Greenaway F T, Hahn J J, Xi N, Sorenson J R
Gustaf H. Carlson School of Chemistry, Clark University, Worcester, MA 01610, USA.
Biometals. 1998 Jan;11(1):21-6. doi: 10.1023/a:1009201206216.
The copper(II) complex of 3,5-diisopropylsalicylate is a lipophilic water-insoluble binuclear complex, Cu(II)2(3,5-DIPS)4, that has attracted interest because of a wide range of pharmacological activities. This study was undertaken to examine bonding interactions between the complex and human serum albumin (HSA) to help elucidate the mode of transport of the complex in vivo. Electron paramagnetic resonance, numerical magnetic resonance and UV-visible absorption spectroscopic studies were performed using 200 microM aqueous solutions (pH 7.5) of HSA to which had been added up to three molar equivalents of CuCl2, CuSO4, or Cu(II)2(3,5-DIPS)4. Both EPR and UV-visible spectra demonstrated the presence of more than one copper bonding site on HSA, and proton NMR spectra showed that the 3,5-DIPS ligand is also bonded to HSA. These results indicate that there is no observable direct coordination of the ligand to copper in the presence of HSA, and that the majority of the copper and 3,5-DIPS bond to HSA at separate sites. Addition of solid Cu(II)2(3,5-DIPS)4 to HSA at pH 7.5 similarly resulted in spectra suggest that there are no ternary Cu(II)(3,5-DIPS), Cu(II)(3,5-DIPS)2, or Cu(II)2(3,5-DIPS)4 complexes formed with HSA. It is concluded that any ternary complexes formed in the presence of HSA are below the spectroscopic detection limits and represent less than 5% of the total copper.
3,5-二异丙基水杨酸铜（II）配合物是一种亲脂性的水不溶性双核配合物Cu(II)2(3,5-DIPS)4，因其具有广泛的药理活性而备受关注。本研究旨在考察该配合物与人血清白蛋白（HSA）之间的键合相互作用，以帮助阐明该配合物在体内的运输方式。使用添加了至多三摩尔当量的CuCl2、CuSO4或Cu(II)2(3,5-DIPS)4的200 microM HSA水溶液（pH 7.5）进行电子顺磁共振、数字磁共振和紫外可见吸收光谱研究。EPR和紫外可见光谱均表明HSA上存在不止一个铜结合位点，质子核磁共振光谱表明3,5-DIPS配体也与HSA结合。这些结果表明，在HSA存在下，未观察到配体与铜的直接配位，并且大部分铜和3,5-DIPS在不同位点与HSA结合。在pH 7.5下向HSA中添加固体Cu(II)2(3,5-DIPS)4同样得到的光谱表明，没有与HSA形成三元Cu(II)(3,5-DIPS)、Cu(II)(3,5-DIPS)2或Cu(II)2(3,5-DIPS)4配合物。得出的结论是，在HSA存在下形成的任何三元配合物低于光谱检测限，占总铜的比例不到5%。
