Bio-inspired engineering of supramolecular hydrogels using guanosine 5′-monophosphate as a primordial biomolecular scaffold: from design strategies to emerging applications

Abstract

This thesis demonstrates that the remarkable self-assembly of biomolecules can be harnessed to transform them into sophisticated functional materials through rational supramolecular design. By establishing 5′-guanosine monophosphate (5′-GMP) as a versatile molecular building block for engineering multifunctional hydrogels, this work shows how simple, low-molecular-weight biomolecules assembled exclusively through reversible non-covalent interactions can generate dynamic soft materials with structural precision and diverse functions. Collectively, the studies presented in this thesis expand the fundamental understanding of nucleotide self-assembly while providing a unified platform for biomedical, catalytic, and bioelectronic applications. At the molecular level, all the developed systems rely on the intrinsic self-assembly capability of 5′-GMP through cooperative Hoogsteen hydrogen bonding, π–π stacking and electrostatic interactions. These interactions drive the formation of G-quadruplexes, and G-dimers, which subsequently organize into one-dimensional fibrillar networks and finally macroscopic hydrogels. More importantly, this work demonstrates that the self-assembly pathway is highly programmable. By introducing complementary biomolecules such as biomass-derived DNA, adenosine phosphates (ADP and ATP), amino acid-metal complexes, solvent engineering, or ionic crosslinking, the molecular packing and supramolecular architecture can be precisely regulated without disrupting the fundamental nucleotide assembly mechanism.