Biocompatible Copper Oxide Nanoparticle Composites from Cellulose and Chitosan: Facile Synthesis, Unique Structure, and Antimicrobial Activity.

Copper in various forms has been known to have bactericidal activity. Challenges to its application include preventing mobilization of the copper, to both extend activity and avoid toxicity, and bioincompatibility of many candidate substrates for copper immobilization. Using a simple ionic liquid, butylmethylimmidazolium chloride as the solvent, we developed a facile and green method to synthesize biocompatible composites containing copper oxide nanoparticles (CuONPs) from cellulose (CEL) and chitosan (CS) or CEL and keratin (KER). Spectroscopy and imaging results indicate that CEL, CS, and KER remained chemically intact and were homogeneously distributed in the composites with CuONPs with size of 22 ± 1 nm. Electron paramagnetic resonance (EPR) suggests that some 25% of the EPR-detectable Cu(II) is present as a monomeric species, chemically anchored to the substrate by two or more nitrogen atoms, and, further, adopts a unique spatially oriented conformation when incorporated into the [CEL + CS] composite but not in the [CEL + KER] composite. The remaining 75% of EPR-detectable Cu(II) exhibited extensive spin-spin interactions, consistent with Cu(II) aggregates and Cu(II) on the surface of CuONPs. At higher levels of added copper (>59 nmol/mg), the additional copper was EPR-silent, suggesting an additional phase in larger CuONPs, in which S > 0 spin states are either thermally inaccessible or very fast-relaxing. These data suggest that Cu(II) initially binds substrate via nitrogen atoms, from which CuONPs develop through aggregation of copper. The composites exhibited excellent antimicrobial activity against a wide range of bacteria and fungi, including methicillin-resistant Staphylococcus aureus; vancomycin-resistant Enterococcus; and highly resistant Escherichia coli, Streptococcus agalactiae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Candida albicans. Expectedly, the antibacterial activity was found to be correlated with the CuONPs content in the composites. More importantly, at CuONP concentration of 35 nmol/mg or lower, bactericidal activity of the composite was complemented by its biocompatibility with human fibroblasts.