Macrocyclic Receptor Showing Extremely High Sr(II)/Ca(II) and Pb(II)/Ca(II) Selectivities with Potential Application in Chelation Treatment of Metal Intoxication
Macrocyclic Receptor Showing Extremely High Sr(II)/Ca(II) and Pb(II)/Ca(II) Selectivities with Potential Application in Chelation Treatment of Metal Intoxication
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DOI：
10.1021/ic200182e
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发表时间：
2011-04-18
影响因子：
4.6
通讯作者：
Rodriguez-Blas, Teresa
中科院分区：
文献类型：
--
作者：
Ferreiros-Martinez, Raquel;Esteban-Gomez, David;Rodriguez-Blas, Teresa
本文详细研究了大环十齿酸受体N，N‘-Bis[(6-carboxy-2-pyridil)methyl]-4，13-diaza-18-crown-6(H(2)BP18C6)在水溶液中与不同二价金属离子[锌(II)、镉(II)、铅(II)、锶(II)、钙(II)]的络合性质。我们发现，这种配体特别适合于大金属离子的络合，如锶(II)和铅(II)，这导致了非常高的铅(II)/钙(II)和铅(II)/锌(II)的选择性(实际上，高于广泛用于治疗铅中毒的配体，如乙二胺四乙酸(EDTA))，以及迄今报道的最高的锶(II)/钙(II)的选择性。根据络合物的结构，这些结果得到了合理的解释。在密度泛函理论(B3LYP)水平上进行了X-射线晶体衍射、H-1和C-13核磁共振谱以及理论计算。结果表明，对于大的金属离子，如铅(II)和锶(II)，最稳定的构象是Delta(Delta Lambda Delta)(Delta Lambda Delta)，而对于Ca(II)，我们的计算预测了Delta(Lambda Delta Lambda)(Lambda Delta Lambda)是最稳定的构象。Bp18C6(2-)对Sr(II)的选择性高于对Ca(II)的选择性，这可以归因于较大的Sr(II)离子与相对较大的配体冠段之间的较好匹配。X-射线晶体结构表明，在溶液中观察到的Delta(Delta Lambda Delta)(Delta Lambda Delta)构象也保持在固态。铅(II)离子是内环配位的，直接与配体的10个给体原子结合。金属离子与冠层给体原子之间的键距(2.92~3.04埃)明显小于金属离子与冠臂上施主原子的键距(2.55~2.60埃)。对于所谓的半定向化合物来说，这是一种典型的情况，在这种情况下，铅(II)孤对具有立体化学活性。锌(II)和镉(II)配合物的X-射线结构表明，这些金属离子被配体以环状配位方式配位，这解释了高的铅(II)/镉(II)和铅(II)/锌(II)选择性。我们的受体bp18c6(2-)有望应用于铅(II)和锶-90(II)金属中毒的螯合治疗。
Herein we report a detailed investigation of the complexation properties of the macrocyclic decadentate receptor N,N'-Bis[(6-carboxy-2-pyridil)methyl]-4,13-diaza-18-crown-6 (H(2)bp18c6) toward different divalent metal ions [Zn(II), Cd(II), Pb(II), Sr(II), and Ca(II)] in aqueous solution. We have found that this ligand is especially suited for the complexation of large metal ions such as Sr(II) and Pb(II), which results in very high Pb(II)/Ca(II) and Pb(II)/Zn(II) selectivities (in fact, higher than those found for ligands widely used for the treatment of lead poisoning such as ethylenediaminetetraacetic acid (edta)), as well as in the highest Sr(II)/Ca(II) selectivity reported so far. These results have been rationalized on the basis of the structure of the complexes. X-ray crystal diffraction, H-1 and C-13 NMR spectroscopy, as well as theoretical calculations at the density functional theory (B3LYP) level have been performed. Our results indicate that for large metal ions such as Pb(II) and Sr(II) the most stable conformation is Delta(delta lambda delta)(delta lambda delta), while for Ca(II) our calculations predict the Delta(lambda delta lambda)(lambda delta lambda) form being the most stable one. The selectivity that bp18c6(2-) shows for Sr(II) over Ca(II) can be attributed to a better fit between the large Sr(II) ions and the relatively large crown fragment of the ligand. The X-ray crystal structure of the Pb(II) complex shows that the Delta(delta lambda delta)(delta lambda delta) conformation observed in solution is also maintained in the solid state. The Pb(II) ion is endocyclically coordinated, being directly bound to the 10 donor atoms of the ligand. The bond distances to the donor atoms of the pendant arms (2.55-2.60 angstrom) are substantially shorter than those between the metal ion and the donor atoms of the crown moiety (2.92-3.04 angstrom). This is a typical situation observed for the so-called hemidirected compounds, in which the Pb(II) lone pair is stereochemically active. The X-ray structures of the Zn(II) and Cd(II) complexes show that these metal ions are exocyclically coordinated by the ligand, which explains the high Pb(II)/Cd(II) and Pb(II)/Zn(II) selectivities. Our receptor bp18c6(2-) shows promise for application in chelation treatment of metal intoxication by Pb(II) and Sr-90(II).