Hydration effect and molecular geometry conformation as critical factors affecting the longevity stability of G4-structure-based supramolecular hydrogels

Abstract

Nucleoside-derived supramolecular hydrogels based on G₄-structures have been extensively developed in the biomedical sector and recognized for superior excellent biocompatibility and biodegradability. However, limited longevity and stability present a significant challenge. Chemical modifications in the molecular structure have been shown to enhance the longevity stability of G₄-structure-based supramolecular hydrogels, but the precise way in which the molecular structure impacts the stability of the G₄-structures and consequently affects the properties of the hydrogel remains to be elucidated. This issue represents a notable challenge in the field, which restricts their further applications to some extent. In this study, single crystals of G_d, αG_d and αG_d* were cultivated and compared with G. Notably, before this study, the single crystal structures of all natural nucleosides, with the exception of G_d, had been determined. The investigation into the molecular structure and supramolecular self-assembly properties of four guanosine analogs at the atomic scale revealed that the formation of G-quartets is critical for their ability to form hydrogels. The stability of the sugar ring geometry conformation (an intrinsic factor) and the disorder and strength of the hydration effect (extrinsic factors) are vital for maintaining the stability of the G₄-structures. The rapid cooling changes the molecular geometry conformation, and the organic solvent changes the hydration effect, which can improve the longevity stability of G₄-structure-based supramolecular hydrogels instead of chemical modifications. Consequently, the lifespan of the hydrogels was extended from 2 h to over one week. This advancement is expected to offer significant insights for future research in designing and developing G₄-structure-based supramolecular hydrogels.