阅读说明：本技术 多孔二氧化硅微球及其制备方法和应用 (Porous silicon dioxide microsphere and preparation method and application thereof ) 是由 李昂 陆嘉伟 N·L·阿伯特 于 2019-01-11 设计创作，主要内容包括：本发明公开了一种多孔二氧化硅微球,所述多孔二氧化硅微球具有射线型构象的内部结构和孔道排列,其粒径为3～300微米。本发明还公开一种制备多孔二氧化硅微球的方法,包括：制备多孔的氨基化聚合物微球,所述氨基化聚合物微球具有射线型构象的内部结构和孔道排列；加入二氧化硅前驱体,水解反应得到二氧化硅/聚合物复合微球；煅烧二氧化硅/聚合物复合微球,得到多孔二氧化硅微球。本发明还公开了多孔二氧化硅微球在色谱分离中的应用。本发明的方法工艺简单,易于操作,重现性好,并且可实现大规模生产。本发明制备的多孔二氧化硅微球粒径可控,内部结构和孔道排列有序,可广泛应用在色谱分离、催化载体、药物控释等领域。(The invention discloses a porous silicon dioxide microsphere which has an internal structure of ray conformation and pore channel arrangement, and the particle size of the porous silicon dioxide microsphere is 3-300 micrometers. The invention also discloses a method for preparing the porous silicon dioxide microspheres, which comprises the following steps: preparing porous aminated polymer microspheres, wherein the aminated polymer microspheres have an internal structure with a ray-type conformation and a pore channel arrangement; adding a silicon dioxide precursor, and performing hydrolysis reaction to obtain silicon dioxide/polymer composite microspheres; and calcining the silica/polymer composite microspheres to obtain the porous silica microspheres. The invention also discloses application of the porous silica microspheres in chromatographic separation. The method has simple process, easy operation and good reproducibility, and can realize large-scale production. The porous silicon dioxide microspheres prepared by the invention have controllable particle size and ordered arrangement of internal structure and pore channels, and can be widely applied to the fields of chromatographic separation, catalytic carriers, drug controlled release and the like.)

1. The porous silica microspheres have an internal structure with ray conformation and pore channel arrangement, and the particle size of the porous silica microspheres is 3-300 micrometers.

2. The porous silica microspheres of claim 1, wherein the porous silica microspheres have a specific surface area of 100 to 1000m²/g。

3. The porous silica microspheres of claim 1, wherein the average pore diameter of the pores of the porous silica microspheres is 1 to 100 nm.

4. A method of making the porous silica microspheres of claim 1, comprising:

(I) preparing porous aminated polymer microspheres, wherein the aminated polymer microspheres have an internal structure with a ray-type conformation and a pore channel arrangement;

(II) adding a silicon dioxide precursor, and performing hydrolysis reaction to obtain silicon dioxide/polymer composite microspheres; and

(III) calcining the silica/polymer composite microspheres to obtain the porous silica microspheres.

5. The method of claim 4, wherein the silica precursor is an orthosilicate or a silane-based compound.

6. The method of claim 4, wherein an organic alcohol is further added to the hydrolysis reaction.

7. The method of claim 4, wherein the step of preparing porous aminated polymeric microspheres comprises:

(1) preparing porous functional polymer microspheres, wherein the functional polymer microspheres have an internal structure with radial conformation and pore channel arrangement; and

(2) aminating the functional polymeric microspheres to form the aminated polymeric microspheres.

8. The method of claim 7, wherein the aminating agent used in the step of amination of the functional polymeric microspheres is ethylenediamine or ammonia.

9. The method of claim 7, wherein the step of preparing porous functional polymeric microspheres comprises:

(a) forming a homogeneous liquid crystal mixture, wherein the liquid crystal mixture comprises reactive liquid crystals, comonomers, non-reactive liquid crystals, and a polymerization initiator;

(b) dispersing liquid crystal droplets formed by emulsifying the liquid crystal mixture in a continuous phase containing a liquid crystal conformation change agent, wherein the liquid crystal conformation change agent can enable liquid crystal molecules in the liquid crystal droplets to be regularly arranged;

(c) polymerizing the reactive liquid crystal in the liquid crystal microdroplets to form intermediate microspheres; and

(d) removing the non-reactive liquid crystal that is not polymerized from the intermediate microspheres to form the functional polymeric microspheres.

10. The method of claim 9, wherein the comonomer comprises functional groups including epoxy, hydroxyl, carboxyl, ester, and halogen groups.

11. The method of claim 9, wherein the reactive liquid crystal is present in an amount of 5% to 40% by weight of the total liquid crystal mixture.

12. The method of claim 9, wherein the molar ratio of the comonomer to the reactive liquid crystal is 1:3 to 3: 1.

13. Use of porous silica microspheres according to any one of claims 1-3 in chromatographic separations.

Technical Field

The invention relates to the field of inorganic porous materials, in particular to porous silicon dioxide microspheres and a preparation method and application thereof.

Background

The high performance liquid chromatography (HP L C) is a novel high-efficiency and rapid analysis and separation technology developed in the last 70 th century, is the most common analysis and separation means, and is mainly applied to the fields of chemical engineering, food sanitation, drug detection, environmental monitoring and the like.

