TY - JOUR
T1 - Multinuclear cytotoxic metallodrugs
T2 - Physicochemical characterization and biological properties of novel heteronuclear gold-titanium complexes
AU - Wenzel, Margot
AU - Bertrand, Benoît
AU - Eymin, Marie Joëlle
AU - Comte, Virginie
AU - Harvey, Jennifer A.
AU - Richard, Philippe
AU - Groessl, Michael
AU - Zava, Olivier
AU - Amrouche, Hedi
AU - Harvey, Pierre D.
AU - Le Gendre, Pierre
AU - Picquet, Michel
AU - Casini, Angela
PY - 2011/10/3
Y1 - 2011/10/3
N2 - An unprecedented series of titanocene-gold bi- and trimetallic complexes of the general formula [[(η 5-C 5H 5)(μ- η 5:κ 1-C 5H 4(CH 2) nPPh 2)TiCl 2] mAuCl x] q+ (n = 0, 2, or 4; m = 1, x = 1, q = 0 or m = 2, x = 0, q = 1) have been prepared and characterized spectroscopically. The luminescence spectroscopy and photophysics of one of the compounds, [[(η 5- C 5H 5)(μ- η 5:κ 1-C 5H 4PPh 2)TiCl 2] 2Au]PF 6, have been investigated in 2MeTHF solution and in the solid state at 77 and 298 K. Evidence for interfragment interactions based on the comparison of electronic band positions and emission lifetimes, namely, triplet energy transfer (ET) from the Au- to the Ti-containing chromophores, is provided. The cytotoxicity of the complexes was evaluated on A2780 ovarian cancer cells and on their cisplatin-resistant cell line A2780cisR; the compounds showed activity in the low micromolar range that was markedly more active than the corresponding titanocene-phosphine precursors [(η 5-C 5H 5)(η 5-C 5H 4(CH 2) nPPh 2)TiCl 2], cisplatin, and, for some of them, the gold analogue [(PPh 3)AuCl]. In an attempt to draw preliminary structure-activity relationships, cell uptake measurements and interaction studies with plasmid DNA and the model protein ubiquitin (Ub) have been undertaken on some of the compounds.
AB - An unprecedented series of titanocene-gold bi- and trimetallic complexes of the general formula [[(η 5-C 5H 5)(μ- η 5:κ 1-C 5H 4(CH 2) nPPh 2)TiCl 2] mAuCl x] q+ (n = 0, 2, or 4; m = 1, x = 1, q = 0 or m = 2, x = 0, q = 1) have been prepared and characterized spectroscopically. The luminescence spectroscopy and photophysics of one of the compounds, [[(η 5- C 5H 5)(μ- η 5:κ 1-C 5H 4PPh 2)TiCl 2] 2Au]PF 6, have been investigated in 2MeTHF solution and in the solid state at 77 and 298 K. Evidence for interfragment interactions based on the comparison of electronic band positions and emission lifetimes, namely, triplet energy transfer (ET) from the Au- to the Ti-containing chromophores, is provided. The cytotoxicity of the complexes was evaluated on A2780 ovarian cancer cells and on their cisplatin-resistant cell line A2780cisR; the compounds showed activity in the low micromolar range that was markedly more active than the corresponding titanocene-phosphine precursors [(η 5-C 5H 5)(η 5-C 5H 4(CH 2) nPPh 2)TiCl 2], cisplatin, and, for some of them, the gold analogue [(PPh 3)AuCl]. In an attempt to draw preliminary structure-activity relationships, cell uptake measurements and interaction studies with plasmid DNA and the model protein ubiquitin (Ub) have been undertaken on some of the compounds.
UR - https://www.scopus.com/pages/publications/80053318081
U2 - 10.1021/ic201155y
DO - 10.1021/ic201155y
M3 - Article
C2 - 21875041
AN - SCOPUS:80053318081
SN - 0020-1669
VL - 50
SP - 9472
EP - 9480
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 19
ER -
