Design, Synthesis And Studies Of Functional Molecules For Sulphide Detection, Squaramide Catalyzation, And Anticancer Activity

This thesis deals with four parts of work. Part I is the preparation and application of a serial of new selective and sensitive fluorescent probes for monitoring sulphide; Part II is the application of squaramide catalysts to catalyze enantioselective Friedel-Crafts reaction of indoles with N-tosyl imines; PartⅢis the synthesis, characterization and biological activities study of chalcones derivatives; PartⅣis synthesis and biological activities study of novel iridium complexes.Aqueous sulfides including hydrogen sulfide play important roles in biological signaling and metabolic processes. We have designed a selective sulfide-trapping chemical strategy comprised of sulfide addition to an aldehyde and the resulting hemithioacetal performing a Michael addition to an adjacent unsaturated acry late ester to form a thioacetal at neutral pH in aqueous solution. Employing this new strategy, two sulfide-selective fluorescent probes, SFP-1 and SFP-2, were synthesized based on two different fluorophore templates. These probes exhibit an excellent fluorescence increase and an emission maximum shift (SFP-1) in response to Na2S and H2S in a high thiol background as found under physiological conditions. We show the utility of the probes for the selective detection of sulfides, and the capacity of our probes to monitor enzymatic H2S biogenesis and image free sulfide in living cells. Then based on these two probes, we have developed other two new sensitive and selective probes SFP-3 and SFP-4 that show a significant emission increase in the fast response to sulfide over the biologically relevant pH range. The excellent linear relationship between emission intensity and sulfide concentration was obtained in bovine plasma system. These probes were successfully applied for the parallel measurement of sulfide concentration in mice blood plasma. This fast, sensitive and selective probe has the potential to be a useful tool for fast and real-time detection of sulfide in more types of biological samples. Hydrogen bond catalysis is playing an increasingly important role in the development of enantioselective reactions. We prepared a small library of new squaramide-based catalysts, and evaluated their capacity to promote Friedel-Crafts reactions of indoles. The results found chiral squaramides are highly enantioselective catalysts for Friedel-Crafts reaction of indoles with N-tosyl imines, affording 3-indolyl methanamine products in 85-96% yields and 84-96% ees.Two novel compounds with the chalcone scaffold have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferative inhibitors. Compound 2n and 4q showed the most potent biological activity in vitro, which inhibited the growth of MCF-7 cells with IC50 of 0.04±0.01μM and 0.09±0.01μM, respectively. To understand the tubulin-inhibitor interaction and the selectivity of the most active compound towards tubulin, molecular modeling studies were performed to dock compound 2n and 4q into the colchicine binding site, which suggested probable inhibition mechanism. We also design, synthesis, and biological evaluation a series of novel iridium (Ⅲ) complexes with bidentate nitrone ligands as anticancer agents. The in vitro studies showed that the complexes have a strong anti-prolifcrative effect in cancer cell lines and the complex 2f with the highest activity in cell culture can induce HepG2 cells to undergo apoptosis. Furthermore, the complex 2f exhibited greater activity in inhibiting tumor growth in vivo.