In situ synthesis of biocompatible imidazolium salt hydrogels with antimicrobial activity.

Infection with antibiotic-resistant bacteria is becoming a significant public health risk. In this study, we synthesized a series of imidazolium salt (IMS)-containing polymers and hydrogels and tested their antimicrobial properties against both gram-positive (Staphylococcus aureus and MRSA) and gram-negative (Escherichia coli and PA01) bacteria. IMSs were either grafted as side chains or functionalized in the main chain of linear polymers, which demonstrated antimicrobial properties with minimum inhibitory concentrations as low as 2 µg/mL. Similarly, the optimized IMS-containing hydrogel effectively killed MRSA with a 96.1% killing efficiency and inhibited the growth of PA01. These hydrogels also demonstrated high performance in terms of mechanical property (compressive strength >2 MPa) and were noncytotoxic toward human dermal fibroblasts. STATEMENT OF SIGNIFICANCE: A series of polyimidazolium hydrogels were fabricated with acrylamide monomer and poly(ethylene glycol) dimethacrylate by thermal-initiated polymerization. These hydrogels completely killed methicillin-resistant Staphylococcus aureus and inhibited the growth of Pseudomonas aeruginosa. More importantly, these hydrogels demonstrated adequate mechanical property and biocompatibility. These antimicrobial hydrogels have the potential as biomaterials for preventing infections associated with multidrug-resistant bacteria.

Optical Control of the GTP Affinity of K-Ras(G12C) by a Photoswitchable Inhibitor.

Photocontrol of protein activity is an emerging field in biomedicine. For optical control of a mutant small GTPase K-Ras(G12C), we developed small-molecule inhibitors with photoswitchable efficacy, where one configuration binds the target protein and exert different pharmacological effects upon light irradiation. The compound design was based on the structure feature of a previously identified allosteric pocket of K-Ras(G12C) and the chemical structure of covalent inhibitors, and resulted in the synthesis and characterization of two representative azobenzene-containing compounds. Nucleotide exchange assays demonstrated the different efficacy to control the GTP affinity by photoswitching of one potent compound PS-C2, which would be a useful tool to probe the conformation of mutational K-Ras. Our study demonstrated the feasibility of designing photoswitchable modulators from allosteric covalent inhibitor of small GTPases.