School of Chemistry, Monash University, Vic 3800, Australia.
Inorg Chem. 2011 Jan 17;50(2):621-35. doi: 10.1021/ic1018136. Epub 2010 Dec 9.
Two new ligands, L(1) and L(2), have been prepared via N-functionalization of 1,4,7-triazacyclononane (tacn) with pairs of ethyl- or propyl-guanidine pendants, respectively. The X-ray crystal structure of CuL(1)2 (C1) isolated from basic solution (pH 9) indicates that a secondary amine nitrogen from each guanidine pendants coordinates to the copper(II) center in addition to the nitrogen atoms in the tacn macrocycle, resulting in a five-coordinate complex with intermediate square-pyramidal/trigonal bipyramidal geometry. The guanidines adopt an unusual coordination mode in that their amine nitrogen nearest to the tacn macrocycle binds to the copper(II) center, forming very stable five-membered chelate rings. A spectrophotometric pH titration established the pK(app) for the deprotonation and coordination of each guanidine group to be 3.98 and 5.72, and revealed that CuL(1) is the only detectable species present in solution above pH ∼ 8. The solution speciation of the CuL(2) complex (C2) is more complex, with at least 5 deprotonation steps over the pH range 4-12.5, and mononuclear and binuclear complexes coexisting. Analysis of the spectrophotometric data provided apparent deprotonation constants, and suggests that solutions at pH ∼ 7.5 contain the maximum proportion of polynuclear complexes. Complex C1 exhibits virtually no cleavage activity toward the model phosphate diesters, bis(p-nitrophenyl)phosphate (BNPP) and 2-hydroxypropyl-p-nitrophenyl phosphate (HPNPP), while C2 exhibits moderate activity. For C2, the respective kobs values measured at pH 7.0 (7.24 (± 0.08) × 10(-5) s(-1) (BNPP at 50 °C) and 3.2 (± 0.3) × 10(-5) s(-1) (HPNPP at 25 °C)) are 40- and 10-times faster than Cu(tacn)(OH2)2 complex. Both complexes cleave supercoiled pBR 322 plasmid DNA, indicating that the guanidine pendants of CuL(1) may have been displaced from the copper coordination sphere to allow for DNA binding and subsequent cleavage. The rate of DNA cleavage by C2 is twice that measured for Cu(tacn)(OH2)2, suggesting some degree of cooperativity between the copper center and guanidinium pendants in the hydrolysis of the phosphate ester linkages of DNA. A predominantly hydrolytic cleavage mechanism was confirmed through experiments performed either in the presence of various radical scavengers or under anaerobic conditions.
通过将 1,4,7-三氮杂环壬烷（tacn）与乙基或丙基胍的偶联物进行 N-官能化，制备了两个新的配体 L(1)和 L(2)。从碱性溶液（pH 9）中分离得到的CuL(1)2（C1）的 X 射线晶体结构表明，每个胍的仲胺氮与铜（II）中心配位，除了 tacn 大环中的氮原子外，导致具有中间正方形-三角双锥几何形状的五配位络合物。胍采用不寻常的配位方式，其最接近 tacn 大环的氨基氮与铜（II）中心结合，形成非常稳定的五元螯合环。分光光度 pH 滴定确定了每个胍基团去质子化和配位的 pK(app)为 3.98 和 5.72，并表明CuL(1)是溶液中 pH 高于约 8 时唯一可检测到的物种。CuL(2)络合物（C2）的溶液形态更为复杂，在 4-12.5 pH 范围内至少有 5 个去质子化步骤，并且单核和双核配合物共存。分光光度数据分析提供了表观去质子化常数，并表明 pH 约为 7.5 的溶液中含有最大比例的多核配合物。C1 对模型磷酸二酯，双（对硝基苯基）磷酸酯（BNPP）和 2-羟丙基-对硝基苯基磷酸酯（HPNPP）几乎没有裂解活性，而 C2 具有中等活性。对于 C2，在 pH 7.0 下测量的相应 kobs 值（50°C 时为 7.24(±0.08)×10(-5) s(-1)（BNPP）和 25°C 时为 3.2(±0.3)×10(-5) s(-1)（HPNPP））分别比Cu(tacn)(OH2)2络合物快 40 倍和 10 倍。两种络合物都能切割超螺旋 pBR 322 质粒 DNA，表明CuL(1)的胍部分可能已从铜配位球中取代，以允许 DNA 结合和随后的切割。C2 的 DNA 切割速率是Cu(tacn)(OH2)2的两倍，这表明在磷酸酯键的水解过程中，铜中心和胍部分之间存在一定程度的协同作用。通过在各种自由基清除剂存在下或在厌氧条件下进行的实验，证实了主要是水解裂解机制。
