Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 + 2118 word(s) 2118 2021-09-22 11:41:49 |
2 update references and layout Meta information modification 2118 2021-09-30 12:52:20 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Chen, Y. Ru(II)-Based Photoactivated Chemotherapy Agents. Encyclopedia. Available online: (accessed on 09 December 2023).
Chen Y. Ru(II)-Based Photoactivated Chemotherapy Agents. Encyclopedia. Available at: Accessed December 09, 2023.
Chen, Yongjie. "Ru(II)-Based Photoactivated Chemotherapy Agents" Encyclopedia, (accessed December 09, 2023).
Chen, Y.(2021, September 30). Ru(II)-Based Photoactivated Chemotherapy Agents. In Encyclopedia.
Chen, Yongjie. "Ru(II)-Based Photoactivated Chemotherapy Agents." Encyclopedia. Web. 30 September, 2021.
Ru(II)-Based Photoactivated Chemotherapy Agents

Photoactivated chemotherapy (PACT) is a novel cancer treatment method that has drawn increasing attention due to its high selectivity and low side effects by spatio-temporal control of irradiation. Compared with photodynamic therapy (PDT), oxygen-independent PACT is more suitable for treating hypoxic tumors. By finely tuning ligand structures and coordination configurations, many Ru(II) complexes can undergo photoinduced ligand dissociation, and the resulting Ru(II) aqua species and/or free ligands may have anticancer activity, showing their potential as PACT agents.

photoactivated chemotherapy (PACT) Ru(II) complexes photoinduced ligand dissociation

1. Introduction

The research of new chemotherapeutic drugs for cancer treatment has been the focus in medicine and related fields for many years. Among them, the development of transition-metal-based agents has always been one of the hotspots [1][2][3][4][5][6][7], which obviously benefits from the long-term and wide clinical application of cisplatin [cis -Pt (NH 3) 2Cl 2]. The unexpected discovery by Rosenberg and his co-workers revealed the antitumor activity of cisplatin in the 1960s [8][9]; subsequently, cisplatin and its analogs ( Figure 1 ) have been successfully used in the clinical treatment of many cancers [10]. Although cisplatin and its derivatives are efficacious against the vast majority of cancers, their selectivity to tumor tissues and normal tissues is poor [11]. This leads to the production of non-cancer cell toxicity; thereby, severe adverse effects are caused, including hair loss, peripheral neuropathy, and myelotoxicity in patients [12][13][14].

Figure 1. Clinically approved Pt (II) anticancer drugs.

Many strategies have been used for solving the above problems, for example, using targeting drug delivery systems and developing reduction responsive Pt(IV) prodrugs [15][16]. In addition, many photoactivated Pt(IV) agents have been reported, which are nontoxic in the dark but can release cytotoxic Pt(II) species upon light irradiation [17][18]. These kinds of prodrugs are commonly known as photoactivated chemotherapy (PACT) agents, which can trigger and limit the drug activity within the tumor tissues by spatio-temporal control of irradiation, thus achieving fewer side effects [19][20][21]. Compared with traditional photodynamic therapy (PDT) [22][23], another phototherapy that is generally oxygen-dependent, PACT offers an oxygen-independent mechanism, and is therefore more suitable for hypoxic tumors, where the concentration of oxygen is remarkably low [24][25].

