模拟叶绿素的新途径：卟吩内酯及其金属配合物的合成，性质及其在活细胞分子成像中的应用

The centrality of pigments such as chlorophylls and bacteriochloropphylls in natural photosynthetic system is well recognized and has led to biomimetic studies for their novel structural and photophysical properties. Despite of significant progress achieved in synthetic models for such pigments, effective methods for stable chlorophyll and bacteriochlorpphylls' anologues still remain challenges. Furthermore, the importance of reduced pyrrole rings located at the macrocycle periphery makes it desirable to develop new class of molecular systems with the aim of establishing more stable and controlable models. From our recent work on porpholactones as chlorophyll mimics, we set out to systematically alter the molecular framework and evaluate structure?property relationships. Thus, the synthesis and properties of structurally related chlorophylls, which represents a relatively electron-rich to electron-deficient aromatic segments, are proposed. Moreover, the tailoring of structures via subtle structural modifications in the presented molecular series highlights the simplicity of accessing this chromophore architecture. Importantly, through metallation with these chlorophyll analogues, a series of metalloporpholactones would be obtained and their physical properties such as absorption spectroscopy, cyclic voltammetry, and luminescence will be examined. Finally, the application of porpholactones and metalloporpholactones will be investigated as optical probes in molecular imaging in living cells. The possiblity of rare earth porpholactone derivatives in Magetic Resonance Imaging (MRI) will be tested. Examination of the resulting complexes' properties relevant to biological application sets forth issues which can be readily predicted by consideration of molecular structure and which lack a systematic understanding. Guidelines can be proposed for the design of new molecules with the possibility of outperforming the current state of biomimitic studies for chlorophyll and bacteriochlorophyll.

本申请项目拟通过模拟叶绿素的生物合成过程，以卟吩内酯为"母体"，突破以往二氢卟吩类叶绿素衍生物的缺点，探索合成在近红外区域吸收光谱可调的叶绿素衍生物，并以此为配体研究金属叶绿素配合物，发展基于叶绿素模拟的金属配位化学。以考察卟吩母环结构的对称性导致的配位场改变为目的，研究金属离子配位金属配合物的化学或物理性质，包括对电子跃迁，环电子流的分布等方面，深化对大环共轭分子的配位化学的理解，为进一步发掘其潜在的应用奠定基础。我们将考察该类分子作为荧光探针检测活体细胞中的分子事件（如活性氧的产生，细胞凋亡过程等）以及将进行稀土离子卟吩内酯配合物作为MRI成像试剂的初步探索，从分子层面上深入研究光毒性的机理，为设计和筛选光敏剂或分子成像试剂提供理论指导和实验基础。

按照申请书内容和计划(NSFC: 21271013, 01/2013-12/2016)，我们从模拟天然四吡咯色素的结构和功能出发构筑卟吩内酯仿生配体库，考察卟啉环beta-修饰对其光物理性质的影响，研究稀土配合物的合成，性质及生物应用。我们进行了三个方面的工作：1. 构筑卟吩内酯仿生配体库，从内酯结构的不饱和度出发，成功模拟叶绿素，菌绿素和异菌绿素三类光收集天线色素；发现beta-取代的相对位置微调引起的光物理性质的改变，与天然叶绿素修饰类似，提供精准合成的新思路；从叶绿素降解途径出发，获得新的beta-位和meso-位共轭的新方法；2.合成新型稀土配合物，系统研究配体到稀土传能过程，合成了钆的卟吩内酯、卟吩二内酯化合物，与未修饰的meso-位五氟苯基取代钆卟啉进行对比，发现内酯化可以有效地提升钆卟啉敏化单线态氧的能力，首次实现钆卟啉类化合物在在光催化中的应用；合成了镱的卟吩二内酯化合物，发现Cis-镱卟吩二内酯化合物的近红外发光量子产率是trans-镱卟吩二内酯化合物的八倍以上，改变内酯化的取向可以有效地调节镱的激发态向配体三线态的能量回传，调控中心镱离子的近红外发光。3.生物应用。通过调节卟吩二内酯基团取向的不同来调节稀土卟啉的敏化发光性质，获得数例稀土金属探针，应用在催化、光动力治疗、敏化发光，细胞成像等方面。综上所述，我们探索生物启发的对卟啉环的修饰手段，构筑应用在稀土的敏化发光上，探究内酯化基团对敏化近红外发光的影响和机理，为精准合成金属配合物提供了新思路。