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In the past decades, ionic liquids (IL) evolved from a “designer solvent” to a well-known and well-characterized class of compounds useful in reactions, extractions, and other applications. By an increasing number of synthesized ILs also new fields of application were uncovered. The todayʼs research interest covers a range for direct use of ILs, application as embedding material or as catalyst. In this brief review, we present diverse applications of pure native ILs as well as these of polymerized ionic liquids (PILs). These charged polymers unite the presented advantages of both, ionic liquids and solid polymer structures. We also show the recent developments in the areas of drug delivery, catalysis and catalyst immobilization where these particular compositions demonstrate improvements compared to existing solutions. Besides the advantages, we likewise discuss some limitations and drawbacks.

A fundamental electrochemical study of several highly diluted ionic liquids (ILs) at the interface between two immiscible electrolyte solutions (ITIES) is reported to evaluate the electrochemical and the solvation properties of [BMIM]Cl, [BMIM]BF4, [BMIM]OTf, [EMIM]Br and [AMIM]Cl. The interface is formed between a hydrophilic electrolyte dissolved in water and a hydrophobic electrolyte dissolved in an organic solvent, here 1,2-dichloroethane (DCE). The transfer of the highly diluted ionic species from the water phase into the organic phase occurs when an electrical potential difference is applied across the interface. Standard Gibbs energy of transfer, the relative hydrophilicity/hydrophobicity and transfer coefficients across the interface of the selected ILs are determined by cyclic voltammetry at large ITIES.

Hydrogels, based on polymerized ionic liquids, are increasingly used in the medical and pharmaceutical industry as implants, drug delivery systems, contact lens material, bone substitutes and stent coatings. Therefore they need to be biocompatible, flexible and resistant to external stress. In order to meet these requirements, there is a large interest in design, synthesis and characterization of these interesting polymers. In this work, mechanical properties such as gelation kinetics, shear strain resistance, and response to compression and stretching of ten different polymerized ionic liquid-based hydrogels were examined, completing the picture of the rheological behavior of these materials. Interestingly, the investigations of stretching measurements showed a wide range of critical strains leading to failure from 4.8 ± 1.1 to 47.9 ± 15.1%and in compression measurements critical strain from 7.8 ± 3.6 to higher than 59.8 ± 17.3%, as well as a linear viscoelastic range in shear from 14 ± 8 to 267 ± 26%. These results allow improved design with a “choose-the-best-material”-toolbox for medical applications.

In this study the fungal laccase from Myceliophthora thermophila (Novozym® 51003) was investigated for oxidative CC couplings of phenolic compounds. This enzyme requires only molecular oxygen as oxidant, which represents a great advantage for oxidative coupling reactions. However, such couplings are typically considered as highly unselective, due to the radical reaction mechanism of laccases. Based on different analytical techniques we gained detailed insights into laccase initiated coupling reactions. A preselection of potential substrates was realized via oxygen measurement during laccase initiated oxidations. Furthermore in situ FT-IR spectroscopy facilitated analyses in-depth, due to feasibility to detect dissolved as well as solid compounds. This technique allowed the detection of the grade of couplings of various laccase substrates, depending on different conditions. As a result oxidative dimerizations of 2,6-disubstituted phenols could be identified as highly selective and were scaled-up to multigram scale. Thereby the oxidation product of 2,6-diisopropyl phenol can be easily reduced to the corresponding biphenol, the antibacterial agent dipropofol. The presented techniques open up new biocatalytical approaches receiving quinoid units as key elements of many natural compounds and pharmaceuticals.

Recovery of carbohydrates from aqueous solution represents a problem due to their large, multivalent and flexible structure and their high hydrophilicity. Organic solvents as well as alternative solvents such as ionic liquids are able to extract carbohydrates from aqueous media by the aid of primary amines. The mechanism of the extraction process has been explored by using galactose and its corresponding O -methyl galactoside. The results indicate that the mechanism is based on formation of an adduct between the aldo -structure of the monosaccharide and the primary amine to provide a hemiaminal, which is extracted into the organic phase. The extraction rate can be influenced by variation of temperature, time, and the amount of amine and depends on the structure of the carbohydrate. The selectivity can also be tuned using different types of ionic liquids. This procedure opens the possibility to recover a carbohydrate selectively from a mixture of different carbohydrates.

