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Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

ABSTRACT: Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model.

SUBMITTER: Yang DD

PROVIDER: S-EPMC7753145 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

Yang Daniel D DD Paterna Nicholas J NJ Senetra Alexandria S AS Casey Kaitlyn R KR Trieu Phillip D PD Caputo Gregory A GA Vaden Timothy D TD Carone Benjamin R BR

iScience 20201123 1

Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on <i>P. aeruginosa, E. coli, S. aureus,</i> and <i>S. cerevisiae.</i> The effects of these treatments in a human cell culture model ...[more]

PMID: 33364575

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Project description:The dynamics of probe molecules is commonly used to investigate the structural dynamics of room-temperature ionic liquids; however, the extent to which this dynamics reflects the dynamics of the ionic liquids or is probe specific has remained debated. Here, we explore to what extent the vibrational and rotational dynamics of the dicyanamide anion, a common ionic liquid anion, correlates with the structural relaxation of ionic liquids. We use polarization-resolved, ultrafast infrared spectroscopy to probe the temperature- and probe-concentration-dependent dynamics of samples with small amounts of 1-ethyl-3-methylimidazolium ([emim]+) dicyanamide ([DCA]-) dissolved in four [emim]+-based ionic liquids with tetrafluoroborate ([BF4]-), bis(trifluoromethylsulfonyl)imide ([NTf2]-), ethylsufate ([EtSO4]-), and triflate ([OTf]-) as anions. The transient spectra after broad-band excitation at 2000-2300 cm-1, resonant with the symmetric and antisymmetric C≡N stretching vibrations, initially contain oscillatory signatures due to the vibrational coherence between both modes. Vibrational population relaxation occurs on two distinct time scales, ∼6-7 and ∼15-20 ps. The vibrational dynamics is rather insensitive to the details of the ionic liquid anion and temperature, except for the slow vibrational relaxation component. The decay of the excitation anisotropy, a measure of the rotational dynamics of [DCA]-, markedly depends on temperature, and the obtained decay time exhibits an activation energy of ∼15-21 kJ/mol. Remarkably, neither the rotation time nor the activation energy can be simply explained by the variation of the macroscopic viscosity. Hence, our results suggest that the dynamics of dicyanamide is only in part representative of the ionic liquid structural dynamics. Rather, the dynamics of the probe anion seems to be determined by the specific interaction of [DCA]- with the ionic liquid's ions for the class of [emim]+-based ionic liquids studied here.

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Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

Publications

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

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