Construction And Applicaition Of Superamolecular Photosensitizers Based On Aggregation-Induced Emission

Photodynamic therapy（PDT）has been widely applied in various avenues such as antitumor,antifungal,antibacterial,and antiviral due to its minimal side effects,negligible drug resistance,and spatiotemporal selectivity.Photosensitizers（PSs）play a crucial role in PDT,and the nature of the PSs determines the effectiveness of PDT.Compared with other photosensitizers,pure organic photosensitizers possess many advantages,including excellent biocompatibility,degradability,low toxicity,easy modification,and adjustable performance.However,conventional organic PSs,encounter the problem of aggregation-caused quenching（ACQ）,resulting in undesired weak emissions and poor generation of ROS,thereby diminishing the efficiency of PDT.Fortunately,PSs with aggregation-induced luminescence（AIE）properties have enhanced fluorescence emission and reactive oxygen species（ROS）generation upon aggregation,rendering them suitable for PDT applications.In addition,enhancing the performance of PSs and achieving on-demand regulation of ROS generation are essential means to improving the effectiveness of PDT.Commonly used strategies include expanding the conjugation of molecules,introducing electron donors,electron acceptor units,heavy atoms,and other chemical modifications to modify PSs.However,not only it requires additional time and money as well as may not achieve the anticipated results,but the complicated chemical structure could lower the solubility of the PSs and bring about a non-negligible dark toxicity.It is convenient and efficient to optimize the performance of PSs,simplify the way to acquisition of PSs,and achieve on-demand tuning of ROS by means of supramolecular assembly.Therefore,in this thesis,we designed and synthesized a series of PSs with AIE properties to construct supramolecular AIE PSs with excellent performance,aiming to enhance the performance of PSs,improve the biosafety of PSs,simplify the way to obtain PSs,achieve on-demand regulation of ROS via supramolecular assembly.Moreover,we employed the constructed supramolecular AIE PSs for photodynamic antifungal and antibacterial applications.Main contents are as follows:（1）We develop stereoisomeric photosensitizers（（Z）-TPE-EPy and（E）-TPE-EPy）by harnessing different spatial configurations of one molecule.The stereo configurations of（Z）-TPE-EPy and（E）-TPE-EPy were confirmed by single crystal diffraction.（Z）-TPE-EPy and（E）-TPE-EPy possess aggregation-induced emission characteristics and ROS,viz.¹O₂and O₂^·-generation capabilities that enable image-guided PDT.Also,the cationization of the PSs realizes the targeting of fungal mitochondria for antifungal PDT killing.Particularly,stereoisomeric engineering assisted by supramolecular assembly leads to enhanced fluorescence intensity and ROS generation efficiency of the stereoisomers due to the excited state energy flow from nonradiative decay to the fluorescence pathway and intersystem（ISC）process.As a result,the supramolecular assemblies based on（Z）-and（E）-TPE-EPy show dramatically lowered dark toxicity without sacrificing their significant phototoxicity in the photodynamic antifungal experiments.This study is the first demonstration of stereoisomeric engineering of supramolecular AIE PSs based on（Z）-and（E）-configurations.（2）Type-Ⅰ photosensitizers（PSs）can generate free radical anions with a broad diffusion range and powerful damage effect,rendering them highly desirable in various areas.However,it still remains a recognized challenge to develop pure Type-Ⅰ PSs due to the lack of a universal molecular design strategy and in-depth theoretical studies.Herein,we report a piperazine-based cationic Type-Ⅰ PS（PPE-DPI）,which can exhibit efficient ISC(ΔE_ST=0.0006 eV)and subsequently capture oxygen molecules by the binding of O₂and lone pair of nitrogen in piperazine.The close spatial vicinity between O₂and PPE-DPI strongly enhances the electron transfer reaction,thereby ensuring the exclusive superoxide radical(O₂^·-)generation via the Type-Ⅰ process.Particularly,PPE-DPI with cationic pyridine groups is able to associate with cucurbit[7]uril（CB[7]）through host-guest interactions to form supramolecular assembly（PPE-DPI@CB[7]）,thereby inhibiting the generation of O₂^·-.By the addition of competitive adamantine,the supramolecular assemblies could undergo disassembly and release PPE-DPI.Thus,supramolecular assembly and disassembly are easily utilized to realize switchable O₂^·-generation.This switchable Type-Ⅰ PS is successfully employed in controllable photodynamic antibacterial.This study is the first to demonstrate the switchable superoxide radical generation based on supramolecular assembly and disassembly.（3）Enhancing the ISC of PSs is an effective means to enhance their ROS generation efficiency,and the strategy of supramolecular assembly combined with intermolecular charge transfer interactions is promising to further enhance the ROS generation efficiency of PSs.We obtained the AIE PS（OPE-DPI）with a push-pull（D-A）structure by careful design and simple synthesis.The cationization of OPE-DPI is able to form different supramolecular assemblies through host-guest interactions with CB[7]or CB[8],which enhances its fluorescence emission as well as the yield of ROS.CB[8]is capable of inducing intermolecular charge transfer interactions between OPE-DPI to form supramolecular assemblies（OPE-DPI@CB[8]）which exhibit a large emission red-shift（from 486 nm to596 nm）as well as a superior yield of ROS than OPE-DPI@CB[7].We have successfully screened supramolecular PSs（OPE-DPI@CB[8]）with superior performance by harnessing different supramolecular assemblies of one molecule.In antibacterial assays,both OPE-DPI and OPE-DPI@CB[8]are able to bind to bacteria and present excellent imaging properties,meanwhile,OPE-DPI@CB[8]show dramatically lowered dark toxicity with enhanced phototoxicity.The strategy of supramolecular assembly provides insights into regulating the reactive oxygen yield of PSs and alleviating the dark toxicity of PSs,thus opening up more opportunities for the invention of novel PSs.