Polymeric monoliths

Yang YN, Li C Kameoka J, Lee KH, Craighead HG (2005) A polymeric microchip with integrated tips and in situ polymerized monolith for electrospray mass spectrometry. Lab Chip 5 869... 

Finally, dye-doped microparticles of irregular form can be produced by grinding or ball milling of polymeric monoliths provided that the material is brittle enough to... 

Packed capillaries with a larger inner diameter may be useful in preparative separations. These will find an application in proteome research as a part of multidimensional separation systems that will replace 2-D gel electrophoresis. The preparative CEC will require solving of the problems related to heat dissipation since the radial temperature gradient negatively affects the separations, and sample injection. The fabrication of sintered frits in larger bore capillaries is also very difficult. However, in situ polymerized monolithic frits can be fabricated in capillaries of virtually any diameter [190]. 

The effect that the quality of the bed structure has on the chromatographic properties of columns packed with particles has been well known for a long time [1]. Similarly, the efficiency of capillary electrophoretic separations reaches its maximum for a specific capillary diameter, and then decreases steeply for both larger and smaller size [ 117]. Therefore, any improvement in the efficiency of the polymeric monolithic columns for the isocratic separations of small molecules is likely to be achieved through the optimization of their porous structure rather than their chemistry. 

A slightly different mechanism of proteins separation results from the use of porous polymeric monoliths containing zwitterionic sulfobetaine groups [68]. 

Process whereby a polymeric monolith is produced through an in situ polymerization or polymer modification reaction. 

Due to the fact that the polymer can chemically be attached to the column wall during polymerization, monolithic stationary phases do not necessitate frits to retain the column packing. 

M.R. Buchmeiser, Polymeric monolithic materials Syntheses, properties, functionalization and applications, Polymer, 48(8) 2187-2198, April 2007. 

Recently, a method for preparing MIP monolithic columns for electrophoresis, chromatography and solid-phase extraction has been developed, which uses a preformed polymeric monolith, onto which an MIP with specific recognition sites is subsequently grafted [149, 179-181]. 

Fig. 6.26. Differential pore size distribution profiles of porous polymeric monolithic capillary columns with mode pore diameters of 255 (curve 1), 465 (2), 690 (3), and 1000 nm (4) (Reprinted with permission from [64]. Copyright 1997 American Chemical Society).

When smaller porous particles are used, the result is a highly efficient packed column with smaller interspatial voids however, this leads to lower permeability of the column, and high backpressures are often generated. To overcome these problems, polymeric monoliths have been developed these are a continuous phase of porous material that can be used without generating the high backpressures observed with fine particles. These systems, popularized by Frechet and Svec, have found application both in separation devices [110] and, more recently, as flow reactors [111-113],... 

Molecularly imprinted polymers with a variety of shapes have also been prepared by polymerizing monoliths in molds. This in situ preparation of MIPs was utilized for filling of capillaries [20], columns [21], and membranes [22, 23]. Each specific particle geometry however needs optimization of the respective polymerization conditions while maintaining the correct conditions for successful imprinting. It would be advantageous to separate these two processes, e.g., to prepare a molecularly imprinted material in one step, which then can be processed in a mold process in a separate step to result the desired shape. 

During the past 10 years, in addition to silica-based monoliths [12], a broad range of organic polymeric monoliths has been studied. Their most advantageous attribute is their chemical stability over a wide pH range. The most common organic monoliths were the results of methacrylate [13] and styrene [14] monomers. Some examples that confirm the utility of monolithic columns in IPC are described below. 

A monolithic silica-based CIS stationary phase was used under high flow rate condition (2 mL/min) without significant back pressure in IPC analysis of a recently discovered new drug candidate for the treatment of Alzheimer s disease [15]. Nanoscale IPC using a monolithic poly(styrene-divinylbenzene) (PS-DVB) nanocolumn coupled to nanoelectrospray ionization mass spectrometry (nano-ESl-MS) was evaluated to separate and identify isomeric oligonucleotide adducts. Triethylammonium bicarbonate was used as the IPR. Interestingly, the performance of the polymeric monolithic PS-DVB stationary phase significantly surpassed that of columns packed with the microparticulate sorbents CIS or PS-DVB [16]. 

