A Potent <i>Trans</i>‐Diimine Platinum Anticancer Complex Photoactivated by Visible Light

Farrer, Nicola J.; Woods, Julie A.; Salassa, Luca; Zhao, Yao; Robinson, Kim; Clarkson, Guy J.; Mackay, Fiona; Sadler, Peter J.

doi:10.1002/ange.201003399

Cited by 81 publications

(104 citation statements)

References 31 publications

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“…Structures of platinum complexes studied in this work: trans , trans , trans -[Pt(N 3 ) 2 (OH) 2 (MA)(Py)] (1), trans , trans , trans -[Pt(N 3 ) 2 (OH) 2 (MA)(Tz)] (2), trans , trans , trans -[Pt(N 3 ) 2 (OH) 2 (NH 3 )(Py)] (3),5 trans , trans , trans -[Pt(N 3 ) 2 (OH) 2 (Py) 2 ] (4),6 trans -[PtCl 2 (MA)(Py)] (5), trans -[PtCl 2 (MA)(Tz)] (6), cisplatin (7), transplatin (8), and trans , trans , trans -[Pt(N 3 ) 2 (OH) 2 (NH 3 )(Tz)] (9).…”

Section: Introductionmentioning

confidence: 99%

Diazido Mixed‐Amine Platinum(IV) Anticancer Complexes Activatable by Visible‐Light Form Novel DNA Adducts

Zhao

Woods

Farrer

et al. 2013

Chemistry A European J

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Platinum diam(m)ine complexes, such as cisplatin, are successful anticancer drugs, but suffer from problems of resistance and side-effects. Photoactivatable PtIV prodrugs offer the potential of targeted drug release and new mechanisms of action. We report the synthesis, X-ray crystallographic and spectroscopic properties of photoactivatable diazido complexes trans,trans,trans-[Pt(N3)2(OH)2(MA)(Py)] (1; MA=methylamine, Py=pyridine) and trans,trans,trans-[Pt(N3)2(OH)2(MA)(Tz)] (2; Tz=thiazole), and interpret their photophysical properties by TD-DFT modelling. The orientation of the azido groups is highly dependent on H bonding and crystal packing, as shown by polymorphs 1 p and 1 q. Complexes 1 and 2 are stable in the dark towards hydrolysis and glutathione reduction, but undergo rapid photoreduction with UVA or blue light with minimal amine photodissociation. They are over an order of magnitude more potent towards HaCaT keratinocytes, A2780 ovarian, and OE19 oesophageal carcinoma cells than cisplatin and show particular potency towards cisplatin-resistant human ovarian cancer cells (A2780cis). Analysis of binding to calf-thymus (CT), plasmids, oligonucleotide DNA and individual nucleotides reveals that photoactivated 1 and 2 form both mono- and bifunctional DNA lesions, with preference for G and C, similar to transplatin, but with significantly larger unwinding angles and a higher percentage of interstrand cross-links, with evidence for DNA strand cross-linking further supported by a comet assay. DNA lesions of 1 and 2 on a 50 bp duplex were not recognised by HMGB1 protein, in contrast to cisplatin-type lesions. The photo-induced platination reactions of DNA by 1 and 2 show similarities with the products of the dark reactions of the PtII compounds trans-[PtCl2(MA)(Py)] (5) and trans-[PtCl2(MA)(Tz)] (6). Following photoactivation, complex 2 reacted most rapidly with CT DNA, followed by 1, whereas the dark reactions of 5 and 6 with DNA were comparatively slow. Complexes 1 and 2 can therefore give rapid potent photocytotoxicity and novel DNA lesions in cancer cells, with no activity in the absence of irradiation.

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Section: Introductionmentioning

confidence: 99%

Diazido Mixed‐Amine Platinum(IV) Anticancer Complexes Activatable by Visible‐Light Form Novel DNA Adducts

Zhao

Woods

Farrer

et al. 2013

Chemistry A European J

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“…Thus, our strategy adds a new brick to the recently proposed approach of metal-based drug activation by light irradiation. [33][34][35]38] Very demonstrative work from Sadler et al [36] showed that irradiation at 420 nm of a platinum(IV) complex can make it one order of magnitude more cytotoxic than in the dark. Like in PDT, the wavelength of the light used to irradiate the tumor should indeed be high enough in the visible (or NIR) region to allow deep and harmless penetration of the photons in living tissues.…”

