Choline Carboxylate Ionic Liquids for Biocompatible Antimicrobial Action
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Solution Overview
Problem
There is a scarcity of ionic liquids that are potent against both Gram-positive and Gram-negative bacteria while being biocompatible and inexpensive to synthesize in bulk quantities, and antimicrobial resistance is a growing concern due to the misuse of existing antimicrobial agents.
Innovation Solution
Development of ammonium carboxylic acid ionic liquids with specific molar ratios and anions, such as choline decanoate, choline 3-decenoate, and choline 2-decenoate, which exhibit high bactericidal activity against both Gram-negative and Gram-positive bacteria, including E. coli and MRSA, while maintaining biocompatibility with mammalian cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antimicrobial agents are used, then antimicrobial activity is achieved, but antimicrobial resistance develops and efficacy decreases over time
Solution Approach 1:
The patent changes the chemical parameters of antimicrobial agents by using ionic liquids with specific cations (choline, ammonium) and carboxylic acid anions with varying carbon chain lengths (C2-C20). This systematic parameter change creates new chemical entities that bypass existing resistance mechanisms while maintaining antimicrobial activity.
Solution Approach 2:
The patent creates composite ionic liquid structures combining specific cation-anion pairs (e.g., choline with various carboxylic acid anions) to achieve synergistic effects. The composite nature of ionic liquids allows tuning of properties to optimize both antimicrobial efficacy and biocompatibility.
2Reliability
If ionic liquids with high antimicrobial activity are developed, then efficacy against bacteria is improved, but biocompatibility with mammalian cells may be compromised
Solution Approach 1:
The patent applies local quality by designing ionic liquids with specific local structures - choline or ammonium cations provide biocompatibility and membrane interaction, while carboxylic acid anions with specific carbon chain lengths (C2-C20) provide targeted bacterial membrane disruption. This local differentiation of functional groups achieves selective toxicity.
Solution Approach 2:
The patent systematically varies parameters including cation type (choline vs. ammonium), anion carbon chain length (C2-C20), and molar ratio (1:1 to 1:4) to optimize the balance between bactericidal activity and cytotoxicity. This parameter optimization creates a window of efficacy where antimicrobial action is strong but mammalian cell toxicity remains minimal.
3Reliability
If complex ionic liquid structures are synthesized, then antimicrobial efficacy is improved, but synthesis cost and complexity increase
Solution Approach 1:
The patent segments the synthesis process into modular components - separate synthesis of cation and anion followed by combination. This segmentation allows independent optimization of each component and simplifies purification. The use of commercially available choline chloride and carboxylic acids as starting materials further reduces synthesis complexity.
Solution Approach 2:
The patent employs inexpensive, readily available starting materials (choline chloride, various carboxylic acids) that can be easily obtained and disposed of, replacing the need for expensive, complex synthesis routes. The ionic liquids themselves serve as the final product without requiring further processing or stabilization.
4Reliability
If high concentrations of antimicrobial agents are used, then bactericidal activity is achieved, but toxicity to mammalian cells increases
Solution Approach 1:
The patent changes the concentration parameter by demonstrating that effective bactericidal activity is achieved at low concentrations (MIC values in the micromolar range), avoiding the need for high doses that would cause toxicity. The optimized ionic liquid structures inherently provide high efficacy at these low concentrations, creating a wide therapeutic window.
Solution Approach 2:
The composite ionic liquid structures combine the membrane-interacting properties of quaternary ammonium/choline cations with the disruptive action of carboxylic acid anions, creating a synergistic effect that achieves high bactericidal activity at low concentrations without proportionally increasing toxicity to mammalian cells.
Data Source
AI summary
In one aspect, the disclosure relates to ammonium carboxylic acid ionic liquids, methods of making the ionic liquids, pharmaceutical compositions comprising the same, and methods of treating both Gram-negative and Gram-positive bacterial infections using same. In one aspect, the ionic liquids are biocompatible with mammalian cells. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.