European Polymer Journal 142 (2021) 110145 Available online 13 November 2020 0014-3057/© 2020 Published by Elsevier Ltd. Microspheres of biomolecules/macromolecules for enantioseparation applications Amruta Mutalikdesai, Sudhakar Pagidi, Alfred Hassner, Aharon Gedanken * Bar Ilan Institute of Nanotechnology and Advanced Materials and Department of Chemistry, Bar-Ilan University, Ramat-Gan 5290002, Israel A R T I C L E INFO Keywords: Biomolecules Protein microspheres Chiral separation DNA nanospheres Amino acids ABSTRACT This review summarizes the recent advances in the enantioselective separation of small molecules using bio- molecules/macromolecules built up by natural inherent chiral moieties. Although different kinds of chiral se- lectors are known to date, the microspheres based on biomolecules have received paramount importance in view of their green synthesis, selective and sensitive separation of enantiomers from the racemic mixture. Direct separation of enantiomers devoid of using high-performance liquid chromatography adds to the elegance of this approach. We have covered the preparation of various biomolecules spheres by different methods. The enan- tiomeric separation of amino acids, drugs and other racemates and the underlying plausible mechanism is discussed. 1. Introduction Chirality is an intrinsic property of building blocks of life, including specifc L- amino acids and D-sugars and hence the peptides, proteins, and nucleic acids. It is well-established that the homochiral nature of these biomolecules is involved in the metabolic and regulatory processes [1]. A chiral molecule that cannot be superimposed on its mirror image and such non-identical mirror images are termed as enantiomers. The physical properties of a pair of enantiomers are the same; however, their functional properties can be different in biology. For instance, enzymes can specifcally bind to only one enantiomer, i.e., messenger–receptor interactions, and are explained based on the lock-key model [2]. When a rac-drug is administered then the two enantiomers cannot show equal potent activity, however, one enantiomer is potentially more active (eutomer) for given purpose, while another one (distomer) may show the different activity that leads to side effects/toxicity [3]. For instance, early 1960s, a tragedy occurred in the usage of thalidomide, the dis- covery of (R)- enantiomer of thalidomide that is active for pain-relieving while the (S) -enantiomer is causing severe deformities in unborn chil- dren [4]. Therefore, pure enantiomer is vital in considering the drugs, food additives, agrochemicals, and fragrances. It has been reported that such chiral molecules exhibit different metabolic, pharmacological, thera- peutic, and/or toxicological properties [5]. It is worth mentioning that most of the marketed drugs are enantiomerically pure chiral compounds [6]. Besides, most of the commercially available agrochemicals are chiral; the non-active or less active enantiomer can contribute to the increase of pollution instead of the desired function. Considering the greater utility of chiral molecules in day-to-day life, separation of enantiomerically pure drugs and agrochemicals is of at most importanance for both academics and industry. Manufacturing industries are at the forefront of the high-volume production of chiral materials. There are different methods for achieving enantiopure com- pounds, including asymmetric synthesis, extraction of natural com- pounds, fermentation, etc. An asymmetric synthesis is an excellent approach for the synthesis of pure enantiomers; however, it to some extent suffers from the laborious syntheses’ procedures and requires expensive catalysts [7]. It is worthy to mention that the Nobel Prize in chemistry was awarded to Knowles & Noyori and Sharpless for asym- metric synthesis in 2001[8]. However, low-cost pharmaceuticals cannot Abbreviations: BSA, bovine serum albumin; CD, cyclodextrin; CE, capillary electrophoresis; CEC, capillary electro chromatography; CSPs, chiral stationary phases; ct-DNA, calf thymus DNA; D-, dextrorotatory; EAMS, egg albumin microspheres; ee, enantiomeric excess; GC, gas chromatography; His, histidine; HPLC, high- performance liquid chromatography; HSA, human serum albumin; L-, levorotatory; LC, liquid chromatography; MCC, microcrystalline cellulose; MMS, magnetic microspheres; MNP, magnetic nanoparticle; MS, microspheres; NP, nanoparticle; NS, nanospheres; Phe, phenylalanine; R-, rectus (right); rac, racemic; S-, sinister (left); Si, Silica; Trp, Tryptophan. * Corresponding author. E-mail address: Aharon.Gedanken@biu.ac.il (A. Gedanken). Contents lists available at ScienceDirect European Polymer Journal journal homepage: www.elsevier.com/locate/europolj https://doi.org/10.1016/j.eurpolymj.2020.110145 Received 28 July 2020; Received in revised form 1 November 2020; Accepted 6 November 2020