Bactericidal polymers: Phosphorus NMR links up activity

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  • Published: Sep 15, 2018
  • Author: David Bradley
  • Channels: NMR Knowledge Base
thumbnail image: Bactericidal polymers: Phosphorus NMR links up activity

Sidestepping standard strategies

Researchers in Canada have used phosphporus-31 nuclear magnetic resonance (NMR) spectroscopy to study hydrophilic phosphonium polymers that have surprising antibacterial activity and selectivity. Credit: Wiley-VCH

Researchers in Canada have used phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy to study hydrophilic phosphonium polymers that have surprising antibacterial activity and selectivity.

Tyler Cuthbert, Benjamin Hisey, Tristan Harrison, John Trant, Elizabeth Gillies, and Paul Ragogna of y, The University of Western Ontario, London, Ontario Canada, were well aware that the conventional chemical wisdom surrounding artificial polymers, like antibiotic peptides, is that they need both hydrophobic and hydrophilic domains in their molecular structure to exert their antibacterial activity. Now, the team has synthesized a phosphonium polymer that could overturn this wisdom. Writing in the journal Angewandte Chemie, the team describes a polymer salt that has no hydrophobic alkyl chains but nevertheless represents a very effective biocide.

The research suggests that we may need to re-examine the standard strategies in antibiotics polymer in order to break through barriers that the conventional wisdom has created. This is especially important at a time when bacterial resistance and multiple-drug resistance are on the rise and represent a serious threat to human and veterinary health.

Bacteria baiting

Indeed, in order to combat multiple drug- resistant bacteria and find potent new antibiotics that can kill bacteria and do not immediately succumb to their evolutionary adaptability, scientists have turned more and more to the design and exploration of short artificial polymers. Such polymers might reveal themselves as mimics of powerful natural peptide antibiotic. Ragogna and Gillies, and their respective research groups have focused on phosphorus-containing polymers, the polyphosphoniums. The molecular structure of these compounds comprises a hydrocarbon backbone and a positively charged phosphorus centre in each repeating unit of the polymer. A balanced display of hydrophobic alkyl chains and positive charges was previously considered essential for effective adhesion to bacterial cells and membrane disruption. As such, the team initially began to optimize the amphiphilic nature of the polyphosphoniums in the expectation that this would lead to more effective bacterial cell lysis.

However, the team varied the relative content of hydrophobic and hydrophilic functional groups by introducing mannose sugar groups into their polymer. The sugar was meant to act as an attractant, a bait, you might say, for the bacteria, given that the likes of Escherichia coli have hair-like appendages called pili with mannose-binding sites. But, this plan failed. “Our initial hypothesis that the mannose-containing phosphonium polymer would provide exceptional targeted activity proved incorrect,” the team explains. However, another functional group was extremely successful - and this one was a rather surprising moiety.

Avoiding haemolysis

The team had assumed that the short alcoholic chain hydroxypropyl would not give any hydrophobicity to the polyphosphonium compound and so would cause neither bacterial cell lysis nor the harmful side effect of haemolysis whereby red blood cells are destroyed. Haemolysis is a good indication of selectivity. If a drug lyses bacterial cells but not red blood cells, then it is likely to be a safer drug. The team intended to use the hydroxy-modified polyphosphonium simply as a control compound. However, they found that it killed the bacteria much more effectively than the true test compounds while leaving red blood cells intact. “This is an unprecedented result in the context of the literature on antimicrobial polyonium or related materials,” the team says.

The findings imply that hydrophobic alkyl chains are not critical functional groups in giving a compound cell lysis activity in phosphonium salt polymers. Rather, the work suggests that the polymer backbone or the single terminal hydrophobic group of the synthesized polymers must play an essential part. Further investigation is now needed in order to establish a new line of enquiry into bactericidal polymer structures.

Related Links

Angew Chem 2018, 57, 1-5: "Surprising Antibacterial Activity and Selectivity of Hydrophilic Polyphosphoniums Featuring Sugar and Hydroxy Substituents"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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