Self-Assembly of Nucleoside-Derived Low-Molecular-Weight Gelators: A Thermodynamics and Kinetics Study on Different Length Scales

Abstract

Biocompatible materials are of paramount importance in numerous fields. Unlike chemically-bridge polymer-based hydrogels, low molecular weight gelators can form a reversible hydrogel as their structure rely on non-covalent interaction. Although many applications with this type of hydrogels can be envisioned, we still lack their understanding due to the complexity of their self-assembly process and the difficulty predicting their behaviors (transition temperature, gelation kinetic, impact of solvent…). In this study, we extend the investigations of a series of nucleoside-derivatives gelators which only differ by subtle chemical modifications. Using a multi-technique approach, we determined their thermodynamic and kinetic features at various scale (molecular to macro) in different conditions. Monitored at supramolecular level by circular dichroism as well as macroscopic scales by rheology and turbidimetry, we found out that sol-gel and gel-sol transition are greatly depending on the concentration and on the mechanisms that are probed. Self-assembly kinetic depends on hydrogel molecules and is modulated by temperature and solvent. This fundamental study provides insight on the impact of some parameters on the gelation process, such as concentration, cooling rate and nature of the solvent.

Nucleoside-Derived Low-Molecular-Weight Gelators as a Synthetic Microenvironment for 3D Cell Culture

“…These results show that their kinetics give enough time for the gels to slightly cool down and for the experimenter to stir together the LMWG solution with the cells before the gelation occurs. It is noteworthy that the induction time for BU and BA corresponds to the supercooling time as it was shown that these hydrogels undergo non-isothermal gelation during cooling …”

“…It is noteworthy that the induction time for BU and BA corresponds to the supercooling time as it was shown that these hydrogels undergo non-isothermal gelation during cooling. 42 Porosity and Molecular Diffusion Timescales. To host cells for culture, the matrix must permit molecular mobility through it, small molecules to biomolecules.…”

“…These LMWGs were previously studied and characterized, especially their kinetics, mechanical, and thermal properties. , In addition to providing biocompatibility properties, the glyco-modified nucleotide moiety brings some interesting supramolecular features, permitting the self-assembly of these gelators. Indeed, it was shown that the thymidine groups undergo base stacking upon fibrillogenesis, hence participating in the formation of the gel units .…”

“…These LMWGs were previously studied and characterized, especially their kinetics, mechanical, and thermal properties. , In addition to providing biocompatibility properties, the glyco-modified nucleotide moiety brings some interesting supramolecular features, permitting the self-assembly of these gelators. Indeed, it was shown that the thymidine groups undergo base stacking upon fibrillogenesis, hence participating in the formation of the gel units . Urea and amide linkers provide oriented hydrogen bonding sites that also play a role in the supramolecular structuration. , In fact, these moieties are found in many LMWG design strategies for their intermolecular bonding properties .…”

“…Indeed, it was shown that the thymidine groups undergo base stacking upon fibrillogenesis, hence participating in the formation of the gel units . Urea and amide linkers provide oriented hydrogen bonding sites that also play a role in the supramolecular structuration. , In fact, these moieties are found in many LMWG design strategies for their intermolecular bonding properties . Additionally, bola designs are also known for their unidirectional self-assembling properties by balancing well the amphiphilicity of the chemical structure, and the combination of all these molecular features led to the GNBs being biocompatible and efficient gelators.…”