Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex

Steven W. Magennis, Abraha Habtemariam, Olga Novakova, John B. Henry, Samuel Meier, Simon Parsons, Iain D. H. Oswald, Viktor Brabec, Peter J. Sadler

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Abstract

The dinuclear Ru-II arene complexes [{(eta(6)-arene)RuCl}(2)(mu-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 [{(eta(6)-indan)RuCl}(2)(mu-2,3-dpp)](PF6)(2) (1), 2,3-dpp bridges two Ru-II centers 6.8529(6) A apart. In water, aquation of 1 in the dark occurs with replacement of chloride with biexponential kinetics and decay constants of 100 +/- 1 min(-1) and 580 +/- 11 min(-1). This aquation was suppressed by 0.1 M NaCl. UV or visible irradiation of 1 in aqueous or methanolic solution led to arene loss. The fluorescence of the unbound arene is similar to 40 times greater than when it is complexed. Irradiation of 1 also had a significant effect on its interactions with DNA. The DNA binding of 1 is increased after irradiation. The non-irradiated form of 1 preferentially formed DNA adducts that only weakly blocked RNA polymerase, while irradiation of 1 transformed the adducts into stronger blocks for RNA polymerase. The efficiency of irradiated 1 to form DNA interstrand 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 intermediate amount 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 can form. These results show that photoactivation of dinuclear Ru-II arene complexes can simultaneously produce a highly reactive ruthenium species that can bind to DNA and a fluorescent marker (the free arene). Importantly, the mechanism of photoreactivity is also independent of oxygen. These complexes, therefore, have the potential to combine both photoinduced cell death and fluorescence imaging of the location and efficiency of the photoactivation process.

LanguageEnglish
Pages5059-5068
Number of pages10
JournalInorganic Chemistry
Volume46
Issue number12
DOIs
Publication statusPublished - 11 Jun 2007

Fingerprint

Ruthenium
ruthenium
deoxyribonucleic acid
Fluorescence
fluorescence
DNA
Irradiation
irradiation
adducts
DNA-Directed RNA Polymerases
Photoreactivity
Pyrazines
DNA Adducts
Photochemical reactions
Cell death
Benzene
pyrazines
Cisplatin
Chlorides
death

Keywords

  • interstrand cross-links
  • absorption-spectra
  • visibile-light
  • cancer
  • ligand
  • photochemistry
  • cytotoxicity
  • mononuclear
  • aquation
  • cleavage

Cite this

Magennis, S. W., Habtemariam, A., Novakova, O., Henry, J. B., Meier, S., Parsons, S., ... Sadler, P. J. (2007). Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex. Inorganic Chemistry, 46(12), 5059-5068. https://doi.org/10.1021/ic062111q
Magennis, Steven W. ; Habtemariam, Abraha ; Novakova, Olga ; Henry, John B. ; Meier, Samuel ; Parsons, Simon ; Oswald, Iain D. H. ; Brabec, Viktor ; Sadler, Peter J. / Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex. In: Inorganic Chemistry. 2007 ; Vol. 46, No. 12. pp. 5059-5068.
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Magennis, SW, Habtemariam, A, Novakova, O, Henry, JB, Meier, S, Parsons, S, Oswald, IDH, Brabec, V & Sadler, PJ 2007, 'Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex' Inorganic Chemistry, vol. 46, no. 12, pp. 5059-5068. https://doi.org/10.1021/ic062111q

Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex. / Magennis, Steven W.; Habtemariam, Abraha; Novakova, Olga; Henry, John B.; Meier, Samuel; Parsons, Simon; Oswald, Iain D. H.; Brabec, Viktor; Sadler, Peter J.

In: Inorganic Chemistry, Vol. 46, No. 12, 11.06.2007, p. 5059-5068.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex

AU - Magennis, Steven W.

AU - Habtemariam, Abraha

AU - Novakova, Olga

AU - Henry, John B.

