Chemists from the Okinawa Institute of Science and Technology Graduate University (OIST) have created an organic catalyst that can drive reactions involving pyruvate, a critical biomolecule in many metabolic pathways, that are difficult or impossible to perform using current commercial procedures.
The study, which was just published in Organic Letters, is a significant step toward simplifying the manufacturing process and expanding the range of compounds that may be made from pyruvates, such as amino acids and glycolic acids, which are utilized in drug development and therapy.
“Catalysts, substances which control and accelerate chemical reactions without being included into the final products, are crucial tools for chemists,” said Santanu Mondal, a Ph.D. candidate in the Chemistry and Chemical Bioengineering Unit at OIST and the first author of the study. “And organic catalysts, in particular, are set to revolutionize the industry and make chemistry more sustainable.”
Metal catalysts are currently utilized in industry, but they are costly to develop and produce hazardous waste. Metal catalysts are also challenging to store and handle since they react readily with air and water.
Organic catalysts, on the other hand, are made out of common components like carbon, hydrogen, oxygen, and nitrogen, making them significantly less expensive, safer, and ecologically benign.
Catalysts, substances which control and accelerate chemical reactions without being included into the final products, are crucial tools for chemists. And organic catalysts, in particular, are set to revolutionize the industry and make chemistry more sustainable.
Santanu Mondal
“On top of these advantages, our newly developed organic catalyst system also promotes reactions using pyruvate that aren’t easily achievable using metal catalysts,” added Santanu.
He went on to say that molecules can react by either donating or receiving electrons in all chemical reactions. Pyruvate is utilized in industry to make organic alcohols and solvents because it is considerably better at accepting electrons when it reacts.
However, enzymes, which are protein catalysts, can drive events in which pyruvate gives electrons to build compounds like fatty acids and amino acids within our cells.
The researchers created a catalyst system composed of two tiny organic molecules, an acid, and an amine, that induces pyruvate to act as an electron donor by drawing inspiration from these enzymes.
The amine bonds to the pyruvate in the process, forming an intermediate molecule. The acid then covers part of the intermediate molecule, leaving another part free to react and generate a new product since it can donate electrons.
Importantly, the catalyst system is quite picky about the type of product it produces. Many biomolecules, like our hands, are asymmetric, meaning they may exist in two forms that are mirror reflections of one other. Although these molecules appear to be the same, they often have different properties.
“Organic catalysts can be designed in a way that at the end of the reaction, only one of these mirror-image forms is made,” said Santanu. “This is particularly beneficial in the pharmaceutical industry, where one of the forms may be an effective treatment, but the other form may be toxic.”
By altering which mirror-image form of the amine was used to catalyze the pyruvate reactions, the researchers were able to choose which of the two mirror-image forms of the final product to make.
Currently, the organic catalyst system only works when pyruvate is combined with cyclic imines, a type of organic molecule. But, in the end, the researchers hope to develop a universal next-generation pyruvate catalyst that can speed up reactions between pyruvate and a wide range of organic compounds.
“With a universal catalyst, chemists would be able to easily make an array of various products from pyruvate, in both mirror-image forms,” said Santanu. “This would have many meaningful impacts on society, such as speeding up the development of new drugs.”
