Development And Photo-Triggered Release Studies Of Flavonol Derived Photo-Releasing CO Fluorescent Donors

Carbon monoxide(CO)is an important gaseous signal molecule in the human body,which plays important regulatory roles in many physiological and pathological processes.The biological activities of CO are closely associated with its spatiotemporal distributions in cells or tissues.Photo-releasing CO fluorescent donors,a special kind of photo-controlled CO releasing molecules(PhotoCORMs),utilize light irradiation to achieve spatiotemporal release of CO and simultaneously generate fluorescence signal changes to quantify and trace the amount of CO released.The development of such fluorescent donors is of great significance to the study of physiological and pathological regulation roles of CO and associated disease treatment.In this thesis,several photo-releasing CO fluorescent donors derived from 3-hydroxyflavone(flavonol)were developed and preliminary studies of their photo-triggered release were performed.The thesis contains mainly two parts.The first part is the design,synthesis,and photo-triggered release studies of a photo-releasing CO fluorescent donor with aggregation-induced emission(AIE).The CO donor 2-1,which contains a 7-diethylaminocoumarin fluorophore connected with 3-hydroxyflavone moiety via an amide bond,is the first photo-releasing CO fluorescent donor with AIE characteristics.In PBS buffer,the CO donor 2-1 forms nanoparticles via aggregation and gives AIE at 552 nm.When irradiated with light,fluorescence emission at 552 nm was decreased due to deaggregation.Further irradiation resulted in the increase of coumarin fluorophore’s fluorescence emission at 456 nm.Therefore,its CO releasing behavior can be tracked by fluorescence signal changes.The second part aims to development of a photo-controlled CO and nitric oxide(NO)dual-releasing molecule 4-1 containing the flavonol structure and N-nitroso group.The parent flavonol dye 4-2,and four intermediates:4-3,4-4,4-5,and 4-6 were synthesized.The photo-trigger CO release of 4-2,the photo-triggered NO release of 4-4,and the fluorescence detection CO and photo-triggered complimentary CO behavior of 4-5 were studied by UV,fluorescence,the addition of another CO or NO fluorescent probe,and MS analysis of the reaction mixture.The photo-releasing fluorescent donors developed in this thesis may provide important molecular tools for the study of the role of the gaseous signaling molecule CO in the biological system and drug development for related disease treatments.