The preparation of polymeric monoliths is relatively simple compared with those of the silica rods. A polymerization mixture consisting of monomer, cross-linker, initiator, and porogenic solvent is introduced into a sealed tube. The reaction can be temperature or redox initiated and in the case of transparent molds UV light can also be used to trigger the polymerization. At the end of the reaction the seals are removed and the tubes are attached to a pump, which flushes solvent through the monolith to remove the porogens and the unreacted components. The obtained monolith can be radial or axial compressed to prevent the formation of voids and further functionalized for different chromatographic modes. The majority of current monolithic supports... 

Figure 13.24 Separation of racemic DNZ-leucine on polymeric monolithic material. Conditions polymerization mixture, chiral monomer 76 8wt%, 2-hydroxyethyl methacrylate 24wt% ethylene dimethacrylate 8wt%, 1-dodecanol 45 wt%, and cyclohexanol 15wt% UV-initiated polymerization for 16 h at room temperature ...

The most common polymer supports used for chiral catalyst immobilization are polystyrene-based crosslinked polymers, although poly(ethylene glycol) (PEG) represents an alternative choice of support. In fact, soluble PEG-supported catalysts show relatively high reactivities (in certain asymmetric reactions) [le] which can on occasion be used in aqueous media [le]. Methacrylates, polyethylene fibers, polymeric monoliths and polynorbornenes have been also utilized as efficient polymer supports for the heterogenization of a variety of homogeneous asymmetric catalysts. 

Luis prepared polymeric monoliths 17 containing TADDOL subunits [13] these were synthesized with a thermally induced radical soluhon polymerization of a mixture containing TADDOL monomer, styrene and DVB, using toluene/1-dodecanol as the precipitating porogenic mixture and azoisobutyronitrile (AIBN) as the radical inilialor. The polymer-supported Ti-TADDOLates generated from 17 and Ti(OiPr)4 were then used for the asymmetric alkylation of benzaldehyde to give 1-phenylethanol in 60% yield and 99% ee [13]. 

Various types of chirally modified Lewis acids have been developed for asymmetric Diels-Alder cycloadditions. Some of these, including Ti-TADDOLates, have been attached to crosslinked polymers [11]. A recent example of this approach involved polymeric monoliths 103 containing TADDOL subunits (Scheme 3.29). The treatment of 103 with 71X4 afforded Ti-TADDOLates, which were used for the asymmetric Diels-Alder reachon of cyclopentadiene 104 and 105. The major product obtained in this reachon was the mdo adduct with 43% ee [58]. The supported Ti-catalysts showed an exhaordinary long-term stabihty, being achve for at least one year. 

Luis, Martens and coworkers developed a closely related flow system [35] which was based on Frechet-type polymeric monoliths (refer also to Sect. 3.2) [36]. They immobilized azabicyclo[3.3.0]octane-3-carboxyhc acid 7 both by grafting and by polymerization (Fig. 4). The addition of diethyl zinc to ben-zaldehyde in a coliunn was studied. It was foimd that the monolithic catalyst prepared by polymerization turned out to be superior (up to 99% ee) compared to the catalyst prepared by grafting (compare with Schemes 7 and 8). Differences in appropriate chiral cavities inside the polymer maybe responsible for these results, the other factors being differences in reaction conditions and most probably the avoidance of diffusional problems in the monolithic catalyst at high flow rates. 

The very good performance of molded polymeric stationary phases in HPLC and CEC at high flow rates is especially important when sensitive biomolecules are separated. Thus, the reversed-phase separation of five proteins was easily achieved in less than 20 s on a styrene—DVB rod with an optimized porous structure [405]. The extensive use of molded polymeric monoliths as stationary phases in HPLC and CEC demonstrated within the last decade their wide applicability and many inherent... 

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