Preparative Separation of Enantiomers Based on Functional Nucleic Acids Modified Gold Nanoparticles

Abstract

The preparative-scale separation of chiral compounds is vitally important for the pharmaceutical industry and related fields. Herein we report a simple approach for rapid preparative separation of enantiomers using functional nucleic acids modified gold nanoparticles (AuNPs). The separation of DL-tryptophan (DL-Trp) is demonstrated as an example to show the feasibility of the approach. AuNPs modified with enantioselective aptamers were added into a racemic mixture of DL -Trp. The aptamer-specific enantiomer (L-Trp) binds to the AuNPs surface through aptamer-L-Trp interaction. The separation of DL-Trp is then simply accomplished by centrifugation: the precipitate containing L-Trp bounded AuNPs is separated from the solution, while the D-Trp remains in the supernatant. The precipitate is then redispersed in water. The aptamer is denatured under 95 °C and a second centrifugation is then performed, resulting in the separation of AuNPs and L-Trp. The supernatant is finally collected to obtain pure L-Trp in water. The results show that the racemic mixture of DL-Trp is completely separated into D-Trp and L-Trp, respectively, after 5 rounds of repeated addition of fresh aptamer-modified AuNPs to the DL-Trp mixture solution. Additionally, the aptamer-modified AuNPs can be repeatedly used for at least eight times without significant loss of its binding ability because the aptamer can be easily denatured and renatured in relatively mild conditions. The proposed approach could be scaled up and extended to the separation of other enantiomers by the adoption of other enantioselective aptamers.

Advances in chiral separations of small peptides by capillary electrophoresis and chromatography

“…Recently, Huang et al. demonstrated the capabilities of aptamer‐based materials in separating amino acid enantiomers. They suggested that stereoisomers of larger molecules such as dipeptides and tripeptides could also be resolved.…”

Enantiomeric Recognition and Separation by Chiral Nanoparticles

“…In addition, nanostructures possess better chemical stability, low cytotoxicity, significant mechanical strength, and are easily modifiable in terms of their size, shape and surface properties [91,103]. Importantly, NPs enhance the performance of enantioseparation process due to their extremely large s / v ratio (e.g., nanospheres of 10 nm diameter can have a surface area as large as 600 m 2 /cm 3 [121]) that maximizes the amount of binding sites [69,81]. In the following sections we summarize some of the recent applications of different types of nanostructures for the separation of enantiomers.…”

“…Recently, nucleic acid aptamer-functionalized AuNPs were used as chiral selector for the separation of racemic d,l -Trp. The method used centrifugation to separate the precipitate formed by the aptamer-specific enantiomer ( l -Trp) bounded AuNPs (Figure 7) [69]. In another work, Su et al [53] demonstrated the potential of laboratory synthesized chiral N -acetyl- l -Cys-capped AuNPs for high throughput enantiomeric separation of amino acid enantiomers via centrifugation.…”

“…In enantiomeric separation, surface-modified NPs, as chiral selectors, are exposed to a racemic mixture of chiral molecules to perform the selective adsorption of one enantiomer, leaving an excess of the other enantiomer in solution to be removed through multiple rounds of centrifugation. Following centrifugation, the target enantiomers co-precipitate with the chiral NPs, whereas their enantiomeric counterparts remain in the supernatant [52,53,69]. Note that the chiral ligands chosen for enantiomeric separation are susceptible to denaturation and renaturation manipulated by external perturbations such as temperature and magnetic field, making them switchable and reusable.…”

Electrospinning of magnetic cellulose tris‐(4‐methylbenzoate) microparticles for enantioselective adsorption of racemic drug

“…To improve the enantioenrichment efficiency, multistage adsorption was performed further according to literature . After each adsorption stage, the supernatant was analyzed by HPLC and the e.e.…”