CN1340552A - Process for preparing chiral separation fixed phase of molecular brand polymer - Google Patents
Process for preparing chiral separation fixed phase of molecular brand polymer Download PDFInfo
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- CN1340552A CN1340552A CN 00122948 CN00122948A CN1340552A CN 1340552 A CN1340552 A CN 1340552A CN 00122948 CN00122948 CN 00122948 CN 00122948 A CN00122948 A CN 00122948A CN 1340552 A CN1340552 A CN 1340552A
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Abstract
A chiral separation fixed phase of molecular brand polymer with higher moleculara recognizing power to ammino acid and its derivative is prepared from two-composite function monomers chosen from one of acrylamide+2-vinylpyridine, methyl acrylamide+2-vinylpyridine, methyl acrylamide+3-vinylpyridine, acrylamide+3-vinylpyridine, acrylamide+4-vinylpyridine, and methyl acrylamide+4-vinylpyridine, and a multi-element cross-linking agent with two vinyl radicals chosen from one of divinylbenzene, glycol dimethyl acrylate, trimethoxypropane trimethyl acrylate, and pentaerythrite triacrylate. The mole ratio of acrylamide to vinylpyridine is 1:(1-3). The mole ratio of function monomer to cross-linking agent is 1:(5-20).
Description
The present invention relates to molecular imprinting technique, a kind of preparation method of molecular brand polymer chiral separation stationary phase is provided especially.
According to the molecular imprinting technique that " key " action principle grows up, be a kind ofly can prepare the novel method that specific compound (promptly branding molecule or template molecule) is had the macromolecular material of predetermined molecules recognition capability.The operating process of synthetic molecules brand polymer is roughly: (1) function monomer and branding molecule at first form reversible compound or mixture by molecular interaction (as covalent effect power/noncovalent interaction power/metal ligand exchange etc.); (2) under the effect of linking agent, crosslinking polymerization becomes the highly cross-linked high molecular polymer with three-dimensional net structure, thereby this compound or mixture are fixed among the high molecular polymer; (3) with appropriate means the branding molecule is discharged from high molecular polymer, form " memory " hole that the branding molecule is had " being scheduled to " molecule distinguishability.Because the G.Wulff (G.Wulff of Germany, Angew.Chem.Int.Ed.Engl.1995,34:1812) and K.Mosbach (the K.Mosbach and O.Ramstrom of Sweden, Biotechnology 1996, Vol.14) contribution of aspect covalent type molecular brand and non-covalent type molecular brand, giving prominence to respectively, molecular imprinting technique has obtained developing rapidly, at aspects such as chiral separation, analog antibody, simulation biosensor, catalysis and organic syntheses wide application prospect is arranged.In stratographic analysis, molecular brand polymer is except can being used as the chiral stationary phase in the chiral analysis, because the distinctive predetermined selectivity of molecular brand polymer, it also can be used for the preparation separation of chipal compounds.
Synthetic is the liquid chromatography molecular brand chiral stationary phase of template molecule with amino acid and derivative thereof at present, generally adopts acid functional monomer or alkaline functional monomers such as acrylamide and 2-vinyl pyridine such as methacrylic acid or trifluoromethyl acrylate; Linking agent then adopts ethylene glycol dimethacrylate.But adopt the amino acid of above-mentioned functions monomer-linking agent system preparation and derivative molecular branding macromolecular material thereof generally all very little, only be suitable for the needs of stratographic analysis, be difficult to the preparation of chipal compounds the molecule distinguishability of branding molecule.
The object of the present invention is to provide a kind of preparation method of molecular brand polymer chiral separation stationary phase, it is by proposing novel function monomer-linking agent branding system, cause prepared molecular brand macromolecular material can improve molecule distinguishability effectively, thereby finish the preparation of amino acid and derivative thereof amino acid and derivative thereof.
The invention provides a kind of preparation method of molecular brand polymer chiral separation stationary phase, be polymerized under the linking agent effect by function monomer and the associated complex that the branding molecule forms, it is characterized in that: adopt two kinds of complex function monomers, be selected from acrylamide+2-vinyl pyridine, acrylamide+3-vinyl pyridine, acrylamide+4-vinylpridine, Methacrylamide+2-vinyl pyridine, Methacrylamide+3-vinyl pyridine, Methacrylamide+4-vinylpridine a kind of; Use dual-functional group or three functional group linking agents, be selected from Vinylstyrene (DVB), ethylene glycol dimethacrylate (EGDMA), trimethoxy propane trimethyl acrylic ester (TRIM), pentaerythritol triacrylate (PETRA) a kind of; The mol ratio of acrylamide and vinyl pyridine is 1: 1～3; The mol ratio of function monomer and linking agent is 1: 5～20.
The present invention is directed to amino acid and derivative thereof, by using the complex function monomer system of several function monomers simultaneously, and adopt the polynary linking agent that has three above vinyl to prepare the molecular brand macromolecular material of amino acid and derivative thereof, improved the molecule distinguishability of the molecular brand macromolecular material that makes greatly, institute's synthetic molecular brand polymer material can be used for amino acid whose preparation.
