Researchers have discovered a way to introduce the heavier hydrogen ‘brother deuterium’ into many molecules. This method allows drugs to be more effective and can be taken in lower doses, or less often. The study was published in the “Angewandte Chemie International Edition Journal”.
Hydrogen, also known as “H”, is the lightest element. It usually consists of a positively-charged proton and a negatively-charged electron. This form is also known protium. There are also two heavier hydrogensotopes, tritium or deuterium. Deuterium’s nucleus has one neutron, while tritium has two. Both are rare, and tritium, unlike protium or deuterium, is radioactive. Deuterium is the focus of pharmaceutical research since it can ensure drugs are broken down 5-10 or 50 times faster.
Prof. Dr Andreas Gansauer of Bonn’s Kekule Institute for Organic Chemistry and Biochemistry explained, “We call it the kinetic isotope effects.” This is because many reactions, such as the degradation of active chemicals, don’t occur naturally. They require a slight push, the activation energy. This is a bit like getting a car to roll up a hill: It works only if the car has enough momentum.
“If you replace hydrogen by deuterium, the activation power usually increases somewhat. Reactions are therefore slower. Gansauer said that this is also true for the metabolism of pharmaceuticals within the liver.” This means that drugs that contain deuterium rather than protium have a longer duration of action. They can also be taken in lower doses and less often. Deuterium is a rare and expensive metal. Deuterium should be avoided at all points where metabolization is occurring. This is the new process.
It is based in a class called epoxides which can now almost be produced in many different ways. These groups can be viewed as a type of “triangle”, where two corners are made by carbon atoms, and the third by an atom of oxygen. These three-membered rings can easily tear on one side due to their high tension. Because epoxides are like a taut spring and store energy, they can be used to perform certain reactions. “We added epoxides to different test molecules, and then we opened the strained rings with our catalyst. Gansauer explained, “This contains a titan atom to which is bonded deuterium.”
Two reactive ends are formed when the epoxy rings is cut open. The catalyst binds with one of them, which then transfers deuterium to the other free end in a second stage. Gansauer explained that this allows them to introduce a deuterium-atom at a single place and with a specific spatial orientation. He is a member of Transdisciplinary Research Area Building Blocks of Matter & Fundamental Interactions (TRA Matter) at University of Bonn.
Another advantage is that the method can be used to create complex molecules with two different ways to bond. You can create almost only one of these two shapes using the new process. Gansauer stated that compounds of mirror-image molecules can be difficult to separate and have different properties in the body. This is why stereoselectivity is so important.
The method was used to create deuterated precursors of the painkiller ibuprofen as well as the antidepressant venlafaxine. The authors are optimistic that it will be useful for many other pharmaceuticals. (ANI)
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