Taking the guesswork out of understanding complex, multi-molecule transformations

Mar 11, 2011
Figure 1: In contrast to a conventional three-component model (left), the artificial force induced reaction (AFIR) revealed that the Passerini reaction involves a fourth component (red arrow). Credit: 2011 Wiley-VCH Verlag GmbH & Co

Multicomponent reactions (MCRs) that chemically combine three or more molecules into a brand new product are faster and generate less waste than traditional step-by-step synthetic procedures, making them invaluable in efforts to improve efficiency and sustainability. Since 1921, chemists have used an MCR called the Passerini reaction to produce bioactive, peptide-like chains made from three partners: carboxylic acids, carbonyl compounds, and cyanide-bearing molecules. However, a full understanding of this process has eluded researchers because its multipart workings are difficult to detect experimentally.

Now, Satoshi Maeda and Keiji Morokuma from Kyoto University and Shinsuke Komagawa and Masanobu Uchiyama from the RIKEN Advanced Science Institute in Wako have developed a computerized way to better identify the hidden mechanisms of one-pot, multi-step . Their technique, the artificial force induced reaction (AFIR), systematically squeezes and joins model compounds together in order to rapidly detect signatures of real MCR energy barriers.

According to Maeda, detailed theoretical understandings of MCRs have been scarce because most calculations require excellent estimates of transition state structures—intermediate and often highly strained geometric arrangements between molecules that correspond to the energetic peak of a reaction barrier. “Consequently, a trial-and-error process based only on [chemistry-based] intuition is unavoidable,” he says.

The AFIR method, on the other hand, requires no such presumptions. Maeda explains that when two molecules are pushed into each other with a weak force, they spontaneously relax into ‘dents’ in the potential barrier created by attractive electronic interactions between the reactants. By methodically pressing over all possible orientations, and inducing an artificial reaction from the relaxed positions, AFIR searches can identify every stable reaction pathway in a system.

To the team’s surprise, applying AFIR calculations to the Passerini reaction revealed that four components, not the long-thought three, must be involved (Fig. 1). Since the reaction barriers were so high, the researchers realized that an additional carboxylic acid—a known proton transfer catalyst—had to participate in the transition states leading to the final product. This finding should enable design of Passerini reactions with improved structural selectivity, notes Maeda.

Once perfected, the researchers anticipate their technique will make MCRs even more widespread. “Unlike standard methods, giving only pathways that are easy to find, the AFIR method has a unique ability to find unknown pathways in MCRs systematically,” says Maeda. “Information on reaction pathways is very important even for processes that do not normally occur, because chemists can initiate such reactions by controlling conditions, modifying substituents, and introducing new catalysts.”

Explore further: Marine pest provides advances in maritime anti-fouling and biomedicine

More information: Maeda, S., et al. Finding reaction pathways for multicomponent reactions: The Passerini reaction is a four-component reaction. Angewandte Chemie International Edition 50, 644–649 (2011). onlinelibrary.wiley.com/doi/10… e.201005336/abstract

add to favorites email to friend print save as pdf

Related Stories

Emory chemists reveal challenge to reaction theory

Dec 17, 2004

For nearly 75 years, transition-state theory has guided chemists in how they view the way chemical reactions proceed. Recent research by Emory University chemists is challenging the long-held theory, showing that in some ...

Recommended for you

Nature inspires a greener way to make colorful plastics

18 hours ago

Long before humans figured out how to create colors, nature had already perfected the process—think stunning, bright butterfly wings of many different hues, for example. Now scientists are tapping into ...

New catalyst converts carbon dioxide to fuel

20 hours ago

Scientists from the University of Illinois at Chicago have synthesized a catalyst that improves their system for converting waste carbon dioxide into syngas, a precursor of gasoline and other energy-rich products, bringing ...

Building the ideal rest stop for protons

Jul 29, 2014

Where protons, or positive charges, decide to rest makes the difference between proceeding towards ammonia (NH3) production or not, according to scientists at Pacific Northwest National Laboratory (PNNL) and ...

Cagey material acts as alcohol factory

Jul 29, 2014

Some chemical conversions are harder than others. Refining natural gas into an easy-to-transport, easy-to-store liquid alcohol has so far been a logistic and economic challenge. But now, a new material, designed ...

User comments : 0