Artistic single-atom catalysts can enable sustainable chemical and pharmaceutical synthesis

The National University of Singapore (NUS) chemists have developed an “anchored open” strategy combined with facet engineering, developing a new class of artistic single-atomic catalysts (ASACS). These catalysts are formed by immobilizing foreign single atoms on specific aspects of the reducing support material, allowing bypassing traditional oxidative addition steps in interconnected reactions widely used in the fine chemical and pharmaceutical industries.

This work has been published in Nature Communications magazine.

A new type of solid catalyst, single-atom catalysts (SACs), attract much attention for their ability to maximize the use of all atoms and create well-defined, highly active reactive sites. They offer a unique combination of the benefits found in both traditional and modern methods used in the manufacture of chemicals.

In general, materials that hold metal atoms must be designed to maintain stability while allowing sufficient flexibility to run efficiently. However, strong bonds between metal atoms and support can limit reactivity as they are necessary to prevent metal atoms from aggregating together. This limitation can make it difficult for a single metal site to function well in certain chemical reactions that involve multiple steps, such as mutual bond reactions.

The research team, led by Associate Professor Lu Jiong of the NUS Chemistry Department, developed a “fixed” strategy. The key idea behind this innovation is to anchor a single metal atom to a specific site on the surface of the metal oxide. These surfaces can “borrow” oxygen atoms from the surroundings while using metal oxides as electron reservoirs, serving as anchor points. This unique design allows the structure to be adapted and varied in a way that avoids the high demand for complex electronic changes in the metal itself. This is a general challenge in traditional mutual bond reactions.

The work is a joint effort with Associate Professor Wu Zi of the Chemistry Bureau, Associate Professor Wang Yanggang of the University of Science and Technology in Southern China, Associate Professor Wu Dongshan of Nanyang Technology University in Singapore, and Associate Professor Hai Xiao of Peking University in China.

Researchers have used cerium oxide (CEO2,110) as a support material and found that the resulting PD1-CEO2 (110) works very well even in difficult-to-react chemicals such as aryl chlorides and complex compounds. This catalyst is better than traditional ones, providing high yields, excellent stability and setting a new benchmark for turnover counts.

This discovery, coupled with its ability to rapidly generate large quantities of catalysts, demonstrates the promising potential of ASACs for the large-scale production of pharmaceuticals and products.

This study shows that ASACS is a highly effective and versatile catalyst for cross-coupling reactions, an important transformation in chemical and pharmaceutical manufacturing. Traditional capsules usually struggle with aryl chloride because they have very strong carbon chlorine bonds, which makes them slow and inefficient. However, ASACS overcomes this problem by achieving consistently high yields by having flexible, adaptive active sites that enhance reactivity with other demanding substrates such as aryl chloride and heterophyletic compounds.

ASAC exhibits wide applicability across other types of reactions, such as the Heck reaction (between aryl halides and alkenes) and the Sonogasilla reaction (between aryl halogenation and alkynes), indicating a wide range of possibilities for a variety of bonding reactions.

Combining experimental and theoretical research, researchers have discovered that ASAC works by dynamically changing the structure of palladium (PD) atoms. CEO2 materials serve as electron reservoirs, providing electrons to stabilize PD atoms and prevent peroxidation. This electronic buffering significantly reduces the energy required for the reaction. Advanced X-ray Absorption Proximity Structure (XANES) measurements confirmed that the PD atoms had little change in their oxidation state during the reaction, and that the catalyst remained active and stable over time.

Association. Professor Lu said, “The new concept of heterogeneous ASAC provides a much more environmentally friendly way to tackle the long-standing challenges of oxidative addition in mutual bond reactions. This strategy goes beyond the limits of traditional homogeneous and heterogeneous catalysts, and has great potential for large-scale, sustainable production of premium chemicals and pharmaceuticals.

“We plan to expand this approach to a wider range of metals that can be used in cross-coupling reactions. By adjusting the type and combination of single atoms and support material, we can improve the performance of more abundant and non-preferred metals in these reactions.”