Below by example the present invention is specifically addressed, but is not limited thereto.
Accompanying drawing 1.N-Cbz-DL-Trp is the chiral separation situation of the molecular brand polymer chiral stationary phase of template molecule at N-Cbz-L-Trp.Moving phase: acetonitrile/acetate 99.0/1.0, (v/v); Detect wavelength: 280nm; Flow velocity: 0.5mL/min. peak 1.N-Cbz-D-Trp, peak 2.N-Cbz-L-Trp
Accompanying drawing 2.N-Cbz-DL-Phe is the chiral separation situation of the molecular brand polymer chiral stationary phase of template molecule at N-Cbz-L-Phe.Moving phase: acetonitrile/acetate 99.5/0.5, (v/v); Detect wavelength: 258nm; Flow velocity: 0.5mL/min. peak 1.N-Cbz-D-Phe, peak 2.N-Cbz-L-Phe
Accompanying drawing 3.N-Cbz-DL-Tyr is the chiral separation situation of the molecular brand polymer chiral stationary phase of template molecule at N-Cbz-L-Tyr.Moving phase: acetonitrile/acetate 99.5/0.5, (v/v); Detect wavelength: 276nm; Flow velocity: 0.5mL/min. peak 1.N-Cbz-D-Tyr, peak 2.N-Cbz-L-Tyr
Raw materials used as follows in the embodiment of the invention:
Monomer: acrylamide (AM), medical procurement supply station, Shanghai 2-vinyl pyridine (2-VP), Fluka, Switzerland
Linking agent: ethylene glycol dimethacrylate (EDMA), Shanghai Shanhu Chemical Factory, Shanghai trimethoxy propane trimethyl acrylic ester (TRIM), Shanghai Shanhu Chemical Factory, Shanghai
Initiator: Diisopropyl azodicarboxylate (AIBN), Beijing Chemical Plant
Template molecule and enantiomorph thereof: benzene methoxycarbonyl-L-tryptophane (N-Cbz-L-Trp), Sigma, U.S.'s benzene methoxycarbonyl-D-tryptophane (N-Cbz-D-Trp), Sigma, U.S.'s benzene methoxycarbonyl-L-tyrosine (N-Cbz-L-Tyr), Sigma, U.S.'s benzene methoxycarbonyl-D-tyrosine (N-Cbz-D-Tyr), Sigma, U.S.'s benzene methoxycarbonyl-L-phenylalanine (N-Cbz-L-Phe), Sigma, U.S.'s benzene methoxycarbonyl-D-phenylalanine (N-Cbz-D-Phe), Sigma, the U.S.
1.1 the preparation of molecular brand polymer (MIP):
With template molecule N-Cbz-L-Trp, 2-VP, AM, EGDMA with certain molar ratio example (1: 2: 2: 20, see Table 1) be dissolved in an amount of acetonitrile, the initiator A IBN that adds monomer weight 1%, through ultrasonic dissolution, fill nitrogen degassing back sealing, under 0 ℃,, obtain hard solid product with uviolizing reaction 48 hours.Through the methyl alcohol extracting, remove template molecule after, the solids crushing screening and repeatedly sedimentation removing smalls, the amorphous granular that obtains, particle diameter is used for the high performance liquid chromatography evaluation less than 30 μ m.
1.2 high performance liquid chromatography is estimated MIP
Stationary phase is packed in 200 * 4.0mm or the 250 * 4.0mm chromatographic column for homogenate and displacing liquid with acetonitrile/water (v/v, 50/50), and the dress column pressure is 10 μ l for the 20MPa. sampling volume, includes sample 20 μ g.Acetone is surveyed the dead time.
1.3 the chiral separation effect of novel molecular brand polymer
The molecular brand polymer that with N-Cbz-L-Trp is template molecule is a chiral stationary phase, the results are shown in Table 1 to what template molecule enantiomorph N-Cbz-DL-Trp carried out chiral separation.
2.1 adopt the method for example 1.1 to prepare molecular brand polymer.
Estimate molecular brand polymer 2.2 adopt the method for example 1.2.
2.3 evaluation result sees Table 1.
Embodiment 3 is the preparation and the evaluation of the molecular brand polymer of branding molecule with N-Cbz-L-Tyr
3.1 adopt the method for example 1.1 to prepare molecular brand polymer.
Estimate molecular brand polymer 3.2 adopt the method for example 1.2.
3.3 evaluation result sees Table 1.
Embodiment 4 application of novel molecular brand polymer in chiral separation
Prepared molecular brand polymer chiral stationary phase is packed in 200 * 4.0mm or the 250 * 4.0mm chromatographic column for homogenate and displacing liquid with acetonitrile/water (v/v, 50/50), and the dress column pressure is 10 μ l for the 20MPa. sampling volume, includes sample 20 μ g.Acetone is surveyed the dead time.The actual analysis spectrogram is seen Fig. 1, Fig. 2 and Fig. 3.
