Porter Meghan R, Zaleski Jeffrey M
Department of Chemistry, Indiana University, Bloomington, IN 47405, United States.
Polyhedron. 2016 Jan 8;103(A):187-195. doi: 10.1016/j.poly.2015.10.041. Epub 2015 Nov 5.
One of the key concerns with the development of radical-generating reactive therapeutics is the ability to control the activation event within a biological environment. To that end, a series of quinoline-metal-loenediynes of the form M()·2Cl (M = Cu(II), Fe(II), Mg(II), or Zn(II)) and their independently synthesized cyclized analogs have been prepared in an effort to elucidate Bergman cyclization (BC) reactivity differences in solution. HRMS(ESI) establishes a solution stoichiometry of 1:1 metal to ligand with coordination of one chloride counter ion to the metal center. EPR spectroscopy of Cu()·2Cl and Cu ()·2Cl denotes an axially-elongated tetragonal octahedron ( > > 2.0023) with a ground state, while the electronic absorption spectrum reveals a pπ Cl→Cu(II) LMCT feature at 19,000 cm , indicating a solution structure with three nitrogens and a chloride in the equatorial plane with the remaining quinoline nitrogen and solvent in the axial positions. Investigations into the BC activity reveal formation of the cyclized product from the Cu(II) and Fe(II) complexes after 12 h at 45 °C in solution, while no product is observed for the Mg(II) or Zn(II) complexes under identical conditions. The basis of this reactivity difference has been found to be a steric effect leading to metal-ligand bond elongation and thus, a retardation of solution reactivity. These results demonstrate how careful consideration of ligand and complex structure may allow for a degree of control and selective activation of these reactive agents.
开发产生自由基的反应性治疗药物的一个关键问题是能否在生物环境中控制激活事件。为此，已制备了一系列形式为M()·2Cl（M = Cu(II)、Fe(II)、Mg(II)或Zn(II)）的喹啉-金属-烯二炔及其独立合成的环化类似物，以阐明溶液中伯格曼环化（BC）的反应性差异。高分辨质谱（电喷雾电离）确定了溶液中金属与配体的化学计量比为1:1，其中一个氯离子抗衡离子与金属中心配位。Cu()·2Cl和Cu ()·2Cl的电子顺磁共振光谱表明其具有轴向拉长的四方八面体结构（ > > 2.0023），基态为 ，而电子吸收光谱显示在19,000 cm 处有一个pπ Cl→Cu(II)配体-金属电荷转移特征，表明溶液结构中赤道平面有三个氮原子和一个氯原子，其余喹啉氮原子和溶剂在轴向位置。对BC活性的研究表明，Cu(II)和Fe(II)配合物在45 °C的溶液中12小时后形成了环化产物，而在相同条件下Mg(II)或Zn(II)配合物未观察到产物。已发现这种反应性差异的基础是一种空间效应，导致金属-配体键伸长，从而使溶液反应性延迟。这些结果表明，仔细考虑配体和配合物结构如何能够对这些反应性试剂进行一定程度的控制和选择性激活。
