Chemists develop chiral DNA catalyst for asymmetric catalysis

Chemists at the National University of Singapore (NUS) have developed a method to create a variety of chiral deoxyribonucleic acid (DNA) catalysts by fusing DNA repair and biorthogonal chemistry, providing a more efficient approach to asymmetric catalysis. paved the way for a versatile approach.

Enzyme catalysis, which uses biological proteins to drive chemical reactions, is emerging as a sustainable approach to produce chiral molecules. However, using proteins as catalysts is challenging because they are often unstable and their design requires complex DNA manipulation.

To address these issues, scientists have turned to DNA as a more stable and cost-effective chiral scaffold for sustainable asymmetric catalysis. Additionally, DNA’s unique base-pairing mechanism makes it highly programmable, allowing precise control over its structure and function.

A research team led by Assistant Professor Zhu Ru-Yi from the NUS School of Chemistry has developed a method to create chiral DNA catalysts by harnessing an enzymatic process called DNA repair and combining it with biorthogonal chemistry.

This method simplifies the production of DNA catalysts, does not require sophisticated equipment or specialized knowledge, and allows non-experts to perform DNA catalysis. Additionally, the bioorthogonal chemical reactions proceed without interfering with functionality, making this method highly compatible with a variety of functional groups.

The research results were published in the Journal of the American Chemical Society.

The researchers used this new approach, which combines chemical reactions and enzymatic processes, to build a library of 44 different DNA catalysts.

These newly developed DNA catalysts showed superior performance over previous versions in terms of enantioselectivity, substrate coverage, and overall reaction efficiency. More importantly, the team also demonstrated the first example of atroposelective DNA catalysis, successfully producing axylchiral compounds that are typically difficult to synthesize using biocatalytic methods.

The robustness of this method was further demonstrated by the ability to assemble a wide variety of structurally different DNA catalysts with unprotected functional groups.

Professor Zhu said: “Our method significantly lowers the barrier to performing DNA-catalyzed reactions that previously required highly specialized, expensive and difficult solid-phase synthesis.”

“We hope that more researchers will realize the great potential of DNA catalysis and join this exciting field of research,” added Professor Zhu.

Looking ahead, the research team is actively designing new strategies to develop selective and sustainable DNA-catalyzed chemical reactions.