Inspired by the success of Pt complexes as antitumor drugs, other transition metal complexes, especially Ruthenium (Ru) complexes, have drawn great attention owing to their potential anticancer properties and selective cytotoxic activity [26]. Investigating new Ru-based complexes as anticancer drugs is an important trend in modern medicinal inorganic chemistry [27][28][29][30]. Up till now, several Ru(III) complexes as chemotherapeutic agents have already entered clinical trials, such as NAMI-A, KP1019, and KP1339 ( Figure 2 ) [31][32][33][34][35]. As the first approved Ru complex to reach clinical investigations, NAMI-A showed success in phase I clinical studies but showed only limited efficacy in the phase II stage, which resulted in the failure of the clinical investigations [27][36]. Afterward, another Ru therapeutic KP1019 showed solubility limited in phase I, but in its place, a more soluble sodium salt, KP1339, is currently undergoing clinical trials [27]. Different from focusing on the chemotherapeutic activity of Ru(III) complexes, more attentions has been paid to the photoactivation of Ru(II) complexes. TLD1433, the first Ru(II)-based photosensitizer for PDT, has already entered human clinical trials [37]. Moreover, studies have also indicated that Ru(II) complexes may possess potential as PACT agents [38][39][40][41]. Through proper structure design, they can undergo photoinduced ligand dissociation; then, the resulting Ru(II) aqua species can covalently bind to DNA in a manner similar to cisplatin. Compared with Pt(IV) complexes, Ru(II)-based PACT agents have some promising advantages. They possess diverse and easy-modified structures, rich photophysical and photochemical properties, and furthermore, the octahedral structures different from that of cisplatin may endow them with good activity against cisplatin-resistant cancer cells [42][43][44].

Figure 2. Three ruthenium(III) complexes in clinical trials.

The lowest energy absorption band of Ru(II) complexes usually comes from 1MLCT (Metal-to-Ligand Charge Transfer) transitions. When irradiated by appropriate light, Ru(II) complexes first achieve the 1MLCT state and then reach the 3MLCT state through ultra-fast intersystem crossing ( Figure 3 ) [19]. The 3MLCT state of Ru(II) complexes can return to the ground state through non-radiative inactivation or luminescence pathways [45][46] or can interact with other molecules such as O 2 to generate singlet oxygen ( 1O 2), showing potential as photodynamic agents [47][48][49]. This paper focuses on another photochemical process: the 3MLCT excited state of Ru(II) complexes may populate the 3MC state (metal-centered state or ligand-field state) by thermal activation. The 3MC state has M-L (σ*) character, which may lead to ligand dissociation and generate Ru(II) aqua species with DNA-binding ability, showing potential in photoactivated chemotherapy. This mini-review aims to present the latest progress in photoinduced ligand dissociation related Ru(II)-based PACT agents for cancer treatment. By reading this article, we hope to not only let our peers know about the all-around development of Ru(II)-based PACT drugs but also inspire more researchers to enter this interesting field.

Figure 3. Jablonski diagram of Ru(II) complexes with photolabile ligands.

2. Extending the Photoactivation Wavelength

As mentioned above, the large conjugated structure of the biq ligand obviously extends the photoactivation wavelengths of complexes 32 and 33. On the one hand, the large conjugate system reduces the π* orbital energy of the biq ligand, thus reducing the energy of 1MLCT [t 2g (Ru) to π*(biq)]. On the other hand, it causes steric hindrance, which reduces the 3MC energy through the distortion of the coordination field, and consequently ensures that efficient ligand dissociation can still occur upon low photon energy excitation. Recently, a nitro-anthraquinone group was attached to a biq-ligand-based Ru(II) complex by Wang and colleagues, endowing the resultant complex 37 ( Figure 6 ) with multiple anticancer mechanisms upon irradiation in the phototherapy window [50]. It was found that 37 can release a biq ligand upon 600 nm irradiation, along with generating O 2•− and oxidizing NADH/NADPH (β-nicotinamide adenine dinucleotide phosphate).

When the ring-metalized-ligands (such as 2-phenylpyridine, phpy) coordinate with Ru, the strong electron-donating capacity of carbon anions can significantly increase the t 2g orbital energy of Ru(II), thus greatly prolongs the MLCT absorption wavelength. Using this strategy, Turro’s group designed and synthesized the complex cis -[Ru(phpy)(phen)(CH 3CN ) 2] + ( 38) [51]. The MLCT absorption peak of Ru(II) to phen ligand was at 490 nm, and the tail band extended to the phototherapy window. The quantum efficiency of ligand exchange between CH 3CN and Cl - was up to 0.25 upon 450 nm excitation. Different from the wavelength dependence of photoinduced ligand dissociation mentioned above, under 400 nm light irradiation, the ligand exchange efficiency of 38 decreased to 0.08. It is believed that the MLCT transition at 400 nm is mainly from Ru(II) to phpy ligand. Since the absorption band at 400 nm also contains too much of the ππ* transition component of the phpy ligand, the ligand photodissociation efficiency decreases instead of increasing. Turro’s group further designed and synthesized the complex [Ru(biq) 2(phpy)] + ( 39) by combining the phpy and biq ligands [45]. Cyclometallation results in a redshift of the MLCT absorption maximum of 39 by about 100 nm relative to that of 32 and 33. Although 39 exhibited a distorted octahedral geometry, photoinduced ligand exchange did not occur. DFT calculations indicated that the difference of reactivity in 39 was ascribed to increased energy of 3MC states resulting from the bonding of the strong σ-donor phpy ligand. Bonnet et al. investigated the cyclometalated Ru complex 40, which contained photolabile N,S bidentate ligand and found that 40 can be active under 521 nm irradiation in CH 3CN, which makes it the first cyclometalated Ru complex capable of undergoing photosubstitution of a bidentate ligand [52].

