Preparation Of Naphthalene/Pyrene Carboxylic Acid-based MOFs And Study On Its 5-FU Slow Release Performance

During drug treatment,emplying the drug carriers to load and sustained-release the drugs,which can improve the curative effect,and reduce the toxic and side effects.5-Fluorouracil（5-FU）is a widely used anticancer drug in clinic,but it degrades rapidly in human body and is highly toxic at high concentration.The development of metal-organic frameworks（MOFs）materials as 5-FU sustained-release carriers,through the appropriate host-guest interactions,can make 5-FU release at an appropriate rate in the human body,so as to prolong the effective time of 5-Fu and improve the drug utilization rate.This paper aims to synthesize 5-FU slow-release MOF materials with appropriate drug release rate.Synthesizednaphthalene/pyrenylcarboxylicacidligands2,2’-（（naphthalene-2,6-dicarbonyl）bis（azadiyl））dipropionicacid（H₂L）and1,3,6,8-tetrakis（p-benzoic acid）pyrene（H₄TBAPy）.Based on the structure of 5-FU molecular,it is found that the carboxyl groups of ligands can be used as hydrogen bond acceptors,and theπ-conjugated aromatic rings can be used as the binding site forπinteractions.This is conducive to the construction of MOFs-based carriers and the formation of suitable host-guest interactions with 5-FU.Three novel complexes Zn-L,Zn/Mn/Co-L and Mg-TBAPy were constructed using H₂L and H₄TBAPy in combination with metal ions.Single crystal structures of the three complexes were analyzed,and then explored the encapsulation and sustained-release propertie of Mg-TBAPy for 5-FU.The specific content is as follows:（1）Designed and synthesized the ligands H₂L and H₄TBAPy,then constructed three novel complexes of Zn-L,Zn/Mn/Co-L and Mg-TBAPy combining with metal ions,and the single crystal structure was analyzed.Studies have shown that Zn-L is a 1D tubular structure,and Zn/Mn/Co-L is a 2D layered microporous structure.On the other hand,Mg-TBAPy exhibits a 3D supramolecular microporous structure,and its one-dimensional rectangular pores（6.2×8.1A2）have abundant potential binding sites,which are conducive to the formation of suitable host and guest functions.（2）Using Mg-TBAPy as a sustained-release carrier of 5-FU and its drug sustained-release performance was studied.The results displayed that Mg-TBAPy can effectively load 5-FU,and the mass percentage of 5-FU load is 28.2 wt%;5-FU@Mg-TBAPy exhibited a suitable and stable drug release rate,releasing 76%of the load within 72 h（a medically reasonable rate）.Additionally,based on the dramatic changes in fluorescence during the release of 5-FU,the mouse breast cancer cells（4T1 cells）were allowed to take up nano-scale5-FU@Mg-TBAPy and perform bio-fluorescence imaging,exhibiting potential applications of Mg-TBAPy in biological systems.5-FU@Mg-TBAPy achieves the expected drug release performance,which is attributed to the host（Mg-TBAPy）-guest（5-FU）interactions（hydrogen bonds,πinteractions）present in the system,with the appropriate intensity allowing 5-FU to be released by5-FU@Mg-TBAPy at an appropriate rate.The release process of 5-FU was monitored by microcalorimetry,and successfully captured and directly quantified these host-guest interactions with a release enthalpy of 22.3 k J/mol.This study provides a thermodynamic explanation for understanding the relationship between MOF design and drug release rate.