Cairns Andrew G, Senn Hans Martin, Murphy Michael P, Hartley Richard C
Chemistry. 2014 Mar 24;20(13):3742-51. doi: 10.1002/chem.201304241.
5,6-Disubstituted phenanthridinium cations have a range of redox, fluorescence and biological properties. Some properties rely on phenanthridiniums intercalating into DNA, but the use of these cations as exomarkers for the reactive oxygen species (ROS), superoxide, and as inhibitors of acetylcholine esterase (AChE) do not require intercalation. A versatile modular synthesis of 5,6-disubstituted phenanthridiniums that introduces diversity by Suzuki–Miyaura coupling, imine formation and microwave-assisted cyclisation is presented. Computational modelling at the density functional theory (DFT) level reveals that the novel displacement of the aryl halide by an acyclic N-alkylimine proceeds by an S(N)Ar mechanism rather than electrocyclisation. It is found that the displacement of halide is concerted and there is no stable Meisenheimer intermediate, provided the calculations consistently use a polarisable solvent model and a diffuse basis set.
5,6-二取代菲啶鎓阳离子具有一系列氧化还原、荧光和生物学特性。一些特性依赖于菲啶鎓插入DNA，但将这些阳离子用作活性氧（ROS）、超氧化物的外源性标记物以及乙酰胆碱酯酶（AChE）的抑制剂并不需要插入。本文介绍了一种通用的模块化合成5,6-二取代菲啶鎓的方法，该方法通过铃木-宫浦偶联、亚胺形成和微波辅助环化引入多样性。密度泛函理论（DFT）水平的计算模型表明，无环N-烷基亚胺对芳基卤化物的新型取代反应是通过S(N)Ar机理进行的，而不是电环化反应。结果发现，卤化物的取代反应是协同进行的，并且不存在稳定的迈森海默中间体，前提是计算始终使用可极化溶剂模型和弥散基组。