The laccase-mediated heterocoupling of 3-methylcatechol and n -hexylamine was investigated at the milligram to gram scale, and an early eco-efficiency analysis and evaluation revealed bottlenecks in enzymatic synthesis. Eco-efficiency analysis was used as an optimisation tool to create more sustainable solutions and improve subsequent reactions, enabling the scaled-up biocatalytic process to become more economical and competitive compared with the chemocatalysed procedure using sodium iodate. When working with higher substrate concentrations (up to 100 mM), the following key aspects must also be considered: (1) the low solubility of n -hexylamine and the reaction products in aqueous solution, and (2) the poor stability of enzymes in unconventional solvents. The present study includes activity and stability experiments using laccases in methanol, a suitable solvent for the hydrophobic compound n -hexylamine. Contrary to previously published reports, excellent activities were obtained using Novozym 51003 at high methanol contents and substrate concentrations up to 100 mM. In addition, the use of this volatile organic solvent drastically simplified downstream processing.

Electrodialysis (ED) is an advancing seawater sample processing tool that enables the separation of analytes from the often interfering salt matrix. In this study, we present the evaluation of a laboratory scale ED system for both dissolved organic matter (DOM) and target pollutant analysis of seawater. The developed sample processing protocol yields reproducible data and was found to be robust towards moderate changes in sample composition. At the final salinity of 0.1, the average recovery of DOM in the form of dissolved organic carbon, nitrogen and phosphorus (DOC, DON and DOP) was 44, 53 and 89%, respectively. DOM loss occurred mainly in the late stage of the ED process. When investigating specific ED processing parameters, it was discovered that the initial sample salinity does not influence DOM recovery. The final salinity, by contrast, is a dominant influence factor on DOM recovery. Furthermore, DOC and DOP recoveries could be improved by 8% by refining the electrical current in the ED cell. Surprisingly, adjustments of the sample pH did not lead to any improvements in DOM recovery. The experiments with target analytes showed that the recovery of individual molecules is determined by their n-octanol water partition coefficients logKow. High recoveries > 80% were achieved for compounds with medium logKow of −1 to 3. Hydrophobic compounds with logKow > 3 were lost through surface adsorption to the system walls and tubing. Small, polar and charged compounds with logKow

Highly porous and crystalline metal–organic framework MIL-101 has been synthesized and used for the preparation of rhodium supported catalyst. Acetylacetonato(1,5-cyclooctadiene)rhodium(I) has been used as catalyst precursor. The material has been characterized by XRD, XPS, SAXS, FTIR, SEM, TEM, AAS, and nitrogen adsorption. The catalytic properties of Rh@MIL-101 have been investigated in the hydroformylation of olefins with different structure and chain length to the corresponding aldehydes. High conversion and selectivity to n -aldehydes have been achieved in the hydroformylation of n -alk-1-enes. The obtained results show that the rhodium species are highly dispersed and preferentially located at internal and less accessible sites at the supertetrahedral units.

Drug-coated balloons (DCB), which have emerged as therapeutic alternative to drug-eluting stents in percutaneous cardiovascular intervention, are well described with regard to clinical efficiency and safety within a number of clinical studies. In vitro studies elucidating the correlation of coating method and composition with DCB performance are however rare but considered important for the understanding of DCB requirements and the improvement of established DCB. In this context, we evaluated the applicability of a pipetting, dip-coating, and spray-coating process for the establishment of DCB based on paclitaxel (PTX) and the ionic liquid cetylpyridinium salicylate (Cetpyrsal) as novel innovative additive in three different compositions. Among tested methods and compositions, the pipetting process with 50 wt.% PTX resulted in most promising coatings as drug load was less controllable by the other processes and higher PTX contents led to considerable drug crystallization, as visualized by electron microscopy, accelerating PTX loss during short-term elution. Applying these conditions, homogeneous coatings could be applied on balloon catheter, whose simulated use in an in vitro vessel model revealed percental drug losses of 36 and 28% during transit and percental drug transfers of 12 and 40% under expansion for coatings applied in expanded and folded balloon condition, respectively. In comparison to literature values, these results support the high potential of Cetpyrsal as novel DCB matrix regarding low drug loss and efficient drug transfer.

