1. Ionic Liquids for Natural Product Extraction
Adam Walker
Bioniqs Ltd.

2. Ionic Liquids - Introduction
NaCl (mp 801°C)
BMIm PF6 (mp -79°C)
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
AAFF-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 g/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 °C.
Artemisinin may be recovered by adding water, precipitating and filtering off.
Residual solvent content of recovered artemisinin <0.001%.
Solvent may then be recycled and re-used
Image provided courtesy of

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 >300g/L; several to >500g/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)