Dana Kralisch

Novel process windows for enabling, accelerating, and uplifting flow chemistry.

Novel Process Windows make use of process conditions that are far from conventional practices. This involves the use of high temperatures, high pressures, high concentrations (solvent-free), new chemical transformations, explosive conditions, and process simplification and integration to boost synthetic chemistry on both the laboratory and production scale. Such harsh reaction conditions can be safely reached in microstructured reactors due to their excellent transport intensification properties. This Review discusses the different routes towards Novel Process Windows and provides several examples for each route grouped into different classes of chemical and process-design intensification.

Conversion of carbohydrates into 5-hydroxymethylfurfural in highly concentrated low melting mixtures

Highly concentrated melt systems consisting of choline chloride (ChCl) and up to 50 wt% of carbohydrates, corresponding to carbohydrate concentrations of 2.9 to 3.1 mol/L, have been used for the conversion of the carbohydrate content into 5-hydroxymethylfurfural (HMF) in the presence of catalysts. Apart from the monosaccharides D-fructose and D-glucose, the disaccharide sucrose and the polyfructan inulin were successfully converted into HMF. The reported conditions with short reaction times at high concentrations may allow for high space-time yields, which may be of interest for the development of efficient continuous processes for the conversion of carbohydrates into HMF. In a preliminary ecological evaluation, the ChCl/D-fructose system is compared to other representative solvents for the synthesis of 5-hydroxymethylfurfural. The melts have an inherent low toxicological impact due to their negligible vapour pressure.

The Biopolymer Bacterial Nanocellulose as Drug Delivery System: Investigation of Drug Loading and Release using the Model Protein Albumin

Although bacterial nanocellulose (BNC) has reached enormous interest for biomedical applications because of its outstanding material properties, investigations about its potential as drug delivery system are very rare. In the present study, for the first time, the applicability of BNC as drug delivery system for proteins using serum albumin as model drug was systematically investigated. Additionally, never-dried BNC was compared with freeze-dried BNC. For both types of BNC, a dependency of concentration, temperature, time, and preswelling for albumin loading and release could be demonstrated. These findings indicated an overlay of diffusion- and swelling-controlled processes, which could be confirmed by Ritger-Peppas equation. Freeze-dried samples showed a lower uptake capacity for albumin than native BNC, which was found to be related to changes of the fiber network during the freeze drying process as demonstrated by electron microscopy and protein staining experiments. The integrity and biological activity of proteins could be retained during the loading and release processes, which was demonstrated by gel electrophoresis and the use of luciferase as biologically active molecule. In conclusion, hydrophilicity, high biocompatibility, and controllable drug loading and release render BNC an innovative and attractive biopolymer for controlled drug delivery.

Rules and benefits of Life Cycle Assessment in green chemical process and synthesis design: a tutorial review

The implementation of Life Cycle Assessment and related methods in green chemical process and synthesis design strongly supports the development of greener concepts on the basis of deep and profound insights into the dependences between the selection of compounds and process parameters and the resulting environmental impacts. This review article provides an overview on things to know about LCA in general, specifics to be considered during its application in the field of chemical (re-)designs and current application examples from emerging research areas such as active pharmaceutical ingredient manufacturing, nanotechnology, flow chemistry, process intensification under harsh synthesis conditions, process integration, waste treatment, the use of alternative energy sources or solvents as well as chemistry based on renewable resources.

Sustainability through green processing – novel process windows intensify micro and milli process technologies

Drawing on sustainability for chemical production processes demands the prior integration of sustainability aspects during process development, when further environmental impacts and production costs become predefined. Micro and milli process technologies provide novel ways for process improvement combined with ecological and economic advantages. This is demonstrated by current developments in this area. In this context, the idea of “Novel Process Windows” is discussed referring to examples of actual research. A short overview on how to assess sustainability using established tools of evaluation is given as well. This is rounded up with a recent case study of the Kolbe–Schmitt synthesis, performed to disclose the key drivers of further green process development.

Energetic, environmental and economic balances : Spice up your ionic liquid research efficiency

The energy requirement, environmental impact and material costs of the synthesis of ionic liquids, and of their subsequent use as reaction media in the metathesis of 1-octene, are compared to conventional solvents. This preliminary study lays the foundation for an ecological and strategic experimental design. Energetic, environmental and economic assessments over all life-cycle stages allow for the identification of both, disadvantages and opportunities of individual process steps, at an early R&D level. Thus, this approach helps to find new and improved solutions, which comply with the concepts of “Green Chemistry”, that cannot be determined by experimental work alone. The potential of innovative methods can be quantitatively compared to current technologies by means of the energy efficiency factor EEF. Interestingly, this study demonstrates that under certain circumstances, a solvent-free reaction mode may not necessarily be ecologically advantageous. Also, the presumption that, due to facile recycling, a bi-phasic reaction mode is always superior to a homogeneous one is questioned: compared to the energy required for the manufacture of a solvent which results in a biphasic reaction mode (e.g. an ionic liquid), the energy needed for the separation of a homogeneous reaction mixture by distillation is comparatively small. Thus, efficient recycling of such a solvent must be guaranteed.