Dispersed colloidal Pt-nanoparticles with mean particle sizes between 1 and 4 nm were prepared continuously in microstructured devices using ethylene glycol as solvent and reducing agent and H 2 PtCl 6 as metal precursor. The Pt-nanoparticles were characterized directly in solution regarding the particle size and particle size distribution by small angle X-ray scattering (SAXS) and after deposition on a grid by TEM. Both methods gave comparable results. The particle size of the Pt-nanoparticles which are formed inside the microstructures can be controlled by the NaOH/Pt ratio. At a high NaOH/Pt-ratio, that means in alkaline medium, the Pt-nanoparticles have a mean particle size lower than 1.7 nm and a narrow size distribution indicating that nanoparticle formation is dominated by nucleation reaction under this condition. At a low NaOH/Pt-ratio, that means in acidic medium, the mean particle size increases to about 3.6 nm whereas also the particle size distribution increases which is mainly attributed to a larger influence of growth reactions on particle formation. Pt-nanoparticles with a similar mean particle size but a clearly narrower particle size distribution were obtained when a two-step process was used. In this process, Pt-seeds were formed in the microreactor in an alkaline medium. After mixing the alkaline Pt-seeds containing solution with a HCl/ethylene glycol solution in a micromixer the now acidic solution flows in a second microreactor where mainly particle growing takes place. The final particle size and its distribution can be influenced by both conditions for seed formation (temperature, flow rate) and particle growth (pH, temperature, flow rate).

A chimeric cyanophycin synthetase gene composed of the cph A Te coding region from the cyanobacterium Thermosynechococcus elongatus BP-1, the constitutive 35S promoter and the plastid targeting sequence of the integral photosystem II protein PsbY was transferred to the tobacco variety Petit Havanna SRI and the commercial potato starch production variety Albatros. The resulting constitutive expression of cyanophycin synthetase leads to polymer contents in potato leaf chloroplasts of up to 35 mg/g dry weight and in tuber amyloplasts of up to 9 mg/g dry weight. Both transgenic tobacco and potato were used for the development of isolation methods applicable for large-scale extraction of the polymer. Two different procedures were developed which yielded polymer samples of 80 and 90% purity, respectively

Extraction of catalytically active biomolecules using ionic liquid-based aqueous two-phase systems (IL-based ATPS) composed of the IL Ammoeng™ 110 and K2HPO4/KH2PO4 represents a powerful tool for the integration of several process steps into one unit operation within downstream processing. The technique can be used in order to combine the purification of active enzymes with the performance of enzyme-catalysed reactions. However, a fundamental understanding of the driving forces which are involved in the partitioning of proteins between the two phases is still lacking. By investigating the distribution of four model proteins at varying system characteristics of the IL-based ATPS, we found a combination of different interactions between the proteins and the ionic liquid to be responsible for the enrichment within the IL-containing upper phase. Among these, the proteins’ charge as well as the molecular weight is of major importance. Therefore, we propose the electrostatic interaction between the charged amino acid residues at a protein's surface and the positively charged IL-cation to be the main driving force of the extraction process. Based on these findings, a model for describing protein partitioning in IL-based ATPS was established and employed for predicting the partition coefficient of two further model proteins, pepsin and hemoglobin.

A new method for the purification of N-acetylneuraminic acid (Neu5Ac) is presented. A mixture of phenylboronic acid (PBA) and trioctylmethylammonium chloride (TOMAC) efficiently extracts the compound, which usually needs to be purified by elaborate chromatographic procedures or precipitation with glacial acetic acid. The presented extraction method is suitable to enrich Neu5Ac referring to pyruvate and the other compounds and facilitate further purification via classical crystallisation or chromatography, thus facilitating the established production process which utilises a large excess of pyruvate. The extraction system was characterised in detail by equilibrium studies for various solvents, pH values and carrier and substrate concentrations. The equilibrium constants determined for the two reaction steps (reaction with phenylboronic acid and reactive extraction) show that the equilibrium of extraction is more important than the extent of reaction with phenylboronic acid. The results obtained for pure compounds could be assigned to mixtures and reaction solutions without difficulty. Furthermore an efficient recovery of the carbohydrates from the organic phase is presented. The treatment of reactions mixtures showed that this system is not only feasible at lab scale and concentrations typical for scientific studies, but also for high substrate concentrations as used in industrial processes. The extraction step was shown to be the limiting factor in the extraction/recovery process.

In this paper, we describe the hydroformylation of terminal and internal olefins to terminal aldehydes using a catalyst system of rhodium and BIPHEPHOS. According to industrial processes, the catalyst concentration lies in a range from 0.01 to 0.001 mol%. The conversions are, depending of the substrate, up to 99% and yields up to 86% of the aldehydes can be found. The ratio of linear to branched products is up to 99:1.

