Synthesis, Characterization, and Biological Evaluation of New Ru(II) Polypyridyl Photosensitizers for Photodynamic Therapy

Abstract

Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)](2+) (2) (DIP = 4,7-diphenyl-1,10-phenanthroline, bdt = 1,2-benzenedithiolate, dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine), ptpy = 4'-phenyl-2,2':6',2 -terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and phototoxic index (PI) of 2 (IC50(light): 25.3 M, 420 nm, 6.95 J/cm(2); PI >4) and particularly of 1 (IC50(light): 0.62 M, 420 nm, 6.95 J/cm(2); PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic acid. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) Staphylococcus aureus and Gram-(-) Escherichia coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm(2)) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(-) E. coli (>4 log10 CFU reduction). Two Ru(II) polypyridyl complexes, Ru(DIP)2(bdt) (1) and [Ru(dqpCO2Me)(ptpy)] 2+ (2) (DIP = 4,7-diphenyl-1,10-phenanthroline; bdt = 1,2-benzenedithiolate; dqpCO2Me = 4-methylcarboxy-2,6-di(quinolin-8-yl)pyridine); ptpy = 4'-phenyl-2,2':6',2''-terpyridine) have been investigated as photosensitizers (PSs) for photodynamic therapy (PDT). In our experimental settings, the phototoxicity and photo-index (PI) of 2 (IC50(light): 25.3 μM, 420 nm, 6.95 J/cm 2 ; PI: >4) and particularly of 1 (IC50(light): 0.62 μM, 420 nm, 6.95 J/cm 2 ; PI: 80) are considerably superior compared to the two clinically approved PSs porfimer sodium and 5-aminolevulinic. Cellular uptake and distribution of these complexes was investigated by confocal microscopy (1) and by inductively coupled plasma-mass spectrometry (1 and 2). Their phototoxicity was also determined against the Gram-(+) S. aureus and Gram-(−) E. coli for potential antimicrobial PDT (aPDT) applications. Both complexes showed significant aPDT activity (420 nm, 8 J/cm 2 ) against Gram-(+) (S. aureus; >6 log10 CFU reduction) and, for 2, also against Gram-(−) E. coli (>4 log10 CFU reduction). 3Introduction.

Unexpected high photothemal conversion efficiency of gold nanospheres upon grafting with two-photon luminescent ruthenium(II) complexes: A way towards cancer therapy?

“…Indeed, it is well-known that certain inert polypyridyl ruthenium complexes can produce 1 O2 upon irradiation in the UV-Vis region [40][41][42]. As expected, using a singlet oxygen sensor (DPBF) [38], we found out that the Ru2@AuNPs were producing H2DCF-DA (2′,7′-dichlorofluorescin diacetate) has been widely used to assess the production of ROS in living cells [42].…”

Evaluation of Perylene Bisimide‐Based RuII and IrIII Complexes as Photosensitizers for Photodynamic Therapy

“…The photoindex (PI) of 1 was about 2 upon light irradiation at 420 nm. In contrast, 2 exhibited a remarkable phototoxicity in the nanomolar range on all cancer cell lines, with a [20,22] …”

Singlet oxygen-mediated transformation of furans into aromatic nitrogen-containing polycycles in water

“…In terms of green chemistry, 10,11 and excluding the molecules that are incorporated in their totality in the product, an environmentally benign solvent (water) and oxidant (singlet oxygen) are used and the only compromises made (in terms both of atom efficiency and reagent safety -towards both humans and the environment) are the use of small amounts of TFA or PTSA to facilitate the last step of the cascade (the Pictet-Spengler cyclisation) and the use of minute amounts of a natural catalyst (rose Bengal) that has a toxicity profile sufficient to allow it to have in vivo human medical applications. 34 Of course, singlet oxygen is used as a cytotoxic agent in photodynamic therapy 35 (generated in situ, in vivo), so it obviously cannot be called a non-toxic reagent; however, as it is generated and used here the operator would never be exposed to the reagent because of its unique characteristics and short lifetime and it can, therefore, not exert any toxic effect. Its toxicity is completely nullified, and, furthermore, no residues remain after its use, toxic or otherwise.…”