Liquid Phase Peptide Synthesis via One-Pot Nanostar Sieving (PEPSTAR).

Herein, a one-pot liquid phase peptide synthesis featuring iterative addition of amino acids to a "nanostar" support, with organic solvent nanofiltration (OSN) for isolation of the growing peptide after each synthesis cycle is reported. A cycle consists of coupling, Fmoc removal, then sieving out of the reaction by-products via nanofiltration in a reactor-separator, or synthesizer apparatus where no phase or material transfers are required between cycles. The three-armed and monodisperse nanostar facilitates both efficient nanofiltration and real-time reaction monitoring of each process cycle. This enabled the synthesis of peptides more efficiently while retaining the full benefits of liquid phase synthesis. PEPSTAR was validated initially with the synthesis of enkephalin-like model penta- and decapeptides, then octreotate amide and finally octreotate. The crude purities compared favorably to vendor produced samples from solid phase synthesis.

Membrane Fractionation of Liquors from Lignin-First Biorefining.

For the utilization of each lignin fraction in the lignin liquors, the development of separation strategies to fractionate the lignin streams by molecular weight ranges constitutes a timely challenge to be tackled. Herein, membrane filtration was applied to the refining of lignin streams obtained from a lignin-first biorefining process based on H-transfer reactions catalyzed by Raney Ni, by using 2-PrOH as a part of the lignin extraction liquor and as an H-donor. A two-stage membrane cascade was considered to separate and concentrate the monophenol-rich fraction from the liquor. Building on the results, an economic evaluation of the potential of membrane filtration for the refining of lignin streams was undertaken. In this proof-of-concept report, a detailed analysis is presented of future developments in the performance required for the utilization of membrane filtration for lignin refining and, more aspiringly, solvent reclamation.

The Selectivity Challenge in Organic Solvent Nanofiltration: Membrane and Process Solutions.

Recent development of organic solvent nanofiltration (OSN) materials has been overwhelmingly directed toward tight membranes with ultrahigh permeance. However, emerging research into OSN applications is suggesting that improved separation selectivity is at least as important as further increases in membrane permeance. Membrane solutions are being proposed to improve selectivity, mostly by exploiting solute/solvent/membrane interactions and by fabricating tailored membranes. Because achieving a perfect separation with a single membrane stage is difficult, process engineering solutions, such as membrane cascades, are also being advocated. Here we review these approaches to the selectivity challenge, and to clarify our analysis, we propose a selectivity figure of merit that is based on the permselectivity between the two solutes undergoing separation as well as the ratio of their molecular weights.

Continuous Consecutive Reactions with Inter-Reaction Solvent Exchange by Membrane Separation.

Pharmaceutical production typically involves multiple reaction steps with separations between successive reactions. Two processes which complicate the transition from batch to continuous operation in multistep synthesis are solvent exchange (especially high-boiling- to low-boiling-point solvent), and catalyst separation. Demonstrated here is membrane separation as an enabling platform for undertaking these processes during continuous operation. Two consecutive reactions are performed in different solvents, with catalyst separation and inter-reaction solvent exchange achieved by continuous flow membrane units. A Heck coupling reaction is performed in N,N-dimethylformamide (DMF) in a continuous membrane reactor which retains the catalyst. The Heck reaction product undergoes solvent exchange in a counter-current membrane system where DMF is continuously replaced by ethanol. After exchange the product dissolved in ethanol passes through a column packed with an iron catalyst, and undergoes reduction (>99 % yield).

Batchwise and continuous nanofiltration of POSS-tagged Grubbs-Hoveyda-type olefin metathesis catalysts.

New molecular-weight-enlarged metathesis catalysts, which bear polyhedral oligomeric silsesquioxane (POSS) tags, were synthesized and characterized. The catalysts can be recovered from the reaction mixture by using nanofiltration techniques and can be reused. It was found that the membranes Starmem 228 and PuraMem 280 successfully separate the catalyst from the post-reaction mixtures to below 3 ppm. The application of these POSS-tagged catalysts in a continuous metathesis reaction was also investigated.

Separation of reaction product and palladium catalyst after a Heck coupling reaction by means of organic solvent nanofiltration.

Organic solvent nanofiltration (OSN) is a recently commercialized technology, which we have used to develop a method for the separation of a target product and the Pd catalyst from a Heck coupling postreaction mixture. The experimental setup included commercially available polyimide copolymer membranes with molecular weight cut-off (MWCO) values in the range of 150-300 Da, acetone as the solvent, and a working pressure (N(2)) of 3 MPa. The investigation of the membranes revealed that a membrane with a MWCO of 200 Da provided quantitative retention of the Pd catalyst and quantitative recovery of the target product by means of a cross-flow dia-nanofiltration procedure.

Membrane enhanced peptide synthesis.

This communication reports a new technology platform that advantageously combines organic solvent nanofiltration (a newly emerging technology capable of molecular separations in organic solvents) with solution phase peptide synthesis-Membrane Enhanced Peptide Synthesis (MEPS).

The use of an oil absorber as a strategy to overcome starvation periods in degrading 1,2-dichloroethane in waste gas.

