Ramadan Saadallah, Hambley Trevor W, Kennedy Brendan J, Lay Peter A
Centre for Heavy Metal Research, School of Chemistry, University of Sydney, NSW, 2006, Australia.
Inorg Chem. 2004 May 3;43(9):2943-6. doi: 10.1021/ic0352811.
Molecular diffusion constants were studied by NMR spectroscopy to provide information about the solution structures of a variety of Cu(II) and Zn(II) monomeric and dimeric complexes of indomethacin (IndoH). These studies showed that monomeric Zn(II)-Indo complexes substantially dimerize in DMF-d7 and DMSO-d6 solutions at room temperature, whereas the Cu(II) and Zn(II) dinuclear complexes remain largely intact in these solutions. There is evidence of an equilibrium between monomers and dimers for the Zn(II) complexes in solution, as shown by a reduced diffusion constant and lower average radius compared to the Cu(II) dimer. Such an equilibrium between monomers and dimers for the Zn(II) complexes is also consistent with previous results obtained from XAFS analysis of DMF solutions of such complexes. The greater lability and lower thermodynamic stability of the Zn(II) dimer complex compared to the Cu(II) analogue, as determined from the NMR experiments, is likely to result in the more ready release of free Indo in the GI tract. This is consistent with the previously observed higher GI toxicities of the Zn-Indo pharmaceutical preparations compared to the Cu(II)-Indo counterparts.
通过核磁共振光谱法研究了分子扩散常数，以提供有关吲哚美辛（IndoH）的多种铜（II）和锌（II）单体及二聚体配合物溶液结构的信息。这些研究表明，在室温下，单体锌（II）-吲哚配合物在DMF-d7和DMSO-d6溶液中会大量二聚，而铜（II）和锌（II）双核配合物在这些溶液中基本保持完整。溶液中锌（II）配合物的单体和二聚体之间存在平衡的证据，这表现为与铜（II）二聚体相比，扩散常数降低且平均半径更小。锌（II）配合物的单体和二聚体之间的这种平衡也与先前通过此类配合物的DMF溶液的XAFS分析获得的结果一致。根据核磁共振实验确定，与铜（II）类似物相比，锌（II）二聚体配合物具有更高的活性和更低的热力学稳定性，这可能导致在胃肠道中更易释放游离的吲哚美辛。这与先前观察到的锌-吲哚药物制剂比铜（II）-吲哚对应物具有更高的胃肠道毒性是一致的。
