The increasing prevalence of antibiotic-resistant bacterial pathogens has created an urgent need for developing new antimicrobial materials with improved efficacy and safety. In this study, novel thiadiazole-based poly(acrylic acid-co-acrylamide) hydrogels incorporated with silver nanoparticles (AgNPs) were synthesized and investigated as potential antibacterial agents. A series of 2-amino-5-substituted-1,3,4-thiadiazole derivatives containing ortho-chloro, meta-chloro, phenyl, and para-nitro groups were prepared and introduced into acrylic acid/acrylamide hydrogel networks through emulsion polymerization. The prepared hydrogel composites were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) to evaluate their structural, morphological, and thermal properties. The antibacterial activity of the synthesized composites was examined against multidrug-resistant clinical isolates of Staphylococcus aureus and Klebsiella pneumoniae using agar well diffusion and minimum inhibitory concentration (MIC) assays. The results demonstrated that the AgNP-loaded hydrogel composites exhibited significant antibacterial activity, with the effectiveness depending on the chemical structure of the thiadiazole substituent. The meta-chloro, phenyl, and para-nitro derivatives showed strong inhibitory effects against S. aureus, whereas the ortho-chloro derivative exhibited the highest activity against K. pneumoniae. The MIC results revealed that the ortho-chloro composite achieved the strongest activity against K. pneumoniae with an MIC value of 16 µg/mL, while the meta-chloro composite showed improved activity against S. aureus with an MIC value of 32 µg/mL. Cytotoxicity assessment indicated good compatibility at concentrations up to 64 µg/mL, with toxicity increasing at higher concentrations. These findings suggest that thiadiazole-functionalized AgNP hydrogel composites are promising candidates for future antimicrobial and biomedical applications.
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