Combination of bacteriophages and vancomycin in a co-delivery hydrogel for localized treatment of fracture-related infections.

Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 103 PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes.

Manganese(III) complexes stabilized with N-heterocyclic carbene ligands for alcohol oxidation catalysis.

The chemistry of N-heterocyclic carbenes with Earth-abundant manganese has largely focused on low-valent systems for reductive catalysis. Here, we have decorated imidazole- and triazole-derived carbenes with phenol substituents to access higher-valent Mn(III) complexes [Mn(O,C,O)(acac)], where acac = acetylacetonato, and O,C,O = bis(phenolate)imidazolylidene (1) or bis(phenolate)triazolylidene (2). Both complexes catalyze the oxidation of alcohols in the presence of tBuOOH as terminal oxidant. Complex 2 is slightly more active than 1 (TOF up to 540 h-1vs. 500 h-1), yet significantly more robust towards deactivation. Secondary and primary alcohols are oxidized, the latter with high selectivity and essentially no overoxidation of the aldehyde product to carboxylic acids unless the reaction time is substantially extended. Mechanistic investigations using Hammett parameters, IR spectroscopy, isotope labelling experiments, and specific substrates and oxidants as probes support the formation of a manganese(V) oxo system as the active species and subsequent turnover-limiting hydrogen atom abstraction.

N-Heterocyclic carbene iron complexes catalyze the ring-opening polymerization of lactide.

Poly(lactic acid), PLA, which holds great promise as a biodegradable substitute of fossil resource-derived polyolefins, is industrially produced by the ring-opening polymerization of lactide using a potentially harmful tin catalyst. Based on mechanistic insights into the reaction of N-heterocyclic carbene (NHC) iron complexes with carbonyl substrates, we surmised and demonstrate here that such complexes are excellent catalysts for the bulk polymerization of lactide. We show that an iron complex with a triazolylidene NHC ligand is active at lactide/catalyst ratios of up to 10 000 : 1, produces polylactide with relatively high number-average molecular weights (up to 50 kg mol-1) and relatively narrow dispersity (D ∼ 1.6), and features an apparent polymerization rate constant k app of up to 8.5 × 10-3 s-1, which is more than an order of magnitude higher than that of the industrially used tin catalyst. Kinetic studies and end-group analyses support that the catalytically active species is well defined and that the polymerization proceeds via a coordination-insertion mechanism. The robustness of the catalyst allows technical grade lactide to be polymerized, thus offering ample potential for application on larger scale in an industrially relevant setting.