Light Trigger-responsive Chemical Tools In The Field Of Chemical Biology

Light irradiation is kind of exogenous stimuli,which is easy to control.In biological researches and practices,the light irradiation can be turned on/off,adjusted and focused optionally according to demand.The advantages mentioned above make the light irradiation play an important role in diseases therapy.However,the usage of light depends on the development of corresponding chemical tools.Therefore,starting from two major aspects:photosensitizer for photodynamic therapy and light-triggered gas transmitter fluorescence donor,we designed and synthesized novel light-triggered chemical tools and the usage of light in chemical biology was also studied.Since the 1970s,the photodynamic therapy has gained more and more attention in cancer treatment.Transition metal compounds have been greatly developed among all kinds of photosensitizers by virtue of their unique photophysical properties.Based on the previous researches,the triplet excited state lifetime of Ru（Ⅱ）complex,named by2-1,was prolonged by increasing the ligandπ-electron delocalization,which made it possess excellent singlet oxygen genration ability.The chemical structure also gave the photosensitizer the DNA binding capacity.The in vitro anticancer evaluation demonstrated that the photosensitizer possesses extraodinary high photocytotoxicity.The mechanism study indicated that the potent anti-tumor ability originite from excellent singlet oxygen initiation ability and DNA binding behavior.Besides,the photosensitizer could initiate the endogenous apoptosis pathway and ER stress pathways and subsequently induce cell apoptosis.Due to the high chemical reactivity and complicated biology functions,the research of gasotransmitter faces many challenges.Therefore,by the use of the advantage of light stimuli,we designed H₂S and NO light trigger-responsive donors,respectively.To further simplify the corresponding studies,we also gave it the ability of fluorescence switching on,so that the donors could make optical signal feedback after releasing the payload.In the research of H₂S donor,the results shown that the target compound 3-1 can release H₂S in solution and cells after the administration of light.In the cell experiments,we found that the donor can remarkably reduce the cellular ROS level and effectively improve the cell survival rate.Importantly,this cell-protecting behavior can be controlled by light.The feedback of the fluorescence signal provided an intuitive method to observe the distribution of the donor and the release of payload.In addition to the light trigger-response capability and fluorescence signal feedback ability,we also enabled the NO donor to target to lysosomals by means of chemical modification.Biological researches revealed that the NO donor 4-1 can specifically release NO in lysosomes and induce cancer cell apoptosis.It was the light trigger-response and fluorescence turning on ability facilitated the biological studies in this work.By detection of the expression level of corresponding proteins in cancer cells,we clearly proposed the specific biological mechanism by which the NO donor exerts the inhibitory activity to tumor cells.By the series of studies in this paper,we believe that light irradiation possess huge application prospect in chemical biology,and the performance of light irradiation depends on the research and development of high-performance light trigger-responsive chemical tools.