γ-cyclodextrin (gamma-cyclodextrin) is an ingenious molecule. It consists of eight sugar molecules strung together, which together form a large ring. It dissolves very well in water – the outside of the ring is very hydrophilic. On the contrary, the inside of the ring is hydrophobic, fatty. That combination is helpful. Cyclodextrins, for example, can carry drugs that are not water-soluble in the hydrophobic interior, so that the entire complex does dissolve in water together. The trapped drug then travels through the body to the right place. For example, a lower dose is required, which reduces the risk of side effects. In addition, cyclodextrins are ‘green’: they break down in the environment or in the body.

Expensive and inefficient process

The great water solubility makes production problematic. The molecule has to be made in water, but it is then hardly possible to get it out. Chemists therefore allow γ-cyclodextrin to stick to a guest molecule, because together they are easier to filter out of water. But separating the molecules afterwards requires an expensive and inefficient distillation process.

The American researchers also used such a guest molecule, but one that changes shape due to light. They found a molecule that fits exactly inside the host’s ring, but no longer fits after the shape change. This way the substances separate easily, without distillation.

“This will lower the price,” said Ivan Aprahamian, professor and supervisor of the study. γ-cyclodextrin now costs $800 per five grams. “In addition, the process is becoming more environmentally friendly.”

“It’s wonderful work,” says Jan van Maarseveen. He is professor of organic chemistry at the University of Amsterdam. He believes that not only the way in which the molecules are separated, but also the reaction itself is cleverly designed. “It is difficult for chemists to make a cyclodextrin of a certain size. Nature strings sugar molecules together with enzymes. The researchers use an enzyme that links sugar molecules together and bites itself in the tail, creating a cyclic molecule.”

That γ-cyclodextrin can then be easily separated from the host molecule by light is “the researchers’ second clever trick,” he says. “That principle appears to work fantastically.”

But the protocol is not yet suitable for the production of large amounts of γ-cyclodextrin, says Van Maarseveen. “The researchers do the separation of guest and host in a way that is difficult to scale up: chromatography.” This separation method is primarily intended for small-scale research in the lab. “Optimization of the process is still necessary”, thinks Aprahamian.