The preparation of embodiment 5 ternary cross-linker molecules brand polymers
With template molecule N-Cbz-L-Trp, 2-VP, AM, TRIM with the certain molar ratio example (as 1: 2: 2: 5) mix, be dissolved in an amount of acetonitrile, the initiator A IBN that adds monomer weight 1%, through ultrasonic dissolution, fill nitrogen degassing back sealing, under 0 ℃,, obtain hard solid product with uviolizing reaction 48 hours.After drying, with the solids crushing screening, and sedimentation with methyl alcohol/acetate extracting, is removed the amorphous granular that obtains behind the template molecule to remove smalls repeatedly, and particle diameter is used for the high performance liquid chromatography evaluation less than 30 μ m.
Embodiment 6 is the preparation of the molecular brand polymer of function monomer with Methacrylamide and 3-vinyl pyridine
With template molecule N-Cbz-L-Tyr, 3-VP, Methacrylamide, EGDMA by 2: 3: 4: 40 (mol ratios) are dissolved in an amount of chloroform, the initiator A IBN that adds total monomer weight 1%, through ultrasonic dissolution, fill nitrogen degassing back sealing, under 0-4 ℃,, obtain hard white solid product with uviolizing reaction 24-48 hour.Through methyl alcohol/acetate (1: 1, v/v) extracting, remove template molecule after, solids pulverize, sieve and repeatedly sedimentation to remove smalls, the amorphous granular that obtains, particle diameter are applicable to high performance liquid chromatography separation N-Cbz-L-Tyr and the close enantiomorph of structure less than 30 μ m.
The chiral separation of table 1 on 2-VP+AM complex function monomer molecule brand polymer
Annotate: column length: 200 * 4.0mm; Sample: N-Cbz-DL-Trp, N-Cbz-DL-Phe, N-Cbz-DL-Tyr; Sample size: each 20 μ g; Moving phase: acetonitrile/acetate, 99.0/1.0 (v/v); Detect wavelength: N-Cbz-DL-Trp 280nm, N-Cbz-DL-Phe 258nm, N-Cbz-DL-Tyr 276nm; Flow velocity: 0.5mL/min.
| Template molecule | Template molecule and 2-VP and acrylamide (mol ratio) | Capacity factor | Chirality is selected factor-alpha | Resolution R | |
| ????k D’ | ????k L’ | ||||
| ?N-Cbz-L-Trp | ????1∶2∶2 | ????1.32 | ????3.66 | ????2.77 | ???1.0 |
| ?N-Cbz-L-Phe | ????1∶2∶2 | ????1.61 | ????3.09 | ????1.92 | ???0.9 |
| ?N-Cbz-L-Tyr | ????1∶2∶2 | ????3.86 | ????13.67 | ????3.54 | ???1.0 |
Claims (2)
1. the preparation method of a molecular brand polymer chiral separation stationary phase, be polymerized under the linking agent effect by function monomer and the associated complex that the branding molecule forms, it is characterized in that: adopt two kinds of complex function monomers, be selected from acrylamide+2-vinyl pyridine, acrylamide+3-vinyl pyridine, acrylamide+4-vinylpridine, Methacrylamide+2-vinyl pyridine, Methacrylamide+3-vinyl pyridine, Methacrylamide+4-vinylpridine a kind of; Use the polynary linking agent of two above vinyl, be selected from Vinylstyrene, ethylene glycol dimethacrylate, trimethoxy propane trimethyl acrylic ester, pentaerythritol triacrylate a kind of; The mol ratio of acrylamide and vinyl pyridine is 1: 1～3; The mol ratio of function monomer and linking agent is 1: 5～20.
2. by the preparation method of the described molecular brand polymer chiral separation of claim 1 stationary phase, it is characterized in that: be linking agent trimethoxy propane trimethyl acrylic ester, pentaerythritol triacrylate.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100335163C (en) * | 2005-07-11 | 2007-09-05 | 天津大学 | Method for preparing built-in nano pore silica absorbent for medicine separation and purification |
| CN1997678B (en) * | 2003-09-19 | 2011-10-26 | 纽约州州立大学研究基金会 | Quasi-interpenetrating networks used as separation media |
| CN110180509A (en) * | 2019-05-24 | 2019-08-30 | 吉林大学 | A kind of fluorescent molecule imprinted polymer tiny balloon and its preparation method and application |
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2000
- 2000-08-30 CN CN 00122948 patent/CN1340552A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1997678B (en) * | 2003-09-19 | 2011-10-26 | 纽约州州立大学研究基金会 | Quasi-interpenetrating networks used as separation media |
| CN100335163C (en) * | 2005-07-11 | 2007-09-05 | 天津大学 | Method for preparing built-in nano pore silica absorbent for medicine separation and purification |
| CN110180509A (en) * | 2019-05-24 | 2019-08-30 | 吉林大学 | A kind of fluorescent molecule imprinted polymer tiny balloon and its preparation method and application |
| CN110180509B (en) * | 2019-05-24 | 2021-08-24 | 吉林大学 | Fluorescent molecularly imprinted polymer hollow microsphere and preparation method and application thereof |
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