The Effect of pH during Fabrication of Platinum-Containing Polymeric Arsenical Hydrogels

Intrinsic and acquired resistance, along with the systemic toxicity of platinum and arsenic therapeutics, necessitate the development of alternative chemistries and delivery strategies for Pt- and As-containing drugs. Stimuli-responsive hydrogels offer dynamic physicochemical adaptability, making them highly suitable for biomedical applications. Herein, we investigate the pH-responsive mechanical and antimicrobial properties of platinum-containing arsenical hydrogels. Poly-(N,N-dimethylacrylamide-co-4-(N-acrylamido)-phenylarsonic acid), P-(DMAm_0.92-co-AsAm_0.08), P _As was cross-linked with Pt^II (from K₂PtCl₄) under varying pH conditions to form hydrogels. Spectroscopic techniques (UV-vis, FT-IR, ¹H, and ¹⁹⁵Pt NMR) revealed that arsenic acid protonation influences Pt^II-O-As^V interactions, impacting hydrogel integrity and dynamic behavior. Rheological analysis confirmed the pH-dependent mechanical properties, where increased pH strengthened metal-ligand interactions, enhancing material's stiffness. Self-healing properties were demonstrated via strain recovery upon cutting for all materials, while resilience upon stretching was enhanced for the looser network environment under acidic conditions. Swelling studies indicated better stability in neutral environments, whereas increased ionic strength contributed to additional structural integrity. SEM-EDX confirmed morphological changes as a function of pH, corroborating the presence of both As and Pt under all pH conditions. The antimicrobial potential of these hydrogels was evaluated against Gram-positive (, ) and Gram-negative (uropathogenic , K12 MG1655) bacteria, demonstrating a similarif not improvedantimicrobial profile in all cases compared to the individual components. This study advances the understanding of pH-modulated mechanical properties and antimicrobial activity of arsenic-platinum hydrogels, which are promising candidates for infection treatment or targeted drug delivery applications.