Relationship between NMR shielding and heme binding strength for a series of 7-substituted quinolines.
Relationship between NMR shielding and heme binding strength for a series of 7-substituted quinolines.
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一系列 7-取代喹啉的 NMR 屏蔽和血红素结合强度之间的关系。
DOI：
10.1021/jp061320t
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
deDios,AngelC
中科院分区：
文献类型：
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作者：
Casabianca,LeahB;deDios,AngelC
计算 7 位具有不同取代基的一系列 4-氨基喹啉中的碳的化学屏蔽张量。 σ11 分量用于衡量每个碳的相对 π 电子密度。通过将每个碳上的 π 电子密度与与血红素结合的 log K 进行比较（Kaschula 等人，J. Med. Chem.2002,45, 3531），发现药物-血红素关联随着取代基间位碳上 π 电子密度的增加以及取代基邻位和对位碳上 π 电子密度的降低而增加。 π电子密度的最大变化是在邻位碳处，并且log K随着含有取代基的环上的π电子密度的减少而增加，这对应于两个环之间的π偶极子的增加。对阿莫地喹和奎宁与血红素形成的 π-π 复合物的溶液结构的检查（Leed et al.Biochemistry2002,41, 10245. de Dios et al.Inorg. Chem.2004,43, 8078）表明每种药物和血红素卟啉环中的 π-偶极子可能是配对的。该氯取代化合物的缔合常数比该系列中的其他化合物高一个数量级，但含有取代基的环处的π电子密度并不相应低。这种相关性的缺乏表明，Cl-取代的化合物可能以不同于该系列中其他化合物的方式与血红素结合。
Chemical shielding tensors are calculated for the carbons in a series of 4-aminoquinolines with different substituents at the 7-position. The σ11component is used as a measure of the relative π-electron density at each carbon. By comparing the π-electron density at each carbon with the log K of binding to heme (Kaschula et al.J. Med. Chem.2002,45, 3531), the drug-heme association is found to increase with increasing π-electron density at the carbons meta to the substituent and with decreasing π-electron density at the carbons ortho and para to the substituent. The greatest change in π-electron density is at the ortho carbons, and log K increases with a decrease in π-electron density on the ring containing the substituent, which corresponds to an increase in the π-dipole between the two rings. An examination of the solution structures of the π−π complexes formed by amodiaquine and quinine with heme (Leed et al.Biochemistry2002,41, 10245. de Dios et al.Inorg. Chem.2004,43, 8078) shows that the π-dipoles in each drug and in the porphyrin ring of heme may be paired. The chloro-substituted compound has an association constant that is an order of magnitude higher than the other compounds in the series, but the π-electron density at the ring containing the substituent is not correspondingly low. This lack of correlation indicates that the Cl-substituted compound may be binding to heme in a manner that differs from the other compounds in the series.