New Design Strategy And Application Of Photosensitizer Based On Pentamethine Cyanine Dye

Triplet photosensitizers（PSs）,as a vital component,have been widely used in photodynamic therapy,photovoltaics,photocatalysis,and triplet-triplet annihilation upconversion.There is a severe dependence on heavy atom effect resulting monotony in terms of molecular design strategy for PS.Meanwhile,the inherent defects caused by heavy atoms should not be ignored,such as short triplet lifetime or high cost.In contrast,the heavy-atom-free PSs can make up the mentioned defects,and enrich the kind of PS.Hence,the exploration of new design strategy of heavy-atom-free PSs has become an urgent need.Due to lacking theoretical guidance and unpredictable effects brought by chemical modification,it is an extreme challenge to propose a design strategy with good applicability.This dissertation aims to develop new design strategies for heavy-atom-free PSs.Because of the simple structure and near infrared（NIR）absorption,Cy5 is selected as the research object.The design and synthesis of Cy5 are used to disclose the structure-activity relationship and apply it to the photodynamic therapy of tumors.Specific researches are as follows:Starting from the original thio-pentamethine cyanine（TCy5-H）,systematic chemical modification has been carried out at the meso-position of TCy5,and a set of TCy5 with different substituents is designed and synthesized.A new strategy has been described:the introduction of powerful electron-withdrawing group（EWG）to the meso-position could transform TCy5 as high-performance PS.When the H was replaced with an EWG,it will enhance of intersystem crossing（ISC）,cut down radiation transition process,and prolong the triplet lifetime compared to PSs bearing heavy-atom.Theoretical calculations proved that the powerful EWG can reduce the singlet-triplet energy gaps(ΔE_st),promoting the singlet oxygen quantum yield（ΦΔ）up to99%.Additionally,the near-infrared（NIR）PSs achieve good therapeutic efficacy for tumor.In order to efficiently trigger antitumor immunotherapy,endoplasmic reticulum-targeting NIR PSs have been synthesized based on the proposed PS design strategy.A polyfluorine-substituted phenyl group was introduced into the meso-position of TCy5,which not only as a strong EWG,but also as a ligand for specific ER targeting.The molecular properties are enhanced with the increase of the number of meso-substituted fluorine atoms,which also lead the decrease ofΔE_st.The designed PS can generate not only singlet oxygen through energy transfer,but also superoxide anion through electron transfer.After NIR irradiation,TCy5-Ph-3F can break endoplasmic reticulum membrane,efficiently induce immunogenic cell death,and activate immune system to suppress tumor growth realizing photodynamic immunotherapy.It is a novel design idea to enhance PS performance through non-conjugate site modification.After the exploration,the side arms,as the non-conjugated sites linking with the N-methyl on both sides of TCy5,can remarkably affect the efficiency of PS.In this process,the steric hindrance effect and electron donating effect are enhanced gradually.The modification of side arms with steric hindrance will promote the methine linkage to be twisted which will lead charge separation and reduce theΔE_st promoting ISC.It will ensure the excited PS to reach triplet state and sensitize oxygen.The non-conjugated modification will provide a new perspective in PS design and expand the design thought for scientist.