Liu Gao-Feng, Filipović Milos, Heinemann Frank W, Ivanović-Burmazović Ivana
Institute for Inorganic Chemistry, University of Erlangen-Nürnberg, Egerlandstrasse 1, 91058 Erlangen, Germany.
Inorg Chem. 2007 Oct 15;46(21):8825-35. doi: 10.1021/ic7012039. Epub 2007 Sep 20.
The reactions of seven-coordinate [Fe(III)(dapsox)(H(2)O)(2)]ClO(4).H(2)O (1), Fe(II)(H(2)dapsox)(H(2)O)(2)(2).H(2)O (2), and Mn(II)(H(2)dapsox)(CH(3)OH)(H(2)O)2(H2O) (3) complexes of the acyclic and rigid pentadentate H(2)dapsox ligand [H2dapsox = 2,6-diacetylpyridinebis(semioxamazide)] with superoxide have been studied spectrophotometrically, electrochemically, and by a submillisecond mixing UV/vis stopped-flow in dimethyl sulfoxide (DMSO). The same studies were performed on the seven-coordinate [Mn(II)(Me(2)[15]pyridinaneN(5))(H(2)O)(2)]Cl(2).H(2)O (4) complex with the flexible macrocyclic Me(2)[15]pyridinaneN(5) ligand (Me(2)[15]pyridinaneN(5) = trans-2,13-dimethyl-3,6,9,12,18-pentaazabicyclo[12.3.1]octadeca-1(18),14,16-triene), which belongs to the class of proven superoxide dismutase (SOD) mimetics. The X-ray crystal structures of 2-4 were determined. All complexes possess pentagonal-bipyramidal geometry with the pentadentate ligand in the equatorial plane and solvent molecules in the axial positions. The stopped-flow experiments in DMSO (0.06% of water) reveal that all four metal complexes catalyze the fast disproportionation of superoxide under the applied experimental conditions, and the catalytic rate constants are found to be (3.7 +/- 0.5) x 10(6), (3.9 +/- 0.5) x 10(6), (1.2 +/- 0.3) x 10(7), and (5.3 +/- 0.8) x 10(6) M(-1) s(-1) for 1-4, respectively. The cytochrome c McCord-Fridovich (McCF) assay in an aqueous solution at pH = 7.8 resulted in the IC(50) values (and corresponding kMcCF constants) for 3 and 4, 0.013 +/- 0.001 microM (1.9 +/- 0.2 x 10(8) M(-1) s(-1)) and 0.024 +/- 0.001 microM (1.1 +/- 0.3 x 10(8) M(-1) s(-1)), respectively. IC(50) values from a nitroblue tetrazolium assay are found to be 6.45 +/- 0.02 and 1.36 +/- 0.03 microM for 1 and 4, respectively. The data have been compared with those obtained by direct stopped-flow measurements and discussed in terms of the side reactions that occur under the conditions of indirect assays.
已通过分光光度法、电化学方法以及在二甲亚砜（DMSO）中进行的亚毫秒混合紫外/可见停流法，研究了无环刚性五齿H₂dapsox配体[H₂dapsox = 2,6 - 二乙酰基吡啶双（半草酰胺）]的七配位[Fe(III)(dapsox)(H₂O)₂]ClO₄·H₂O（1）、Fe(II)(H₂dapsox)(H₂O)₂₂·H₂O（2）和Mn(II)(H₂dapsox)(CH₃OH)(H₂O)₂(H₂O)（3）配合物与超氧化物的反应。对具有柔性大环Me₂[15]吡啶烷N₅配体（Me₂[15]吡啶烷N₅ = 反式 - 2,13 - 二甲基 - 3,6,9,12,18 - 五氮杂双环[12.3.1]十八碳 - 1(18),14,16 - 三烯）的七配位[Mn(II)(Me₂[15]吡啶烷N₅)(H₂O)₂]Cl₂·H₂O（4）配合物进行了相同的研究，该配体属于已证实的超氧化物歧化酶（SOD）模拟物类别。测定了2 - 4的X射线晶体结构。所有配合物均具有五角双锥几何构型，五齿配体位于赤道平面，溶剂分子位于轴向位置。在DMSO（0.06%水）中的停流实验表明，在应用的实验条件下，所有四种金属配合物均催化超氧化物的快速歧化反应，发现1 - 4的催化速率常数分别为(3.7 ± 0.5)×10⁶、(3.9 ± 0.5)×10⁶、(1.2 ± 0.3)×10⁷和(5.3 ± 0.8)×10⁶ M⁻¹ s⁻¹。在pH = 7.8的水溶液中进行的细胞色素c麦考德 - 弗里多维奇（McCF）测定得出3和4的IC₅₀值（以及相应的kMcCF常数），分别为0.013 ± 0.001 μM（1.9 ± 0.2×10⁸ M⁻¹ s⁻¹）和0.024 ± 0.001 μM（1.1 ± 0.3×10⁸ M⁻¹ s⁻¹）。硝基蓝四唑测定的IC₅₀值对于1和4分别为6.45 ± 0.02和1.36 ± 0.03 μM。已将这些数据与通过直接停流测量获得的数据进行比较，并根据间接测定条件下发生的副反应进行了讨论。
