemical Concept with Medical Applications. Revue Roumaine de Chimie, 52, 1093-1102.
[51]
de Oliveira, K.T., de Souza, J.M., Gobo, N.R.S., de Assis, F.F. and Brocksom, T.J. (2015) Basic Concepts and Applications of Porphyrins, Chlorins and Phthalocyanines as Photosensitizers in Photonic Therapies. Revista Virtual de Quimica, 7, 310-335. https://doi.org/10.5935/1984-6835.20150016
[52]
Musa, K.A.K., Matxain, J.M. and Eriksson, L.A. (2007) Mechanism of Photoinduced Decomposition of Ketoprofen. Journal of Medicinal Chemistry, 50, 1735-1743. https://doi.org/10.1021/jm060697k
[53]
Sousa, F.F.R., Quartarolo, A.D., Sicilia, E. and Russo, N. (2012) A Time-Dependent Density Functional Study of a Non-Aromatic [1.1.1.1.1]-Pentaphyrin and Its Lutetium Complex. The Journal of Physical Chemistry B, 116, 10816-10823. https://doi.org/10.1021/jp3068359
[54]
Shen, L., Ji, H.F. and Zhang, H.Y. (2006) A TD-DFT Study on Photo-Physicochemical Properties of Hypocrellin A and Its Implications for Elucidating the Photosensitizing Mechanisms of the Pigment. Journal of Photochemistry and Photobiology A: Chemistry, 180, 65-68. https://doi.org/10.1016/j.jphotochem.2005.09.019
![\"\"](\"Edit_17bbaac1-501f-4de4-bc6b-4f8b513cc344.png\")
. Therefore, the Ru(III) complexes are assumed to be active both at a fundamental state and under the effect of light for photodynamic therapy. We come to conclude that Ru(II) complexes are not active by excitation as their valence electrons are paired thereby making these complexes more stable. Besides, ![\"\"](\"Edit_30d3bea0-3cbe-4e08-8438-551a2fa7de22.png\")
？, a Ru(II) molecule that is not active at ground state owing certainly to its C3 symmetry or Azpy ligand presents all the same a difficult activity on generating ![\"\"](\"Edit_758504e6-51fe-4300-baef-d6a9f1c4f535.png\")
. For the coming paper, we intend to check whether Ru(II) complex can be active under the effect of light if it is in a triplet charge state.
