具[Fe]-氢化酶 (Hmd) 活性中心整体骨架分子的合成、结构和功能研究

In recent years，the biomimetic chemistry of [Fe]-hydrogenase has attracted great interest. This is because [Fe]-hydrogenase is a class of highly effective enzyme that can catalyze the heterolytic cleavage of H2 and stereospecific hydride transfer to C14a of methenyl-H4MPT+ to form methylene-H4MPT and H+ under mild conditions. The synthetic study of this project includes (i) the synthesis of 2-methoxy-4-oxophosphoryldichloro-3,5,6-trimethyl pyridine derivative in order to form the central skeleton structure of the active site of [Fe]-hydrogenase; (ii) further reaction study of the 4-oxophosphoryldichloride functionality of the aforementioned pyridine derivative with the hydroxomethyl functionality of the Boc- and isopropylene-protected guanosine in order to form the skeleton structure in the outer coordination sphere of the active site of [Fe]-hydrogenase; and (iii) a series of reaction studies involving the o-methyl group transformation of the trimethylpyridine ring to TsOCH2 (Ts = p-MeC6H4SO2) group and the subsequent reactions of the TsOCH2 group with Na2Fe(CO)4 and the corresponding reagents in order to form the skeleton structure of the inner coordination sphere in the active site of [Fe]-hydrogenase. The targeted complexes of this study are the first examples of the [Fe]-hydrogenase models with the whole active site framework of [Fe]-hydrogenase. On the basis of synthesis and structural characterization of the first examples of such a type of [Fe]-hydrogenase model complexes, this project will further study the heterolytic cleavage of H2 catalyzed by such model complexes and study the relationship between the structures of such models and their catalytic function. This project will be helpful not only to deepen the understanding of the relationship between structure and catalytic function of [Fe]-hydrogenase, but also to promote the development of biomimetic chemistry of [Fe]-hydrogenase. This project is a frontier project of organometallic chemistry and biomimetic chemistry of hydrogenases, which is closely related to energy source and material science and thus it is of theoretical and practical significance.

近年来，人们对于研究[Fe]-氢化酶的仿生化学产生了浓厚的兴趣。本项目拟首先研究与[Fe]-氢化酶活性中心中央部分结构相似的甲氧基(氧磷酰二氯)三甲基吡啶衍生物的合成，然后研究该吡啶衍生物的氧磷酰二氯官能团与含Boc和亚异丙基保护基的鸟苷羟甲基的反应(以构成与[Fe]-氢化酶活性中心外配位圈相似的结构单元)，再研究其吡啶环上的邻位甲基转化为对甲苯磺酸酯甲基及其与Na2Fe(CO)4等试剂所发生的相应后续反应(以构成与[Fe]-氢化酶活性中心配位内圈相似的结构单元), 并最终合成首批具[Fe]-氢化酶活性中心整体骨架的[Fe]-氢化酶模型物。本项目还将进一步研究这类模型物的结构以及它们的结构与催化氢气异裂功能的关系规律。本项目是一项金属有机化学和生物酶仿生化学相互交叉的前沿课题，它与能源和材料科学密切相关，具有重要的理论和实际意义。

本项目通过我们所设计的新方法合成了一系列新型[Fe]-氢化酶模型物，特别是首次合成具有Hmd活性中心整体骨架的[Fe]-氢化酶模型物。用现代物理化学方法充分表征了它们的结构，研究了模型物的电化学性质及催化功能。发现它们具有良好的催化质子还原为氢气以及活化氢气进而发生负氢转移的类酶催化功能，进一步研究了化合物结构对其催化活性的影响。本项目取得的了创新性研究成果，对促进金属有机和氢化酶仿生化学、催化及能源材料等多种学科的发展，具有重要理论和实际意义。