Turro et al. introduced new ancillary ligand platforms that consist of anionic acetylacetonate-based ligand along with tridentate 2,6-di(quinolin-2-yl)pyridine (dqpy) ligand into complex 41 [53]. Acetylacetonate ligands are strong π-donor ligands that used to destabilize the HOMO (highest occupied molecular orbital), whereas the dqpy ligand with its extended conjugation lowers the LUMO (lowest unoccupied molecular orbital) energy; both effects make the ligand substitution of 41 accessible with near-infrared (NIR) light (≥ 715 nm).

The MLCT absorption band of binuclear or polynuclear Ru(II) complexes constructed with bridged ligands tends to be significantly redshifted compared with that of corresponding mononuclear complexes [54][55][56]. As a result, the bridging concept was utilized to design the first dinuclear Ru(II) complex ( 42) capable of undergoing ligand dissociation at both metal centers upon ≥ 610 nm irradiation in H 2O [57]. To further explore the effect of the bridging ligand on Ru(II)-based PACT agents, Dunbar et al. used quinoxaline-functionalized bridging ligand platforms to prepare corresponding binuclear complexes [58]. These complexes were capable of absorbing green light with tails extending beyond 650 nm, which is a promising feature for applications in PACT.

3. Ru(II) PACT Agents with Multiple Functions

The complexes 50 and 51 were designed and synthesized by using pyridine sulfonic acid (py-SO 3) as the leaving group [59][60]. It was found that 50 and 51 can undergo py-SO 3 dissociation upon visible light irradiation and produce reactive free radical species, and is therefore able to photobind and photocleave DNA simultaneously in hypoxic conditions. Unexpectedly, poor cell phototoxicity was observed for these two complexes. Lately, another py-SO 3- based complex 52 was synthesized and studied by the same research group [61], which displayed efficient phototoxicity towards a series of cancer cells, including cisplatin-resistant human ovarian adenocarcinoma cells (SKOV3) and human lung adenocarcinoma cells (A549). Detailed studies indicated that the high cytotoxicity of 52 may be attributed to its enhanced cell uptake and nuclear accumulation levels. Patra et al. designed and synthesized two Ru complexes of saccharin with dipyridoquinoxaline and dipyridophenazine. Upon irradiation with UV-A light of 365 nm, both complexes can undergo photoinduced dissociation of saccharin ligand and generate reactive oxygen species, showing dual PDT and PACT activities [62].

By replacing the photolabile ligands in Ru-based PACT drugs with bioactive molecules, such as small molecule drugs and enzyme inhibitors, the resulting Ru(II) complexes may possess dual activity. Upon light activation, these complexes can release active ligands that may directly kill cancer cells, while the Ru(II) aqua species are able to damage DNA simultaneously.

Due to the dual PACT and PDT activity presented by 46, [Ru(tpy)(Me 2dppn)] fragment was used to cage bioactive molecules for the purpose of achieving triple functions. Epoxysuccinyl-based inhibitors of cathepsin B (CTSB), a cysteine protease strongly associated with invasive and metastatic behavior, was conjugated to [Ru(tpy)(Me 2dppn)] fragment by Kodanko et al. The study confirmed that the conjugate was capable of releasing ligand to form Ru(II) active center, generating 1O 2 under light conditions, and irreversibly inhibiting CTSB, eventually causing efficient cell death [63].

