Eric J. Beckman

Green processing using ionic liquids and CO2

Many organic solvents evaporate into the atmosphere with detrimental effects on the environment and human health. But room-temperature ionic liquids, with low viscosity and no measurable vapour pressure, can be used as environmentally benign media for a range of industrially important chemical processes, despite uncertainties about thermal stability and sensitivity to oxygen and water. It is difficult to recover products, however, as extraction with water works only for hydrophilic products, distillation is not suitable for poorly volatile or thermally labile products, and liquid-liquid extraction using organic solvents results in cross-contamination. We find that non-volatile organic compounds can be extracted from ionic liquids using supercritical carbon dioxide, which is widely used to extract large organic compounds with minimal pollution. Carbon dioxide dissolves in the liquid to facilitate extraction, but the ionic liquid does not dissolve in carbon dioxide, so pure product can be recovered.

Supercritical and near-critical CO2 in green chemical synthesis and processing

Abstract Carbon dioxide is often promoted as a sustainable solvent, as CO 2 is non-flammable, exhibits a relatively low toxicity and is naturally abundant. However, injudicious use of carbon dioxide in a process or product can reduce rather than enhance overall sustainability. This review specifically examines the use of CO 2 to create greener processes and products, with a focus on research and commercialization efforts performed since 1995. The literature reveals that use of CO 2 has permeated almost all facets of the chemical industry and that careful application of CO 2 technology can result in products (and processes) that are cleaner, less expensive and of higher quality.

Non-fluorous polymers with very high solubility in supercritical CO2 down to low pressures

Liquid and supercritical carbon dioxide have attracted much interest as environmentally benign solvents, but their practical use has been limited by the need for high CO2 pressures to dissolve even small amounts of polar, amphiphilic, organometallic, or high-molecular-mass compounds. So-called ‘CO2-philes’ efficiently transport insoluble or poorly soluble materials into CO2 solvent, resulting in the development of a broad range of CO2 -based processes, including homogeneous and heterogeneous polymerization, extraction of proteins and metals, and homogeneous catalysis. But as the most effective CO2-philes are expensive fluorocarbons, such as poly(perfluoroether), the commercialization of otherwise promising CO2-based processes has met with only limited success. Here we show that copolymers can act as efficient, non-fluorous CO2-philes if their constituent monomers are chosen to optimize the balance between the enthalpy and entropy of solute–copolymer and copolymer–copolymer interactions. Guided by heuristic rules regarding these interactions, we have used inexpensive propylene and CO2 to synthesize a series of poly(ether-carbonate) copolymers that readily dissolve in CO2 at low pressures. Even though non-fluorous polymers are generally assumed to be CO2-phobic, we expect that our design principles can be used to create a wide range of non-fluorous CO2-philes from low-cost raw materials, thus rendering a variety of CO2-based processes economically favourable, particularly in cases where recycling of CO2-philes is difficult.

Biodegradable poly(ether ester urethane)urea elastomers based on poly(ether ester) triblock copolymers and putrescine: synthesis, characterization and cytocompatibility

Polymers with elastomeric mechanical properties, tunable biodegradation properties and cytocompatibility would be desirable for numerous biomedical applications. Toward this end a series of biodegradable poly(ether ester urethane)urea elastomers (PEEUUs) based on poly(ether ester) triblock copolymers were synthesized and characterized. Poly(ether ester) triblock copolymers were synthesized by ring-opening polymerization of epsilon-caprolactone with polyethylene glycol (PEG). PEEUUs were synthesized from these triblock copolymers and butyl diisocyanate, with putrescine as a chain extender. PEEUUs exhibited low glass transition temperatures and possessed tensile strengths ranging from 8 to 20MPa and breaking strains from 325% to 560%. Increasing PEG length or decreasing poly(caprolactone) length in the triblock segment increased PEEUU water absorption and biodegradation rate. Human umbilical vein endothelial cells cultured in a medium supplemented with PEEUU biodegradation solution suggested a lack of degradation product cytotoxicity. Endothelial cell adhesion to PEEUUs was less than 60% of tissue culture polystyrene and was inversely related to PEEUU hydrophilicity. Surface modification of PEEUUs with ammonia gas radio-frequency glow discharge and subsequent immobilization of the cell adhesion peptide Arg-Gly-Asp-Ser increased endothelial adhesion to a level equivalent to tissue culture polystyrene. These biodegradable PEEUUs thus possessed properties that would be amenable to applications where high strength and flexibility would be desirable and exhibited the potential for tuning with appropriate triblock segment selection and surface modification.

