Design,Synthesis,and Bioimaging Applications Of Complex Lanthanide Arrays Constructed From Modular Ln-DOTA Derivatives

The science of chemistry is about creation,which is an important way to understand our world.The goal of chemistry is to synthesize useful new substances.Organometallic complexes exhibit the special physicochemical properties such as optical/magnetic properties because of the presence of metallic elements.In the past decades,the flourishing development of supramolecular chemistry has led to a great expansion of structural possibilities of organometallic complexes,which are not limited to mononuclear or oligonuclear complexes,and one can synthesize magnificent molecular structures.However,most of the current construction of large organometallic structures is based on metal-directed coordination-assembly.This approach has some limitations,such as poor predictability of the structures,instability of the synthesized molecular structures,etc.In this thesis,we briefly illustrated the applications and synthetic challenges of heterometallic lanthanide complexes.Then we described the strategy we developed to define complex multimetallic arrays by using kinetically inert metal building blocks,and we also investigated the property and application studies of these complex multimetallic arrays.In Chapter 1,we presented the background and current status of this area,including the history and structural studies of DOTA ligand and its related derivatives,various applications of lanthanide complexes as well as heterometallic lanthanide complexes,and the current synthetic methods and synthetic challenges of heterometallic lanthanide complexes.In Chapter 2,we described a new synthetic method for the rapid construction of well-ordered giant heterometallic lanthanide complex-based dendritic architectures,termed as Sequence-controlled HEterolayered Lanthanide-Lego structures(SHELLs in short).Through this strategy,we are able to overcome the difficulties in the synthesis of heterometallic lanthanide complexes caused by the similar chemical properties of lanthanides,which allows for active and precise control on the array of lanthanide building blocks within a giant molecule.Using different lanthanide ions chelated by DOTA derivatives as kinetically inert Lego bricks,we built a series of Sequencecontrolled HEterolayered Lanthanide-Lego structures.We also studied the special photophysical properties,which demonstrates the feasibility of our approach as a quick access to multifunctional agents.In Chapter 3,we further extended the strategy of constructing Sequence-controlled HEterolayered Lanthanide-Lego structures with kinetically inert building blocks.By carefully designing the structure of each lanthanide coded building blocks,we successfully achieved the rapid synthesis of SHELLs via "one-pot" strategy.In Chapter 4,we successfully constructed elegant cage structures by assembling kinetically inert metal building blocks.There are several advantages in this strategy,for example,its predictability for the construction of heterometallic functional structures.The molecular cages we designed and synthesized have superior properties such as good water solubility and high stability.In Chapter 5,we developed a target-specific theranostic prodrug containing GdDOTA,biotin,and camptothecin(CPT)along with a disulfide self-immolative linker.The prodrug could selectively target biotin-receptor overexpressed cancer cells with high uptake,effectively release CPT in reducing environments,and kill cancer cells with low IC50 values.The excellent T1 contrast-enhanced performance of prodrug enables real-time monitoring of drug uptake in cells and accurate diagnosis of tumor with high sensitivity.Moreover,the prodrug could achieve a considerable improvement on tumor treatment with higher efficacy and reduced side effects.All these features demonstrated the great potential of the prodrug for accurate diagnosis and precise treatment of tumors.In conclusion,we have constructed a series of organometallic structures by using kinetically inert lanthanide building blocks.Our synthetic strategy is different from metal-directed coordination-assembly and has unique advantages in the synthesis of multimetallic lanthanide complexes.The structures synthesized by this strategy can be both giant and well-ordered,precise and perfect,and convenient allowing the introduction of other unique functional groups.These findings suggest that this strategy is powerful in the synthesis of new structures.More importantly,this new strategy could be easily extended to the construction of various heterometallic array structures and be inspiring for the fabrication of multifunctional materials.