有机双过氧钒化合物的合成及其与小分子相互作用研究

在过去的20年里，双过氧钒化合物的合成及其与小分子相互作用一直是化学和生物学研究的热点之一．本文在合成并表征数种双过氧钒化合物的基础上，利用多核（¹H、¹³C、¹⁴N、¹⁵N和⁵¹V）、多维（¹H-¹H COSY、¹³C-¹H COSY和DOSY）和变温NMR等谱学手段，结合ESI-MS技术和理论计算，系统研究了相互作用前后体系中各物种的溶液结构，对一些实验现象进行了解释，探讨了相互作用的模式和规律．主要结果总结如下：  1. 在合成草酸双过氧钒的基础上，利用多种NMR谱学手段研究了双过氧钒和组氨酸类化合物的相互作用，在溶液中观察到His和Carns等有机配体主要以其咪唑环上的ε-N与中心金属钒配位，这和从海洋生物 Curvularia inaequalis 分离出来的氯过氧化物酶(Chloroperoxidase)的活性中心His496有着相同的配位方式．理论计算表明溶剂效应对该配位方式起着关键的作用．此外，利用ESI-MS技术结合理论计算，通过比较体系在溶液和气相中行为的异同，对气相中物种[OV(O₂)₂(L)₂]-（L为配体）可能的结构给予了解释，认为中心金属钒与溶液中一样还是6配位而不是Conte等人认为的7配位，第二个配体分子通过氢键与物种[OV(O₂)₂(L)₂]-结合在一起． 2. 在合成数种双过氧钒化合物的基础上，利用多种NMR技术结合ESI-MS等谱学方法系统研究了双过氧钒化合物和咪唑、吡啶、取代吡啶、精氨酸、皮考啉酯以及皮考啉酰胺等有机配体的相互作用，建立了一套适合研究过氧钒化合物与有机小分子相互作用的谱学方法．利用核磁共振中扩散排序（DOSY）技术，实现了混合物中各组分在样品管中的“虚”分离，并利用谱图编辑技术得到混合物中各组分的化学位移即结构信息．由于DOSY的使用避免了繁琐的分离，因此它是一种非常有应用前景的研究混合物的谱学方法． 3. 在相互作用体系NH₄VO₃/H₂O₂/2-(2′-Py)Imi中合成了一种新的双过氧钒化合物．经NMR、IR、X-ray衍射和元素分析等谱学方法或分析手段确定其组成[NH₄{OV(O₂)₂{2-(2′-Py)-Imi}·4H₂O}]和结构，其⁵¹V的化学位移在单核双过氧钒化合物中是最大的．目前已报道双过氧钒化合物的晶体结构约为10个，本文所合成的为第一个具有不对称双氮双齿配体的双过氧钒化合物．

Syntheses of Organic Diperoxovanadates and Interactions with Small Molecules

In the past two decades, the interactions between peroxovanadates and organic ligands have attracted great interest in both chemistry and biology. In this work, multinuclear NMR (¹H, ¹³C, ¹⁴N, ¹⁵N, and ⁵¹V), multidimensional (DOSY, ¹H-¹H COSY, and ¹³C-¹H COSY), and variable temperature NMR, together with ESI-MS and theoretical calculations were utilized to study the above interaction systems. Through the combination of these methods, structures of all species in the interaction systems were obtained and a better understanding of the experimental phenomena was achieved. These studies shed some light on the essence of the vanadium-contained enzyme such as chloroperoxidase. The main conclusions are summarized as follows: 1. NMR study on the interactions between diperoxovanadates and histidine like ligands shows that histidine or carnosine coordinates to vanadate(V) by its ε-N, which is the same as His496 in the active site of chloroperoxidase from the fungus Curvularia inaequalis. Theoretical study indicates that the solvation effect plays a key role in stabilizing the products. ESI-MS and theoretical calculations were also performed to explore the different behaviors of the species in the interaction systems in solution and gas phases. The species [OV(O₂)₂(L)₂]^- in gas phase, ever reported to be seven-coordinated, was found to be actually six-coordinated, the same as in solution. The second ligand links to the oxo or peroxo groups through hydrogen bonds. 2. NMR and ESI-MS techniques were used to study the interactions between diperoxovanadates and small organic molecules such as pyridine, imidazole, arginine, picoline ester, and picoline amide. Spectroscopic methods were established to explore this type of interactions. It is worth mentioning that DOSY can be used to analyze the chemical structures and components of mixtures without chemical separation．This makes it important for the investigation of complicated mixtures avoiding time-consuming separation and purification that may destroy the inspected systems. 3. A new diperoxovanadate crystal NH₄{OV(O₂)₂{2-(2′-pyridyl)-imidazole}}·4H₂O was synthesized. The crystal was obtained from the interaction system, NH₄VO₃/H₂O₂/ 2-(2′-pyridyl) imidazole, in aqueous solution under the physiological conditions, and the complex was characterized by solution NMR, IR, X-ray crystal diffraction and elementary analysis. The complex may be of great chemical interest because it is the first diperoxovanadate complex having an asymmetrical N,N′-chelating biheteroaromatic ligand. To the best of our knowledge, its ⁵¹V NMR chemical shift is at the highest field among this kind of complexes reported in the literature.