Porous Aromatic Frameworks Based On N-H Insertion Reaction:Design,Synthesis And Properties

In recent years,porous aromatic frameworks（PAFs）have attracted a significant attention in the field of organic porous materials owing to their structural monomer tunability,structural designability,excellent chemical stability,high specific surface area and good biocompatibility.Currently,organic porous materials are being explored in biomedical research areas,such as drug delivery,phototherapy,bioimaging,biosensing and antibacterial applications.However,the poor solubility and dispersion of PAFs in physiological media and their low cellular uptake have severely limited the applications of PAFs in living organisms as well as in vitro.Therefore,it is of great theoretical as well as practical importance to develop PAFs with small size,excellent water dispersibility and high biofunctionality to promote their further development in the field of biomedical research.Based on this research background,this thesis is introducesα-diazocarbonyl compounds as building blocks into the framework of PAFs for the first time.A series of PAFs with superior bioactive structural units in their structures have been designed and synthesized through the N-H insertion polymerization strategy,and their structural and biological properties have been systematically and thoroughly investigated.The details of the research are described in the following:1.In an attempt to design PAFs with small size,good water dispersibility and beneficial applications in biomedical research.In this thesis,two different chain-lengthα-diazoester compounds were designed and synthesized as building blocks,while two different configurations of amino building blocks[1,3,5-tris（4-aminophenyl）benzene and tetrakis（4-aminophenyl）methane]were selected to synthesise three PAFs by the N-H insertion reaction strategy（PAF-150,PAF-151 and PAF-153）.As the abundant ester groups in the material design precursors were introduced into the backbone of the PAFs to facilitate their post-modification hydrolysis,it resulted in a backbone of PAFs with a large number of hydrophilic carboxyl side chains.The hydrolysed PAFs have a large number of quasi-α-phenylglycine fragments in the frameworks,resulting in a good biocompatibility and excellent water dispersibility.The hydrolysed amino acid PAFs were determined to have high drug loading and release capacity.2.As structure determines properties,the design of PAFs with photosensitive properties is more beneficial for their applications in the field of phototherapy and antitumour treatment.In this work,a porphyrin-based building block with photosensitive properties was introduced into the backbone of PAFs,and a nano-sized porphyrin-based PAF-152 was designed and synthesized through the N-H insertion reaction ofα-diazoester compounds.Based on the previous study,it was found that the PAF-152 synthesized using this building block has abundant ester groups in its structure,which can significantly improve the hydrophilicity of the material after hydrolysis.In turn,PAF-152-COONa with a quasi-amino acid structure was obtained,which exhibited good water dispersibility.After assembling PAF-152-COONa with DSPE-PEG₂₀₀₀,which has a drug solubilisation effect,we can obtain a PAF-152-COONa-M with excellent colloidal stability in aqueous solution.It was shown that PAF-152-COONa-M has favourable biocompatibility,with the photothermal conversion efficiency of up to 49.6%as well as the singlet oxygen quantum efficiency of 0.54 under the irradiation of single-band light source.Effective tumour elimination was achieved in mice whose tumours were injected with PAF-152-COONa-M under 685 nm laser irradiation,confirming that the designed and synthesized porphyrin-based PAF-152 is a highly promising combined photothermal and photodynamic anti-tumour drug.3.Quinoxalines are important structural motifs in synthetic bioactive molecules and natural heterocyclic substances,whilst molecules containing this structural units have been studied for their wide range of biological activities.Therefore,designing porous materials with quasi-quinoxaline structures for biomedical applications is of great importance.In this work,a novel tri-dentateα-diazocarbonyl ketone compound monomer was designed and utilised to react with two different configurations of o-phenylenediamine monomers by an N-H insertion reaction strategy to synthesise two porous aromatic framework materials with quasi-quinoxaline structures,namely PAF-156 and PAF-157.Multiple characterization tools verified that the materials were successfully synthesised,while electron spin resonance spectroscopy（ESR）tests revealed that the synthesized PAFs exhibited favourable singlet oxygen production under UV irradiation.In vitro antibacterial experiments showed that PAF-156 and PAF-157 have potential photodynamic antibacterial properties.