Simple, direct carboxylation method developed for use in heteraromatic compounds using CO2
A method developed using recent studies in carboxylation processes achieved an efficient and more sustainable method of turning lower-reactivity carbon molecules into compounds with use in materials, medical and organic chemistry with a lower cost.
image: The use of SiW12@Cu NP on CF adds a carboxyl group to aromatic hydrocarbons using CO2
Credit: Polyoxometalates, Tsinghua University Press
Chemistry isn’t always known for its sustainable methodologies and simple execution, though the possibilities for finding more direct and efficient ways to synthesize products are limitless. Conventional methods for modifying drug intermediates with the addition of a carboxyl group (a functional group consisting of a carbon double-bonded to an oxygen molecule, with a single bond to a hydroxyl group, or -OH) using carbon dioxide (CO2) in a process called carboxylation often are expensive, have poor stability and high activation energy costs. Alternatively, this study focuses on newer advances in the carboxylation of heteroaromatic compounds, which are organic molecules arranged in a ring format, making them very stable and necessary building blocks for many organic compounds. The advancements shown here use CO2 as a raw material to develop a greener, highly selective and efficient way to add CO2 to heteroaromatic compounds under mild conditions.
Dejin Zang and his team published their results in Polyoxometalates in March 2026.
Polyoxometalates, or POMs, are a distinct class of metal oxide clusters with utility in multiple applications, such as medicine, catalysis and materials sciences. The POM used in this study is polyoxometalate@copper, or SiW12@Cu, with its substrate being copper foam, or CF.
“POMs constitute an excellent class of functional materials that efficiently mediate electron transfer, stabilize reaction intermediates and optimize electrocatalytic efficiency,” said Dejin Zang, author and associate professor at Shandong First Medical University.
Using electrodeposition, a process that utilizes electrical currents to place a thin layer of material upon a conductive surface (CF), the carboxylation process of electron-deficient aromatic heterocycles (aromatic compounds where one carbon is replaced by another atom, in this case a halogen, and has a positive charge due to its electron deficiency) was achieved directly and without the use of precious metals and using CO2 as a raw material to feed the process. Results showed a product yield of over 65% at room temperature, normal atmospheric conditions and without the presence of noble metals, and only taking around 40 minutes for the reaction to occur start to finish.
“This strategy simplifies the modification of drug intermediates, avoids structural damage to sensitive molecules, and optimizes drug properties through post-carboxylation, providing sustainable technical support for innovation in medicinal chemistry,” said Zang.
The use of CO2 as a raw material, along with the lack of precious metals required to activate the reaction, allows a greener method for modifying drug intermediates while prioritizing stability and yield of the product. The carboxylation modification process allows for drug intermediates to have better water solubility, biological activity and metabolic stability. All of this means the drug intermediates can be better controlled, leading to improved dosing intervals and overall improvements in drug interactions within the body.
The limits of this research appear to be far-reaching, with this method being applicable across disciplines and reaching past just the use of halogenated aromatics.
Teng-Teng Wang, Shi Ru, Si-Yu Jiang, Shu-Jun Zhu, Wei-Yao Wang, Min Zhang, Yong-Kai Deng and Dejin Zang of the School of Pharmaceutical Sciences & Institute of Materia Medica, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission, Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, Cong-Cong Zhao of the Department of Mathematics and Physics, Hebei University of Architecture, Bin Liu of The Third, affiliated Hospital of Shandong First Medical University & Affiliated Hospital of Shandong Academy of Medical Science and Yulv Yu of Chambroad Institute contributed to this research.
The National Natural Science Foundation of China, the Natural Science Foundation of Shandong Province, the Joint Innovation Team for Clinical & Basic Research, the Scientific Research Project of Hebei Education Department, and the Scientific Research Program of Hebei University of Architecture made this research possible, along with resources from the Institute of Functional Material Chemistry from Northeast Normal University.
DOI Link:
https://doi.org/10.26599/POM.2026.9140126
About Polyoxometalates
Polyoxometalates (ISSN 2957-9821) is a peer-reviewed (single-blind), open-access and interdisciplinary journal, sponsored by Tsinghua University. Polyoxometalates publishes original high-quality research papers and significant review articles that focus on cutting-edge advancements in Polyoxometalates, and clusters of metals, metal oxides and chalcogenides. Rapid review to ensure quick publication is a key feature of Polyoxometalates. The journal is indexed by ESCI (IF 2025 = 10.4, Top 3), Scopus (CiteScore 2025 = 17.6, Top 3), Ei Compendex, CAS, and DOAJ. For details about Polyoxometalates, please visit: https://www.sciopen.com/journal/2957-9821.