Title

Using Aldehyde Synergism to Direct the Design of Degradable Pro-Antimicrobial Networks

Document Type

Article

Publication Date

11-14-2018

Department

Biological Sciences; Polymers and High Performance Materials

Abstract

We describe the design and synthesis of degradable, dual-release, pro-antimicrobial poly(thioetheracetal) networks derived from synergistic pairs of aromatic terpene aldehydes. Initially, we identified pairs of aromatic terpene aldehydes derivatives exhibiting synergistic antimicrobial activity against Pseudomonas aeruginosa by determining fractional inhibitory concentrations. Synergistic aldehydes were converted into dialkene acetal monomers and copolymerized at various ratios with a multifunctional thiol via thiol-ene photopolymerization. The step-growth nature of the thiol-ene polymerization ensures every crosslink junction contains a degradable acetal linkage enabling a fully crosslinked polymer network to revert into its small molecule constituents upon hydrolysis, releasing the synergistic aldehydes as active antimicrobial compounds. A three-pronged approach was used to characterize the poly(thioether acetal) materials: (i) determination of the degradation/aldehyde release behavior, (ii) evaluation of the antimicrobial activity, and (iii) identification of the cellular pathways impacted by the aldehydes on a library of mutated bacteria. From this approach, a polymer network derived from a 40:60 p-bromobenzaldehyde:p-anisaldehyde monomer ratio exhibited potent antimicrobial action against Pseudomonas aeruginosa– a common opportunistic human pathogen. From a transposon mutagenesis assay, weshowed that these aldehydes target porins and multidrug efflux pumps. The aldehydes released from the poly(thioether acetal) networks exhibited negligible toxicity to mammalian tissue culture cells, supporting the potential development of these materials as dual-release antimicrobial biomaterial platforms.

Publication Title

ACS Applied Bio Materials

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