| This thesis deals with three parts of works. Part I is the synthesis, characterizations of Indy-N-heterocyclic carbene complexes of rhodium, palladium and gold, and the catalytic hydration of alkynes with gold NHC complexe. Part Ⅱ is the design, synthesis and the activity of novel Schiff-base-dervied FabH inhibitors with dioxygenated rings as antibiotic agents. Part III the establishment of hydrogen sulifide fluorescent probe library and the screening for highly selective and sensitive fluorescent probe with good solubility.Comparing with the phosphine ligands, N-heterocyclic carbenes metal complexes often promoted higher catalytic activity and stablity owing to the strong σ-donation and the excellent stability of NHC ligands, and now N-Heterocyclic carbenes have been working as a useful role as ligands in organometallic chemistry. We designed and synthesized novel Indy-NHC ligands that their phenyl group on the nitrogen modified with various substituents. Via the mild Ag-carben transfer route, the new carbene ligands reacted with rhodium, palladium, and gold salts to yield the corresponding air-stable metal complexes. The product complexes were characterized by NMR spectroscopic methods and X-ray diffraction analysis. The IR stretching frequencies of CO and the13C NMR shifts of Rh-C(ligand) in dicarbonyl rhodium complex RhCl(CO)2L show most of the ligands have high stronger donating abilities than most konwn ligands. The catalytic property of the gold complex was also evaluated in hydration of alkynes to give the corresponding ketone products. This new type gold N-heterocyclic carbene complex showed a high catalytic activity with the yield80-99%.The FabH inhibitors as a new antibacterial drugs has been the hotspot in the field of druy research, and their structure-activity relationship has been in-depth study for many years. On this basis, we designed and syntheized21new Schiff base derivatives through molecular docking and the development of a FabH pharmacophore model. Within this research, several compounds with potent and selective anti-Gram-negative bacteria activities were obtained. Compounds2.2-10d—2.2-10f, and2.2-10u exhibited excellent activities against Gram-negative E.coli and P.aeruginosa. Particularly, compound2.2-10f showed the most potent E.coli FabH inhibitory activity with an IC50value of1.6μm, which was compared with the positive control, kanamycin B. Molecular docking simulation was performed to position compound2.2-10f into the E.coli FabH active site in order to determine the probable binding conformation. Based on the data obtained in this study, we concluded that compound2.2-10f is the E.coli FabH inhibitor most deserving of further research as a potential antibiotic.Aqueous sulfides including hydrogen sulfide play important roles in biological signaling and metabolic processes. We synthesized a series of hydrogen sulfide fluorescent probes based on the our published articles. We further evaluated the the fluorescence characteristics, hydrogen sulfide reaction rate, selectivity and solubility of these probes. All the results showed that the introduction of electron withdrawing groups will decrease the fluorescence intensity of the probe SFP-1, and the introduction of a trifluoromethyl group can significantly improve solubility of the probe. So screening these series probes, we finalized the probe3.2-19c as the potential fluorescent probes for detecting hydrogen sulfide in living cell for the futher research. |
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