Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity
Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity
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DOI：
10.1007/s00775-012-0917-9
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发表时间：
2012-10-01
影响因子：
3
通讯作者：
Habtemariam, Abraha
中科院分区：
文献类型：
--
作者：
Betanzos-Lara, Soledad;Novakova, Olga;Habtemariam, Abraha
配合物 [(eta(6)-芳烃)Ru(N,N')X][PF6] 的合成和表征，其中芳烃为对伞花烃 (p-cym)、联苯 (bip)、苯甲酸乙酯 (etb)、六甲基苯 (hmb)、茚满 (ind) 或 1,2,3,4-四氢萘 (thn)，N,N' 为 2,2'-联嘧啶报道了[(eta(6)-p-cym)Ru(bpm)I][PF6]、[(eta(6)-bip)Ru(bpm)Cl][PF6]、[(eta(6)-bip)Ru(bpm)I][PF6]和[(eta(6)-etb)Ru(bpm)Cl][PF6]的X射线晶体结构。研究了 N,N' 为 1,10-菲咯啉 (phen)、1,10-菲咯啉-5,6-二酮或 4,7-二苯基-1,10-菲咯啉 (bathophen) 的络合物进行比较。 Ru-II 芳烃配合物在 310 K 的水溶液中发生配体交换反应；它们的水解半衰期为 14 至 715 分钟。 [(eta(6)-p-cym)Ru(bpm)Cl][PF6]、[(eta(6)-p-cym)Ru(bpm)Br][PF6]、[(eta(6)-p-cym)Ru(bpm)I][PF6]、[(eta(6)-bip)Ru(bpm)Cl][PF6]、的密度泛函理论计算[(eta(6)-bip)Ru(bpm)Br][PF6] 和 [(eta(6)-bip)Ru(bpm)I][PF6] 表明水合通过缔合途径发生，并且当离去配体为 I > Br 千分之一 Cl 时，该反应在热力学上是有利的。配合物的水加合物的 pK (a)* 值范围为 6.9 至 7.32。与 9-乙基腺嘌呤 (9-EtA) 相比，观察到 [(eta(6)-p-cym)Ru(bpm)Cl][PF6]、[(eta(6)-hmb)Ru(bpm)Cl](+)、[(eta(6)-ind)Ru(bpm)Cl](+) 对 9-乙基鸟嘌呤 (9-EtG) 的结合偏好， 310 K 水溶液中的 [(eta(6)-thn)Ru(bpm)Cl](+)、[(eta(6)-p-cym)Ru(phen)Cl](+) 和 [(eta(6)-p-cym)Ru(bathophen)Cl](+)。鸟嘌呤配合物的 X 射线晶体结构[(eta(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF6](2)显示多重氢键。密度泛函理论计算表明，与 9-EtA 相比，所有配合物的 9-EtG 加合物在热力学上都是优选的。然而，bmp 复合物对 A2780 人卵巢癌细胞没有活性。小牛胸腺 DNA 与 [(eta(6)-p-cym)Ru(bpm)Cl][PF6] 和 [(eta(6)-p-cym)Ru(phen)Cl][PF6] 的相互作用包括弱配位、插入和单功能配位。与谷胱甘肽等生物分子的结合可能在使 bpm 复合物失活中发挥作用。
The synthesis and characterization of complexes [(eta(6)-arene)Ru(N,N')X][PF6], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N' is 2,2'-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(eta(6)-p-cym)Ru(bpm)I][PF6], [(eta(6)-bip)Ru(bpm)Cl][PF6], [(eta(6)-bip)Ru(bpm)I][PF6] and [(eta(6)-etb)Ru(bpm)Cl][PF6]. Complexes in which N,N' is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The Ru-II arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(eta(6)-p-cym)Ru(bpm)Cl][PF6], [(eta(6)-p-cym)Ru(bpm)Br][PF6], [(eta(6)-p-cym)Ru(bpm)I][PF6], [(eta(6)-bip)Ru(bpm)Cl][PF6], [(eta(6)-bip)Ru(bpm)Br][PF6] and [(eta(6)-bip)Ru(bpm)I][PF6] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br a parts per thousand Cl. pK (a)* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(eta(6)-p-cym)Ru(bpm)Cl][PF6], [(eta(6)-hmb)Ru(bpm)Cl](+), [(eta(6)-ind)Ru(bpm)Cl](+), [(eta(6)-thn)Ru(bpm)Cl](+), [(eta(6)-p-cym)Ru(phen)Cl](+) and [(eta(6)-p-cym)Ru(bathophen)Cl](+) in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(eta(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF6](2) shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(eta(6)-p-cym)Ru(bpm)Cl][PF6] and [(eta(6)-p-cym)Ru(phen)Cl][PF6] consist of weak coordinative, intercalative and monofunctional coordination. Binding to biomolecules such as glutathione may play a role in deactivating the bpm complexes.