Synthesis and dynamic covalent chemistry of heterocyclic-based aminals

Synthesis and dynamic covalent chemistry of heterocyclic-based aminals

        The theme how to develop effective strategy in designing new drugs is always a hot issue to scientists. Structure-based and computer-aided drug designs are the two conventional ways to discover new drugs. Recently, some research groups have tried to introduce the concept of dynamic combinatorial chemistry (DCL) for developing new antibacterial agents. The primary condition that implementing DCL method to screen drug candidates is to develop a system exhibiting proper dynamic covalent chemistry properties. Dynamic covalent bonds are the covalent bonds that can form or break reversibly. In addition, the formation and the breaking of the covalent bonds can be controlled by the environmental stimuli, such as solvents, temperatures, and acid-base conditions. Dr. Ya-Fan Lin, who is an associate professor in Department of Fragrance and Cosmetic Science, and her team members, including Mr. Ji-Ming Ciou, obtaining his Master degree from Department of Fragrance and Cosmetic Science in the spring of 2020, Mr. Hong-Feng Zhu, a senior student in Department of Medicinal and Applied Chemistry, Miss Chia-Wen Chang, completing her bachelor degree from Department of Fragrance and Cosmetic Science in 2020, and Miss Jing-Yun Chen, currently a second year master’s student in Department of Fragrance and Cosmetic Science, succeeded in the synthesis of a series of novel heterocyclic-based aminals. After investigating the physical organic properties combined with the theoretical calculation study, they confirmed this aminal system displays dynamic covalent properties. The aminals can give different responses and convert to different derivatives in accordance with different solvent environments. For example, the pyrimidyl-based aminal structure can be kept in DMSO, while 10% of them will be transformed to imine form in acetonitrile nitromethane or acetone. Moreover, all of aminals have become hemiaminal ethers if using alcohol as solvents. Noteworthily, the environmental dependent transformations are all reversible, and therefore the molecular species can be switched by solvents. As a result, the dynamic covalent system can generate molecular diversity through solvent effect. The Lin’s group further proved that the existence of the dynamic covalent behaviors in this system is correlated to the nàπ* interaction between the solvent molecule and the aminal. This system is expected to have drug activities since the molecule consists heterocyclic fragments. In the future, the system can be utilized in drug design. Through creating more diversity by dynamic covalent properties, the “from one to more” strategy can generate more candidates in one time and hopefully leads to the buildup of an efficient approach for drug development. 

Main researcher Intro.

Dr. Ya-Fan Lin, Associate Professor in Department of Fragrance and Cosmetic Science

Ya-Fan Lin obtained her PhD degree in Department of Chemistry, National Taiwan University. Her main research interests are in bioinorganic and computational chemistry. Her current research emphasizes a combination of computational and dynamic covelent chemistry strategies to design potential metallodrugs for application in antimicrobial, anticancer, and environmental medicine.

Author Email

yafan@kmu.edu.tw

Paper cited from:

RSC Adv., 2020, 10, 40421

Research Paper available online on website

(Title: Physical organic studies and dynamic covalent chemistry of picolyl heterocyclic amino aminals)

https://pubs.rsc.org/en/content/articlepdf/2020/ra/d0ra08527h