title: Highly effective, water-soluble, hemocompatible 1,3-propylene oxide-based antimicrobials: poly[(3,3-quaternary/PEG)-copolyoxetanes].
abstract: This study focuses on the solution antimicrobial effectiveness of a novel class of copolyoxetanes with quaternary ammonium and PEG-like side chains. A precursor P[(BBOx-m)(ME2Ox)] copolyoxetane was prepared by cationic ring-opening copolymerization of 3-((4-bromobutoxy)methyl)-3-methyloxetane (BBOx) and 3-((2-(2-methoxyethoxy)ethoxy)methyl)-3-methyloxetane (ME2Ox) to give random copolymers with 14-100 (m) mol % BBOx. Reaction of P[(BBOx-m)(ME2Ox)] with dodecyl dimethylamine gave the corresponding quaternary P[(C12-m)(ME2Ox)] polycation salts, designated C12-m, as viscous liquids in 100% yield. BBOx/ME2Ox and C12/ME2Ox ratios were obtained by (1)H NMR spectroscopy. C12-m molecular weights (M(n), 3.5-21.9 kDa) were obtained from (1)H NMR end group analysis. DSC studies up to 150 °C showed only thermal transitions between -69 and -34 °C assigned to T(g) values. Antibacterial activity for the C12-m copolyoxetanes was tested by determining minimum inhibitory concentrations (MICs) against Gram(+) Staphylococcus aureus and Gram(-) Escherichia coli and Pseudomonas aeruginosa . MIC decreased with increasing C12 mol percent, reaching a minimum in the range C12-43 to C12-60. Overall, the antimicrobial with consistently low MICs for the three tested pathogenic bacteria was C12-43: (bacteria, MIC, μg/mL) E. coli (6), S. aureus (5), and P. aeruginosa (33). For C12-43, minimum biocidal concentration (MBC) to reach 99.99% kill in 24 h required 1.5× MIC for S. aureus and 2× MIC for E. coli and P. aeruginosa . At 5× MIC against a challenge of 10(8) cfu/mL, C12-43 kills ≥99% S. aureus , E. coli , and P. aeruginosa within 1 h. C12-m copolyoxetane cytotoxicity toward human red blood cells was low, indicating good prospects for biocompatibility. The tunability of C12-m copolyoxetane compositions, effective antimicrobial behavior against Gram(+) and Gram(-) bacteria, and promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents.
authors.affiliation: Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, Virginia 23284, USA.
authors.forename: Souvik
authors.initials: S
authors.lastname: Chakrabarty
authors.forename: Allison
authors.initials: A
authors.lastname: King
authors.forename: Pinar
authors.initials: P
authors.lastname: Kurt
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Ohman
authors.forename: Lynn F
authors.initials: LF
authors.lastname: Wood
authors.forename: C
authors.initials: C
authors.lastname: Lovelace
authors.forename: Raj
authors.initials: R
authors.lastname: Rao
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Wynne
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D001419:Bacteria / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry*; D004852:Epoxy Compounds; D008826:Microbial Sensitivity Tests; D011108:Polymers; D011409:Propylene Glycols; D012995:Solubility
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D004852:Epoxy Compounds; D011108:Polymers; D011409:Propylene Glycols; C524812:poly(oxetane); C009068:propylene oxide