Chiral resolution method mimicking magnetic beneficiation and the magnetic nano-inhibitors for selective enrichment

Patent metadata

Field	Value
Publication number	US-12104022-B2
Application number	US-201917267156-A
Country	US
Kind code	B2
Filing date	Apr 9, 2019
Priority date	Sep 3, 2018
Publication date	Oct 1, 2024
Grant date	Oct 1, 2024

Abstract

A core-shell nanocomposite is formed by co-assembly of an amphiphilic polymer and hydrophobically modified magnetic nanoparticles, with its core being a hydrophobically modified magnetic nanomaterial and its shell being the amphiphilic polymer, wherein hydrophilic segments in the amphiphilic polymer are located at an outermost layer of the shell. The above composite can be used as additives in the crystallization of conglomerates and obtain optically pure crystals of both enantiomers in a single process. The key thereof is that the composite is used to enrich molecules with the same configuration while inhibit the crystallization of the other enantiomer in a supersaturated solution of conglomerates, such that a non-magnetic crystal and a magnetic crystal (which are enantiomers of each other) are generated in a unit operation. Optically pure crystals of both enantiomers with over 90 ee % can be obtained by one-time crystallization, and the total yield can be as high as 40%.

First claim

The invention claimed is:

1. A core-shell nanocomposite, which is formed by co-assembly of an amphiphilic polymer and hydrophobically modified magnetic nanoparticles, with a hydrophobically modified magnetic nanomaterial as its core and the amphiphilic polymer as its shell,
wherein hydrophilic segments in the amphiphilic polymer are located at an outermost layer of the shell;
wherein a crosslinking reaction is carried out between the hydrophilic segments to form a cross-linked shell;
wherein the hydrophilic segments in the amphiphilic polymer are at least one selected from the group consisting of the following structural formulas:

wherein R 2 in formulas a-c is a functional group capable of being adsorbed on a crystal surface of a crystal to be resolved through non-covalent bond interaction, thus inhibiting crystallization and the following enrichment to promote nucleation;
wherein R 1 in formula a is at least one selected from the group consisting of methyl and hydrogen atoms;
wherein the hydrophobic segments in the amphiphilic polymer comprise at least one polymer selected from the group consisting of hydrophobic polymers, block copolymers comprising repeating units of the hydrophobic polymers, random comprising repeating units of the hydrophobic polymers, graft copolymers comprising repeating units of the hydrophobic polymers, and hyperbranched polymers comprising repeating units of the hydrophobic polymers;
further wherein the hydrophobic polymers comprise least one polymer selected from the group consisting of polystyrene, polyethylene, polypropylene, polybutadiene, polyisoprene, polydimethylsiloxane, polymethylhydrosiloxane, polymethacrylate, polymethacrylamide, polyamide, polyimide, polyformaldehyde, polycarbonate, cellulose, and derivatives thereof; and
wherein in formulas a-c, m represents the polymerization degree of the hydrophilic segments and ranges from 10 to 60.

2. The core-shell nanocomposite according to claim 1 , wherein:
R 2 in formulas a-c is at least one selected from the group consisting of the following groups:

wherein in the above groups, * represents a bonding position.

3. The core-shell nanocomposite according to claim 1 , wherein the magnetic nanomaterial is selected from magnetic nanoparticles formed by the following materials: Fe, Co, Ni, FePt, CoPt, FeAu, FePd, SmCo 5 , Fe 3 O 4 , γ-Fe 2 O 3 , M 1 Fe 2 O 4 , MO·6Fe 2 O 3 , and M 2 Fe 12 O 19 , wherein M 1 in M 1 Fe 2 O 4 represents Zn, Mn, Ni, or Co, and M 2 in M 2 Fe 12 O 19 represents Ba or Sr;
wherein the magnetic nanoparticles have a diameter in the range from 3 nm to 500 nm; and
wherein hydrophobic molecules used in the hydrophobically modified magnetic nanomaterial are at least one selected from the group consisting of oleic acid, oleamine, pyrrolidone, 11,11-dihydroxymethyl undecane, poly(tetravinylpyridine), and block copolymers of poly(tetravinylpyridine) and polyethylene.

