Membranes, chiral preparation

Duan, W., Kitamura, S., Uechi, 1., Katsuki, A. and Tanimoto, Y. (2005) Three-dimensional morphological chirality induction using high magnetic fields in membrane tubes prepared by a silicate garden reaction. J. Phys. Chem. B, 109, 13445-13450. 

The first successful chiral resolutions through enantioselective membranes have been published recently, but few cases are applicable to the preparative scale, mainly due to mechanical and technical limitations. Low flow rates, saturation of the chiral selectors and loss of enantioselectivity with time are some of the common problems encountered and that should be solved in the near future. 

Another possibility of constructing a chiral membrane system is to prepare a solution of the chiral selector which is retained between two porous membranes, acting as an enantioselective liquid carrier for the transport of one of the enantiomers from the feed solution of the racemate to the receiving side (Fig. 1-5). This system is often referred to as membrane-assisted separation. The selector should not be soluble in the solvent used for the elution of the enantiomers, whose transport is driven by a gradient in concentration or pH between the feed and receiving phases. As a drawback common to all these systems, it should be mentioned that the transport of one enantiomer usually decreases when the enantiomer ratio in the permeate diminishes. Nevertheless, this can be overcome by designing a system where two opposite selectors are used to transport the two enantiomers of a racemic solution simultaneously, as it was already applied in W-tube experiments [171]. 

Liquid-liquid extraction is a basic process already applied as a large-scale method. Usually, it does not require highly sophisticated devices, being very attractive for the preparative-scale separation of enantiomers. In this case, a chiral selector must be added to one of the liquid phases. This principle is common to some of the separation techniques described previously, such as CCC, CPC or supported-liquid membranes. In all of these, partition of the enantiomers of a mixture takes place thanks to their different affinity for the chiral additive in a given system of solvents. 

Possible applications of MIP membranes are in the field of sensor systems and separation technology. With respect to MIP membrane-based sensors, selective ligand binding to the membrane or selective permeation through the membrane can be used for the generation of a specific signal. Practical chiral separation by MIP membranes still faces reproducibility problems in the preparation methods, as well as mass transfer limitations inside the membrane. To overcome mass transfer limitations, MIP nanoparticles embedded in liquid membranes could be an alternative approach to develop chiral membrane separation by molecular imprinting [44]. 

Membranes offer a format for interaction of an analyte with a stationary phase alternative to the familiar column. For certain kinds of separations, particularly preparative separations involving strong adsorption, the membrane format is extremely useful. A 5 x 4 mm hollow-fiber membrane layered with the protein bovine serum albumin was used for the chiral separation of the amino acid tryptophan, with a separation factor of up to 6.6.62 Diethey-laminoethyl-derivatized membrane disks were used for high-speed ion exchange separations of oligonucleotides.63 Sulfonated membranes were used for peptide separations, and reversed-phase separations of peptides, steroids, and aromatic hydrocarbons were accomplished on C18-derivatized membranes. 

FIGURE 1.35 SLM process using O-9-(l-adamantylcarbamoyl)-10,ll-dihydro-ll-octadecylsulfinylquinme and corresponding quinidine derivative as chiral carriers for the preparative separation of enantiomers of Al-derivatized amino acids (e.g., DNB-Leu). (a) ftinciple of the carrier SLM process with carrier-mediated transport (top) and (nonstereoselective) nonspecific transport processes (bottom), (b) General experimental setup of the SLM production unit with two membrane modules, (c) Multistage SLM purification process. P, permeate QD/QN, membrane modnles snpported with quinidine-derived and quinine-derived chiral carriers. R, S, D, L refers to the respective enantiomers of the selectand (DNB-Leu). (Reproduced from A. Maximini et al., J. Membr. ScL, 276 221 (2006). With permission.)... 

Initial preparative work with oxynitrilases in neutral aqueous solution [517, 518] was hampered by the fact that under these reaction conditions the enzymatic addition has to compete with a spontaneous chemical reaction which limits enantioselectivity. Major improvements in optical purity of cyanohydrins were achieved by conducting the addition under acidic conditions to suppress the uncatalyzed side reaction [519], or by switching to a water immiscible organic solvent as the reaction medium [520], preferably diisopropyl ether. For the latter case, the enzymes are readily immobilized by physical adsorption onto cellulose. A continuous process has been developed for chiral cyanohydrin synthesis using an enzyme membrane reactor [61]. Acetone cyanhydrin can replace the highly toxic hydrocyanic acid as the cyanide source [521], Inexpensive defatted almond meal has been found to be a convenient substitute for the purified (R)-oxynitrilase without sacrificing enantioselectivity [522-524], Similarly, lyophilized and powered Sorghum bicolor shoots have been successfully tested as an alternative source for the purified (S)-oxynitrilase [525],... 

Table 8. Preparation of chiral alcohols by enzyme-catalyzed reduction of the corresponding ketones with ADH from Lactobacillus kefir. The production of phenylethanol with formate and formate dehydrogenase (FDH) for coenzyme regeneration was carried out continuously in an enzyme-membrane-reactor...

Shinkai and coworkers prepared numerous novel amphiphilic crowns (Shinkai, 1990) and incorporated them into membranes, formed membranes from them, or used them in liquid crystalline assemblies to control properties (He et al., 1990). Interest in this area continues. Four chiral amphiphilic crown ethers were recently reported that recognize enantiomeric amino acids when examined as Langmuir films (Badis et al., 2004). Finally, it is interesting to note that liposomes formed from amphiphiles (e.g., crown ethers) having neutral headgroups (i. e., niosomes) have been studied as drug delivery vehicles (Uchegbu and Vyas, 1998). 

Enantioselective polyelectrolyte materials suitable for use as capillary tube and chromato-graphic packing material and consisting of polyvinyl pyridinium salts, (I), were prepared by Schlenoff [2] for use in analytical and membrane separations of chiral agents. 

Up until 1977, the non-covalent polymeric assemblies found in biological membranes rarely attracted any interest in supramolecular organic chemistry. Pure phospholipids and glycolipids were only synthesized for biophysical chemists who required pure preparations of uniform vesicles, in order to investigate phase transitions, membrane stability and leakiness, and some other physical properties. Only very few attempts were made to deviate from natural membrane lipids and to develop defined artificial membrane systems. In 1977, T. Kunitake published a paper on A Totally Synthetic Bilayer Membrane in which didodecyl dimethylammonium bromide was shown to form stable vesicles. This opened the way to simple and modifiable membrane structures. Since then, organic chemists have prepared numerous monolayer and bilayer membrane structures with hitherto unknown properties and coupled them with redox-active dyes, porous domains and chiral surfaces. Recently, fluid bilayers found in spherical vesicles have also been complemented by crystalline mono-... 

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