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confidence: 98%

N‐Acetylmethionine and Biotin as Photocleavable Protective Groups for Ruthenium Polypyridyl Complexes

Goldbach

Rodriguez‐Garcia

Lenthe

et al. 2011

Chemistry A European J

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“…Since photogenerated singlet oxygen ( 1 O 2 ) is a key species in photodynamic therapy (PDT), complexes 6 a-9 a have the potential to be developed into new PDT photosensitizers. [21] Nanostructures from 3 a and 8 a: We have previously reported that square-planar platinum(II) complexes can self-assemble into nanoscale molecular materials driven by intermolecular Pt II ···Pt II and ligand···ligand (p···p) interactions. [5b, 19] In this work, the continuous p···p interactions in 1D column chains revealed in the X-ray crystal structure of 3 a prompted us to study the morphology of the self-assembled structures from these complexes.…”

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confidence: 99%

Luminescent Organoplatinum(II) Complexes with Functionalized Cyclometalated C^N^C Ligands: Structures, Photophysical Properties, and Material Applications

Kui

Hung

Lai

et al. 2011

Chemistry A European J

113

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A series of [(R'-C^N^C-R'')Pt(L)] complexes with doubly deprotonated cyclometalated R'-C^N^C-R'' ligands (R'-C^N^C-R''=2,6-diphenylpyridine derivatives) functionalized with carbazole, fluorene, or thiophene unit(s) have been synthesized and their photophysical properties studied. The X-ray crystal structures reveal extensive intermolecular π···π and C-H···π interactions between the cyclometalated C^N^C ligands. Compared to previously reported cyclometalated platinum(II) complexes [(C^N^C)Pt(L)], which are non-emissive in solution at room temperature, the carbazole-, fluorene- and thiophene-functionalized [(R'-C^N^C-R'')Pt(L)] (L=DMSO 1-9, C≡N-Ar, 1a-9a) complexes are emissive in solution at room temperature with λ(max) at 564-619 nm and Φ=0.02-0.26. The emissions of the [(R'-C^N^C-R'')Pt(L)] complexes are attributed to electronic excited states with mixed (3)MLCT and (3)IL character. The carbazole/fluorene/thiophene unit(s) allow the tuning of the electronic properties of the [(R'-C^N^C-R'')Pt] moiety, with the emission maxima in a range of 564-619 nm. These are the first examples of organoplatinum(II) complexes bearing doubly deprotonated cyclometalated C^N^C ligands that are emissive in solution at room temperature. In non-degassed DMSO, the emission intensities of 6a-9a are enhanced upon exposure to ambient light. This phenomenon is caused by reacting photogenerated (1)O(2) with a DMSO molecule to form dimethyl sulfone, leading to the removal of dissolved oxygen in solution. Self-assembled nanowires and nanorods are obtained from precipitation of 3a in THF/H(2)O and 8a in DMSO/Et(2)O, respectively. The [(R'-C^N^C-R'')Pt(L)] complexes are soluble in common organic solvents with a high thermal stability (>300 °C), rendering them as phosphorescent dopants for organic light-emitting diode (OLEDs) applications. Red OLEDs with CIE coordinates of (0.65±0.01, 0.35±0.01) were fabricated from 7a or 8a. A maximum external efficiency (η(Ext)) of 12.6% was obtained for the device using 8a as emitter.

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A Potent Trans‐Diimine Platinum Anticancer Complex Photoactivated by Visible Light

Abstract: Platin mit Licht aktiviert: Der inerte PtIV‐Diazidokomplex trans,trans,trans‐ [Pt(N3)2(OH)2(py)2] verwandelt sich bei der Bestrahlung mit geringen Dosen sichtbaren Lichts in einen potenten zytotoxischen Wirkstoff gegen Krebszellen.

Cited by 81 publications

References 31 publications

Diazido Mixed‐Amine Platinum(IV) Anticancer Complexes Activatable by Visible‐Light Form Novel DNA Adducts

Diazido Mixed‐Amine Platinum(IV) Anticancer Complexes Activatable by Visible‐Light Form Novel DNA Adducts

N‐Acetylmethionine and Biotin as Photocleavable Protective Groups for Ruthenium Polypyridyl Complexes

Luminescent Organoplatinum(II) Complexes with Functionalized Cyclometalated C^N^C Ligands: Structures, Photophysical Properties, and Material Applications

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