Ionic liquids (IL) offer new possibilities for solvent engineering for biocatalytic reactions. The deracemization of (±)-mandelic acid using a lipase-mandelate racemase two-enzyme system was used to investigate the scopes and limitations of ionic liquids as new reaction media for a dynamic resolution approach. Mandelate racemase [EC 5.1.2.2] from Pseudomonas putida ATCC 12633 was observed to be active in ionic liquids such as 1,3-dimethylimidazolium methylsulfate ([MMIM][MeSO 4 ]) or 1-butyl-3-methylimidazolium octylsulfate ([BMIM][OctSO 4 ]) at water activities a w >0.74. Mandelate racemase activity could also be obtained in a biphasic system consisting of water and 1-octyl-3-methylimidazolium hexafluorophosphate ([OMIM][PF 6 ]) in a ratio of 1:10.

Isobaric (vapour + liquid) equilibrium of (1,3-dioxolane or 1,4-dioxane + 2-methyl-1-propanol or 2-methyl-2-propanol) at 40.0 kPa and 101.3 kPa has been studied with a dynamic recirculating still. The experimental VLE data are thermodynamically consistent. From these data, activity coefficients were calculated and correlated with the Margules, van Laar, Wilson, NRTL and UNIQUAC equations. The VLE results have been compared with the predictions by the UNIFAC and ASOG methods.

( R )-Ethyl 2-hydroxy-4-phenylbutyrate is an important intermediate for the synthesis of several ACE-inhibitors (ACE = a ngiotensin- c onverting e nzyme). A possible preparation of this intermediate is the kinetic resolution of the racemic 2-hydroxy compound. The enantioselective hydrolysis is catalyzed by the lipase from Pseudomonas cepacia in a two-phase system consisting of aqueous buffer and in organic solvent solubilized substrate. Production was carried out in a diafiltration reactor. A ceramic ultrafiltration membrane retained both the organic phase and the lipase that was solubilized in the aqueous phase. The aqueous phase was pumped continuously through the reactor, removing the inhibiting product 2-hydroxy-4-phenylbutyrate. Due to the use of this membrane reactor a kinetic resolution, which is limited by a strong product inhibition, can be carried out efficiently. By operating this membrane reactor in a repetitive batch mode, enzyme consumption could be greatly reduced. The remaining ( R )-2-hydroxy ester could be produced with enantiomeric excess > 99.5% and a space-time yield of 275 g L −1 d −1 .

A micellar enlarged Rh-(2 S ,4 S )- N - tert -butoxycarbonyl-4-diphenylphosphino-2-diphenyl-phosphino-methyl-pyrrolidine (BPPM) catalyst was used for the enantioselective hydrogenation of α-amino acid precursors in a membrane reactor, equipped with an ultrafiltration membrane. The chiral α-amino acid derivatives were obtained with good enantioselectivity and space–time yields. The catalyst, embedded in micelles, obtained from triblock copolymers as surfactants, was retained and reused several times without loss of activity and enantioselectivity. Only a minimal leaching of the catalyst components was found.

2-Deoxy-α -d- glucose-1-phosphate, 3-deoxy-α -d- arabino-hexose-1-phosphate, 4-deoxy-α -d- lyxo-hexose-1-phosphate, and α -d- lyxose-1-phosphate were synthesised chemically, and evaluated as substrates for a recombinant G D P-mannose pyrophosphorylase (Salmonella enterica, group B, cloned in Escherichia coli). The deoxy derivatives were all substrates for the enzyme, with slightly reduced Vmax values but significantly higher Km values than those recorded for the native substrate, mannose-1-phosphate. The pyrophosphorylase was used for the synthesis of GDP-mannose analogues GDP-2-deoxy-glucose and GDP-lyxose on a milligram scale.

Dendrimers are a rather new class of macromolecules, which are by now at the edge of technical application. A number of dendritic catalysts have been described, but in most cases catalyst recyclization is an unsolved problem. The present article describes the retention of diaminopropyl-type dendrimers bearing palladium phosphine complexes by ultra- or nanofiltration membranes and their use as catalysts for the allylic substitution in a continuously operating chemical membrane reactor. Retention rates are higher than 99.9% resulting in a sixfold increase of the total turnover number for the Pd catalyst.

The enantioselective reduction of acetophenone was studied in two different ways. Chemical borane reduction using a homogeneously soluble polymer-bound oxazaborolidine catalyst was carried out in a continuously operated membrane reactor and yielded (R)-phenylethanol in good enantiomeric excess with high space–time yields. An enzymatic reduction using a dehydrogenase two-enzyme system as the catalyst and formate as the hydrogen source was carried out in an extractive bi-membrane reactor and yielded (S)-phenylethanol in excellent enantiomeric excess with a low enzyme consumption. A comparison of the two systems with respect to space–time yield, total turnover number and other parameters is made.

