Design,Synthesis And Application Of Small Molecule Fluourescent Probes Based On BODIPY

Due to its biological role in cardiovascular, inflammatory and other aspects, hydrogen sulfide ?H₂S? has been regarded as a third gaseous signal molecule in addition to CO and NO. H₂S can exert vasodilation through opening KATP channels in vascular smooth muscle cells. In inflammation H₂S can inhibit the activation of the NF-?B to downregulate many proinflammatory genes ?such as iNOS, COX-2 etc.? and decrease inflammatory cell adhesion molecules level. As a potent antioxidant, H₂S can upregulate antioxidant defense under chronic conditions. Inadequate levels of H₂S are linked to a variety of diseases including Down syndrome, Alzheimer's disease, diabetes and liver cirrhosis. Therefore, the establishment of a reliable method for real-time quantitative H₂S detection in complex biological system will facilitate its function research.In the research of H₂S physiological and pathological roles, its concentration at the specific site of action remains the key. Compared to other traditional methods, including chromatography and methylene blue method, that bearing drawbacks exemplified by narrow linearity ranges and complicated sample preparations, small molecular fluorescent probes can avoid the detection error owing to their good biological membrane permeability. By virtue of this merit, small molecular fluorescent probes have received more and more attention.In the past two years, numerous H₂S specific fluorescent probes with structural diversity have appeared and they can be divided into three categories according to their interaction mode with H₂S. Copper sulfide precipitation, H₂S-mediated reduction probe and trapping H₂S via nucleophilic addition, among which FP1 and FP2 reported by Chuan He, etc have received considerable attention because of their trapping group 2-formylphenyl methyl acrylate with perfect selectivity.Here in this dissertation, we report our related work in the field of small molecule fluorescent probes for detecting hydrogen sulfide.On the basis of Chuan He's work, the first part of this thesis on the design, synthesis and biological evaluation of ZS1, which is obtained via attaching the 2-formylphenyl methyl acrylate to the a position of BODIPY through double bond. It serves as an ICT fluorescent turn-on probe for highly sensitive and selective detection of H₂S. within 50 minutes. ZSl showed 62-fold fluorescence enhancement and a linear fluorescence intensity enhancement with a wide range of concentrations of NaHS. Moreover, it has been illustrated that the probe is capable of detecting endogenously produced H₂S in intact cells and even has the potential to quantify H₂S in living cells.The second part:in order to reduce the response time of ZSl, by using the strategy of reducing the electron density of the capturing group, ZS2 was designed through replacing the phenyl methyl acrylate with ?,? unsaturated phenyl ketone. The results revealed that the response time of ZS2 to H₂S was shortened to 17 minutes with about 100-fold fluorescent enhancement. ZS2 was also found to respond to glutathione at its biological concentration. By HPLC-MS and NMR analysis, the reaction mechanism of ZS2 with hydrogen sulfide and glutathione was recognized.In conclusion, the combination ZSl with ZS2 has a bright prospect for he detection of biological H₂S and GSH in physiological environment. The further evaluation at cellular level are still being carried out.