Considering the inherent acidity surrounding cancer cells, Papish and co-workers reported a series of pH-activated PACT agents, which can be activated by light- and pH-triggered ligand dissociation [64][65][66]. At a low pH value (pH = 5), complexes 57– 61 existed in their acidic form, and the quantum yields for photodissociation were higher than in deprotonated form. Further studies validated that these complexes can produce 1O 2 under illumination. Thus, they investigated how synthetic changes to ligands and ligand protonation states can influence the quantum yields for 1O 2 and photodissociation. Cytotoxicity studies showed that 1O 2 formation is a more plausible cause of photocytotoxicity [66].

4. Conclusions and Future Perspectives

The research on Ru(II)-based PACT agents has been a hotspot in the field of metal anticancer drugs in recent years. Thanks to the efforts of many groups, continuous progress has been achieved in recent years. However, there is still a long way to realize the clinical applications of these Ru(II)-based PACT agents.

Second, most of the current studies focus on the ligand photodissociation-related photophysical and photochemical properties, while less attention is paid to the structure–activity relationship of antitumor activity. Many Ru(II) complexes displayed efficient photoinduced ligand dissociation; however, little anticancer activity was observed. Therefore, in addition to the ligand photodissociation, more efforts are needed to disclose how the other factors (such as DNA binding, cellular uptake, subcellular localization, etc.) influence the anticancer activity of Ru(II) PACT agents.

Third, the real cellular anticancer targets of Ru(II) PACT agents are still unknown. DNA is proposed as the potential target, and indeed many studies have verified that Ru(II) complexes with photolabile ligands can form Ru–DNA covalent binding in solutions after photoinduced ligand dissociation. However, some of the reported Ru(II) complexes with efficient PACT activity cannot attend the nucleus, which may hint to us that DNA should not be the only target. To disclose the real anticancer mechanism can undoubtedly promote the rational design of efficient Ru(II) PACT agents.

Fourth, among the existing reports on Ru(II)-based PACT agents, only a few studies were conducted at the living animal level. Although some promising results in vitro have been achieved so far, the lack of research in vivo is not conducive to promoting the clinical application of these complexes. Obviously, Ru(II) PACT agents may not be suitable to treat all kinds of cancers; thus, finding the possible indications of Ru(II) PACT is meaningful.