Enzyme Activity in Supercritical Fluids

AbstractSupercritical fluids are materials above their critical point that represent a unique class of nonaqueous media for biocatalysis and bioseparation. The inherent gas-like low viscosities and high diffusi vities of supercritical fluids increase the rates of mass transfer of substrates to enzyme. Conversely, the liquid-like densities of supercritical fluids result in higher solubilizing power than those observed for gases. Unlike the behavior of gases and liquids, the physical properties of a supercritical fluid can be adjusted over a wide range by a relatively small change in pressure or temperature. In a supercritical fluid, the careful regulation of the density enables reactant and product solubility to be controlled, thus simplifying downstream separations. The extraction power of supercritical carbon dioxide has been used extensively in both the chemical and food industries.The use of supercritical fluids as a dispersent for biocatalysis was first described in 1985, and there is now a growing tr...

A new peptide-based urethane polymer: Synthesis, biodegradation, and potential to support cell growth in vitro

A novel non-toxic biodegradable lysine-di-isocyanate (LDI)-based urethane polymer was developed for use in tissue engineering applications. This matrix was synthesized with highly purified LDI made from the lysine diethylester. The ethyl ester of LDI was polymerized with glycerol to form a prepolymer. LDI-glycerol prepolymer when reacted with water foamed with the liberation of CO2 to provide a pliable spongy urethane polymer. The LDI-glycerol matrix degraded in aqueous solutions at 100, 37, 22, and 4 degrees C at a rate of 27.7, 1.8, 0.8, and 0.1 mM per 10 days, respectively. Its thermal stability in water allowed its sterilization by autoclaving. The degradation of the LDI-glycerol polymer yielded lysine, ethanol, and glycerol as breakdown products. The degradation products of LDI-glycerol polymer did not significantly affect the pH of the solution. The glass transition temperature (Tg) of this polymer was found to be 103.4 degrees C. The physical properties of the polymer network were found to be adequate to support the cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSC) attached to the polymer matrix and remained viable on its surface. Culture of BMSC on LDI-glycerol matrix for long durations resulted in the formation of multilayered confluent cultures, a characteristic typical of bone cells. Furthermore, cells grown on LDI-glycerol matrix did not differ phenotypically from the cells grown on the tissue culture polystyrene plates as assessed by the cell growth, and expression of mRNA for collagen type I, and transforming growth factor-beta1 (TGF-beta1). The observations suggest that biodegradable peptide-based urethane polymers can be synthesized which may pave their way for possible use in tissue engineering applications.

An Extracellular Matrix Scaffold for Esophageal Stricture Prevention After Circumferential EMR

BACKGROUND EMR is an accepted treatment for early esophageal cancer and high-grade dysplasia. One of the limitations of this technique is that extensive mucosal resection and endoscopic submucosal dissection may be required to obtain complete removal of the neoplasm, which may result in significant stricture formation. OBJECTIVE The objective of the current study was to evaluate the efficacy of an endoscopically deployed extracellular matrix (ECM) scaffold material for prevention of esophageal stenosis after circumferential EMR. DESIGN Ten mongrel dogs were subjected to surgical plane anesthesia and circumferential esophageal EMR by the cap technique. In 5 animals, an ECM scaffold material was endoscopically placed at the resection site; the remaining 5 animals were subjected to circumferential esophageal EMR without ECM placement. Follow-up endoscopy was performed at 4 and 8 weeks; necropsy with histologic assessment was performed at 8 weeks. SETTING Animal laboratory. INTERVENTIONS Circumferential esophageal EMR by the cap technique, followed by endoscopic placement of an ECM scaffold material. MAIN OUTCOME MEASUREMENTS Degree of esophageal stricture and histologic assessment of remodeled esophageal tissue. RESULTS All 5 control dogs had endoscopic evidence of esophageal stenosis. Three required early euthanasia because of inability to tolerate oral intake. Incomplete epithelialization and inflammation persisted at the EMR site in control animals. Endoscopic placement of an ECM scaffold material prevented clinically significant esophageal stenosis in all animals. Histologic assessment showed near-normal esophageal tissue with a lack of inflammation or scar tissue at 8 weeks. CONCLUSIONS Endoscopic placement of an ECM scaffold material prevented esophageal stricture formation after circumferential EMR in this canine model during short-term observation.

