Department of Physical Chemistry, Faculty of Science and Technology, University of Debrecen, Debrecen H-4032, Hungary.
Doctoral School of Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, Debrecen H-4032, Hungary.
Inorg Chem. 2022 Aug 29;61(34):13497-13509. doi: 10.1021/acs.inorgchem.2c02050. Epub 2022 Aug 16.
The discovery of the nephrogenic systemic fibrosis (NSF) and its link with the dissociation of certain Gd(III)-based contrast agents (CAs) applied in the magnetic resonance imaging (MRI) induced a still growing research to replace the compromised agents with safer alternatives. In recent years, several ligands were designed to exploit the luminescence properties of the lanthanides, containing structurally constrained aromatic moieties, which may form rigid Gd(III) complexes. One of these ligands is (1,10-phenanthroline-2,9-diyl)bis(methyliminodiacetic acid) (HFENTA) designed and synthesized to sensitize Eu(III) and Tb(III) luminescence. Our results show that the conditional stability of the [Gd(FENTA)] chelate calculated for physiological pH (pGd = 19.7) is similar to those determined for [Gd(DTPA)] (pGd = 19.4) and [Gd(DOTA)] (pGd = 20.1), routinely used in the clinical practice. The [Gd(FENTA)] complex is remarkably inert with respect to its dissociation ( = 872 days at pH = 7 and 25 °C); furthermore, its relaxivity values determined at different field strengths and temperatures (e.g., = 4.3 mMsat 60 MHz and 37 °C) are one unit higher than those of [Gd(DTPA)] ( = 3.4 mM s) and [Gd(DOTA)] ( = 3.1 mM s) under the same conditions. Moreover, significant improvement on the relaxivity was observed in the presence of serum proteins ( = 6.9 mM s at 60 MHz and 37 °C). The luminescence lifetimes recorded in HO and DO solutions indicate the presence of a water molecule ( = 1) in the inner sphere of the complex directly coordinated to the metal ion, possessing a relatively high water exchange rate ( = 29(2) × 10 s). The acceleration of the water exchange can be explained by the steric compression around the water binding site due to the rigid structure of the complex, which was supported by DFT calculations. On the basis of these results, ligands containing a phenanthroline platform have great potential in the design of safer Gd(III) agents for MRI.
肾源性系统性纤维化 (NSF) 的发现及其与某些用于磁共振成像 (MRI) 的镧系元素基造影剂 (CA) 的解离有关，促使人们进行了越来越多的研究，以寻找更安全的替代品来替代有问题的造影剂。近年来，设计了几种配体来利用包含结构约束芳香部分的镧系元素的发光特性，这些部分可能形成刚性的 Gd(III) 配合物。其中一种配体是（1,10-菲咯啉-2,9-二基）双（甲基亚氨基二乙酸）（HFENTA），它被设计并合成以敏化 Eu(III) 和 Tb(III) 的发光。我们的结果表明，在生理 pH 值下计算出的 [Gd(FENTA)] 配合物的条件稳定性（pGd = 19.7）与在临床实践中常规使用的 [Gd(DTPA)]（pGd = 19.4）和 [Gd(DOTA)]（pGd = 20.1）的稳定性相似。[Gd(FENTA)] 配合物对其解离非常惰性（在 pH = 7 和 25°C 时 = 872 天）；此外，在不同场强和温度下测定的弛豫率值（例如，在 60 MHz 和 37°C 时 = 4.3 mMsat）比相同条件下的 [Gd(DTPA)]（= 3.4 mM s）和 [Gd(DOTA)]（= 3.1 mM s）高一个单位。此外，在存在血清蛋白时，弛豫率显著提高（在 60 MHz 和 37°C 时为 6.9 mM s）。在 HO 和 DO 溶液中记录的荧光寿命表明，在配合物的内球中存在一个水分子（= 1），该水分子直接与金属离子配位，具有相对较高的水交换速率（= 29(2)×10 s）。水交换的加速可以通过配合物的刚性结构引起的配体结合位点周围的空间压缩来解释，这一结果得到了 DFT 计算的支持。基于这些结果，含有菲咯啉平台的配体在设计更安全的 MRI 用 Gd(III) 造影剂方面具有很大的潜力。
