1. Substituents' Effect of Subsi on Green Synthesis Efficiency/Chalcones' Optical Properties

​

During my chemistry studies, I encountered an intriguing concept called the substitution effect, which suggests that the presence of substituents can influence the properties of compounds. Inspired by this, I designed the experiments, adding both electron-withdrawing and electron-donating substituents to the precursor, and then characterized the products. Having learned about Claisen-Schmidt condensation reactions, I chose chalcone as the precursor, prepared by base-catalyzed aldol condensation of acetophenone with benzaldehyde. 

The chalcone was then substituted and examined by UV-Vis spectroscopy. I noticed red shifts induced by two different types of substituents, which indicate a smaller energy gap between the lowest unoccupied molecular orbitals (LUMO) and the highest occupied molecular orbitals (HOMO) on the products. Curious about the reasons, I began to make assumptions and rationalise the red shifts’ results by applying my A-level knowledge: In an electron-withdrawing group like a 4-nitro group, these changes might be due to resonance and electronegativity. Resonance increases the extent of electron delocalisation, while the high electronegativity of the nitro group stabilises the system by weakening electron-electron repulsion. Both result in lowering the LUMO energy, whereas the electron-donating groups like 4-methoxy can raise the energy of HOMO through pi conjugation. It was rewarding to find my hypotheses aligned with the literature’s explanation. This first independently designed experiment has allowed me to apply theory into practice, fueling my passion for chemistry while gaining actual lab experience.

​

2. Synthesis of Glycoside Derivatives, quinoline, and attempt to complete the extension of the project of synthesizing a novel compound with tumor-inhibitory potential

​

Design and synthesis of chemical molecules have always been a field of deep interest to me. My curiosity about the synthesis methodology was piqued after learning about anti-cancer drugs. After reviewing literatures, I was introduced to glycoside, a commonly used compound in drug synthesis, and later started to explore the corresponding synthesis (methodology) when working as an intern in Professor Wu’s group. I selected a mild Schmidt type glycosylation sequence as my synthesis method. The reaction was intractable because all reactive hydroxyl groups on the sugar needed to be protected first. Without masking them, glycosylation could occur at unfavorable positions, forming inseparable mixture of regioisomers and stereoisomers.

​

Another problem I encountered was low yield due to poor reactant selection. After the previous steps, selective deprotection at the anomeric position was required, converting the benzyl ester group into a reactive free hydroxyl. However, the original method for this step produced unsatisfying results. The literature indicates that this is due to benzoate being a poor leaving group, which confused me at first since the resulting benzoate ion is resonance-stabilised. The mystery was solved when I came to understand that its basicity remains relatively high, impeding its departure under neutral or basic conditions. Therefore, I decided to use the highly electronegative hydrobromic acid instead to provide not only a better leaving group but also a strongly acidic environment enabling the subsequent substitution. Based on the results, I discovered a novel glycoside-derived molecule that shows potential inhibitory activity against brain tumour cells. Although unable to finish the plan of synthesis due to time limits, I am eager to explore it further in follow-up experiments. Just like my experience in the medical factory during COVID-19, this engagement made me see the tangible impacts chemistry can have on the world, further intensifying my enthusiasm towards the subject.