'Heavy' Hydrogen Stabilizes Drugs: University Of Bonn Scientists

Researchers have presented a method that allows the heavier hydrogen 'brother' deuterium to be introduced specifically into many different molecules. The deuterated compounds obtained in this way are more stable against degradation by certain enzymes.

Photo Insert: Deuterium ionized

Drugs produced using this method can be effective for longer, meaning they have to be taken in lower doses or less frequently, the University of Bonn reported late in Dec. 2021 for ScienceDaily.

Hydrogen (abbreviated "H") is the lightest of all elements. It usually consists only of a positively charged proton and a negatively charged electron and is also called protium in this form. But there are also two heavier hydrogen isotopes, deuterium and tritium.

The deuterium nucleus contains one neutron in addition to the proton, in the case of tritium there are even two. Both are very rare; tritium is also -- in contrast to deuterium and protium -- radioactive.

Deuterium has been the focus of pharmaceutical research for some years, because it can ensure that drugs are broken down 5, 10, or even 50 times more slowly. "We call this the kinetic isotope effect," explains Prof. Dr. Andreas Gansäuer of the Kekulé Institute for Organic Chemistry and Biochemistry at the University of Bonn (Germany).

The reason for this is that many reactions, including the degradation of active substances, do not occur spontaneously. They first need a slight "push," the activation energy. This is somewhat like getting a model car to roll over a hill: That too only works if the car has sufficient momentum.

"If you replace hydrogen with deuterium, the activation energy usually increases somewhat," says Gansäuer. "As a result, reactions are slower. This also applies to the metabolism of pharmaceuticals in the liver."

This means that introducing deuterium instead of protium into drugs causes them to have a longer effect. They can therefore be taken in lower doses or less frequently. However, deuterium is rare and thus comparatively expensive. Consequently, deuterium should ideally only be introduced at the points where metabolization occurs primarily.

This is where the new process comes in. It is based on a class of substrates called epoxides, which can now be produced almost at will in many different ways. These groups can be visualized as a kind of "triangle" in which two corners are formed by carbon atoms and the third by an oxygen atom. Such three-membered rings are under great tension, which means they tear easily on one side. Epoxides, therefore, store energy like a taut spring, which can then be used for certain reactions.

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