Study details gelation in water media

The Laboratory of Synthesis of New Biomedical Materials published a paper in Journal of Molecular Liquids.

Co-author Shamil Akmetshin comments, "It is impossible to imagine the modern world without gels. Everyone has at least once used shower gels, aftershave gels, lotions, creams, pastes, everyone has tried marmalade, marshmallows, jellies, or jellied meat. Gels belong to the class of soft materials and are popular objects of study as they have great practical importance for biomedical applications."

Gels have been studied at KFU since 2017 under the guidance of Professor Marat Ziganshin, now Director of the Institute of Chemistry.

"Gels are usually divided into physical and supramolecular gels. The peculiarity of the latter is the formation of gel matrix due to spontaneous ordering of small molecules—gel formers. Dipeptides, consisting of a pair of amino acid residues and a protecting group, belong to the class of gelators. The advantages of dipeptide-based supramolecular gels are their biocompatibility and intrinsic biological activity, ease of synthesis, and low cost. Such gels are used in biomedicine, for example, as drug delivery systems or matrices for tissue culture," explains Dr. Ziganshin.

According to Ziganshin, in order to obtain a gel, it is necessary to transfer a gel-forming agent, usually a powder, into a solution. In solution, interacting with each other, the molecules form a kind of three-dimensional nano-network capable of holding solvent molecules and molecules of biologically active compounds.

"Today, the most popular methods for producing hydrogels are: mechanical action, such as ultrasonic treatment; repeated heating and cooling; and pH switching. There is another method based on solvent replacement: the gelator is first dissolved in a suitable organic solvent and then water is added. At first glance, this seems to be the simplest and safest way, but scientists have encountered two problems. Some gels in this way for some unknown reason could not be obtained, and in those that were obtained, the content of organic solvent was too high. Such gels are not safe for humans," continues the Director.

The team conducted a comprehensive study of the gelation process in a number of dipeptides differing in the structure of side substituents and containing a protective fluorenylmethyloxycarbonyl group (FMOC).

"We compared the gel formation ability of four FMOC-substituted dipeptides, which differ only by side substituents in amino acid residues. It was found: the smaller the size of the side substituents (hydrogen atom or CH3 group), the faster gels are formed, but they are less stable. In this case, the gel framework is formed due to the interaction of FMOC-substituents between neighboring dipeptide molecules. If the side substituent is a benzyl fragment, the gel also forms quickly, but it is very stable, because in addition to the FMOC-substituent bond between neighboring dipeptide molecules, bonds are formed due to side substituents. The most surprising thing turned out to be a gel based on FMOC-LL. Such a gel is sometimes mentioned in the literature, but no systematic experimental data on it have been presented. It turned out that gels based on FMOC-LL are very unstable. They disintegrate rapidly. We proved that the large C4H9 substituents in FMOC-LL have an antagonistic effect on Fmoc-group interactions and prevent the formation of fibrillar structures. As a result, FMOC-LL forms a colloidal gel in which the formation of a three-dimensional mesh is due to adhesion forces between spherical aggregates. Such gels are characterized by non-reproducibility and low mechanical strength compared to supramolecular gels. They are very difficult to obtain and even more difficult to study," says Akhmetshin.

The chemists have obtained stable hydrogels. Now they are experimenting with injecting such gels with an antitumor medication. They further plan to study its release kinetics.

"With the help of colleagues from the Kazan Scientific Center of the Russian Academy of Sciences, we were able to peek at dipeptide molecules as they assembled into ordered structures. We studied the kinetics of gel formation, evaluated the strength of interaction between gel-forming molecules and the rheological properties of the resulting gels, the type of structural organization in the gel and in the xerogel that is obtained after solvent removal, and characterized the gel mesh structure using atomic force microscopy. As a result of this study, it was found that depending on the length of the alkyl radical in the side substituent of the studied dipeptides, the hydrophobic parts of the dipeptide either work together and form a fibrous structure and a stable gel, or, on the contrary, compete with each other for the right to determine the type of the final structure. This results in the formation of compact spherical particles 20-100 nanometers in diameter that form an unstable colloidal gel," concludes Marat Ziganshin.

The researchers think that dipeptide-based gels have a huge potential in pharmaceutics and cosmetics, as well in environmental protection technology for waste removal.

More information:
Peculiarities of some Fmoc-dipeptides gelation in DMSO/water medium
www.sciencedirect.com/science/ … ii/S0167732223014174

Provided by Kazan Federal University