Neutral and charged phosphine/scorpionate copper(I) complexes: effects of ligand assembly on their antiproliferative activity.
Neutral and charged phosphine/scorpionate copper(I) complexes: effects of ligand assembly on their antiproliferative activity.
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DOI：
10.1016/j.ejmech.2012.11.022
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发表时间：
2013
影响因子：
6.7
通讯作者：
M. Porchia;A. Dolmella;V. Gandin;C. Marzano;M. Pellei;V. Peruzzo;F. Refosco;C. Santini;F. Tisato-F.-T
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文献类型：
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作者：
M. Porchia;A. Dolmella;V. Gandin;C. Marzano;M. Pellei;V. Peruzzo;F. Refosco;C. Santini;F. Tisato-F.-T
铜（I）前体（[Cu（CH3CN）4]BF4，CuCl）与一组双（唑基）硼酸盐或聚（吡唑基）甲烷和叔单齿膦（PTA = 1,3,5-三氮杂-7-磷金刚烷，PCN = 三（氰乙基）膦）的配体交换反应产生了两个系列的杂配体， ‘2 + 1 + 1’-或‘3 + 1’型配合物，已通过元素分析、FT-IR、ESI-MS和多核31P和1H NMR进行表征。 “2+1+1”型络合物包含 N,N-二齿螯合物和两个单齿膦 (1-8)，“3+1”型络合物包含 N,N,O- 或 N,N,N-三齿螯合物和一个单齿膦 (9-12)。所有这些复合物均采用四坐标四面体几何形状。 “3+1”复合物表现出更好的氧化还原稳定性，并且更倾向于保留天然的“3+1”混合配体结构。相反，“2 + 1 + 1”复合物表现出增加的解离倾向，如聚合物复合物 {[H2B(tzNO2)2]Cu[PCN]}n6b 在低温 (150 K) 下的 ESI-MS 测量和 X 射线结构测定所示。在该复合物中，双（三唑基）硼酸酯和 PCN 配体充当双齿配体，PCN 也是相邻单体之间的 μ2 桥接连接体。化合物 6b 是第一个报道的具有四配位金属中心的聚合 PCN 化合物的例子。所有化合物的细胞毒性活性均通过针对多种人类肿瘤细胞系的 MTT 测试进行了评估，包括乳腺癌 (MCF-7)、结肠癌 (HCT-15 和 LoVo)、肺癌 (A549)、子宫颈 (A431) 和卵巢癌 (2008 及其顺铂耐药变体，C13*) 癌、黑色素瘤 (A375) 和早幼粒细胞白血病 (HL60)。铜配合物通常表现出与顺铂相当的体外抗肿瘤活性。特别是，中性“3 + 1”型配合物 9 和 10 的 IC50 值明显低于参考金属药物的 IC50 值。
Ligand-exchange reactions of copper(I) precursors ([Cu(CH3CN)4]BF4, CuCl) with a panel of bis(azolyl)borates or poly(pyrazolyl)methanes and a tertiary monodentate phosphine (PTA = 1,3,5-triaza-7-phosphaadamantane, PCN = tris(cyanoethyl)phosphine) produced two series of heteroleptic, either ‘2 + 1 + 1’- or ‘3 + 1’-type complexes, which have been characterized by elemental analysis, FT-IR, ESI-MS and multinuclear31P and1H NMR. ‘2 + 1 + 1’-type complexes include a N,N-bidentate chelate and two monodentate phosphines (1–8) and ‘3 + 1’-type complexes comprise a N,N,O- or N,N,N-tridentate chelate and one monodentate phosphine (9–12). All these complexes adopt a four-coordinate, tetrahedral geometry. ‘3 + 1’ complexes show better red-ox stability and a greater tendency to retain the native ‘3 + 1’ mixed-ligand structure. Conversely, ‘2 + 1 + 1’ complexes exhibit increased propensity to dissociation as shown by ESI-MS measurements and X-ray structure determination at low temperature (150 K) of the polymeric complex {[H2B(tzNO2)2]Cu[PCN]}n6b. In this complex, either the bis(triazolyl)borate and the PCN ligands act as bidentate, with PCN being also the μ2–bridiging linker between adjacent monomers. Compound 6b is the first reported example of a polymeric PCN compound with a tetra-coordinate metal centre. Cytotoxic activity of all compounds has been evaluated by MTT test against a panel of several human tumor cell lines including examples of breast (MCF-7), colon (HCT-15 and LoVo), lung (A549), cervix (A431) and ovarian (2008 and its cisplatin resistant variant, C13*) carcinoma, melanoma (A375) and promyelocytic leukemia (HL60). Copper complexes generally show in vitro antitumour activity comparable to that of cisplatin. In particular, neutral ‘3 + 1’-type complexes 9 and 10, show IC50values appreciably lower than those exhibited by the reference metallodrug.