4. A method for preparing the core-shell nanocomposite according to claim 1 comprising the steps of:
1) dissolving the amphiphilic polymer in a cosolvent to obtain an amphiphilic polymer solution; dispersing the hydrophobically modified magnetic nanoparticles in a cosolvent to obtain a dispersion of the hydrophobically modified magnetic nanoparticles; and
2) mixing the amphiphilic polymer solution with the dispersion of the hydrophobically modified magnetic nanoparticles in proportion to form a mixed solution, and then adding deionized water to the mixed solution until a stable assembly is formed;
wherein in step 1), the cosolvent is at least one selected from the group consisting of dimethyl sulfoxide (DMSO), N,N-dimethylformamide, tetrahydrofuran, dioxane, CH 3 CN, acetone, methanol, ethanol, and isopropanol;
wherein in step 2), the mass ratio of the amphiphilic polymer to the hydrophobically modified magnetic nanoparticles in the mixed solution is in the range from 1:0.1 to 1; and
further wherein in step 2), the deionized water is dropwise added into the mixed solution, and the volume ratio of the mixed solution to the deionized water is in the range from 1:2 to 8;
wherein the method further comprises the step of adding a crosslinking agent into a reaction system in which the stable assembly is formed to perform a shell crosslinking reaction, followed by dialysis in pure water to remove an organic solvent and unreacted small molecules, centrifugal separation, and freeze drying, and
wherein the crosslinking agent is at least one selected from the group consisting of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and glycol bis 2-aminoethyl ether.

5. A chiral resolution method mimicking magnetic beneficiation, comprising the steps of:
(1) formulating a racemic substrate to be resolved into a supersaturated solution, followed by hot filtration;
(2) adding the core-shell nanocomposite of claim 1 to the supersaturated solution, followed successively by ultrasonic dispersion, cooling to a crystallization temperature, addition of an optical pure seed of the racemic substrate to be resolved, and a standing is performed, wherein if the core-shell nanocomposite has S-hydrophilic segments, R-optically pure seeds are added, or otherwise, S-seeds are added;
(3) obtaining mixed crystals of colored crystals and colorless crystals at the end of crystallization; and
(4) approaching the mixed crystals with a magnet, wherein the colored crystals of one enantiomer is attracted by the magnet, while the colorless crystals of the other enantiomer is not attracted by the magnet to effectuate resolution of two enantiomers.

6. The method according to claim 5 , wherein the method further comprising:
dissolving the colored crystal in water; and
recycling the core-shell nanocomposite by magnetic attraction, wherein the recycled core-shell nanocomposite is reused after being washed.

7. The method according to claim 5 wherein in step (1), the racemic substrate is asparagine monohydrate with a concentration in the range from 50 mg·mL −1 to 150 mg·mL −1 .

8. The method according to claim 5 , wherein the substrate to be resolved is asparagine monohydrate or threonine, and the hydrophilic segments of the amphiphilic polymer in the core-shell nanocomposite are poly(N 6 -methacryloyl-S-lysine hydrochloride); or the substrate to be resolved is p-hydroxyphenylglycine p-methylbenzene sulfonate, and the hydrophilic segments of the amphiphilic polymer in the core-shell nanocomposite are poly(p-methacryloyl-S-phenylalanine hydrochloride).

9. The method according to claim 5 , wherein
in step (2), the core-shell nanocomposite accounts for 0.1-2.0 wt % of the racemic substrate to be resolved;
the amount of the optically pure seeds of the racemic substrate added accounts for 0.1-0.5 wt % of the racemic substrate to be resolved; and
the ultrasonic dispersion is performed in water at a temperature in the range from 40° C. to 60° C., at a power in the range from 40 KHz to 80 KHz, and for a period in the range from 15 min to 60 min; and
wherein the standing is performed at a temperature in the range from 0° C. to 40° C. for a period in the range from 6 h to 144 h.

Assignees

• Univ Beijing

Inventors

• Wan Xinhua
• Ye Xichong
• Li Bowen
• Zhang Jie

Classifications

• B82Y25/00

  Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance · CPC title

• B03C1/035

  Open gradient magnetic separators, i.e. separators in which the gap is unobstructed, characterised by the configuration of the gap · CPC title

• C08F220/603

  and containing oxygen in addition to the carbonamido oxygen and nitrogen · CPC title

• B03C2201/18

  Magnetic separation whereby the particles are suspended in a liquid · CPC title

• B03C1/01

  by addition of magnetic adjuvants · CPC title