  1. Romero-Canelón, I.; Sadler, P.J. Next-generation metal anticancer complexes: Multitargeting via redox modulation. Inorg. Chem. 2013, 52, 12276–12291.
  2. Mjos, K.D.; Orvig, C. Metallodrugs in Medicinal Inorganic Chemistry. Chem. Rev. 2014, 114, 4540–4563.
  3. Das, U.; Kar, B.; Pete, S.; Paira, P. Ru(II), Ir(III), Re(I) and Rh(III) based complexes as next generation anticancer metallopharmaceuticals. Dalton Trans. 2021, 50, 11259–11290.
  4. Ma, D.L.; He, H.Z.; Leung, K.H.; Chan, D.S.; Leung, C.H. Bioactive luminescent transition-metal complexes for biomedical applications. Angew. Chem. Int. Ed. 2013, 52, 7666–7682.
  5. Ohata, J.; Ball, Z.T. Rhodium at the chemistry-biology interface. Dalton Trans. 2018, 47, 14855–14860.
  6. Ma, D.L.; Wu, C.; Wu, K.J.; Leung, C.H. Iridium(III) Complexes Targeting Apoptotic Cell Death in Cancer Cells. Molecules 2019, 24, 2739.
  7. Omondi, R.O.; Ojwach, S.O.; Jaganyi, D. Review of comparative studies of cytotoxic activities of Pt(II), Pd(II), Ru(II)/(III) and Au(III) complexes, their kinetics of ligand substitution reactions and DNA/BSA interactions. Inorg. Chim. Acta. 2020, 512, 119883.
  8. Rosenberg, B.; Vancamp, L.; Krigas, T. Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode. Nature 1965, 205, 698–699.
  9. Rosenberg, B.; VanCamp, L.; Trosko, J.E.; Mansour, V.H. Platinum Compounds: A new class of potent antitumor agents. Nature 1969, 222, 385–386.
  10. Wheate, N.J.; Walker, S.; Craig, G.E.; Oun, R. The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans. 2010, 39, 8113–8127.
  11. Galanski, M.; Jakupec, M.A.; Keppler, B.K. Update of the Preclinical Situation of Anticancer Platinum Complexes: Novel Design Strategies and Innovative Analytical Approaches. Curr. Med. Chem. 2005, 12, 2075–2098.
  12. Zheng, Y.R.; Suntharalingam, K.; Johnstone, T.C.; Yoo, H.; Lin, W.; Brooks, J.G.; Lippard, S.J. Pt(IV) Prodrugs Designed to Bind Non-Covalently to Human Serum Albumin for Drug Delivery. J. Am. Chem. Soc. 2014, 136, 8790–8798.
  13. Graf, N.; Bielenberg, D.R.; Kolishetti, N.; Muus, C.; Banyard, J.; Farokhzad, O.C.; Lippard, S.J. αVβ3 Integrin-Targeted PLGA-PEG Nanoparticles for Enhanced Anti-tumor Efficacy of a Pt(IV) Prodrug. ACS Nano. 2012, 6, 4530–4539.
  14. Suntharalingam, K.; Song, Y.; Lippard, S.J. Conjugation of vitamin E analog α-TOS to Pt(IV) complexes for dual-targeting anticancer therapy. Chem. Commun. 2014, 50, 2465–2468.
  15. Johnstone, T.C.; Suntharalingam, K.; Lippard, S.J. The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs. Chem. Rev. 2016, 116, 3436–3486.
  16. Fanelli, M.; Formica, M.; Fusi, V.; Giorgi, L.; Micheloni, M.; Paoli, P. New trends in platinum and palladium complexes as antineoplastic agents. Coord. Chem. Rev. 2016, 310, 41–79.
  17. Farrer, N.J.; Woods, J.A.; Salassa, L.; Zhao, Y.; Robinson, K.S.; Clarkson, G.; Mackay, F.S.; Sadler, P.J. A Potent Trans-Diimine Platinum Anticancer Complex Photoactivated by Visible Light. Angew. Chem. Int. Ed. 2010, 49, 8905–8908.
  18. Kasparkova, J.; Kostrhunova, H.; Novakova, O.; Křikavová, R.; Va nčo, J.; Trávníčk, Z.; Brabec, V. A Photoactivatable Platinum(IV) Complex Targeting Genomic DNA and Histone Deacetylases. Angew. Chem. Int. Ed. 2015, 54, 14478–14482.
  19. Farrer, N.J.; Salassa, L.; Sadler, P.J. Photoactivated chemotherapy (PACT): The potential of excited-state d-block metals in medicine. Dalton Trans. 2009, 10690–10701.
