Antibacterial and Hemolytic Activities of Quaternary Pyridinium Functionalized Polynorbornenes

Abstract

In this study, amphiphilic polyoxanorbornene with different quaternary alkyl pyridinium side chains were synthesized. The biological efficiencies of these polymers, with various alkyl substituents, were determined by bacterial growth inhibition assays and hemolytic activity (HC 50 ) against human red blood cells (RBCs) to provide selectivity of these polymers for bacterial over mammalian cells. A series of polymers with different alkyl substituents (ethyl, butyl, hexyl, octyl, decyl and phenylethyl) and two different molecular weights (3 and 10 kDa) were prepared. The impact of alkyl chain length divided the biological activity into two different cases: those with an alkyl substituent containing four or fewer carbons had a minimum inhibitory concentration (MIC) of 200 mg Á mL À1 and a HC 50 greater than 1 650 mg Á mL À1 , while those with six or more carbons had lower MICs 12.5 mg Á mL À1 and HC 50 250 mg Á mL À1 . Using MSI-78, the potent Magainin derivative which has an MIC ¼ 12.0 mg Á mL À1 and HC 50 ¼ 120 mg Á mL À1 , as a comparison, the polymers with alkyl substituents C 4 (four carbons) were not very potent, but did show selectivity values greater than or equal to MSI-78. In contrast, those with alkyl substituents !C 6 were as potent, or more potent, than MSI-78 and in three specific cases demonstrated selectivity values similar to, or better than, MSI-78. To understand if these polymers were membrane active, polymer induced lipid membrane disruption activities were evaluated by dye leakage experiments. Lipid composition and polymer hydrophobicity were found to be important factors for dye release.

Antimicrobial Polymers Prepared by Ring‐Opening Metathesis Polymerization: Manipulating Antimicrobial Properties by Organic Counterion and Charge Density Variation

“…A SMAMP with an MIC 90 of 4 mg mL properties of a high HC 50 value and a low MIC 90 lead to the desired high selectivity. 3 Magainin (MSI 78), a frog host defense peptide, has a selectivity of 10, [8] and human defensins are even more selective (> 40 for nNP-1, [9] > 100 for human b-defensin 3 [10] ). Several studies investigating structureproperty relationships of SMAMPs have highlighted the importance of an appropriate amphiphilicity: [8,[11][12][13][14] a polymer with too much hydrophobicity will be toxic to mammalian cells, yet too little hydrophobicity will render it inactive.…”

“…Several studies investigating structureproperty relationships of SMAMPs have highlighted the importance of an appropriate amphiphilicity: [8,[11][12][13][14] a polymer with too much hydrophobicity will be toxic to mammalian cells, yet too little hydrophobicity will render it inactive. [8,13,[15][16][17] To complement these reports, the aim of this paper is: 1) to first study the effect of different organic counterions of a model SMAMP on its antimicrobial properties, and 2) to subsequently investigate the influence of molecular charge density on the antimicrobial properties.…”

Activity and Mechanism of Antimicrobial Peptide-Mimetic Amphiphilic Polymethacrylate Derivatives

“…This approach was successfully applied to the development of new types of polymer antimicrobials over the last decade, including copolymers of β-lactams [27], polynorbornenes [28], polymethacrylates [29,30], and polystyrenes [31]. Further fine-tuning of the polymers' physiochemical properties by modifying the cationic functionality, amphiphilic balance, and polymer sizes has yielded favorable improvements in antimicrobial activity and selective toxicity to bacteria relative to human red blood cells [30,[32][33][34][35]. In addition to these examples of peptidomimetic polymers, it has been recently reported that several other polymer scaffolds such as oligo(oxazoline)s [36], PEGylated poly(vinyl pyridine)s [37], and polyoxetanes with quaternary ammonium and PEG-like side chains [38] display antibacterial activity and selectivity.…”

Antibacterial efficacy of functionalized silk fabrics by radical copolymerization with quaternary ammonium salts

“…It can be seen clearly that with the increase of carbon number in the alkyl chain, antibacterial activity of the treated silk fabrics is generated, which is in accordance with other studies. 24 As for Gramnegative bacteria E. coli, 100% of these bacteria were killed within 60, 10, and 10 min for samples of silk-g-C 8 , silk-g-C 12 , and silk-g-C 18 , respectively. In the Exp 2, samples of silk-g-C 8 could only inactivate 94.98% (1.30 logs reduction) and 93.45% (1,18 logs reduction) of S. aureus and E. coli O157:H7, respectively, within 60 min.…”