NSU scientists are exploring an alternative to paracetamol

Maxim Abaev, "Science and Life" based on the materials of NSU 

Chemists from Novosibirsk State University have studied the structure of a new form of metacetamol – an analogue of the well-known paracetamol.

Any medicine can both help the body and harm it, sometimes very, very much. Surely everyone who has ever had a cold has taken medications that include paracetamol. This substance reduces the high temperature and has an analgesic effect. Its effect has long been studied and tested, probably, on millions of patients. However, in a number of countries, paracetamol occupies the first line in the list of causes of liver damage, which leads, among other things, to death. But a lot of people have taken and are taking paracetamol and are not experiencing serious problems, so what's the matter?

The whole point is in the dosage, or rather its gross violation. A daily dose of 4 grams of the drug is considered safe. Taking more than 10 grams can lead to poisoning and damage to liver cells. This is due to the fact that paracetamol is metabolized in the liver in three ways. The first two are safe for the body, while the third method leads to the formation of a toxic product, which causes poisoning and organ damage. If the dose of paracetamol does not exceed the permissible one, then the first two methods are implemented, but if the dose is exceeded, then the first two ways do not cope with the processing of the substance and it begins to be metabolized along the third way – which eventually leads to serious consequences. 

How to avoid this? The easiest and most effective way is to read the instructions where the dosage and warnings are written, for example, that you should not take medications with alcohol. Another way to protect unconscious citizens may be the addition of special substances that block harmful metabolites of paracetamol, even in the case of taking large doses. However, this is a double–edged sword - those who take the drug according to the instructions will be exposed to unnecessary exposure to these substances. There is a third method, the key to which, perhaps, will give chemistry and the study of the structure of substances.

Their properties depend on the structure of molecules, this seems to be quite an obvious fact. You change one group of atoms for another, and the medicine can become poison or vice versa. However, it is equally important how these molecules are arranged relative to each other. If we imagine molecules as bricks, then a solid substance consists of many such blocks arranged relative to each other in a certain way. For example, if a bricklayer, when building a house, will put bricks strictly one on top of the other, then the walls built in this way will soon be covered with cracks, or even completely fall apart. That is why bricks are laid with displacement – this gives strength to the structure. The same is true in chemistry, molecules can fit in different ways relative to each other, as a result, substances are obtained, sometimes with radically different properties. This general phenomenon is called polymorphism. A vivid example of polymorphism is the diamond gemstone and ordinary soot from the furnace. Both of these substances are nothing but different forms of the same chemical element – carbon. Polymorphism is also inherent in medicines. For example, the well-known antibiotic levomycetin exists in two polymorphic forms: α and β, moreover, one of them is active, and the other does not have a therapeutic effect, and the difference is only in the arrangement of molecules in the crystal lattice.

Paracetamol has not bypassed polymorphism either: this molecule has three polymorphic modifications, one of which is stable at room conditions, and the other two – at elevated and very high pressure. However, the interest of chemists from Novosibirsk State and Edinburgh Universities was attracted not by paracetamol itself, but by its, one might say, sibling, metacetamol. The difference in the structure of these two molecules lies in the position of one group of atoms (hydroxyl). According to a number of studies, metacetamol may be less toxic to the liver of patients than a similar paracetamol. The researchers were able to detect a second polymorphic form in metacetamol. They established its physico-chemical properties and described the structure of this substance. 

It turned out that the structure of this polymorphic modification is strikingly different from both other forms of metacetamol and paracetamol. Instead of chains of molecules connected by hydrogen bonds, the new form of metacetamol consists of molecules combined into pairs, which is quite unusual. In addition, chemists have found out that the new form is stable in a dry atmosphere, and under the action of water vapor it passes into a known form. 

Denis Rychkov, one of the participants of the international group, a junior researcher at NSU and a graduate student of the Institute of Solid State Chemistry and Mechanochemistry SB RAS, noted that although this work was exclusively for scientific purposes, obtaining new polymorphs is also important from a practical point of view, for example, for subsequent use in pharmaceuticals. Polymorphs of the same substance may have different solubility, biological activity, hardness, compaction ability, etc. Accordingly, the effectiveness of the drug and the form of release will depend on these indicators. Therefore, there is a possibility that such knowledge about the structure of substances will help make known medicines more effective and safe, which may save someone's liver, or even life.

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28.08.2015