Novel Low Molecular Weight Hydrogels From Alkyl-β-Glycosides: Synthesis, Properties and Applications

Abstract

Low Molecular Weight (LMW) Hydrogels are three-dimensional networks made up of noncovalently bonded molecules capable of absorbing and retaining large amounts of water or biological fluids. Due to their composition, they are considered highly biocompatible, attracting significant interest from scientists and finding applications in drug delivery, cell encapsulation, agriculture, cosmetics, and more. Among all kinds of LMW gelators, glycolipids stand out as one of the most attractive types given the unique biological role of sugars in organisms and nature. Numerous sugar-based hydrogelators have been reported and studied, demonstrating incredible potential in diverse areas such as neural cell cultures, stem cell scaffolds, cell-responsive capsules, ionogels as electrolytes for electrochemical cells, mercury ion sensors, water purification, gel electrophoresis, optical devices, and others. However, the discoveries of new LMWGs are often unintentional due to the unpredictable self-assembly process, which makes empirical knowledge the primary foundation for molecular design. This dissertation presents a systematic study of a series of glycolipids with different sugar head groups, glycosidic linkers, anomers to the glycosidic bonds, and lipid tails. These synthesized glycolipids are investigated for their gelation properties through various characterizations, including rheology, electron microscopy, differential scanning microscopy, fluorescence spectroscopy, and more, with the intention to characterize their fundamental physicochemical properties. Furthermore, a few strong candidates are explored for their stability in extreme pH conditions and their loading and releasing behaviors as potential drug delivery systems. Additionally, attempts to fabricate microgel particles have been made, showing some early success characterized by microscopy as well as AFM force spectroscopy. The overall impact of this work is twofold. Firstly, the systematic study of glycolipids by varying their sugar head groups, glycosidic linker atoms, glycosidic linker configurations (α or β), and lipid tails provides a valuable library for the molecular design of hydrogelators. This is a crucial component that is rarely seen but of paramount importance in an area heavily relying on empirical knowledge. Secondly, the glycolipid-based LMW hydrogels synthesized demonstrate unique properties with rarely seen structures. Moreover, they show promise as strong candidates in drug delivery and can be engineered into microgels, opening up further potential applications with further refinement of the systems.