Dual Triggering of DNA Binding and Fluorescence via Photoactivation of a Dinuclear Ruthenium(II) Arene Complex
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- 作者：Steven W. Magennis ; Abraha Habtemariam ; Olga Novakova ; John B. Henry ; Samuel Meier ; Simon Parsons ; Iain D. H. Oswald ; Viktor Brabec ; Peter J. Sadler
- 刊名：Inorganic Chemistry
- 出版年：2007
- 出版时间：June 11, 2007
- 年：2007
- 卷：46
- 期：12
- 页码：5059 - 5068
- 全文大小：239K
- 年卷期：v.46,no.12(June 11, 2007)
- ISSN：1520-510X
文摘
The dinuclear RuII arene complexes [{(
6-arene)RuCl}2(
-2,3-dpp)](PF6)2, arene = indan (1), benzene (2), p-cymene(3), or hexamethylbenzene (4) and 2,3-dpp = 2,3-bis(2-pyridyl)pyrazine, have been synthesized and characterized.Upon irradiation with UVA light, complexes 1 and 2 readily underwent arene loss, while complexes 3 and 4 did not.The photochemistry of 1 was studied in detail. In the X-ray structure of [{(6-indan)RuCl}2(-2,3-dpp)](PF6)2 (1),2,3-dpp bridges two RuII centers 6.8529(6) Å apart. In water, aquation of 1 in the dark occurs with replacement ofchloride with biexponential kinetics and decay constants of 100 ± 1 min-1 and 580 ± 11 min-1. This aquation wassuppressed by 0.1 M NaCl. UV or visible irradiation of 1 in aqueous or methanolic solution led to arene loss. Thefluorescence of the unbound arene is ~40 times greater than when it is complexed. Irradiation of 1 also had asignificant effect on its interactions with DNA. The DNA binding of 1 is increased after irradiation. The non-irradiatedform of 1 preferentially formed DNA adducts that only weakly blocked RNA polymerase, while irradiation of 1transformed the adducts into stronger blocks for RNA polymerase. The efficiency of irradiated 1 to form DNAinterstrand cross-links was slightly greater than that of cisplatin in both 10 mM NaClO4 and 0.1 M NaCl. In contrast,the interstrand cross-linking efficiency of non-irradiated 1 in 10 mM NaClO4 was relatively low. An intermediateamount of cross-linking was observed when the sample of DNA already modified by non-irradiated 1 was irradiated.DNA unwinding measurements supported the conclusion that both mono- and bifunctional adducts with DNA canform. These results show that photoactivation of dinuclear RuII arene complexes can simultaneously produce ahighly reactive ruthenium species that can bind to DNA and a fluorescent marker (the free arene). Importantly, themechanism of photoreactivity is also independent of oxygen. These complexes, therefore, have the potential tocombine both photoinduced cell death and fluorescence imaging of the location and efficiency of the photoactivationprocess.
6-arene)RuCl}2(-2,3-dpp)](PF6)2, arene = indan (1), benzene (2), p-cymene(3), or hexamethylbenzene (4) and 2,3-dpp = 2,3-bis(2-pyridyl)pyrazine, have been synthesized and characterized.Upon irradiation with UVA light, complexes 1 and 2 readily underwent arene loss, while complexes 3 and 4 did not.The photochemistry of 1 was studied in detail. In the X-ray structure of [{(6-indan)RuCl}2(-2,3-dpp)](PF6)2 (1),2,3-dpp bridges two RuII centers 6.8529(6) Å apart. In water, aquation of 1 in the dark occurs with replacement ofchloride with biexponential kinetics and decay constants of 100 ± 1 min-1 and 580 ± 11 min-1. This aquation wassuppressed by 0.1 M NaCl. UV or visible irradiation of 1 in aqueous or methanolic solution led to arene loss. Thefluorescence of the unbound arene is ~40 times greater than when it is complexed. Irradiation of 1 also had asignificant effect on its interactions with DNA. The DNA binding of 1 is increased after irradiation. The non-irradiatedform of 1 preferentially formed DNA adducts that only weakly blocked RNA polymerase, while irradiation of 1transformed the adducts into stronger blocks for RNA polymerase. The efficiency of irradiated 1 to form DNAinterstrand cross-links was slightly greater than that of cisplatin in both 10 mM NaClO4 and 0.1 M NaCl. In contrast,the interstrand cross-linking efficiency of non-irradiated 1 in 10 mM NaClO4 was relatively low. An intermediateamount of cross-linking was observed when the sample of DNA already modified by non-irradiated 1 was irradiated.DNA unwinding measurements supported the conclusion that both mono- and bifunctional adducts with DNA canform. These results show that photoactivation of dinuclear RuII arene complexes can simultaneously produce ahighly reactive ruthenium species that can bind to DNA and a fluorescent marker (the free arene). Importantly, themechanism of photoreactivity is also independent of oxygen. These complexes, therefore, have the potential tocombine both photoinduced cell death and fluorescence imaging of the location and efficiency of the photoactivationprocess.