Multinuclear Cytotoxic Metallodrugs: Physicochemical Characterization and Biological Properties of Novel Heteronuclear Gold鈥揟itanium Complexes

详细信息    查看全文

• 作者：Margot Wenzel ; Beno卯t Bertrand ; Marie-Jo毛lle Eymin ; Virginie Comte ; Jennifer A. Harvey ; Philippe Richard ; Michael Groessl ; Olivier Zava ; Hedi Amrouche ; Pierre D. Harvey ; Pierre Le Gendre ; Michel Picquet ; Angela Casini
• 刊名：Inorganic Chemistry
• 出版年：2011
• 出版时间：October 3, 2011
• 年：2011
• 卷：50
• 期：19
• 页码：9472-9480
• 全文大小：958K
• 年卷期：v.50,no.19(October 3, 2011)
• ISSN：1520-510X

文摘

An unprecedented series of titanocene鈥揼old bi- and trimetallic complexes of the general formula [[(畏⁵-C₅H₅)(渭-畏⁵:魏¹-C₅H₄(CH₂)_nPPh₂)TiCl₂]_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, [[(畏⁵-C₅H₅)(渭-畏⁵:魏¹-C₅H₄PPh₂)TiCl₂]₂Au]PF₆, 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鈥損hosphine precursors [(畏⁵-C₅H₅)(畏⁵-C₅H₄(CH₂)_nPPh₂)TiCl₂], cisplatin, and, for some of them, the gold analogue [(PPh₃)AuCl]. In an attempt to draw preliminary structure鈥揳ctivity relationships, cell uptake measurements and interaction studies with plasmid DNA and the model protein ubiquitin (Ub) have been undertaken on some of the compounds.