Synthesis and DNA binding of novel water-soluble cationic methylcobalt porphyrins.
Synthesis and DNA binding of novel water-soluble cationic methylcobalt porphyrins.
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DOI：
10.1021/ic010232e
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发表时间：
2001-07
影响因子：
4.6
通讯作者：
J. S. Trommel;L. Marzilli
中科院分区：
文献类型：
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作者：
J. S. Trommel;L. Marzilli
四阳离子水溶性卟啉的有机钴衍生物难以通过Co（II）（por）（porH（2）=卟啉配体）的典型还原烷基化来制备。没有任何报告。这个问题可能是因为卟啉核被带正电荷的外围基团变得相对缺乏电子。我们已经通过使用[Co（III）（NH（3））（5）CH（3）]（2+）试剂规避了这个问题，该试剂在碱性条件下将Co（III）-CH（3）部分直接插入水中的porH（2）中。该方法得到了两个新的[CH（3）Co（por）]（4+）衍生物[CH（3）CoTMPyP（4）]（4+）和[CH（3）CoTMAP]（4+），其中[TMPyP（4）]（4+）和[TMAP]（4+）分别是meso-四（N-甲基-4-吡啶鎓）卟啉和meso-四（N，N，N-三甲基苯胺鎓）卟啉的配位、NH-去质子化形式。研究了两个新的[CH（3）Co（por）]（4+）阳离子与DNA及合成的DNA聚合物[poly（dA-dT）]（2）和[poly（dG-dC）]（2）的结合。使用公布的标准，DNA粘度的变化，在Soret区域的可见光和CD光谱可以用来评估DNA结合，我们得出结论，这两个都是外部的粘合剂。当[CH（3）Co（por）]（4+）阳离子与DNA结合时，其Soret带的大的减色性可能表明其具有高度的自堆积。在[poly（dA-dT）]（2）和[poly（dG-dC）]（2）的1：1混合物存在下，[CH（3）Co（por）]（4+）阳离子的可见吸收光谱和圆二色性光谱几乎与单独的[poly（dA-dT）]（2）的相同，而与单独的[poly（dG-dC）]（2）的不同。因此，这两种阳离子显示出高的偏好外结合在AT丰富的GC丰富的DNA位点。当每个[CH（3）Co（por）]（4+）阳离子与所有DNA聚合物结合时，Soret带显示蓝移，而相应的[（H（2）O）（2）Co（por）]（5+）阳离子的Soret带显示红移。蓝移强烈地表明[CH（3）Co（por）]（4+）阳离子，特别是[CH（3）CoTMAP]（4+），在DNA结合上在一定程度上变成五配位形式;这一结果是五配位CH（3）Co（III）（N（4））形式在水中平衡存在的第一个好的证据。
Organocobalt derivatives of tetracationic water-soluble porphyrins are difficult to prepare via the typical reductive alkylation of the Co(II)(por) (porH(2) = porphyrin ligand). None have been reported. The problem may arise because the porphyrin core is made relatively electron poor by the positively charged peripheral groups. We have circumvented this problem by using the [Co(III)(NH(3))(5)CH(3)](2+) reagent, which inserts the Co(III)-CH(3) moiety directly into porH(2) in water under basic conditions. The method afforded two new [CH(3)Co(por)](4+) derivatives, [CH(3)CoTMpyP(4)](4+) and [CH(3)CoTMAP](4+), where [TMpyP(4)](4+) and [TMAP](4+) are the coordinated, NH-deprotonated forms of meso-tetrakis(N-methyl-4-pyridiniumyl)porphyrin and meso-tetrakis(N,N,N-trimethylaniliniumyl)porphyrin, respectively. The binding of the two new [CH(3)Co(por)](4+) cations to DNA and to the synthetic DNA polymers [poly(dA-dT)](2) and [poly(dG-dC)](2) was studied. Using published criteria by which changes in DNA viscosity and in the visible and CD spectra in the Soret region can be used to assess DNA binding, we conclude that both are outside binders. A large hypochromicity of the Soret bands of the [CH(3)Co(por)](4+) cations observed upon outside binding to DNA may indicate a high degree of self-stacking. The visible absorption and CD spectra of the [CH(3)Co(por)](4+) cations in the presence of 1:1 mixtures of [poly(dA-dT)](2) and [poly(dG-dC)](2) are nearly identical to those with [poly(dA-dT)](2) alone and are very different from those of [poly(dG-dC)](2) alone. Thus, both cations show a high preference for outside binding at AT-rich over GC-rich DNA sites. Upon binding of each of the [CH(3)Co(por)](4+) cations to all of the DNA polymers, the Soret bands exhibit blue shifts, whereas the Soret bands of the corresponding [(H(2)O)(2)Co(por)](5+) cations exhibit red shifts. The blue shifts strongly suggest that the [CH(3)Co(por)](4+) cations, particularly [CH(3)CoTMAP](4+), become five-coordinate forms to some extent on DNA binding; this result is the first good evidence for the presence at equilibrium of five-coordinate CH(3)Co(III)(N(4)) forms in water.