Cationic, linear Au(I) N-heterocyclic carbene complexes:: synthesis, structure and anti-mitochondrial activity
Cationic, linear Au(I) N-heterocyclic carbene complexes:: synthesis, structure and anti-mitochondrial activity
复制标题
DOI：
10.1039/b602560a
复制
发表时间：
2006-01-01
影响因子：
4
通讯作者：
White, Allan H.
中科院分区：
文献类型：
--
作者：
Baker, Murray V.;Barnard, Peter J.;White, Allan H.
通过两当量的适当二烷基咪唑-2-亚基 (R(2)Im) 与(Me2S) AuCl 的 dmf 溶液。单晶结构研究 1． PF6, 2 . PF6, 3 . Cl和4-6。 PF6表明，对于所有六种配合物，金(I)中心都具有准线性C-Au-C配位，具有准平行对的芳香族咪唑平面，除了5 。 PF6 是准正常的；后者中，Au - C 为 2.038(3)、2.033(3) 埃，参见。 （例如）3 2.027(2) 埃。 1 中的阳离子Au中心点与Au中心点中心点Au接近于3.487(2)、3.525(2)埃。 PF6 和 2 . PF6。结构研究和低温核磁共振实验没有为这一系列配合物中存在 pi 背键提供支持证据。根据正辛醇-水分配系数的对数 (log P) 估算，六种化合物的亲脂性在整个系列中变化范围为 - 1.09 至 1.73。为了研究它们作为抗线粒体抗肿瘤药物的潜力，对其中五种化合物在离体大鼠肝线粒体中诱导线粒体膜透化（MMP）的倾向进行了评估。浓度在 1 - 10 μM 之间的化合物 1 。 Br和3-6。 Cl 诱导剂量依赖性、Ca2+ 敏感的线粒体肿胀，其速率随着复合物的亲脂性而增加，其中亲脂性最强的化合物诱导肿胀发生最快。线粒体通透性转换孔的特异性抑制剂环孢菌素 A 完全抑制了肿胀。
Six linear, two-coordinate cationic Au( I) N-heterocyclic carbene complexes of the form [(R(2)Im)(2)Au](+) (R = Me 1, Me, Et 2, i-Pr 3, n-Bu 4, t-Bu 5 and Cy 6) have been prepared by the reaction of two equivalents of the appropriate dialkylimidazol-2-ylidene (R(2)Im) with (Me2S) AuCl in dmf. Single crystal structural studies for 1 . PF6, 2 . PF6, 3 . Cl and 4 - 6 . PF6 show that for all six complexes the gold( I) centres have quasi-linear C - Au - C coordination, with quasi-parallel pairs of aromatic imidazole planes, except in 5 . PF6 where they are quasi- normal; in the latter, Au - C are 2.038( 3), 2.033( 3) angstrom, cf. ( e. g.) 3 2.027( 2) angstrom. Inter-cation Au center dot center dot center dot Au are close at 3.487( 2), 3.525( 2) angstrom in 1 . PF6 and 2 . PF6. The structural studies and low temperature NMR experiments provide no supportive evidence for the presence of pi back-bonding within this series of complexes. The lipophilicities of the six compounds, as estimated from the logarithm of the n-octanol-water partition coefficients ( log P), varied across the series within the range - 1.09 to 1.73. To investigate their potential as possible anti-mitochondrial anti-tumour agents, five of the compounds have been evaluated for their propensities to induce mitochondrial membrane permeabilization (MMP) in isolated rat liver mitochondria. At concentrations between 1 - 10 mu M compounds 1 . Br and 3 - 6 . Cl induced dose-dependent, Ca2+-sensitive mitochondrial swelling at rates that increased with the lipophilicities of the complexes, with the most lipophilic compounds inducing the most rapid onset of swelling. The swelling was completely inhibited by cyclosporin A, the specific inhibitor of the mitochondrial permeability transition pore.