Synthetic catalysts that mimic enzymes can greatly enhance drug manufacture, say Dutch scientists

Organic catalysts are essential for a number of industrial applications, but their inability to work together or in water means that their efficiency is limited. Researchers from Eindhoven University believe they may have solved this problem by mimicking the structure of nature's own catalysts - enzymes. Using their new synthetic catalysts, they believe they can greatly speed up drug manufacture

Mimicking enzyme structures for improved organic catalysis

Organic catalysts are essential for a number of industrial applications, but their inability to work within the same system or in water means that their efficiency is somewhat limited. Researchers from the Eindhoven University of Technology believe that they may have solved this problem by taking a leaf out of the structure of nature’s own catalysts – enzymes.

Enzymes are highly selective and effective catalysts, used both in the body and for industrial applications. Their well-defined, compartmentalised three-dimensional structures mean that their active sites are very specific for their particular substrates, making enzyme catalysis extremely efficient. A crucial characteristic of enzymes is that their outsides are hydrophilic, allowing them to work in the watery environment of the body, while the insides – where the active site is situated – are hydrophobic.

Catalysts used in organic chemistry, on the other hand, are quite different to enzymes. They are typically much smaller molecules that do not have large three-dimensional structures around them, and thus tend to be much less selective. However, it is often the case that these catalysts can stimulate reactions that enzymes cannot.

Is there a way to get the best of both worlds? Dr Anja Palmans of the Eindhoven University of Technology thinks so. “We can mimic the three-dimensional structure of an enzyme using polymer chains,’ she explains. “Using what is known as a supramolecular recognition unit, we can fold these chains into compartmentalized architectures much similar to enzymes, which we can then insert a catalytic core into. The folded polymer chain will have a hydrophilic outer surface similar to an enzyme, allowing this synthetic catalyst to work in water.”

The possibilities opened up by this research are numerous. Enzyme-like activity in a completely synthetic system could be used for reaction cascades in which multiple reactions are occurring at once in the same environment. “When making drugs, for example, the current process involves carrying out one reaction, isolating the product and then purifying the product before moving on to the next reaction and repeating the whole process,” explains Palmans. “This is because standard organic catalysts tend to inhibit or alter each other’s activity and so cannot be used within the same system.”

“However, with these synthetic catalysts the active site is shielded and so they do not interfere with each other. This allows one to have a system in which a number of reactions can be happening simultaneously within a single procedure."

The Eindhoven University of Technology has been the base at which this research has taken place, and the unique multidisciplinary environment it has provided has been fundamental to the success of the work, according to Palmans. “The institute we work in, the Institute for Complex Molecular Systems, was specifically created so that researchers from a number of different disciplines can work within the same building,” she says. “We have polymer chemists to work with the polymer chains, organic chemists to develop the catalysts and supramolecular recognition units, polymer physicists to aid our understanding of the folding and to bring complex methods of analysis, as well as mathematicians who utilize their knowledge of modelling."

This wide array of scientists have worked together on the research from the beginning, approaching the task from different directions but with one common goal. This has resulted in a far more thorough understanding of what has been achieved than is normally realised with a narrower field of researchers. “When we take steps forward, they are not just in the sense of improved catalysis; we also understand why these catalysts are behaving like they are and why the polymers are folding like they are. We know the exact shapes of the particles and how the supramolecular recognition units will affect the shape. It is only through working in an institute such as this by which you can achieve such a depth of knowledge. Rather than consulting someone via email or at a conference, you can just drop in to their office and ask them directly.”

Working with people from different scientific fields does sometimes have its problems, as Palmans illustrates: “There are often issues when it comes to the language we use. When a physicist explains something to a chemist and starts talking about phase transitions, the chemist is usually left with a confused expression on their face! Likewise, when a chemist talks to a physicist using fairly standard chemistry terms, the physicist is equally perplexed. It has taken some getting used to, but I feel that we have all ended up learning a lot about each other’s subjects."

The research has now reached the stage at which a good understanding of the polymer folding has been reached, as well as a fairly high level of catalysis. The first experiments on the cascade catalytic systems are now running, but the next step will be to relate the structure of the polymers back to the catalytic activity. “We can now shield the catalysts within the polymer; that has been proven,” says Palmans, “but what we really want to do now is to get back to design principals so that we can improve the levels of catalysis. The mathematicians we are working with will be crucial for this step, as their knowledge of models will allow us to work on molecular design.”

It will be another few years before the final results of this intriguing research are published, and it could be that it helps to revolutionise the use of organic catalysts. Until then, it is good to know that scientists from different backgrounds are able to work in harmony so well, which is surely something to note for anyone with aspirations of starting a new research project.

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