Drug Delivery System Based On Coordination Cage Incorporating Sulfonylcalix[4]arene

Coordination cages,also known as metal-organic polyhedrons,are one of the most fascinating classes of porous material formed via coordination-driven self-assembly process.They have been widely used in molecular sensing,guest recognition,catalysis,and biomedical owing to various characteristics such as unique nanocavity structure,easy design and modulation,and excellent stability.Among them,metal coordination cages constructed with the sulfonylcalix[4]arene-based container precursor have been attained to attract extensive attention,owing to their unique dual multi-cavity structure that mimic the topology of biological virus and is suitable for multiple guest encapsulation.In this thesis,a series of sulfonylcalix[4]arene-based coordination cages have been design and synthesized.The host-guest chemistry and drug delivery properties were studied by encapsulating one or more types of drug molecules.1.Iodine capture and release via coordination cages based on naphthalene-1,8-dicarboxylateTwo coordination cages,named as Co-NDC and Co-NDC-Br,with cylindrical configuration were constructed by self-assembly reactions of C_O²⁺,sulfonylcalix[4]arene（TBSC）,and bridging ligands of naphthalene-1,8-dicarboxylates derivatives bearing two parallel and highly twisted carboxylate groups.The results of single-crystal X-ray diffraction analysis and gas adsorption experiments demonstrated that introduction of a bromo atom at the 4-position of 1,8-NDC ligand promotes double non-classical Br···πinteractions between the bromo atoms and naphthyl rings mutually from two adjacent molecules,thus giving rise to a more robust packing model helpful for maintaining the extrinsic solid-state porosity,as well as a much better nitrogen adsorption capacity.Importantly,these coordination cages exhibited effective iodine capture ability from vapor phase or hexane solution.Moreover,they also showed excellent recyclability of repeated sequestration and release of iodine,thus opening up a new approach for the design of porous coordination cages for radioactive iodine capture and transport.2.Internal cavity functionalization of coordination cages for the encapsulation of antineoplastic drugsIsophthalic acid was employed as a bridging ligand to construct a tetragonal zinc（Ⅱ）-based coordination cage via the self-assembly reaction.By Incorporating functional group onto the 5-position of isophthalic acid,another coordination cage,termed as Zn-PMTC,with similar structure was successfully prepared.Antineoplastic drug molecules such as doxorubicin hydrochloride（DOX）and sorafenib（SFB）,were selected as the guest molecules to investigate host-guest interaction.The host-guest chemistry was systematically characterized by ¹H NMR,2D NOESY NMR and UV spectroscopic titration.The host-guest interaction was thoroughly analyzed between drug molecules and coordination cages.The results revealed that the coordination cage Zn-PMTC modified by the endo cavity functionalization exhibits higher drug loading capacity for DOX and SFB,alonging with stronger binding affinity.This work provides a solid experimental basis for the design and construction of high-loading drug delivery systems.3.Drug delivery and inflammation therapy of pentagonal coordination cageA pentagonal coordination cage was designed and synthesized from self-assembly reaction of chelidonic acid,Zn²⁺,and TBSC.It possesses five outer cavities（with a diameter of ca.1.1 nm）and an inner cavity（with a dimension of ca.1.2×1.2 nm）with two wide windows（ca.0.7×0.7 nm）.The host-guest chemistry studies displayed that drug molecules can be gradually encapsulated in the inner and outer cavities of the coordination cage.With anti-inflammatory drug（Curcumin）,targeting agent（D-mannosamine hydrochloride）and fluorescent dye（Rhodamine B）could be gradually encapsulating into the inner and outer cavities of the coordination cage,a novel multi-drug co-loaded drug delivery system was successfully built.The vitro studies indicated that the multi-drug co-loading system based on coordination cage exhibited a better therapeutic effect on inflammation,thus providing a promising strategy for the treatment of inflammation.