Dipartimento di Scienze e Tecnologie Avanzate, Corso Borsalino 54, 15100 Alessandria, Italy.
Org Biomol Chem. 2004 Feb 21;2(4):570-7. doi: 10.1039/b313677a. Epub 2004 Jan 21.
Five novel Gd(iii) complexes based on the structure of the heptadentate macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) ligand have been synthesized and their (1)H and (17)O NMR relaxometric properties investigated in detail. The complexes have been functionalised on the secondary nitrogen atom of the macrocyclic ring with different pendant groups for promoting their ability to interact non-covalently with human serum albumin (HSA). The analysis of the proton relaxivity, measured as a function of pH and magnetic field strength, have revealed that the three complexes bearing a poly(ethylene glycol)(PEG) chain possess a single coordinated water molecule, whereas the complexes functionalised with 1-[3-(2-hydroxyphenyl)]-propyl and 1-[3-(2-carboxyphenyloxy)]-propyl pendant groups have two inner sphere water molecules. The water exchange rates, measured by variable temperature (17)O NMR, cover a broad range of values (from 18 to 770 ns) as a function of their charge, the chemical nature of the substituent and its ability to organize a second sphere of hydration near the water(s) binding site. All the complexes have shown some degree of interaction with HSA, with a stronger binding affinity measured for those bearing an aromatic moiety on the pendant group. However, upon binding the expected relaxation enhancement has not been observed and this has been explained with the displacement of the coordinated water molecules by the protein and formation of ternary adducts.
已经合成了基于七齿大环 1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸（DO3A）配体结构的五种新型 Gd(iii) 配合物，并详细研究了它们的（1）H 和（17）O NMR 弛豫性质。这些配合物在大环环的仲氮原子上用不同的侧基官能化，以提高它们与人血清白蛋白（HSA）非共价相互作用的能力。质子弛豫率的分析，作为 pH 和磁场强度的函数进行测量，表明带有聚乙二醇（PEG）链的三个配合物具有单个配位水分子，而带有 1-[3-(2-羟苯基)]-丙基和 1-[3-(2-羧基苯氧基)]-丙基侧基的配合物具有两个内球水分子。通过变温（17）O NMR 测量的水交换速率值范围很广（从 18 到 770 ns），这取决于它们的电荷、取代基的化学性质及其在水（s）结合部位附近组织第二水合层的能力。所有配合物都显示出与 HSA 具有一定程度的相互作用，带有芳基部分的侧基的配合物具有更强的结合亲和力。然而，在结合时，没有观察到预期的弛豫增强，这可以用蛋白质取代配位水分子并形成三元加合物来解释。
