Peripherally-Functionalised Porphyrazines and seco-Porphyrazines: Synthesis and Applications of Novel Metallomacrocycles

研究了一类新型的卟啉多金属配合物的合成、表征和应用，这些配合物是由2-trans-salen或4-salen残基，或4个或8个柯林斯配体[NHCOC（Me 2）OH]或草酰胺基（NHCOCO 2 H）取代的卟啉衍生的。这些多齿配体将被转化为衍生的三金属和五金属配合物。在四氮杂卟啉腔和外围结合的金属实体将系统地变化，特别关注顺磁性和/或氧化还原活性金属络合物。选择的多锰配合物将被分析为潜在的光学和双光学MRI药物在医学上的应用。此外，相同的配合物应该是相关的潜在的双光学PET剂的锝配合物的模型。其次，我们将发展一种新的无色谱法的开环四氮杂卟啉的大规模合成方法，该方法依赖于聚合物-捕获-释放策略。这种新方法将大大促进这些大环化合物作为生物医学成像剂和光动力学治疗的应用。新的潜在应用的四氮杂卟啉将重点检查抗E-选择素共轭大环化合物的检测和治疗（光血管成形术）的病变与重大疾病，如动脉粥样硬化，类风湿性关节炎和克罗恩病。本论文主要研究新型高偶极矩四氮杂卟啉的合成、表征及应用，包括六氨基四氮杂卟啉-托品体系。

Research is proposed on the synthesis, characterisation and application of new classes of multimetallic coordination complexes derived from porphyrazines, which are peripherally fused to 2-trans- or 4 salen residues, or functionalised with 4 or 8 Collins ligands [NHCOC(Me2)OH] or oxamido groups (NHCOCO2H). These polydentate ligands will be converted into the derived trimetallic and pentametallic complexes. The metallic entities within the porphyrazine cavity and peripherally bound will be systematically varied with particular focus on paramagnetic and/or redox-active metallic complexes. Selected multi-manganese complexes will be assayed as potential optical and dual optical-MRI agents for application in medicine. In addition, the same complexes should be models for related technetium complexes of potential as dual optical-PET agents. Secondly, a new chromatography-free large-scale synthesis of seco-porphyrazines will be developed, which relies on a polymer-capture-release strategy. This new approach will greatly facilitate the application of these macrocycles as both biomedical-imaging agents and in photodynamic therapy. New potential applications of porphyrazines will be examined with focus on anti-E-selectin-conjugated macrocycles for the detection and treatment (photoangioplasty) of lesions associated with major diseases such as atherosclerosis, rheumatoid arthritis and Crohn's disease. The synthesis, characterisation and application of novel high dipole moment porphyrazines will be undertaken including hexaamino-porphyrazine-tropyllium systems.