Design,Construction And Function Exploration Of Three-Dimensional Metallo-Supramolecular Structures

Coordination-driven self-assembly has become one of the most effective methods for constructing precise discrete supramolecular assemblies,due to its suitable bond energy and orientation.In recent years,supramolecular chemists have used this approach to develop many supramolecular architectures with exquisite structures and diverse functions.Among them,three-dimensional metal-organic supramolecules show great advantages and application prospects in many fields,such as host-guest chemistry,catalysis,recognition and separation,and drug loading,due to their special cavity structure and easy modification of functional groups.Reasonable design of building blocks and accurate adjustment of cavity size are key factors for the functions of three-dimensional supramolecular structures.In this thesis,three types of 3D metallo-supramoleculer structures are designed and obtained based on metal-organic coordination assembly:Porphyrin-based organoplatinum molecular cages,helix molecular cages and pyrazinyl columnar structures.These structures were characterized by nuclear magnetic resonance spectroscopy(NMR),electrospray ionization-mass spectrometry(ESI-MS),traveling wave ion mobility-mass spectrometry(TWIM-MS)and single-crystal X-ray diffraction technology.Based on the regulation of 3D structural space,they were used in photodynamic therapy,molecular interlocking and molecular recognition,and biological antibacterial field.The main research contents are as follow:In chapter one,we summarized the progress and current status of the research and development of supramolecular chemistry based on metal organic molecular cages.From the construction methods of 3D supramolecular component,such as the construction of two-component molecular cages,multi-component molecular cages and sub-component molecular cages,to its application prospects in various fields,such as host-guest chemistry,catalysis,biomedicine and mechanically interlocked structures,etc.Through reviewing literatures,we analyzed the current development challenges and propose the research topic of this article.In chapter two,the traditional photosensitizer porphyrin derivative and the organoplatinum receptor are assembled to form two molecular cages(1 and 2).The structures were characterized by ¹H NMR,³¹P NMR,ESI-MS,and single-crystal structure.These characterizations proved the geometric configuration of the molecular cage.Due to the reasonable design,the distance between the surfaces of the porphyrin were increased,which can effectively inhibit the aggregation of molecules.The UV-vis absorption spectra indicate that the molecular cage 1 has a larger absorption wavelength,which means cage 1 has a deeper tissue penetration ability and more suitable for actual biological treatment experiments.The molecular cage 1 was compounded with the amphiphilic block copolymer to form nanoparticles with uniform size distribution,which effectively improves water solubility and targeting in cancerous tissues.The results of in vitro cell experiments and in vivo experiments show that compared with the coordinated porphyrin precursor,the efficiency of the reactive oxygen generation of the supramolecular cage was greatly increased and obtained an excellent photodynamic therapy effect,which can effectively inhibit and treat 4T1 in situ Breast cancer cells and cisplatin-resistant ovarian cancer cells(A2780CIS).In addition,due to the stability of the molecular cage,the toxic and side effects on normal cells and tissues are negligible for circulating in the body.In chapter three,we designed and synthesized three convergent terpyridine ligands with the same diameter and different coordination numbers,and assembled with Zn(II)to obtain three types of spiral supramolecular structures(SA,SBH,SBH,SB,SCH,SC).NMR spectroscopy,ESI-MS and diffusion ordered spectrum(DOSY)show that double(SA)and triple(SB and SBH)helical supramolecular structures show mechanically interlocked phenomena with increasing concentration,including[2]catenane and[3]catenane and interlocked molecular cages.However,six alkyl side chains have an inhibitory effect on the formation of interlocked structures,and no interlocking phenomenon was observed in the SB molecular cage at a concentration of less than 10 mg/m L.Due to the significant space constraints,no interlocked structures were observed in complexes SC and SCH constructed by hexatopic tpy ligands.However,the single-crystal structure data shows that the increased space limitation and the formation of a relatively closed cavity by terpyridine steric hindrance bring possibility to the encapsulation and recognition of guest molecules.According to the matching of the shape and size of the cavity,which showed excellent host-guest properties for different calixarenes,especially the high affinity for calix[6]arene.In chapter four,we designed and synthesized three four-arm terpyridine ligands containing pyrazine moieties through the condensation of amino groups and carbonyl groups.¹H NMR,¹³C NMR and matrix-assisted laser time-of-flight mass spectrometry(MALDI-TOF-MS)proved the successful synthesis of target ligands L3,L3-1,and L4.The prismatic supramolecular structures S3,S3-1 and S4 were obtained by assembling ligands with zinc ions.Concentration-dependent NMR and ESI-MS indicate that the introduction of acetylene bonds reduces the structural rigidity,resulting in a dimer at low concentrations and a trimer at high concentrations for S4.The metal ions of these prismatic structures are distributed on the surface of the structure,and the shapes are symmetrical and regular.The experiment of ion transport across the membrane proves that the prismatic structure has a certain ability to embed membrane.The antibacterial experiment and the TEM image of this process show that due to the electrostatic effect,the rigid structure of the large cavity of the molecular cage and the hydrophilic and hydrophobic effect caused by the side chain,S3-1 can effectively aggregate on the bacterial cell membrane,thereby destroying the bacterial cell membrane structure,showing good antibacterial activity against Staphylococcus aureus.