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氨基氧肟酸的[(η(6)-对异丙基苯)钌(H2O)3](2+)结合能力——溶液和固态研究

[(η(6)-p-cymene)Ru(H2O)3](2+) binding capability of aminohydroxamates - A solution and solid state study.

作者信息

Parajdi-Losonczi Péter László, Bényei Attila Csaba, Kováts Éva, Timári István, Muchova Tereza Radosova, Novohradsky Vojtech, Kasparkova Jana, Buglyó Péter

机构信息

Department of Inorganic and Analytical Chemistry, University of Debrecen, H-4010 Debrecen, P.O. Box 21, Hungary.

Department of Physical Chemistry, University of Debrecen, H-4010 Debrecen, P.O.Box 7, Hungary.

出版信息

J Inorg Biochem. 2016 Jul;160:236-45. doi: 10.1016/j.jinorgbio.2016.02.032. Epub 2016 Feb 27.

Abstract

Complex forming capabilities of (η(6)-p-cymene)Ru(H2O)3 with aminohydroxamates (2-amino-N-hydroxyacetamide (α-alahaH), 3-amino-N-hydroxypropanamide (β-alahaH) and 4-amino-N-hydroxybutanamide (γ-abhaH)) having the primary amino group in different chelatable position to the hydroxamic function were studied by pH-potentiometry, NMR and MS methods. Formation of stable [O,O] and mixed [O,O][N,N] chelated mono- and dinuclear species is detected in partially slow with α-alahaH and β-alahaH or in fast processes with γ-abhaH and the formation constants of the complexes present in aqueous solution are reported. Synthesis, spectral (NMR, IR) and ESI mass spectrometric characterization of novel dinuclear α-alaninehydroximato complexes containing the half-sandwich type Ru(II) core is described. The crystal and molecular structure of [{(η(6)-p-cymene)Ru}2(μ(2)-α-alahaH-1)(H2O)Br]Br∙H2O (1) and [{(η(6)-p-cymene)Ru}2(μ(2)-α-alahaH-1)(H2O)Cl]BF4∙H2O (2) was determined by single crystal X-ray diffraction method. In the complexes one half-sandwich core is coordinated by a hydroxamate [O,O] chelate while the other one by [Namino,Nhydroxamate] fashion of the bridging ligand. In both cases the remaining coordination sites of one of the Ru cores are taken by a halide ion whiles the other one by a water molecule. Reaction of 2 with 9-methylguanine indicates the N7 coordination of this simple DNA model. Complexes 1 and 2 were tested for their in vitro cytotoxicity using human-derived cancer cell lines (A2780, MCF-7, SKOV-3, HCT-116, HeLa) and showed no anti-proliferative activity in the micromolar concentration range.

摘要

采用pH电位滴定法、核磁共振(NMR)法和质谱(MS)法研究了(η(6)-对异丙基苯)钌(H2O)3与氨基异羟肟酸(2-氨基-N-羟基乙酰胺(α-alahaH)、3-氨基-N-羟基丙酰胺(β-alahaH)和4-氨基-N-羟基丁酰胺(γ-abhaH))的络合形成能力,这些氨基异羟肟酸的伯氨基与异羟肟酸官能团处于不同的可螯合位置。在与α-alahaH和β-alahaH的反应中,以部分缓慢的过程检测到稳定的[O,O]和混合的[O,O][N,N]螯合单核和双核物种,而在与γ-abhaH的反应中则以快速过程检测到,并报道了水溶液中存在的络合物的形成常数。描述了含有半夹心型Ru(II)核的新型双核α-丙氨酸异羟肟酸络合物的合成、光谱(NMR、IR)和电喷雾电离质谱表征。通过单晶X射线衍射法测定了[{(η(6)-对异丙基苯)钌}2(μ(2)-α-alahaH-1)(H2O)Br]Br∙H2O(1)和[{(η(6)-对异丙基苯)钌}2(μ(2)-α-alahaH-1)(H2O)Cl]BF4∙H2O(2)的晶体和分子结构。在这些络合物中,一个半夹心核由异羟肟酸[O,O]螯合物配位,而另一个由桥连配体的[氨基N,异羟肟酸N]方式配位。在两种情况下,其中一个Ru核的其余配位位点由卤离子占据,而另一个由水分子占据。2与9-甲基鸟嘌呤的反应表明了这种简单DNA模型的N7配位。使用人源癌细胞系(A2780、MCF-7、SKOV-3、HCT-116、HeLa)测试了络合物1和2的体外细胞毒性,结果表明在微摩尔浓度范围内它们没有抗增殖活性。

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