Synthesis of Multi Amino Acid Chiral Polymeric Microparticles for Enantioselective Chemistry

Abstract

Chiral polymeric particles have emerged as a new and exciting field of research and in the last years due to their possible use for many applications in chiral chemistry. In this article, an important question is focused upon that has not been explored in detail in the field of chiral polymeric particles. The main question is whether the chiral composition of the polymeric particles affects their chiral recognition. The hypothesis is that chiral polymeric particles with a variety of different chiral groups will improve chiral recognition and improve their use of enantioselectivity crystallization. Consequently, chiral microparticles based on one up to three different amino acids based monomers are prepared by precipitation polymerization. The chiral microspheres are characterized by dynamic light scattering, scanning electron microscope (SEM), mass spectrometry (MS), and nuclear magnetic resonance (NMR) and display a narrow size distribution in the range of 1–2 μm. The chiral discrimination ability of these chiral microspheres for enantioselective crystallization is studied in the crystallization of DL‐leucine crystallization, as a model system. Time‐resolved polarimetry, X‐ray diffraction (XRD), and differential scanning calorimetry (DSC) are used to provide evidence for enantioselective crystallization. Surprisingly the results show that only particles composed of one amino acids monomers show the best results for enantioselective crystallization.

Enantioselective Separation of Amino Acids Using Chiral Polystyrene Microspheres Synthesized by a Post-Polymer Modification Approach

“…37,38 There are recent reports on microspheres prepared from amino acid-based acrylate polymers, amino acid-containing chiral metal−organic frameworks, and chitosan-functionalized (P(S-DVB) particles that were used to carry out the enantioselective crystallization of a racemic mixture of amino acids with 25% ee or used as chiral selectors in chiral high-performance liquid chromatography (HPLC) for the separation of several racemates with separation factors (α) of 7.55 and 5.70 for naproxen and benzoin, respectively. 28,29,39 In the present work, we report the enantioselective separation of racemic mixtures of native amino acids achieved by chiral PS microspheres. Chiral PS was synthesized by a post-polymer modification approach starting from PS with well-defined molecular weights and molar mass distribution, synthesized by solvent-free reversible addition−fragmentation chain-transfer (RAFT) polymerization.…”

“…The enantioselective separation efficiency could be improved [enantiomeric excess (ee) of ∼95%] by applying the chiral polyfluorenes on commercially available mesoporous anodic aluminum oxide (AAO) membranes . Polymeric microspheres are getting more attention in recent years due to their easy modification and processability, where shape, size, and surface functionality can be easily modified . Chiral polymeric microspheres with particle sizes ranging from 1 to 200 μm with a high surface area are increasingly reported as the stationary phase in chiral chromatography. − Reports are available using polymeric microspheres or polymer coated-inorganic materials such as modified silica or metal nanoparticles as chiral selectors. , In 2007, Mastai et al synthesized hollow poly­( N -vinyl-α- l -phenylalanine microspheres using polystyrene (PS) microspheres as a template and used them to carry out the enantioselective crystallization of a racemic mixture of valine with 25% ee .…”

“…Small changes in the composition were reported to have a significant impact on the separation efficiency. The enantioselective separation of racemic mixtures was achieved using magnetic microspheres immobilized with chiral substituents such as human serum albumin or β-cyclodextrins. , There are recent reports on microspheres prepared from amino acid-based acrylate polymers, amino acid-containing chiral metal–organic frameworks, and chitosan-functionalized (P­(S-DVB) particles that were used to carry out the enantioselective crystallization of a racemic mixture of amino acids with 25% ee or used as chiral selectors in chiral high-performance liquid chromatography (HPLC) for the separation of several racemates with separation factors (α) of 7.55 and 5.70 for naproxen and benzoin, respectively. ,, …”

Organocatalytic chiral polymeric nanoparticles for asymmetric aldol reaction

“…Chirality is a key factor in molecular recognition, which is extremely important in many chemical, biological and medical applications. 1 Chiral polymeric particles (CPPs) were used as typical functional polymeric particles in recent decades and explored as a special kind of chiral material in asymmetric catalysis, enantioselective release and crystallization, and enantioseparation. 2 Efficient methods to produce and separate chiral compounds are important, in particular for enhancement of pharmaceuticals due to the different pharmacological and toxicological effects of the enantiomers.…”

“…3 Previous work in our lab examined enantioselective crystallization of CPPs based on leucine, phenylalanine and alanine in their own supersaturated solution. 1 Recently, a chiral membrane was formed by combining polysulphone and CPPs based on phenylalanine, and chiral recognition by the membrane was explored. 4 In other works [5][6][7][8][9][10][11][12][13][14][15][16] different kinds of functional CPPs were formed with narrow size distribution and controllable properties such as the surface area.…”