| dc.description.abstract | Part I Design and Synthesis of Barbiturate-Conjugated Derivatives as Potential Anti-Cancer Agents
Through high-throughput screening (HTS), extensively optimized drug discovery can be carried out these days. Aromatic and non-aromatic heterocyclic rings usually play key roles in interacting with the target biological macromolecules such as the active sites of enzymes. Based on the observations published, these heterocyclic rings can be a quick identification of “hits” to evaluate which heterocyclic derivatives can be the most potential structures in drug discovery.
With our investigation in this research, we have found that a series of barbiturate derivatives have quite potential bioactivities as pharmacophore. Besides, some published reports have mentioned the synthesized cinnamaldehydes or piperonals derivatives have great potential as anti-cancer or antibacterial agents. Herein, we have synthesized the conjugates of 3,4-methylenedioxycinnamaldehyde and barbiturate. By combining the bioactive aldehydes to barbiturates, the conjugates formed may have a more noticeable activity.
In this research, we have successfully synthesized a series of modified barbiturates by Knoevenagel condensation with 3,4-methylenedioxy- cinnamaldehyde and barbiturates. And we also synthesize the products with simpler aldehyde structure like benzaldehyde and cinnamaldehyde to discuss the differences. The bio-evaluation of these derivatives was also held to check their activities as anti-hepatoma and anti-fibrosis agent.
Part II Develop New Water-Based Synthesis of Zirconium-
Organic Framework
Metal-Organic Frameworks (MOFs) have numerous applications due to their good chemical/thermal stability, extraordinary porosity and high specific surface area. However, the synthetic methodologies for MOFs are limited in organic solvent system that may damage the environment. As a consequence, developing an environmental friendly approach for synthesizing MOFs is in urgent need. More specifically, inventing a method with water, an absolutely clean resource, as solvent to obtain MOFs is of great value, not to mention the possible huge impact water may have on the reaction. In our previous report, we successfully obtained ZIF-90 under water-based system. Besides, we demonstrated a de novo approach to acquire an enzyme@ZIF-90 composite with substrate selectivity and shielding capability. Nevertheless, the small aperture size of 3.5 Å in ZIF-90 restricted its catalysis ability--that is, the small size of window shields other oversized substrates as well as denaturants. Therefore, to solve the above problem, obtaining other MOFs with bigger size in aperture with water-based approach is what we are trying to do in this thesis.
UiO-66 with aperture size of 6.0 Å is the most thermal stable structure for MOFs. Our previous research revealed that different functional groups on benzene-1,4-dicarboxylic acid (BDC) could manipulate the bonding strength between Zr and carboxylate groups. Therefore, based on our previous results, we intend to optimize the synthetic condition of UiO-66 under water. Herein, we report the improved condition in which tetrafluoroterephthalic acid acted as organic linkers, and successfully synthesized UiO-66-F4 in minutes under acid aqueous solution. | en_US |