AU - Meier, Samuel

AU - Parsons, Simon

AU - Oswald, Iain D. H.

AU - Brabec, Viktor

AU - Sadler, Peter J.

PY - 2007/6/11

Y1 - 2007/6/11

N2 - The dinuclear Ru-II arene complexes [{(eta(6)-arene)RuCl}(2)(mu-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 [{(eta(6)-indan)RuCl}(2)(mu-2,3-dpp)](PF6)(2) (1), 2,3-dpp bridges two Ru-II centers 6.8529(6) A apart. In water, aquation of 1 in the dark occurs with replacement of chloride with biexponential kinetics and decay constants of 100 +/- 1 min(-1) and 580 +/- 11 min(-1). This aquation was suppressed by 0.1 M NaCl. UV or visible irradiation of 1 in aqueous or methanolic solution led to arene loss. The fluorescence of the unbound arene is similar to 40 times greater than when it is complexed. Irradiation of 1 also had a significant effect on its interactions with DNA. The DNA binding of 1 is increased after irradiation. The non-irradiated form of 1 preferentially formed DNA adducts that only weakly blocked RNA polymerase, while irradiation of 1 transformed the adducts into stronger blocks for RNA polymerase. The efficiency of irradiated 1 to form DNA interstrand 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 intermediate amount 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 can form. These results show that photoactivation of dinuclear Ru-II arene complexes can simultaneously produce a highly reactive ruthenium species that can bind to DNA and a fluorescent marker (the free arene). Importantly, the mechanism of photoreactivity is also independent of oxygen. These complexes, therefore, have the potential to combine both photoinduced cell death and fluorescence imaging of the location and efficiency of the photoactivation process.

AB - The dinuclear Ru-II arene complexes [{(eta(6)-arene)RuCl}(2)(mu-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 [{(eta(6)-indan)RuCl}(2)(mu-2,3-dpp)](PF6)(2) (1), 2,3-dpp bridges two Ru-II centers 6.8529(6) A apart. In water, aquation of 1 in the dark occurs with replacement of chloride with biexponential kinetics and decay constants of 100 +/- 1 min(-1) and 580 +/- 11 min(-1). This aquation was suppressed by 0.1 M NaCl. UV or visible irradiation of 1 in aqueous or methanolic solution led to arene loss. The fluorescence of the unbound arene is similar to 40 times greater than when it is complexed. Irradiation of 1 also had a significant effect on its interactions with DNA. The DNA binding of 1 is increased after irradiation. The non-irradiated form of 1 preferentially formed DNA adducts that only weakly blocked RNA polymerase, while irradiation of 1 transformed the adducts into stronger blocks for RNA polymerase. The efficiency of irradiated 1 to form DNA interstrand 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 intermediate amount 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 can form. These results show that photoactivation of dinuclear Ru-II arene complexes can simultaneously produce a highly reactive ruthenium species that can bind to DNA and a fluorescent marker (the free arene). Importantly, the mechanism of photoreactivity is also independent of oxygen. These complexes, therefore, have the potential to combine both photoinduced cell death and fluorescence imaging of the location and efficiency of the photoactivation process.

KW - interstrand cross-links

KW - absorption-spectra

KW - visibile-light

KW - cancer

KW - ligand

KW - photochemistry

KW - cytotoxicity

KW - mononuclear

KW - aquation

KW - cleavage

U2 - 10.1021/ic062111q

DO - 10.1021/ic062111q

M3 - Article

VL - 46

SP - 5059

EP - 5068

JO - Inorganic Chemistry

T2 - Inorganic Chemistry

JF - Inorganic Chemistry

SN - 0020-1669

IS - 12

ER -

Magennis SW, Habtemariam A, Novakova O, Henry JB, Meier S, Parsons S et al. Dual triggering of DNA binding and fluorescence via photoactivation of a dinuclear ruthenium(II) arene complex. Inorganic Chemistry. 2007 Jun 11;46(12):5059-5068. https://doi.org/10.1021/ic062111q