Ever since their development in the late 19th century, Schiff bases have been a popular group of organic compounds, owing to their wide variety of desirable properties. The presence of both nitrogen and oxygen in their structure makes them versatile molecules with an array of applications, ranging from dyes and catalysts to environmental sensors and raw materials for chemical synthesis.
Recently, there has been growing interest in the biological activity of Schiff bases, as researchers have discovered that metal complex derivatives of Schiff bases can serve as antioxidant, antimicrobial, and anticancer agents. Among these compounds, studies have shown that amino acid Schiff base copper (Cu) complexes have the most promising antimicrobial properties; however, the reaction time taken to create these compounds can range from hours to days.
In a recent breakthrough published on 18 June 2022 in Applied Microbiology, a team of researchers led by Professor Takashiro Akitsu from the Tokyo University of Science reported a two-step synthesis procedure that produced amino acid Schiff base Cu (II) complexes within a mere 10 minutes! The team included Dr. Estelle Léonard and Dr. Antoine Fayeulle from ESCOM, TIMR (Integrated Transformations of Renewable Matter), Centre de Recherche Royallieu, University of Technology of Compiègne, France.
“Amino acid Schiff base Cu (II) complexes have the potential to be used as antimicrobial agents but their wider applications are being limited by conventional methods for synthesis that often takes several hours and sometimes days. With our research, we aim to overcome this challenge by making the synthesis process more facile,” comments Prof. Akitsu on the rationale behind their study.
The team used microwave irradiation to prepare these compounds, owing to its ability to greatly accelerate the reaction while providing controlled heating. This method also ensures higher yields, better purity, and fewer by-products. Additionally, they chose methanol as the solvent for the reactions. With a high loss tangent of 0.659, which determines the ability to convert microwave energy into heat, and a high microwave absorption rate, methanol was ideal for accelerating the reactions and lowered the global reaction time to 10 minutes.
To gauge the antibacterial properties of the compounds, the researchers tested them against various bacteria. They found that the one- and two-chlorine substituted complexes showed better action against bacteria, with remarkable activity against E. coli, than the molecules with no chlorine groups. The team also noted the presence of light antioxidant properties in the one- and two-chlorinated complexes. In the future, the team aims to check for the toxicity of these compounds toward kidney, liver, and skin cells.
This new synthesis technique minimizes the global reaction time, maximizes the reaction conditions, and produces high purity products with promising antibacterial activity. The insights from this study can be used as a framework for the development of fast and facile synthesis techniques for biologically active amino acid derivatives of Schiff base metal complexes. “Bacterial infectious diseases are a major threat to public health. Our study aims to contribute towards the improvement of health care systems in developing nations that are often affected by infectious epidemics,” concludes Prof Akitsu.
About The Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science by inculcating the love for science in researchers, technicians, and educators.
With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society”, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today’s most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.
About Professor Takashiro Akitsu from Tokyo University of Science
Prof. Takashiro Akitsu is a professor in the Department of Chemistry, Faculty of Science, Tokyo University of Science (TUS), Japan. He graduated from Osaka University and obtained his Ph.D. in Physical and Inorganic Chemistry in 2000 and went on to study physical and bioinorganic chemistry at Stanford before moving to TUS. He joined the TUS as a Junior Associate Professor in 2008 and became a Professor in 2016. He has published 220 articles and book chapters and served as an editorial board member in many international peer-reviewed journals. His current research areas involve the study of imines, Schiff bases, coordination chemistry, and crystal structures.
This research was funded by TIMR UTC‐ESCOM, and this work was supported by a Grant‐in‐Aid for Scientific Research (A) KAKENHI (20H00336).