Active wound dressings based on bacterial nanocellulose as drug delivery system for octenidine

Although bacterial nanocellulose (BNC) may serve as an ideal wound dressing, it exhibits no antibacterial properties by itself. Therefore, in the present study BNC was functionalized with the antiseptic drug octenidine. Drug loading and release, mechanical characteristics, biocompatibility, and antimicrobial efficacy were investigated. Octenidine release was based on diffusion and swelling according to the Ritger-Peppas equation and characterized by a time dependent biphasic release profile, with a rapid release in the first 8h, followed by a slower release rate up to 96 h. The comparison between lab-scale and up-scale BNC identified thickness, water content, and the surface area to volume ratio as parameters which have an impact on the control of the release characteristics. Compression and tensile strength remained unchanged upon incorporation of octenidine in BNC. In biological assays, drug-loaded BNC demonstrated high biocompatibility in human keratinocytes and antimicrobial activity against Staphylococcus aureus. In a long-term storage test, the octenidine loaded in BNC was found to be stable, releasable, and biologically active over a period of 6 months without changes. In conclusion, octenidine loaded BNC presents a ready-to-use wound dressing for the treatment of infected wounds that can be stored over 6 months without losing its antibacterial activity.

Evaluating the greenness of alternative reaction media

The solvent performances and ecological (dis)advantages of different solvent systems for the Diels–Alder reaction of cyclopentadiene and methyl acrylate were investigated. Promising solvent alternatives, especially [C6MIM][BF4](1-hexyl-3-methylimidazolium tetrafluoroborate), citric acid/N,N′-dimethyl urea as well as a solvent-free alternative were compared to the conventional solvent systems methanol, cyclohexane, acetone and methanol/water. By means of the ECO (Ecological and Economic Optimisation) method these solvent alternatives were evaluated already during an R&D (Research and Development) stage in a holistic approach. This method is a screening tool that employs a Simplified Life Cycle Assessment (SLCA) approach in combination with an optimisation procedure. All life cycle stages from the production of reactants, solvents etc., synthesis and workup, recycling and disposal are considered within this methodology. With the help of the ECO method, some significant environmental issues depending on the solvent selection are compared in order to make a contribution to the assessment of the greenness of chemical processes and products during R&D.

White biotechnology for cellulose manufacturing—The HoLiR concept

A variety of approaches are available for generation of bacteria‐produced nanocellulose (BNC) in different forms. BNC production under static cultivation conditions usually results in fleeces or foils, characterized by a homogeneous, three‐dimensional network of nanofibers and a uniform surface. However, under static cultivation conditions in batch vessels, the widths and the lengths of the BNC sheets cultured are determined by the dimensions of the culture vessel. In this contribution, a novel, efficient process for a (semi‐)continuous cultivation of planar BNC fleeces and foils with a freely selectable length and an adjustable height is presented. By means of comprehensive investigations, the comparability of the BNC harvested to that gained from static cultivation under batch conditions is demonstrated. A first estimation of the production costs further shows that this type of processing allows for significant cost reductions compared to static cultivation of BNC in Erlenmeyer flasks. Biotechnol. Bioeng. 2010. 105: 740–747.

Antimicrobial porous hybrids consisting of bacterial nanocellulose and silver nanoparticles

The increasing resistance of pathogens and bacteria is a serious problem in the medical treatment of wounds and injuries. Therefore, new therapeutic agents are not solely based on antibiotics, but also on the use of antimicrobial metal nanoparticles. In this paper we present an innovative method to prepare porous hybrids consisting of bacterial nanocellulose (BNC) and silver nanoparticles (AgNPs). The stepwise modification is based on fairly simple chemical reactions already described for two-dimensional cellulose films. We transferred this method to the three-dimensional, porous network of BNC leading to an antimicrobial activation of its surface. Compared to former approaches, the ultrafine network structure of BNC is less damaged by using mild chemicals. The amount and distribution of the AgNPs on the modified BNC was investigated using scanning electron microscopy. The AgNPs are firmly immobilized on the top and bottom surface of the BNC by chemical interactions. Their size and quantity increase with an increasing concentration of AgNO3 and extended reaction time in the AgNO3 solution. A strong antimicrobial activity of the BNC-AgNP hybrids against Escherichia coli was detected. Furthermore, agar diffusion tests confirmed that this activity is restricted to the modified dressing itself, avoiding a release of NPs into the wound. Therefore, the produced hybrids could be potentially suited as novel antimicrobial wound dressings.