Anna K. Ressmann

From plant to drug: ionic liquids for the reactive dissolution of biomass

We present an ionic liquid (IL) strategy for the reactive dissolution of star anise seeds using different Bronsted-acidic ionic liquids as the solvent and reaction media towards the isolation of important pharmaceutical intermediates; this procedure provides a single-step, higher yielding and environmentally benign strategy towards the synthesis of the anti-influenza drug Tamiflu™.

New aspects for biomass processing with ionic liquids: towards the isolation of pharmaceutically active betulin

By utilising ionic liquids the pharmaceutically active triterpene betulin can be extracted from biomass with significantly improved extraction yield and purity. The recovery of the ionic liquid 1-ethyl-3-methylimidazolium acetate via azeotropic distillation of EtOH/H2O was successfully demonstrated.

Surface-active Ionic Liquids for Micellar Extraction of Piperine from Black Pepper

We present the application of ionic liquid-aqueous micellar solutions as isolation media for the pharmaceutically active ingredient piperine from black pepper. Several surface-active ionic liquids including a biodegradable betaine derivative were used for the extraction of piperine, and a strong correlation between extraction yield and the critical micelle concentration of the respective ionic liquid was found. A scaled strategy for the isolation of piperine was developed that allowed recovery and recycling of the aqueous ionic liquid micellar solution for five runs without any loss in extraction efficiency. Graphical Abstract Surface-active Ionic Liquids for Micellar Extraction of Piperine from Black Pepper

From waste to value - direct utilization of limonene from orange peel in a biocatalytic cascade reaction towards chiral carvolactone

In this proof of concept study we demonstrate direct utilization of limonene containing waste product orange peel as starting material for a biocatalytic cascade reaction. The product of this cascade is chiral carvolactone, a promising building block for thermoplastic polymers. Four different concepts were applied to augment limonene availability based on either water extraction solely, addition of extraction enhancers or biomass dissolution.

Kinetic modeling of an enzymatic redox cascade in vivo reveals cofactor‐caused bottlenecks

We describe the development of a kinetic model for the simulation and optimization of an in vivo redox cascade in E. coli in which a combination of an alcohol dehydrogenase, an enoate reductase, and a Baeyer–Villiger monooxygenase is used for the synthesis of lactones. The model was used to estimate the concentrations of active enzyme in the sequential biotransformations to identify bottlenecks together with their reasons and how to overcome them. We estimated adapted Michaelis–Menten parameters from in vitro experiments with isolated enzymes and used these values to simulate the change in the concentrations of intermediates and products during the in vivo cascade reactions. Remarkably, the model indicated that the fastest enzyme was rate‐determining because of the unexpectedly low concentration of the active form, which opens up reversible reaction channels towards byproducts. We also provide substantial experimental evidence that a low intracellular concentration of flavin and nicotinamide cofactors drastically decreased the performance of the in vivo cascade drastically.

Fast and efficient extraction of DNA from meat and meat derived products using aqueous ionic liquid buffer systems

A short, simple and inexpensive process for the extraction of DNA from meat was developed investigating a set of 20 ionic liquids including imidazolium, choline and guanidinium derivatives in combination with aqueous buffer systems. The environmentally benign ionic liquid choline hexanoate–phosphate buffer mixture gave the most promising results and DNA was extracted within 20 minutes from different types of meats, such as beef, chicken, pork and horse in significantly higher yields compared to the pure phosphate buffer. The influence of the ionic liquid on the amplification process during the PCR was further investigated, showing an inhibitory effect with increasing chain length of the ionic liquid and with higher ionic liquid concentrations. Additionally, extracted DNA was stable for 20 days when stored at room temperature in aqueous ionic liquid–buffer mixtures.

Design and synthesis of basic ionic liquids for the esterification of triterpenic acids

We present the design and synthesis of Brønsted-basic ionic liquids and investigate their application in the microwave-assisted esterification of betulinic acid, aiming towards a benign and pyridine-free manufacturing process of the anti-HIV drug, bevirimat.Graphical abstract

Automated evaluation of protein binding affinity of anti-inflammatory choline based ionic liquids

In this work, an automated system for the study of the interaction of drugs with human serum albumin (HSA) was developed. The methodology was based on the quenching of the intrinsic fluorescence of HSA by binding of the drug to one of its binding sites. The fluorescence quenching assay was implemented in a sequential injection analysis (SIA) system and the optimized assay was applied to ionic liquids based on the association of non-steroidal anti-inflammatory drugs with choline (IL-API). In each cycle, 100 µL of HSA and 100 µL of IL-API (variable concentration) were aspirated at a flow rate of 1 mL min(-1) and then sent through the reaction coil to the detector where the fluorescence intensity was measured. In the optimized conditions the effect of increasing concentrations of choline ketoprofenate and choline naproxenate (and respective starting materials: ketoprofen and naproxen) on the intrinsic fluorescence of HSA was studied and the dissociation constants (Kd) were calculated by means of models of drug-protein binding in the equilibrium. The calculated Kd showed that all the compounds bind strongly to HSA (Kd<100 µmol L(-1)) and that the use of the drugs in the IL format does not affect or can even improve their HSA binding. The obtained results were compared with those provided by a conventional batch assay and the relative errors were lower than 4.5%. The developed SIA methodology showed to be robust and exhibited good repeatability in all the assay conditions (rsd<6.5%).

Leaching of Active Ingredients from Plants with Ionic Liquids

Recently, there was a tremendous interest in the use of ionic liquids for cost-effective and environmentally friendly dissolution and processing of biomass as diverse as cellulose, chitin, and wood. There are several aspects of ionic liquids that are potentially advantageous for the leaching of active ingredient isolation: Ionic liquids are not only a suitable extraction media for valuable components from plant matter but do allow a better access to the active ingredient via dissolution of the biomass that cannot be obtained with traditional solvents. We report the benefits of ionic liquids for the extraction of valuable ingredients including important pharmaceutical intermediates and essential oils from plant materials and discuss different isolation strategies as well as the recovery of the ionic liquids.