Light-induced tailoring of PEG-hydrogel properties

We have previously reported (Andreopoulos et al. J Am Chem Soc 118 (1996) 6235-6240) the synthesis of hydrogels via the photopolymerization of water-soluble PEG molecules. In this paper, PEG-hydrogel membranes were prepared by the irradiation (> 300 nm) of aqueous solutions of photosensitive 4-armed PEG (nominal molecular weight of 20000), in the absence of photo-initiators. The hydroxyl termini of the PEGs were functionalized with cinnamylidene acetate groups to form photosensitive PEG macromers (PEG-CA), which upon irradiation (>300 nm) formed crosslinks between adjacent cinnamylidene groups resulting in highly crosslinked networks (hydrogels) (Andreopoulos et al. J Am Chem Soc 118 (1996) 6235-6240). The hydrogel membranes were highly swellable with equilibrium volume fractions ranging from 0.02 to 0.05. Their swellability was a function of irradiation light (>300 nm) and degree of modification of the PEG molecules. The effect of light on the permeation fluxes of myoglobin (Mb), hemoglobin (Hb), and lactate dehydrogenase-L (LDH) through PEG membranes was also assessed and the diffusion coefficients of the proteins were determined accordingly. The PEG-CA membranes exhibited photoscissive behavior upon exposure to UV irradiation (254 nm). Therefore, UV light was used as a trigger to control the mesh size of the membranes, and thereby the permeation fluxes of Mb, Hb, and LDH. Equilibrium swelling experiments with membranes prepared under different irradiation conditions were performed, and the Flory-Huggins model was utilized to determine the mesh size and the average molecular weight between crosslinks of the synthesized hydrogels.

Synthesis, Biodegradability, and Biocompatibility of Lysine Diisocyanate–Glucose Polymers

The success of a tissue-engineering application depends on the use of suitable biomaterials that degrade in a timely manner and induce the least immunogenicity in the host. With this purpose in mind, we have attempted to synthesize a novel nontoxic biodegradable lysine diisocyanate (LDI)- and glucose-based polymer via polymerization of highly purified LDI with glucose and its subsequent hydration to form a spongy matrix. The LDI-glucose polymer was degradable in aqueous solutions at 37, 22, and 4 degrees C, and yielded lysine and glucose as breakdown products. The degradation products of the LDI-glucose polymer did not significantly affect the pH of the solution. The physical properties of the polymer were found to be adequate for supporting cell growth in vitro, as evidenced by the fact that rabbit bone marrow stromal cells (BMSCs) attached to the polymer matrix, remained viable on its surface, and formed multilayered confluent cultures with retention of their phenotype over a period of 2 to 4 weeks. These observations suggest that the LDI-glucose polymer and its degradation products were nontoxic in vitro. Further examination in vivo over 8 weeks revealed that subcutaneous implantation of hydrated matrix degraded in vivo three times faster than in vitro. The implanted polymer was not immunogenic and did not induce antibody responses in the host. Histological analysis of the implanted polymer showed that LDI-glucose polymer induced a minimal foreign body reaction, with formation of a capsule around the degrading polymer. The results suggest that biodegradable peptide-based polymers can be synthesized, and may potentially find their way into biomedical applications because of their biodegradability and biocompatibility.

Treatment of rat pancreatic islets with reactive PEG

Covalent attachment of polymers to cells and tissues could be used to solve a variety of problems associated with cellular therapies. Insulin-dependent diabetes mellitus is a disease resulting from the autoimmune destruction of the beta cells of the islets of Langerhans in the pancreas. Transplantation of islets into diabetic patients would be an attractive form of treatment, provided that the islets could be protected from the hosts immune system in order to prevent graft rejection. If reaction of polyethylene glycol (PEG) segments with the islet surface did not damage function, the immunogenicity and cell binding characteristics of the islet could be altered. To determine if this process damages islets, rat islets have been isolated and treated with protein-reactive PEG-isocyanate (MW 5000) under mild reaction conditions. An assessment of cell viability using a colorimetric mitochondrial activity assay showed that treatment of the islets with PEG-isocyanate did not reduce cell viability. Insulin release in response to secretagogue challenge was used to evaluate islet function after treatment with the polymer. The insulin response of the PEG-treated islets was not significantly different than untreated islets in a static incubation secretagogue challenge. In addition, PEG-isocyanate-treated islets responded in the same manner as untreated islets in a glucose perifusion assay. Finally, the presence of PEG on the surface of the islets after treatment with the amine-reactive N-hydroxysuccinimide-PEG-biotin (not PEG-isocyanate) was confirmed by indirect fluorescence staining. These results demonstrate the feasibility of treating pancreatic islets with reactive polymeric segments and provide the foundation for further investigation of this novel means of potential immunoisolation.