A conformationally flexible dinuclear Pt(II) complex with differential behavior of its two states toward quadruplex DNA.
A conformationally flexible dinuclear Pt(II) complex with differential behavior of its two states toward quadruplex DNA.
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DOI：
10.1002/chem.201301400
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发表时间：
2013-08
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通讯作者：
Philipp von Grebe;K. Suntharalingam;R. Vilar;Pablo J. Sanz Miguel;S. Herres‐Pawlis;B. Lippert
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文献类型：
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作者：
Philipp von Grebe;K. Suntharalingam;R. Vilar;Pablo J. Sanz Miguel;S. Herres‐Pawlis;B. Lippert
四（吡啶-2-基）吡嗪（tppz）与2当量的（2，2 '-bpy）Pt（II）在水中反应产生两个同分异构的双核阳离子[{Pt（2，2'-bpy）}2（tppz）]（4+），其中Pt仅通过两对吡啶-2-基氮原子配位。这两种构象异构体的整体形状不同，形成“Z”和“U”形，分别在40 °C（Z异构体，1）和回流条件下（U异构体，2）形成。对Z异构体[{Pt（2，2 '-bpy）}2（tppz）]（PF 6）4 <$3 CHCl 3 <$4 H2 O（1 a）和U异构体[{Pt（2，2'-bpy）}2 ]（PF 6）4 <$2 CH 3 CN <$1.5 H2 O（2 a）进行了X射线晶体结构分析。化合物2与PtCl 2（2，2 '-bpy）共结晶得到[{Pt（2，2'-bpy）}2（tppz）]（BF 4）4 <$[PtCl 2（2，2 '-bpy）]<$4.5 H2 O（3），其中PtCl 2（2，2'-bpy）实体夹在U形阳离子（2）的两个2，2 '-bpy面之间。量子化学计算表明，U异构体比Z异构体更稳定，无论是在气相中还是在水环境中。这两种异构体显示不同的亲和力对双链体DNA和人端粒四链体DNA（Htelo），从CD光谱和FID分析得出的结论。因此，U异构体与四链体DNA的结合（DC 50 =0.38 μM）显著强于Z异构体（DC 50 =8.50 μM）。
The reaction of tetrakis(pyridine-2-yl)pyrazine (tppz) with 2 equiv of (2,2'-bpy)Pt(II) in water yields two isomeric dinuclear cations, [{Pt(2,2'-bpy)}2 (tppz)](4+) , in which Pt coordination exclusively takes place through the two pairs of pyridine-2-yl nitrogen atoms. The two conformational isomers differ in their overall shape, with the formation of "Z" and "U" shapes, which are formed at 40 °C (Z isomer, 1) and under reflux conditions (U isomer, 2), respectively. X-ray crystal-structure analyses of the Z isomer, [{Pt(2,2'-bpy)}2 (tppz)](PF6 )4 ⋅3 CHCl3 ⋅4 H2 O (1 a), and of the U isomer, [{Pt(2,2'-bpy)}2 ](PF6 )4 ⋅2 CH3 CN⋅1.5 H2 O (2 a), were carried out. Co-crystallization of compound 2 with PtCl2 (2,2'-bpy) yielded [{Pt(2,2'-bpy)}2 (tppz)](BF4 )4 ⋅[PtCl2 (2,2'-bpy)]⋅4.5 H2 O (3), in which the PtCl2 (2,2'-bpy) entity was sandwiched between the two 2,2'-bpy faces of the U-shaped cation (2). Quantum chemical calculations revealed that the U isomer was more stable than the Z isomer, both in the gas phase and in an aqueous environment. These two isomers display different affinities toward duplex DNA and human telomeric quadruplex DNA (Htelo), as concluded from CD spectroscopy and FID assays. Thus, the U isomer binds significantly more strongly to quadruplex DNA (DC50 =0.38 μM) than the Z isomer (DC50 =8.50 μM).