Oligomeric cationic polymethacrylates: a comparison of methods for determining molecular weight.

This study compares three common laboratory methods, size-exclusion chromatography (SEC), (1)H nuclear magnetic resonance (NMR), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), to determine the molecular weight of oligomeric cationic copolymers. The potential bias for each method was examined across a series of polymers that varied in molecular weight and cationic character (both choice of cation (amine versus guanidine) and relative proportion present). SEC was found to be the least accurate, overestimating Mn by an average of 140%, owing to the lack of appropriate cationic standards available, and the complexity involved in estimating the hydrodynamic volume of copolymers. MALDI-TOF approximated Mn well for the highly monodisperse (D < 1.1), low molecular weight (degree of polymerization (DP) <50) species but appeared unsuitable for the largest polymers in the series due to the mass bias associated with the technique. (1)H NMR was found to most accurately estimate Mn in this study, differing to theoretical values by only 5.2%. (1)H NMR end-group analysis is therefore an inexpensive and facile, primary quantitative method to estimate the molecular weight of oliogomeric cationic polymethacrylates if suitably distinct end-groups signals are present in the spectrum.

Guanylated polymethacrylates: a class of potent antimicrobial polymers with low hemolytic activity.

We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure-activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition-fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.

Silole nanocrystals as novel biolabels.

A novel class of biofunctional silole nanocrystals with the potential to create highly sensitive immunoassay was firstly demonstrated. Biolabels were constructed by encapsulating nanocrystalline hexaphenylsilole [Ph2Si(CPh)4HPS] within ultrathin polyelectrolyte layers via the layer-by-layer (LbL) technique that provided an "interface" for the attachment of antibodies. A high ratio of fluorescent dyes to biomolecules (F/P ratio; 2.4 x 10(3)) was achieved without self-quenching problem. The aggregation-induced emission (AIE) feature offered silole biolabels the sensitivity 40- to 140-fold higher than that of a start-of-the-art immunoassay using directly fluorescent-labeled antibodies.

Antimicrobial Polymethacrylates Synthesized as Mimics of Tryptophan-Rich Cationic Peptides.

This study describes a facile and high yielding route to two series of polymethacrylates inspired by the naturally occurring, tryptophan-rich cationic antimicrobial polymers. Appropriate optimization of indole content within each gave rise to polymers with high potency against Staphylococcus epidermidis (e.g., PGI-3 minimum inhibitory concentration (MIC) = 12 µg/mL) and the methicillin-resistant strain of Staphylococcus aureus (e.g., PGI-3 MIC = 47 µg/mL) with minimal toxicity toward human red blood cells. Future work will be directed toward understanding the cooperative roles that the cationic and indole pendant groups have for the mechanism of these polymers.