Polymer enlarged oxazaborolidines that are homogeneously soluble were used as catalysts for the enantioselective reduction of ketones in a continuously operated membrane reactor equipped with a nanofiltration membrane. The amount of chiral product per mole of catalyst could be enhanced from 10 up to 560 moles (≡0.18 mol% catalyst). The chiral alcohols are obtained in good to excellent ee and space–time yield (up to 99% ee and 1.4 kg/[Lreactor volume×day)].

Reductions of poorly soluble ketones often suffer from low total turnover numbers conferring to the coenzyme and large volumes which are needed for the conversion. The novel emulsion membrane reactor overcomes these limitations. From an emulsion consisting of an organic substrate and an aqueous buffer phase, the aqueous phase is separated selectively by using a hydrophilic ultrafiltration membrane and fed to a subsequent enzyme membrane reactor. The product outflow is recirculated to the emulsion stirred vessel and, due to the partition coefficients, the aqueous phase is recharged with substrate while the product is extracted. This new reactor concept will be compared to the classical enzyme membrane reactor. The latter was operated under the same conditions over a period of 4 months at a space-time yield of 21.2 g l −1 day −1 . As a model system the enantioselective reduction of 2-octanone to ( S )-2-octanol (ee > 99.5%) is used, carried out by a carbonyl reductase from Candida parapsilosis . NADH is regenerated by formate dehydrogenase from Candida boidinii . In comparison to the classical enzyme membrane reactor the total turnover number could be increased by a factor 9 using the novel emulsion membrane reactor.

The aim of the presented work is the chemoenzymatic synthesis of GDP-mannose (GDP-Man). Mannose-1-phosphate (Man-1-P) is synthesised by a very convenient chemical method and is activated with GTP and recombinant GDP-mannose pyrophosphorylase (GDP-Man PP) to give GDP-Man. The productivity of the process is improved using reaction engineering techniques. Detailed kinetic studies, modelling of the reaction and simulations of different reaction systems revealed that besides a strong product inhibition the cofactor Mg 2+ is a key switch for effective enzymatic synthesis. Using a two-stage cascade of enzyme membrane reactors, GDP-Man could be produced continuously with a space-time yield of 28 g L −1 d −1 and an enzyme consumption of 0.9 U g −1 , which means a six-fold improvement related to batch synthesis.

A two-enzyme system consisting of a cyclohexanone mono-oxygenase from Acinetobacter NCIMB 9871 and a protein-engineered formate dehydrogenase for the regeneration of the cofactor NADPH was used for the synthesis of chiral e-lactones. 4-Methylcyclohexanone was used as the model substrate yielding ( S )-(−)-5-methyl-oxepane-2-one with high chemical and enantiomeric purity. Syntheses were carried out in a repetitive-batch reactor with integrated bubble-free aerationby means of a thin-walled silicon tube.

NAD + and NADP + were retained in continuously operated enzyme membrane reactors by nanofiltration membranes with retention rates between 0.86–0.98. For lower molecular weight substrates and products, retention rates below 0.35 were found. For the reductive amination of trimethylpyruvate to l - tert -leucine, the reactor was stably operated for 10 days. The total turnover number could be increased 3.4 times to values higher than 7,900 by this approach.

The trisaccharide moenomycin analogue 1c has been synthesized. One starting material was N-acetyllactosamine obtained by an enzyme-catalyzed transglycosylation. 1c differs from moenomycin degradation product 1a only in two positions of unit C. In contrast to 1a the synthetic 1c is antibiotically inactive.

A NADPH regenerating system using a new, protein engineered formate dehydrogenase (FDH) is investigated. The new enzyme is the first known NAD(P)H dependent FDH. It can be successfully employed in synthesis with other enzymes requiring a NADPH regeneration. All advantages of the known NAD(H) dependent FDH's in these enzyme coupled synthesis can now be transferred to NADP(H) dependent systems.

( S )-2-N,N-dibutylamino-3-butyl-1-[4-(4-Phenylmethoxy)-phenyl]heptan-3-ol 3 based on ( S )-tyrosine has been synthesised. For the diethylzinc addition to both aliphatic and aromatic aldehydes, high enantiomeric excesses up to 95% were obtained.