  20. Imberti, C.; Zhang, P.; Huang, H.; Sadler, P.J. New Designs for Phototherapeutic Transition Metal Complexes. Angew. Chem. Int. Ed. 2020, 59, 61–73.
  21. Bonnet, S. Why develop photoactivated chemotherapy? Dalton Trans. 2018, 47, 10330–10343.
  22. Detty, M.R.; Gibson, S.L.; Wagner, S.J. Current Clinical and Preclinical Photosensitizers for Use in Photodynamic Therapy. J. Med. Chem. 2004, 47, 3897–3915.
  23. Fan, W.; Huang, P.; Chen, X. Overcoming the Achilles’ heel of photodynamic therapy. Chem. Soc. Rev. 2016, 45, 6488–6519.
  24. Eales, K.L.; Hollinshead, K.E.R.; Tennant, D.A. Hypoxia and metabolic adaptation of cancer cells. Oncogenesis 2016, 5, e190.
  25. Cosse, J.P.; Michiels, C. Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression. Anticancer Agents Med. Chem. 2008, 8, 790–797.
  26. Alagesan, M.; Sathyadevi, P.; Krishnamoorthy, P.; Bhuvanesh, N.S.; Dharmaraj, N. DMSO containing ruthenium(II) hydrazone complexes: In vitro evaluation of biomolecular interaction and anticancer activity. Dalton Trans. 2014, 43, 15829–15840.
  27. Thota, S.; Rodrigues, D.A.; Crans, D.C.; Barreiro, E.J. Ru(II) Compounds: Next-Generation Anticancer Metallotherapeutics? J. Med. Chem. 2018, 61, 5805–5821.
  28. Notaro, A.; Gasser, G. Monomeric and dimeric coordinatively saturated and substitutionally inert Ru(II) polypyridyl complexes as anticancer drug candidates. Chem. Soc. Rev. 2017, 46, 7317–7337.
  29. Sun, Q.; Li, Y.; Shi, H.; Wang, Y.; Zhang, J.; Zhang, Q. Ruthenium Complexes as Promising Candidates against Lung Cancer. Molecules 2021, 26, 4389.
  30. Poynton, F.E.; Bright, S.A.; Blasco, S.; Williams, D.C.; Kelly, J.M.; Gunnlaugsson, T. The development of ruthenium(II) polypyridylcomplexes and conjugates for in vitro cellular and in vivo applications. Chem. Soc. Rev. 2017, 46, 7706–7756.
  31. Bergamo, A.; Zorzet, S.; Gava, B.; Sorc, A.; Alessio, E.; Iengo, E.; Sava, G. Effects of NAMI-A and some related ruthenium complexes on cell viability after short exposure of tumor cells. Anti-Cancer Drugs. 2000, 11, 665–672.
  32. Bratsos, I.; Jedner, S.; Gianferrara, T.; Alessio, E. Ruthenium Anticancer Compounds: Challenges and Expectations. CHIMIA 2007, 61, 692–697.
  33. Rademaker-Lakhai, J.M.; van den Bongard, D.; Pluim, D.; Beijnen, J.H.; Schellens, J.H. A Phase I and Pharmacological Study with Imidazolium-trans-DMSO-imidazole-tetrachlororuthenate, a Novel Ruthenium Anticancer Agent. Clin. Cancer Res. 2004, 10, 3717–3727.
  34. Hartinger, C.G.; Zorbas-Seifried, S.; Jakupec, M.A.; Kynast, B.; Zorbas, H.; Keppler, B.K. From bench to bedside—preclinical and early clinical development of the anticancer agent indazolium trans- (KP1019 or FFC14A). J. Inorg. Biochem. 2006, 100, 891–904.
  35. Bytzek, A.K.; Koellensperger, G.; Keppler, B.K.; Hartinger, C.G. Biodistribution of the novel anticancer drug sodium trans- KP-1339/IT139 in nude BALB/c mice and implications on its mode of action. J. Inorg. Biochem. 2016, 160, 250–255.
  36. Leijen, S.; Burgers, S.A.; Baas, P.; Pluim, D.; Tibben, M.; Werkhoven, E.; Alessio, E.; Sava, G.; Beijnen, J.H.; Schellens, J.H.M. Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy. Investig. New Drugs. 2015, 33, 201–214.
