Chirality synthetic polymers

Chiral synthetic polymer phases can be classified into three types. In one type, a polymer matrix is formed in the presence of an optically pure compound to moleculady imprint the polymer matrix (Fig. 10) (107,108). Subsequent to the polymerisation, the chiral template is removed, leaving the polymer matrix... 

Polymers derived from natural sources such as proteins, DNA, and polyhy-droxyalkanoates are optically pure, making the biocatalysts responsible for their synthesis highly appealing for the preparation of chiral synthetic polymers. In recent years, enzymes have been explored successfully as catalysts for the preparation of polymers from natural or synthetic monomers. Moreover, the extraordinary enantioselectivity of lipases is exploited on an industrial scale for kinetic resolutions of secondary alcohols and amines, affording chiral intermediates for the pharmaceutical and agrochemical industry. It is therefore not surprising that more recent research has focused on the use of lipases for synthesis of chiral polymers from racemic monomers. 

Microcrystalline cellulose triacetate, cyclodextrin- and crown ether-derived CSPs, as well as some chiral synthetic polymers, achieve enantiomer separation primarily by forming host-guest complexes with the analyte in these cases, donor-acceptor interactions are secondary. Solutes resolved on cyclodextrins and other hydrophobic cavity CSPs often have aromatic or polar substituents at a stereocenter, but these CSPs may also separate compounds that have chiral axes. Chiral crown ether CSPs resolve protonated primary amines. 

Another type of synthetic polymer-based chiral stationary phase is formed when chiral catalyst are used to initiate the polymerisation. In the case of poly(methyl methacrylate) polymers, introduced by Okamoto, the chiraUty of the polymer arises from the heUcity of the polymer and not from any inherent chirahty of the individual monomeric subunits (109). Columns of this type (eg, Chiralpak OT) are available from Chiral Technologies, Inc., or J. T. Baker Inc. 

Polyacetylenes are the most important class of synthetic polymers containing conjugated carbon-carbon double bonds. Some optically active monomers have been used with the following conclusions. Polymers of 1-alkynes having a branched side-chain assume in solution a helical conformation. A chiral side-chain induces a predominant screw sense in these helices. In particular, for alkyl branching, it has been shown that (S) monomers lead to a left-handed screw sense. 

The screw models of Figure 7.4 are, of course, an abstraction, and real macromolecules are much more complex. In particular, apart from DNA and G-wires, which have sugar-phosphate backbones as external ridges, but are also charged, most natural and synthetic polymers have external side chains which could generate a secondary chiral surface, which might interfere with the chirality of the polymer backbone.28 Even if the qualitative estimate of Sq based on the models of Figure 7.4 seems rather primitive, the estimate of Hq... 

Different classifications for the chiral CSPs have been described. They are based on the chemical structure of the chiral selectors and on the chiral recognition mechanism involved. In this chapter we will use a classification based mainly on the chemical structure of the selectors. The selectors are classified in three groups (i) CSPs with low-molecular-weight selectors, such as Pirkle type CSPs, ionic and ligand exchange CSPs, (ii) CSPs with macrocyclic selectors, such as CDs, crown-ethers and macrocyclic antibiotics, and (iii) CSPs with macromolecular selectors, such as polysaccharides, synthetic polymers, molecular imprinted polymers and proteins. These different types of CSPs, frequently used for the analysis of chiral pharmaceuticals, are discussed in more detail later. 

Synthetic polymers This type of chiral selectors (polyacrylamides, polymethacrylamide, etc.) was first developed by the group of Blaschke by polymerization of chiral monomers with cross-linking agents to form a three-dimensional polymer network. 

Interest in optically active polymers arose from analogy with macromolecules of biological origin. In addition, there was the hope to obtain new information to clarify the stereochemical features of synthetic polymers this, in fact, did come about. Attempts to direct the course of polymerization using chiral reagents had been made already prior to the discovery of stereospecific polymerization. It was only after the 1950s, however, that the problem of polymer chirality was tackled in a rational way. The topic has been reviewed by several authors (251-257). In this section I shall try to illustrate three distinct aspects the prediction of chirality in macromolecular systems, the problems regarding the synthesis of optically active polymers, and polymer behavior in solution. 

Wulff G, Grobe-Einsler R, Vesper W, Sarhan A. Enzyme-analog built polymers. 5. The specificity distribution of chiral cavities prepared in synthetic polymers. Makromol Chem... 

Introducing chirality into polymers has distinctive advantages over the use of nonchiral or atactic polymers because it adds a higher level of complexity, allowing for the formation of hierarchically organized materials. This may have benefits in high-end applications such as nanostructured materials, biomaterials, and electronic materials. Synthetically, chiral polymers are typically accessed by two methods. Firstly, optically active monomers - often obtained from natural sources - are polymerized to afford chiral polymers. Secondly, chiral catalysts are applied that induce a preferred helicity or tacticity into the polymer backbone or activate preferably one of the enantiomers [59-64]. 

Enzymatic polymerizations have been established as a promising and versatile technique in the synthetic toolbox of polymer chemists. The applicability of this technique for homo- and copolymerizations has been known for some time. With the increasing number of reports on the synthesis of more complex structures like block copolymers, graft copolymers, chiral (co)polymers, and chiral crosslinked nanoparticles, its potential further increases. Although not a controlled polymerization technique itself, clever reaction design and integration with other polymerization techniques like controlled radical polymerization allows the procurement of well-defined polymer structures. Specific unique attributes of the enzyme can be applied... 

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

In addition to the classification of liquid chromatographic enantioseparation methods by technical description, these methods could further be classified according to the chemical structure of the diverse CSPs. The chiral selector moiety varies from large molecules, based on natural or synthetic polymers in which the chirality may be based on chiral subunits (monomers) or intrinsically on the total structure (e.g., helicity or chiral cavity), to low molecular weight molecules which are irreversibly and/or covalently bound to a rigid hard matrix, most often silica gel. 

I.6.2. Chiral Stationary Phases (CSPs) Based on Synthetic Polymers... 

As discussed in Section 3.1.6.1., natural biopolymers are useful chiral selectors, some of which are readily available they are constructed from chiral subunits (monomers), for instance, from L-amino acids or D-glucose. If synthetic chiral polymers of similar type are to be synthesized, appropriate chiral starting materials and subunits, respectively, must be found. Chiral polymers with, for example, a helical structure as the chiral element, are built using a chiral catalyst as chirality inducing agent in the polymerization step. If the chirality is based on a chiral subunit, the chirality of the polymer is inherent, whereas if the polymer is constructed from chiral starting materials, chiral subunits are formed which lead to chirally substituted synthetic polymers that in addition may order or fold themselves to a supramolecular structure (cf. polysaccharides). 

Schlitzer, D. S. Novak, B. M. Trapped Kinetic States, Chiral Amplification and Molecular Chaperoning in Synthetic Polymers Chiral Induction in Polyguanidines through Ion Pair Interactions, J. Am. Chem. Soc. 1998, 120, 2196-2197. 

A third type of synthetic polymer-based chiral stationary phase, developed hy Blaschke. is produced when a chiral selecior is either incorporated within the polymer network or attached as pendant groups onto the polymer matrix. Both arc analogous to methods used lo produce polymeric chiral stationary phases for gc. 

---