Takács Anett, Napolitano Roberta, Purgel Mihály, Bényei Attila Csaba, Zékány László, Brücher Ernő, Tóth Imre, Baranyai Zsolt, Aime Silvio
Department of Inorganic and Analytical Chemistry, ‡MTA-DE Homogeneous Catalysis and Reaction Mechanisms Research Group, §Department of Physical Chemistry, University of Debrecen , H-4032 Debrecen, Egyetem tér 1, Hungary.
Inorg Chem. 2014 Mar 17;53(6):2858-72. doi: 10.1021/ic4025958. Epub 2014 Feb 24.
The Gd(3+)-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) ions are similar, whereas the logKLnL values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log KMHL) of the sulphonamide nitrogen in the Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) complexes is very similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A-SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln(3+) ions and the sulphonamide N atom. The Ln(HDO3A-SA) complexes are formed via triprotonated *Ln(H3DO3A-SA) intermediates which rearrange to the final complex in an OH(-)-assisted deprotonation process. The transmetalation reaction of Gd(HDO3A-SA) with Cu(2+) is very slow (t1/2 = 5.6 × 10(3) h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The (1)H and (13)C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A-SA) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A-SA), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86-14, 93-7, and 94-6%, respectively. Line shape analysis of the (13)C NMR spectra of La-, Y- , and Lu(DO3A-SA) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A-SA) complexes are less rigid due to the larger flexibility of the ethylene group in the sulphonamide pendant arm. The fast isomerization and the lower activation parameters of Ln(DO3A-SA) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H2DO3A-SA) shows distorted octahedral coordination. The coordination sites of Cu(2+) are occupied by two ring N- and two carboxylate O-atoms in equatorial position. The other two ring N-atoms complete the coordination sphere in axial positions. The solid state structure also indicates that a carboxylate O atom and the sulphonamide nitrogen are protonated and noncoordinated.
钆（III）-DO3A-芳基磺酰胺（DO3A-SA）配合物是一种很有前景的pH敏感型磁共振成像（MRI）造影剂。DO3A-SA与镁（II）、钙（II）、锰（II）、锌（II）和铜（II）离子形成的配合物的稳定常数相似，而Ln（DO3A-SA）配合物的logKLnL值比Ln（DO3A）配合物高2个数量级。镁（II）、钙（II）、锰（II）、锌（II）和铜（II）配合物中磺酰胺氮的质子化常数（log KMHL）与游离配体的非常相似，而Ln（DO3A-SA）配合物的logKLnHL值低约4个logK单位，表明Ln（III）离子与磺酰胺N原子之间有强烈的相互作用。Ln（HDO3A-SA）配合物通过三质子化的*Ln（H3DO3A-SA）中间体形成，该中间体在OH（-）辅助的去质子化过程中重排为最终配合物。钆（HDO3A-SA）与铜（II）的转金属化反应非常缓慢（在pH = 7.4时t1/2 = 5.6 × 10（3）h），并且主要通过配合物的质子辅助解离发生。使用二维相关光谱（COSY、EXSY、HSQC）对镧、铕、钇和镥（DO3A-SA）配合物的（1）H和（13）C NMR光谱进行了归属。对于铕、钇和镥（DO3A-SA）观察到两组信号，表明溶液中有两种配位异构体，即方形反棱柱体（SAP）和扭曲方形反棱柱体（TSAP）几何结构，比例分别为86 - 14%、93 - 7%和94 - 6%。与Ln（DOTA）相比，镧、钇和镥（DO3A-SA）的（13）C NMR光谱的线形分析给出了更高的速率和更低的臂旋转活化熵值，这表明由于磺酰胺侧链中乙烯基的更大灵活性，Ln（DO3A-SA）配合物的刚性较小。Ln（DO3A-SA）的快速异构化和较低的活化参数已通过真空理论计算和使用极化连续介质模型得到证实。Cu（H2DO3A-SA）的固态X射线结构显示出扭曲的八面体配位。铜（II）的配位点在赤道位置被两个环N原子和两个羧酸根O原子占据。另外两个环N原子在轴向位置完成配位球。固态结构还表明一个羧酸根O原子和磺酰胺氮被质子化且未配位。
