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Small Particles Bring Great Benefit


Chemistry teams from two universities – Lomonosov Moscow State University and Texas A&M University (USA) have improved the efficacy of pharmaceutical substance synthesis by simplifying the process. The Russian team is guided by Academician Irina Beletskaya, and the US team by Professor David Edward Bergbreiter. These two teams play on the same side because the nanoreactor concept they are using will in the long run allow to simplify in many respects chemical and pharmaceutical technology and, most importantly, to make it cleaner from the ecological point of view. The research has been sponsored by the CRDF foundation and the Federal Agency for Science and Innovation (Rosnauka).

Synthesis of biologically active molecules, such as pharmaceutical drugs, is connected with a number of complications. It is easy on paper to “assemble” chains of various atoms into required structures, but in nature, enzymes – natural catalysts – help to synthesize these substances. The synthesis can not be performed without catalysts in the laboratory and, accordingly, in the industry.

In live systems, catalysts are a natural part of these systems, which have been perfected over millions of years of evolution, to the minutest detail. However in the human body, even the best of known catalysts, such as platinum metals and palladium suffer from at least two drawbacks.

Firstly, these processes involve unsafe organic matters – dissolvents and ligands, i.e., complexing agents for catalyst metals – which are rather toxic. Secondly, separation of the product from metal is a complicated task. It is difficult to wash their traces from the drug, in the drug they are not only unneeded, but also harmful. Also, it is impossible to collect all of palladium when washing.

To solve these problems, i.e. to create such palladium nanoparticles, which would allow to synthesize necessary substances easily and quickly and would not get into the final product, will be permitted by the approach being developed by chemists under the guidance of Irina Beletskaya and David Bergbreiter. As a result of this, stable palladium particles of the size of only several nanometers may be synthesized directly in the polymeric matrix. The process will be going in the smallest pores of this matrix – tiny, extremely active particles of palladium will be formed, which in turn, will help to get reaction products from inters.

Groups of ligands (included in the polymer composition in advance) will help to retain the catalyst inside the matrix. These are “suspended”, as chemists put it, in the main chain of the polymer, where they will strongly retain metal in the matrix from which it is impossible to wash out.

It is certainly an enormous effort to develop the required polymer and to synthesize such polymers in order to choose the best ones. Rather diverse requirements need to be considered, such as the stability of palladium nanoparticles, their activity, ease of regeneration, accessibility for reagents, and freedom of movement of inters and reaction products.

On top of that, the researchers plan to investigate another approach using polymeric micellas. Palladium nanoparticles are formed in the nucleus of polymeric micellas and the target product is found at the border of phase division between the nucleus and the so-called corona of micellas. In this case, it consists of long and flexible “tails” of polyethylene oxide, which are, in contrast to the nuclei of polystyrene micellas, well-soluble in water. Constructing these micellas allows the team to carry out the reaction in water, without organic solvents, in strict compliance with the requirements of the so-called “green” (safe) chemistry. However, the researchers have polymers available that are capable to form micellas in an nonaqueous environment.

In any case, all these polymeric systems, both micellas and nanoporomeric cross-linked ones, i.e. three-dimensional polymers, will be easy to separate from the solution of obtained drug together with the harmful ligand being part of the polymer and reliably connected to it.

“The main goal of our project is to develop new efficient catalysts, which can be reused, says Academician Irina Beletskaya. With the help of these catalysts we shall be able to receive drugs not contaminated by phosphines or traces of metals, this would significantly simplify drugs’ extraction and purification and minimize organic solvent application. In the long run, our project would solve a diversity of problems connected with the synthesis of biologically important compounds from simple parent substances."

Sergey Komarov | alfa
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