Ionic Liquids for Natural Product Extraction

1
Ionic Liquids for Natural Product
Extraction Adam Walker Bioniqs Ltd.
2
Ionic Liquids - Introduction
BMIm PF6 (mp -79C)
NaCl (mp 801C)

• Ionic liquids are salts, with melting points
  below ambient temperature
• They are composed solely of anions and cations
  no water is present
• Their regular, ordered structure gives them very
  different properties to conventional liquids
• Ionic liquids based on imidazole have been well
  studied as novel solvents

3
Ionic Liquids - Properties

• Extremely good solvents for many compounds
  organic, inorganic, mineral, polymeric and
  biological
• Non-volatile do not evaporate
• Non-flammable
• Stabilize sensitive compounds
• Many possible combinations of ions can design
  the solvent for a particular application

4
Applications

• Solvents for chemical and biochemical reactions
• Extraction media for natural product isolation
• Cleaning agents
• Storage media for unstable compounds
• Lubricants
• Electrochemical/battery materials

5
First Generation Ionic Liquids - Disadvantages

• Expensive in comparison with molecular solvents.
• Very few commercially available.
• Viscous
• Poorly biodegradable and potentially toxic.

6
Second Generation Ionic Liquids

• Bioniqs has developed new types of simple ionic
  liquids, based on ammonium salts.
• These retain the advantages of ionic liquids,
  but also offer
• - reduced viscosity.
• - low cost.
• - straightforward preparation from sustainable
  precursors.
• - minimal toxicity and environmental impact.
• - recyclability and biodegradability.

7
Example Applications

• Stabilization of enzymes for biocatalysis
• Dissolution and processing of biomass
• Natural product isolation and purification
• Reactor decontamination

8
Stabilization of Biomolecules
Activity of alcohol dehydrogenase enzyme after
storage in water compared to standard (purple)
and optimized (red) ionic liquids. H2O AEFF-390 AA
FF-015
Enzyme in water deactivated after 10 days at room
temperature. Enzyme in AEFF-390 retains activity
after 90 days at room temperature.
9
Biomass Processing

• Ionic liquids can dissolve numerous polymers,
  including biological macromolecules such as-
• Cellulose (up to 10 wt. solutions)
• Lignin
• Proteins
• DNA/RNA
• Bioprocessing requires solvent to dissolve
  substrate without denaturing enzyme.
• Ionic liquid can be designed accordingly.

10
Natural Product Extraction Processing
H2O 0.15
Et2O 1.2
CHCl3 3.3
BMIm PF6 77.6
Morphine (free base) solubility (gL-1)

• Solubility of natural products in ionic liquids
  often very much higher than in conventional
  solvents.
• Can be used to extract high concentrations from
  natural sources, using small extractor volumes.

11
Natural Product Extraction Processing

• Dissolution of penicillin in ionic liquids
  varies between solvent formulations
• Solubility limit ranges from 20-270g/L
• Can design solvent to optimize extraction
  efficiency

12
Natural Product Extraction Processing

• With support from MMV, Bioniqs has developed
  ionic liquids for artemisinin extraction, from
  both wet and dry plant material.
• Extraction up to 4 times faster than in hexane
• Solubility in ionic liquids up to 110 gL-1 _at_
  25C.
• Artemisinin may be recovered by adding water,
  precipitating and filtering off.
• Residual solvent content of recovered
  artemisinin lt0.001.
• Solvent may then be recycled and re-used

Image provided courtesy of www.pp.clinet.fi
13
Decontamination Cleaning

• Solubility of two nitroaromatic pollutants in
  ionic liquids compared to water.
• Ionic liquid may be designed to dissolve one
  compound even in presence of structurally similar
  materials.

14
Decontamination Cleaning
ILs designed to remove specified contaminant
(amoxicillin) All ILs tested dissolve contaminant
to gt300g/L several to gt500g/L
15
Ecotoxicity and Biodegradation

• ILs have been widely touted as green solvents
• recyclable
• non-flammable
• non-volatile
• BUT early imidazole-based ILs were
• poorly biodegradable
• toxic to micro-organisms
• may form hazardous hydrolysis products
• Biodegradability must be built in to an ionic
  liquid at the design stage.

16
Biodegradation of Ionic Liquids

• Ordinary soil organisms can grow on Bioniqs
  ionic liquids and completely degrade them within
  48 hours (above).
• Degradation products are water, carbon dioxide
  and ammonium ion.
• No significant toxic effects at concentrations
  below 80mM.

17
Summary

• Ionic liquids are not a panacea, but can offer
  major benefits in certain key areas-
• Can now compete on comparable cost footing with
  conventional solvents for bulk applications.
• Reduced pollution and waste
• Improved process safety
• Enhanced efficiency of reaction and extraction
  processes
• Facilitate improved processes.
• Increased solubilities smaller volumes
• Improved turnover rates and yields
• Stabilization of sensitive molecules
• Application to poorly soluble substrates

18
Acknowledgements
19
Further Information
Bioniqs Ltd. Biocentre York Science
Park Heslington York YO10 5DG United
Kingdom 0(44)1904 561538 office_at_bioniqs.com www.
bioniqs.com