Camorali Sara, Leone Loredana, Piscopo Laura, Tei Lorenzo
Department of Science and Technological Innovation, Università del Piemonte Orientale, Viale T. Michel 11, 15121 Alessandria, Italy.
Molecules. 2024 Sep 30;29(19):4663. doi: 10.3390/molecules29194663.
In the last three decades, high-relaxivity Magnetic Resonance Imaging (MRI) contrast agents (CAs) have been intensively sought, aiming at a reduction in the clinically injected dose while maintaining the safety of the CA and obtaining the same pathological information. Thus, four new Gd(III) complexes based on modified 10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (HP-DO3A) macrocyclic structure were designed and synthesized by introducing further polar and protic functional groups (amides, phosphonates, and diols) adjacent to the metal-coordinated hydroxyl group. A detailed H NMR relaxometric analysis allowed us to investigate the effect of these functional groups on the relaxivity, which showed a 20-60% increase (at 0.5 T, 298 K, and pH 7.4) with respect to that of clinically approved CAs. The contribution of the water molecules H-bonded to these peripheral functional groups on the relaxivity was evaluated in terms of the second sphere effect or prototropic exchange of labile protons.
在过去三十年中，人们一直在积极寻找高弛豫率的磁共振成像（MRI）造影剂（CAs），目的是在保持造影剂安全性的同时减少临床注射剂量，并获取相同的病理信息。因此，通过在与金属配位的羟基相邻处引入更多极性和亲质子官能团（酰胺、膦酸酯和二醇），设计并合成了四种基于修饰的10-(2-羟丙基)-1,4,7,10-四氮杂环十二烷-1,4,7-三乙酸（HP-DO3A）大环结构的新型钆（III）配合物。详细的氢核磁共振弛豫分析使我们能够研究这些官能团对弛豫率的影响，结果表明，相对于临床批准的造影剂，弛豫率提高了20%-60%（在0.5 T、298 K和pH 7.4条件下）。通过第二球效应或不稳定质子的质子交换来评估与这些外围官能团形成氢键的水分子对弛豫率的贡献。
