SATURATION TRANSFERENCE DIFFERENCE NMR APPLIED TO THE STUDY OF POLYMERS AND IONIC LIQUID INTERACTIONS

The Saturation Transfer Difference Nuclear Magnetic Resonance (STD-NMR) technique is a powerful tool for studying intermolecular interactions, particularly between small molecules (ligands) and macromolecules such as proteins, polymers, or supramolecular complexes. Its principle is based on the selective transfer of magnetization by saturation from the nucleus of one molecule to the nuclei of another molecule in close spatial proximity. This technique enables the mapping of which atoms or functional groups of a molecule are in direct contact with another during the interaction, without the need for isotopic labeling or chemical modification, making it especially valuable for studies on molecular affinity and recognition [1], [2].

The way molecules organize and interact directly influences physicochemical properties such as solubility, stability, rheological behavior, encapsulation capacity, and more. Therefore, the insights provided by STD-NMR allow researchers to correlate molecular interactions with the macroscopic performance of materials, enabling their rational design and use in the development of new functional materials.

Polymeric gels are semi-solid materials composed of polymers with a three-dimensional (3D) network structure formed through covalent or non-covalent bonds, dispersed in a liquid medium that provides the gel’s elastic characteristics [3]. The properties of these systems depend on factors such as the type of polymeric matrix, the nature of the cross-linking, and the intermolecular interactions. Consequently, polymeric gels can exhibit a wide range of properties (e.g., swelling capacity, pseudoplastic rheological behavior, interaction with charged surfactants) [3].

Water-based gels — known as hydrogels — exhibit excellent biodegradability and biocompatibility due to their structural similarity to living tissue and show great potential for carrying active additives such as antimicrobial and antioxidant agents. Hydrogels can be formed by mixing a cationic polymer with an anionic one, resulting in a polyelectrolyte complex. Chitosan is considered one of the most promising natural polysaccharides in the food field due to its biodegradability, antimicrobial activity, and good film-forming ability [4]. Sodium alginate is a naturally occurring, versatile polymer with high potential for gel production, owing to its non-toxicity and wide application in food, cosmetics, and pharmaceutical products. As a polyanionic polymer, alginate can form characteristic composites with polycationic polymers like chitosan through electrostatic interactions [4], [5].

These polyelectrolyte complexes may exhibit distinct complexation behaviors depending on the mass ratio of the components, which can lead to different physicochemical properties (e.g., increased viscosity, gelation). Additionally, active additives can be incorporated into these composites to improve their physicochemical, mechanical, and antimicrobial properties.

In this context, ionic liquids (ILs) — defined as organic salts with melting points around 100 °C — are promising candidates for modulating the properties of gels. These compounds exhibit properties such as low vapor pressure, high thermal stability, high conductivity, and strong solvating ability for a wide range of compounds [6], [7]. Furthermore, the physicochemical properties of ILs can be tuned according to the combination of cation and anion that defines their structure, potentially resulting in non-toxic compounds with high thermal stability and unique biological activities. Their well-known ability to interact with polymers also enables the modulation or emergence of special properties in the resulting composite materials [6], [7], [8]. Based on this, the purpose of the lecture is to:
(i) provide an overview of the STD-NMR technique; (ii) demonstrate how these experiments can be used to elucidate interaction mechanisms and the supramolecular organization of hydrogels based on polymers and ionic liquids; and (iii) correlate supramolecular structural information with hydrogel properties relevant to the development of smart materials.

REFERENCES

[1]       S. Walpole, S. Monaco, R. Nepravishta, and J. Angulo, “STD NMR as a Technique for Ligand Screening and Structural Studies,” in Methods in Enzymology, vol. 615, Academic Press Inc., 2019, pp. 423–451. doi: 10.1016/bs.mie.2018.08.018.

[2]       S. Monaco, L. E. Tailford, N. Juge, and J. Angulo, “Differential Epitope Mapping by STD NMR Spectroscopy To Reveal the Nature of Protein–Ligand Contacts,” Angewandte Chemie, vol. 129, no. 48, pp. 15491–15495, Nov. 2017, doi: 10.1002/ange.201707682.

[3]       A. K. Nayak and B. Das, “Introduction to polymeric gels,” in Polymeric Gels, Elsevier, 2018, pp. 3–27. doi: 10.1016/b978-0-08-102179-8.00001-6.

[4]       K. Thirupathi et al., “Update on Chitosan-Based Hydrogels: Preparation, Characterization, and Its Antimicrobial and Antibiofilm Applications,” Jan. 01, 2023, MDPI. doi: 10.3390/gels9010035.

[5]       N. K. Sachan, S. Pushkar, A. Jha, and A. Bhattcharya, “Sodium alginate: the wonder polymer for controlled drug delivery,” J Pharm Res, vol. 2, no. 8, pp. 1191–1199, 2009, [Online]. Available: www.phresearchjournal.info

[6]       A. M. S. Freitas et al., “Ionic liquids based on carboxylate anions: Auto and hetero assembly with methylcellulose in diluted and semi-diluted regime,” Journal of Ionic Liquids, vol. 4, no. 1, p. 100082, Jun. 2024, doi: 10.1016/j.jil.2024.100082.

[7]       C. R. Bender, F. A. Vicente, B. L. Kuhn, C. P. Frizzo, M. A. Villetti, and P. J. Carvalho, “Effect of dicationic ionic liquids on cloud points of tergitol surfactant and the formation of aqueous micellar two-phase systems,” J Mater Sci, vol. 56, no. 21, pp. 12171–12182, Jul. 2021, doi: 10.1007/s10853-021-06055-1.

[8]       B. L. Hennemann et al., “Antifungal Activity and Stability of Fluconazole Emulsion Containing Ionic Liquids Explained by Intermolecular Interactions,” Pharmaceutics, vol. 14, no. 4, Apr. 2022, doi: 10.3390/pharmaceutics14040710.