Photochemical & Photobiological Sciences PAPER Cite this: Photochem. Photobiol. Sci., 2014, 13, 272 Received 15th September 2013, Accepted 5th November 2013 DOI: 10.1039/c3pp50327e www.rsc.org/pps New cyclometallated Ru(II) complex for potential application in photochemotherapy?† Bryan A. Albani, a Bruno Peña, b Kim R. Dunbar* b and Claudia Turro* a In an effort to create a molecule that absorbs further into the optimum window for photochemotherapy (PCT), the new cyclometallated complex [Ru(biq) 2 ( phpy)](PF 6 )(1, biq = 2,2’-biquinoline, phpy - = deproto- nated 2-phenylpyridine) was synthesized, characterized and compared to the known photoactive complexes [Ru(biq) 2 (bpy)](PF 6 ) 2 (2, bpy = 2,2’-bipyridine) and [Ru(biq) 2 ( phen)](PF 6 ) 2 (3, phen = 1,10-phe- nanthroline), both of which undergo exchange of one biq ligand when irradiated with red light in co- ordinating solvents. Excited state ligand dissociation in 2 and 3 is believed to be related to the steric hindrance afforded by the presence of two coordinated biq ligands. The ligand exchange quantum yield of 2 is ∼2-fold greater than that of 3, which was shown to be cytotoxic when irradiated with visible light. Cyclometallation results in a red shift of the MLCT absorption maximum of 1 by ∼100 nm relative to those of 2 and 3, but, although 1 exhibits a distorted octahedral geometry, photoinduced ligand exchange does not occur. DFT calculations were used to aid in our understanding of the lack of photochemistry of 1 which is explained by the destabilization of the e g (σ*) orbitals upon cyclometallation. Introduction Ruthenium(II) polypyridyl complexes with extended aromatic ligands have been shown to interact with DNA as chemothera- peutic agents and molecular light switches through intercala- tion and electrostatic interactions. 1–4 Recent studies indicate that certain Ru(II) complexes have the ability to undergo photo- induced ligand exchange forming covalent bonds with DNA in a manner akin to cisplatin, such that these lesions may result in cell death. Unlike traditional photodynamic therapy (PDT) agents that rely on the generation of singlet oxygen for action, these photo-cisplatin analogs achieve cell death via mecha- nisms that are independent of oxygen; in order to differentiate the two methods, the latter is referred to as photochemotherapy (PCT). 5–7 PCT involving transition metal complexes has generally focused on the exchange of monodentate ligands upon irradiation. 5,8,9 The photoinduced ligand exchange of biden- tate ligands bound to ruthenium(II), however, is well documen- ted for sterically strained complexes including those with ligands such as 2,2′-biquinoline (biq). 10 For example, the photoinduced exchange of a biq ligand in [Ru(biq) 2 (bpy)] 2+ (bpy = 2,2′-bipyridine) in CH 3 CN results in the formation of the intermediate cis-[Ru(biq)(bpy)(CH 3 CN) 2 ] 2+ , which can be used in the synthesis of tris-heteroleptic Ru(II) complexes of the type [Ru(biq)( phen)(L)] 2+ in the presence of a variety of bidentate ligands, L. 10 It was not until decades later that [Ru(biq)(phen) 2 ] 2+ and [Ru(biq) 2 (phen)] 2+ (phen = 1,10-phenan- throline) were shown to exhibit cytotoxicity upon irradiation with visible light, while being relatively non-toxic under similar conditions in the dark. 11 Both Ru(II) complexes undergo ligand dissociation in water following the absorption of visible light to generate the corresponding bis-aqua com- plexes; the latter species covalently bind to DNA in vitro and these adducts are believed to result in cell death. 6,11 Photoinduced ligand exchange occurs in complexes with 3 LF (ligand field) dd states that are thermally accessible from the lower-lying energy 3 MLCT (metal-to-ligand charge transfer) state(s). 12–15 The thermal population of the metal centered 3 LF state results in electron density on the e g -type orbitals with Ru–L(σ*) character, thus resulting in ligand dissociation. 12–15 The exchange of bidentate ligands, however, is unusual because both bonds must be cleaved upon MLCT excitation. Bulky biq ligands that sterically strain the conventional octa- hedral geometry in Ru(II) complexes are believed to lower the energy of the 3 LF state relative to the 3 MLCT state, thus result- ing in enhanced photochemistry. 6,11 The maximum of the MLCT absorption of [Ru(biq) 2 - ( phen)] 2+ located at 550 nm in H 2 O is outside the optimal exci- tation range for PCT which is 600–850 nm. 11 Therefore, † Electronic supplementary information (ESI) available: Additional crystal struc- ture and crystallographic data, calculations, 1 H NMR data, emission spectra. See DOI: 10.1039/c3pp50327e a Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA. E-mail: turro.1@osu.edu b Department of Chemistry, Texas A&M University, College Station, TX, USA. E-mail: dunbar@mail.chem.tamu.edu 272 | Photochem. Photobiol. Sci. , 2014, 13, 272–280 This journal is © The Royal Society of Chemistry and Owner Societies 2014 Published on 13 November 2013. 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