  37. Monro, S.; Colón, K.L.; Yin, H.; Roque, J.; Konda, P.; Gujar, S.; Thummel, R.P.; Lilge, L.; Gameron, C.G.; McFarland, S.A. Transition Metal Complexes and Photodynamic Therapy from a Tumor-Centered Approach: Challenges, Opportunities, and Highlights from the Development of TLD1433. Chem. Rev. 2019, 119, 797–828.
  38. Mari, C.; Pierroz, V.; Ferrari, S.; Gasser, G. Combination of Ru(II) complexes and light: New frontiers in cancer therapy. Chem. Sci. 2015, 6, 2660–2686.
  39. Knoll, J.D.; Turro, C. Control and utilization of ruthenium and rhodium metal complex excited states for photoactivated cancer therapy. Coord. Chem. Rev. 2015, 282, 110–126.
  40. Zeng, L.; Gupta, P.; Chen, Y.; Wang, E.; Ji, L.; Chao, H.; Chen, Z.S. The development of anticancer ruthenium(II) complexes: From single molecule compounds to nanomaterials. Chem. Soc. Rev. 2017, 46, 5771–5804.
  41. Li, A.; Turro, C.; Kodanko, J.J. Ru(II) polypyridyl complexes as photocages for bioactive compounds containing nitriles and aromatic heterocycles. Chem. Commun. 2018, 54, 1280–1290.
  42. Zhang, C.X.; Lippard, S.J. New metal complexes as potential therapeutics. Curr. Opin. Chem. Biol. 2003, 7, 481–489.
  43. Grover, N.; Welch, T.W.; Fairley, T.A.; Cory, M.; Thorp, H.H. Covalent Binding of Aquaruthenium complexes to DNA. Inorg. Chem. 1994, 33, 3544–3548.
  44. Gill, M.R.; Thomas, J.A. Ruthenium (II) polypyridyl complexes and DNA-from structural probes to cellular imaging and therapeutics. Chem. Soc. Rev. 2012, 41, 3179–3192.
  45. Albani, B.A.; Peña, B.; Dunbar, K.R.; Turro, C. New cyclometallated Ru(II) complex for potential application in photochemotherapy. Photochem. Photobiol. Sci. 2014, 13, 272–280.
  46. Durham, B.; Walsh, J.L.; Carter, C.L.; Meyer, T.J. Synthetic applications of photosubstitution reactions of poly(pyridyl) complexes of ruthenium(II). Inorg. Chem. 1980, 19, 860–865.
  47. Hu, X.; Liu, N.Y.; Deng, Y.Q.; Wang, S.; Liu, T.; Liu, X.W. Photoinduced DNA Cleavage and Photocytotoxic of Phenanthroline-Based Ligand Ruthenium Compounds. Molecules 2021, 26, 3471.
  48. Zhou, Q.X.; Lei, W.H.; Sun, Y.; Chen, J.R.; Li, C.; Hou, Y.J.; Wang, X.S.; Zhang, B.W. 2+: Unusual Photophysical Property and Efficient DNA Photocleavage Activity. Inorg. Chem. 2010, 49, 4729–4731.
  49. Jakubaszek, M.; Goud, B.; Ferrari, S.; Gasser, G. Mechanisms of action of Ru(II) polypyridyl complexes in living cells upon light irradiation. Chem. Commun. 2018, 54, 13040–13059.
  50. Zhang, C.; Guo, X.; Da, X.; Wang, Z.; Wang, X.; Zhou, Q. A Ru-anthraquinone dyad with triple functions of PACT, photoredox catalysis and PDT upon red light Irradiation. Dalton Trans. 2021, 50, 10845–10852.
  51. Sears, R.B.; Joyce, L.E.; Ojaimi, M.; Gallucci, J.C.; Thummel, R.P.; Turro, C. Photoinduced ligand exchange and DNA binding of cis-+ with long wavelength visible light. J. Inorg. Biochem. 2013, 121, 77–78.
  52. Cuello-Garibo, J.A.; James, C.C.; Siegler, M.A.; Hopkins, S.L.; Bonnet, S. Selective Preparation of a Heteroleptic Cyclometallated Ruthenium Complex Capable of Undergoing Photosubstitution of a Bidentate Ligand. Chem. Eur. J. 2019, 25, 1260–1268.
  53. Al-Afyouni, M.H.; Rohrabaugh, T.N.; Al-Afyouni, K.F.; Turro, C. New Ru(ii) photocages operative with near-IR light: New platform for drug delivery in the PDT window. Chem. Sci. 2018, 9, 6711–6720.
