This manuscript describes a new route to prepare rapidly Ca2+-free hydrogels from unmodified sodium alginate by simply mixing with small organic molecules such as poly(carboxylic acid) compounds as cross-linker agents instead of classical divalent metal salts such as CaCl2. Dimethyl sulfoxide (DMSO) was also found to induce the rapid gelation of aqueous alginate solutions. The gelation process takes place at room temperature, and depending on the composition, gels with good thermal (90-100 °C) and mechanical properties compared to classical metal-containing analogs are obtained. DMSO-based gels showed remarkable self-supporting and thixotropic properties, which can be tuned by the biopolymer concentration. Furthermore, oxalic acid-based gels show superior elasticity than HCl, CaCl2 and DMSO-based gels. The possibility to prepare monoliths, beads, and films of these gels provide them with significant versatility. In particular, films made of alginate and oxalic acid show good potential as synergistic anticancer drug delivery carrier. Computational studies using both quantum mechanical and classical force-field methodologies reveal that hydrogen bonding networks between water and DMSO molecules located close to the alginate chains are responsible for the stability of DMSO-based gels. In contrast, the cohesion of oxalic acid-based gels is a consequence of the coexistence of multiple ionic associations involving oxalate, alginate, and Na+ counterions, which stabilize the system and keep all the interacting species grouped.

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