Ferrand Anne-Claire, Imbert Daniel, Chauvin Anne-Sophie, Vandevyver Caroline D B, Bünzli Jean-Claude G
Ecole Polytechnique Fédérale de Lausanne, Laboratory of Lanthanide Supramolecular Chemistry, BCH 1402, 1015 Lausanne, Switzerland.
Chemistry. 2007;13(31):8678-87. doi: 10.1002/chem.200700819.
A new macrocyclic ligand, L3, has been synthesised, based on the cyclen framework grafted with three phenacyl light-harvesting groups and a C5-alkyl chain bearing a carboxylic acid function as a potential linker for biological material. Acidity constants are determined by spectrophotometric titrations, as well as conditional stability constants for the resulting 1:1 complexes with trivalent lanthanide ions. The complexes have stabilities comparable to 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (dtma) complexes, with pLn approximately 12-13. Photophysical properties of the ligand and of the EuL3 and TbL3 complexes have been determined for both microcrystalline samples and solutions in water and acetonitrile. They point to the metal ion being present in an environment with axial symmetry derived from the C4 point group. The hydration number determined for TbL3 decreases with increasing pH value and becomes fractional at pH 7.5, which points to an equilibrium between two differently solvated species and probably to the participation of the deprotonated carboxylic acid chain in the complexation. The quantum yields in water (1.9% for EuIII, 3.4% for TbIII) are smaller than those for complexes with the symmetrically substituted parent macrocycle, but efficient luminescence resonant energy transfer (LRET) was observed when Cy5 dye was added to the solutions. Finally, the influence of the TbL3 complex on cell viability is tested on both malignant (5D10 mouse hybridoma, Jurkat human T leukaemia, MCF-7 human breast carcinoma) and non-malignant (Hacat human keratinocyte) cell lines. Cell viability after 24 h incubation at 37 degrees C with 500 microM TbL3 was >90% for all cell lines, except Jurkat (>70%). All of these properties make LnL3 complexes interesting potential probes for bioanalyses.
基于接枝有三个苯甲酰基光捕获基团的轮环框架和带有羧酸官能团作为生物材料潜在连接基的C5-烷基链，合成了一种新的大环配体L3。通过分光光度滴定法测定酸度常数以及所得与三价镧系离子形成的1:1配合物的条件稳定常数。这些配合物的稳定性与1,4,7,10-四（氨甲酰甲基）-1,4,7,10-四氮杂环十二烷（dtma）配合物相当，pLn约为12-13。已测定了配体以及EuL3和TbL3配合物在微晶样品以及水和乙腈溶液中的光物理性质。结果表明金属离子存在于具有源自C4点群的轴对称环境中。为TbL3测定的水合数随pH值升高而降低，并在pH 7.5时变为分数，这表明两种不同溶剂化物种之间存在平衡，并且可能表明去质子化的羧酸链参与了络合作用。在水中的量子产率（EuIII为1.9%，TbIII为3.4%）低于具有对称取代母体大环的配合物，但当向溶液中加入Cy5染料时观察到了有效的发光共振能量转移（LRET）。最后，在恶性（5D10小鼠杂交瘤、Jurkat人T白血病、MCF-7人乳腺癌）和非恶性（Hacat人角质形成细胞）细胞系上测试了TbL3配合物对细胞活力的影响。在37℃下用500μM TbL3孵育24小时后，除Jurkat（>70%）外，所有细胞系的细胞活力均>90%。所有这些性质使得LnL3配合物成为生物分析中有趣的潜在探针。