This work investigates the use of an oil absorber as an operational strategy in vapor phase bioreactors exposed to starvation periods, during the treatment of inhibitory pollutants. After being exposed to 1,2-dichloroethane (DCE) starvation periods, the response and stability of a combined oil-absorber-bioscrubber (OAB) system was compared to that of a bioscrubber only (BO) system. In the BO system, after a 5.2 days starvation period, the DCE removal efficiency was reduced to 12%, and 6 days were needed to recover the initial removal efficiency when the DCE feed resumed. The total organic discharged (TOD(DCE)) was 16,500 g(DCE) m(bioscrubber) (-3) after the DCE starvation. Biomass analysis performed using fluorescence in situ hybridisation (FISH) showed that the microbial activity was significantly reduced during the starvation period and that 5 days were needed to recover the initial activity, after the re-introduction of DCE. In contrast, the performance of the OAB system was stable during 5.2 days of DCE starvation. The DCE removal efficiency was not affected when the DCE feed resumed and the TOD(DCE) was significantly reduced to 2,850 g(DCE) m(bioscrubber) (-3). During starvation, the activity of the microbial culture in the OAB system showed a substantially lower decrease than in the BO system and recovered almost immediately the initial activity after the re-introduction of DCE. Additionally, a mathematical model describing the performance of the OAB system was developed. The results of this study show that the OAB system can effectively sustain the biological treatment of waste gas during starvation periods of inhibitory pollutants.

Stability and performance of Xanthobacter autotrophicus GJ10 during 1,2-dichloroethane biodegradation.

A nucleic acid-based approach was used to investigate the dynamics of a microbial community dominated by Xanthobacter autotrophicus GJ10 in the degradation of synthetic wastewater containing 1,2-dichloroethane (DCE). This study was performed over a 140-day period in a nonsterile continuous stirred-tank bioreactor (CSTB) subjected to different operational regimens: nutrient-limiting conditions, baseline operation, and the introduction of glucose as a cosubstrate. The microbial community was analyzed by a combination of fluorescence in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE). Under nutrient-limiting conditions, DCE degradation was restricted, but this did not affect the dominance of strain GJ10, determined by FISH to comprise 85% of the active population. During baseline operation, DCE degradation improved significantly to over 99.5% and then remained constant throughout the subsequent experimental period. DGGE profiles revealed a stable, complex community, while FISH indicated that strain GJ10 remained the dominant species. During the addition of glucose as a cosubstrate, DGGE profiles showed a proliferation of other species in the CSTB. The percentage of strain GJ10 dropped to 8% of the active population in just 5 days, although this did not affect the DCE biodegradation performance. The return to baseline conditions was accompanied by the reestablishment of strain GJ10 as the dominant species, suggesting that this system responds robustly to external perturbations, both at the functional biodegradation level and at the individual strain level.

An oil-absorber-bioscrubber system to stabilize biotreatment of pollutants present in waste gas. Fluctuating loads of 1,2-dichloroethane.

Biotreatment technologies offer a cost-effective and efficient method for dealing with point-source releases of solvents. However, a major problem hampering these technologies is the fluctuating pollutant loads, which is especially critical for inhibitory pollutants. Provision of biotreatment systems able to cope with this problem is a significant technological and environmental challenge. This study investigates the potential for an absorber to act as buffer for shock loadings of inhibitory pollutants in waste-gas streams undergoing biological treatment. 1,2-Dichloroethane (DCE) was used as an example of a toxic and inhibitory organic pollutant. The stability of a combined oil-absorber-bioscrubber (OAB) system was compared to that of a bioscrubber only (BO) system when each was subjected to shock loads of DCE. The BO system was inoculated with Xanthobacter autotrophicus strain GJ10 and was submitted to sharp, sequential pulses in DCE inlet load, which caused system instability. Complete inhibition of the BO process occurred for a 3 h DCE pulse, leading to 9125 g of DCE m(-3)bioscrubber total organic discharged (TODDCE). Following the pulse, fluorescence in situ hybridization (FISH) showed that the active strain GJ10 was effectively washed-out. In contrast, the performance of the OAB system was stable during DCE shock loads. The carbon dioxide production remained stable, and low levels of effluent DCE and total organic carbon concentrations were found. For the 3 h pulse TODDCE was only 173 g of DCE m(-3)bioscrubber, and FISH indicated that the GJ10 strain remained active. We conclude that the OAB system offers an effective solution to the biological treatment of waste-gas containing fluctuating pollutant concentrations.

Membrane separation in green chemical processing: solvent nanofiltration in liquid phase organic synthesis reactions.

This paper describes ideas together with preliminary experimental results for applying solvent nanofiltration to liquid phase organic synthesis reactions. Membranes for organic solvent nanofiltration have only recently (during the 1990s) become available and, to date, have been applied primarily to food processing (vegetable oil processing, in particular) and refinery processes. Applications to organic synthesis, even at a laboratory feasibility level, are few. However, these membranes have great potential to improve the environmental performance of many liquid phase synthesis reactions by reducing the need for complex solvent handling operations. Examples that are shown to be feasible are solvent exchanges, where it is desired to swap a high molecular weight molecule from one solvent to another between separate stages in a complex synthesis, and recycle and reuse of homogeneous catalysts. In solvent exchanges, nanofiltration is shown to provide a fast and effective means of swapping from a high boiling point solvent to a solvent with a lower boiling point-this is a difficult operation by means of distillation. Solvent nanofiltration is shown to be able to separate two distinct types of homogeneous catalysts, phase transfer catalysts and organometallic catalysts, from their respective reaction products. In both cases the application of organic solvent nanofiltration allows several reuses of the same catalyst. Catalyst stability is shown to be an essential requirement for this technique to be effective. Finally, we present a discussion of scale-up aspects including membrane flux and process economics.