Ru(II) dyads derived from α-oligothiophenes: A new class of potent and versatile photosensitizers for PDT

Shi, Ge; Monro, Susan; Hennigar, Robie; Colpitts, Julie; Fong, Jamie; Kasimova, Kamola; Yin, Huimin; DeCoste, Ryan; Spencer, Colin; Chamberlain, Lance; Mandel, Arkady; Lilge, Lothar; McFarland, Sherri A.

doi:10.1016/j.ccr.2014.04.012

Cited by 253 publications

(266 citation statements)

References 65 publications

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“…Overall, two factors influence the stability of these complexes and the stereoselectivity of the coordination of mtpa: octahedral distortion and inter-ligand repulsion. In the case of the non-strained complex [1] 2+ , only the octahedral distortion plays a role, whereas when hindering methyl substituents are introduced in the complex, inter-ligand repulsion becomes the driving force for the diastereoselectivity of the reaction.…”

Section: Characterization By Dft and Noesy Studiesmentioning

confidence: 99%

“…Single crystals suitable for X-Ray structure determination were obtained for complexes [1] 2 by slow vapor diffusion of the solvent of a methanol solution of the complex into toluene, ethyl acetate, and di-tert-butyl ether, respectively. In all structures, the six-membered ring resulting from the coordination of mtpa to the Ru center was found in a chair conformation, as modelled by DFT.…”

Section: X-ray Crystallographymentioning

confidence: 99%

“…Complex [1](PF 6 ) 2 , when irradiated with blue light (445 nm), showed a bathochromic shift in the MLCT band with a change in the maximum absorption from 450 to 486 nm, and clear isosbestic points at 325, 390, and 460 nm, indicating a one-step process (Figure 5a). After six minutes at ~3·10 −8 mol·s −1 photon flux the photoreaction had reached the steady state.…”

Section: Photochemistry and Thermal Stabilitymentioning

confidence: 99%

“…Mass spectrometry performed at that point showed major peaks at m/z = 260. The reversibility of the ring opening photoreaction was also studied using UV-Vis spectroscopy by irradiating [1](PF 6 ) 2 four times during 5 min, each time followed by ~2 h of equilibration in the dark at 37 °C (to increase the rate of back coordination). As shown in Figure 6a, the ring opening is clearly reversible.…”

Section: Photochemistry and Thermal Stabilitymentioning

confidence: 99%

“…Whereas in Photodynamic Therapy (PDT) cytotoxicity is obtained by the photochemical generation of reactive oxygen species (ROS) such as singlet oxygen [1,2,3], in metal-based PACT a new cytotoxic drug is formed in situ via photosubstitution of at least one of the ligands of the original pro-drug [4,5]. In many reported examples, ruthenium PACT agents are based on complexes of the [Ru(bpy) 2 (dmbpy)] 2+ family, where bpy is 2,2'-bipyridine and dmbpy is the sterically hindering ligand 6,6'-dimethyl-2,2'-bipyridine, which increases the distortion of the coordination octahedron [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Ruthenium-based PACT compounds based on an N,S non-toxic ligand: a delicate balance between photoactivation and thermal stability

Cuello-Garibo¹,

James²,

Siegler³

et al. 2017

Chem.Sq.

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Abstract:In photoactivated chemotherapy, the photocleavable protecting group that prevents the bioactive compound from interacting with biomolecules in the dark is sometimes cytotoxic, which makes interpretation of phototoxicity challenging. For ruthenium polypyridyl complexes new, non-toxic protecting ligands that prevent a toxic metal complex from binding to biomolecules in the dark, but that can be efficiently photosubstituted upon visible light irradiation to recover the high toxicity of the metal complex, are necessary. In this work, we report on the synthesis, stereochemical characterization and cytotoxicity of a series of polypyridyl complexes; [Ru(bpy) 2 (mtpa)](PF 6 ) 2 ([1](PF 6 ) 2 , bpy = 2,2'-bipyridine), [Ru(bpy)(dmbpy)(mtpa)](PF 6 ) 2 ([2](PF 6 ) 2 , dmbpy = 6,6'-dimethyl-2,2'-bipyridine), and [Ru(dmbpy) 2 (mtpa)](PF 6 ) 2 ([3](PF 6 ) 2 ) based on the non-toxic 3-(methylthio)propylamine protecting ligand (mtpa). The number of methyl groups had a crucial effect on the photochemistry and cytotoxicity of these complexes. The non-strained complex [1] 2+ was not capable of fully releasing mtpa and was not phototoxic in lung cancer cells (A549). In the most strained complex [3] 2+ , thermal stability was lost, leading to poor photoactivation in vitro and a generally high toxicity also without light activation. The heteroleptic complex [2] 2+ with intermediate strain showed, upon blue light irradiation, efficient mtpa photosubstitution and increased cytotoxicity in cancer cells, but photosubstitution was not selective. Overall, fine-tuning of the lipophilicity and steric strain of ruthenium complexes appears as an efficient method to obtain phototoxic ruthenium-based photoactivated chemotherapeutic prodrugs, at the cost of synthetic simplicity and photosubstitution selectivity.

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Section: Characterization By Dft and Noesy Studiesmentioning

confidence: 99%

Section: X-ray Crystallographymentioning

confidence: 99%

Section: Photochemistry and Thermal Stabilitymentioning

confidence: 99%

Section: Photochemistry and Thermal Stabilitymentioning

confidence: 99%