  54. Wang, J.; Lu, Y.; McCarthy, W.; Conway-Kenny, R.; Twamley, B.; Zhao, J.Z.; Drapera, S.M. Novel ruthenium and iridium complexes of N-substituted carbazole as triplet photosensitisers. Chem. Commun. 2018, 54, 1073–1076.
  55. Wadman, S.H.; Havenith, R.W.A.; Hartl, F.; Lutz, M.; Spek, A.L.; van Klink, G.P.M.; van Koten, G. Redox Chemistry and Electronic Properties of 2,3,5,6-Tetrakis(2-pyridyl)pyrazine-Bridged Diruthenium Complexes Controlled by N,C,N′-BisCyclometalated Ligands. Inorg. Chem. 2009, 48, 5685–5696.
  56. Ruminski, R.R.; Degroff, C.; Smith, S.J. Synthesis and characterization of tetracarbonylmolybdenum(0) complexes bound to the novel bridging ligand dipyridophenazine (DPOP). Inorg. Chem. 1992, 31, 3325–3328.
  57. Albani, B.A.; Peña, B.; Saha, S.; White, J.K.; Schaeffer, A.M.; Dunbar, K.R.; Turro, C. A dinuclear Ru(II) complex capable of photoinduced ligand exchange at both metal centers. Chem. Commun. 2015, 51, 16522–16525.
  58. Saha, S.; Peña, B.; Dunbar, K.R. Partially Solvated Dinuclear Ruthenium Compounds Bridged by Quinoxaline-Functionalized Ligands as Ru(II) Photocage Architectures for Low-Energy Light Absorption. Inorg. Chem. 2019, 58, 14568–14576.
  59. Zheng, Y.; Zhou, Q.X.; Lei, W.H.; Hou, Y.J.; Li, K.; Chen, Y.J.; Zhang, B.W.; Wang, X.S. DNA photocleavage in anaerobic conditions by a Ru(II) complex: A new mechanism. Chem. Commun. 2015, 51, 428–430.
  60. Zheng, Y.; Zhou, Q.X.; Zhang, Y.Y.; Li, C.; Hou, Y.J.; Wang, X.S. Substituent effect and wavelength dependence of the photoinduced Ru-O homolysis in the +-type complexes. Dalton Trans. 2016, 45, 2897–2905.
  61. Tian, N.; Feng, Y.; Sun, W.; Lu, J.; Lu, S.; Yao, Y.; Li, C.; Wang, X.; Zhou, Q. A nuclear permeable Ru(II)-based photoactivated chemotherapeutic agent towards a series of cancer cells: In vitro and in vivo studies. Dalton Trans. 2019, 48, 6492–6500.
  62. Kumar, P.; Dasari, S.; Patra, A.K. Ruthenium(II) complexes of saccharin with dipyridoquinoxaline and dipyridophenazine: Structures, biological interactions and photoinduced DNA damage activity. Eur. J. Med. Chem. 2017, 136, 52–62.
  63. Arora, K.; Herroon, M.; Al-Afyouni, M.H.; Toupin, N.P.; Rohrabaugh, T.N.; Loftus, L.M.; Podgorski, I.; Turro, C.; Kodanko, J.J. Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers. J. Am. Chem. Soc. 2018, 140, 14367–14380.
  64. Qu, F.; Park, S.; Martinez, K.; Gray, J.L.; Thowfeik, F.S.; Lundeen, J.A.; Kuhn, A.E.; Charboneau, D.J.; Gerlach, D.L.; Lockart, M.M.; et al. Ruthenium Complexes are pH-Activated Metallo Prodrugs (pHAMPs) with Light-Triggered Selective Toxicity Toward Cancer Cells. Inorg. Chem. 2017, 56, 7519–7532.
  65. Qu, F.; Martinez, K.; Arcidiacono, A.M.; Park, S.; Zeller, M.; Schmehl, R.H.; Paul, J.J.; Kim, Y.; Papish, E.T. Sterically demanding methoxy and methyl groups in ruthenium complexes lead to enhanced quantum yields for blue light triggered photodissociation. Dalton Trans. 2018, 47, 15685–15693.
  66. Qu, F.; Lamb, R.W.; Cameron, C.G.; Park, S.; Oladipupo, O.; Gray, J.L.; Xu, Y.; Cole, H.D.; Bonizzoni, M.; Kim, Y.; et al. Singlet Oxygen Formation vs. Photodissociation for Light Responsive Protic Ruthenium Anticancer Compounds: The Oxygenated Substituent Determines Which Pathway Dominates. Inorg. Chem. 2021, 60, 2138–2148.
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 363
Revisions: 2 times (View History)
Update Date: 30 Sep 2021