At present, the high performance liquid chromatography packing taking silica gel as a matrix accounts for more than 90 percent, and most of the packing is porous spherical silica gel (porous silica microspheres). Since the shape, particle size and pore structure of the porous silica microspheres can directly influence the column efficiency, selectivity and separation effect of the chromatographic packing, how to accurately control these factors becomes a key point for determining the separation capacity of the chromatographic column, and the control of the internal structure of the microspheres is more difficult. The existing preparation method can successfully prepare the silica microspheres with ideal particle size, such as Chinese patent CN102070152B, which discloses a method for preparing functional uniform-particle porous silica microspheres, but the preparation process is complicated, and the arrangement of internal pore channels of the microspheres cannot be further controlled. The traditional sol-gel method can prepare silica microspheres with ordered internal pore channel arrangement, such as Chinese patent CN105236427B, which discloses a nanoscale silica sphere with ordered mesopores and a preparation method thereof. However, the size of the microspheres used in chromatographic packing is generally required to be 3-10 μm, and it is difficult to obtain such large size spheres by the conventional sol-gel method.

Therefore, it is required to provide a porous silica microsphere with micron-sized and controllable size and ordered arrangement of internal structure and pore channel, which provides a breakthrough in the field of high performance liquid chromatography packing and improves the capacity and effect of chromatographic separation. Meanwhile, the preparation method is simple and easy to operate, and can be used for large-scale production.

Disclosure of Invention

In order to meet the requirements, the invention discloses a porous silica microsphere which has an internal structure with a ray-type conformation and pore canal arrangement, and the particle size of the porous silica microsphere is 3-300 micrometers. In a preferred embodiment, the particle size of the porous silica microspheres is 5-80 microns.

In some embodiments, the porous silica microspheres have a specific surface area of 100 to 1000m²(ii) in terms of/g. In a preferred embodiment, the specific surface area of the porous silica microspheres is 100-500 m²/g。

In some embodiments, the porous silica microspheres have channels with an average pore size of 1 to 100 nm. In a preferred embodiment, the average pore diameter of the pore channels of the porous silica microspheres is 10-50 nm.

Another aspect of the present invention provides a method for preparing porous silica microspheres, comprising: preparing porous aminated polymer microsphere with ray conformation internal structure and pore canal arrangement; adding a silicon dioxide precursor, and performing hydrolysis reaction to obtain silicon dioxide/polymer composite microspheres; and calcining the silica/polymer composite microspheres to obtain the porous silica microspheres.

In a preferred embodiment, the silica precursor is an orthosilicate or a silane-based compound.

In a preferred embodiment, organic alcohols may be further added to the hydrolysis reaction.

In some embodiments, the step of preparing porous aminated polymeric microspheres comprises: preparing porous functional polymer microspheres, wherein the functional polymer microspheres have an internal structure with ray-type conformation and pore channel arrangement; and aminated functional polymeric microspheres to form aminated polymeric microspheres.

In a preferred embodiment, the aminating agent used in the step of aminating the functional polymeric microspheres is ethylenediamine or aqueous ammonia.

In some embodiments, the step of preparing porous functional polymeric microspheres comprises: forming a homogeneous liquid crystal mixture, wherein the liquid crystal mixture comprises reactive liquid crystals, comonomers, non-reactive liquid crystals and a polymerization initiator; dispersing liquid crystal microdroplets formed by emulsifying the liquid crystal mixture into a continuous phase containing a liquid crystal conformation change agent, wherein the liquid crystal conformation change agent can enable liquid crystal molecules in the liquid crystal microdroplets to be regularly arranged; polymerizing reactive liquid crystals in the liquid crystal microdroplets to form intermediate microspheres; and removing the unpolymerized non-reactive liquid crystal from the intermediate microspheres to form functional polymeric microspheres.

In a preferred embodiment, the comonomer comprises a functional group, such as an epoxy, hydroxyl, carboxyl, ester or halogen group.

In a preferred embodiment, the reactive liquid crystal is present in an amount of 5% to 40% by weight of the total liquid crystal mixture. More preferably, the reactive liquid crystal accounts for 5 to 25% of the total mass of the liquid crystal mixture.

In a preferred embodiment, the molar ratio of comonomer to reactive liquid crystal is from 1:3 to 3: 1.

The invention also discloses application of the porous silica microspheres in chromatographic separation.

The preparation method disclosed by the invention takes the porous functional polymer microspheres with the ordered internal structure as the template to prepare the porous silicon dioxide microspheres with the ordered internal structure and the pore canal arrangement, and the preparation method has the advantages of simple process, easiness in operation, good reproducibility and capability of realizing large-scale production. Meanwhile, the porous silicon dioxide microspheres prepared by the preparation method have controllable particle size and ordered arrangement of internal structure and pore channels, and can be widely applied to the fields of chromatographic separation, catalytic carriers, controlled drug release and the like.

Drawings

The invention may be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings, in which:

FIG. 1 is an orthographic view of a porous silica microsphere prepared according to an embodiment of the present invention;

FIG. 2 is a schematic illustration of a membrane emulsification technique for preparing liquid crystal droplets;

FIG. 3 is (a) parallel and (b) cross-polarized microscopy images (same scale for multiple microscopy images) of functional polymeric microspheres prepared according to an embodiment of the present invention;

FIG. 4 is a graph of an infrared spectrum of functional polymeric microspheres made according to an example of the present invention;

FIG. 5 is a graph of an infrared spectrum of an aminated polymer microsphere made in accordance with an embodiment of the present invention;

FIG. 6 is a parallel (top) and orthogonal (bottom) polarization microscope images of porous silica microspheres prepared according to an example of the invention, wherein the molar ratio of comonomer to reactive liquid crystal is (a)1:2, (b)1:1, and (c)2:1 (the same scale for multiple microscope images);

FIG. 7 is an internal SEM image of porous silica microspheres made according to an example of the invention;

FIG. 8 is a parallel (top) and orthogonal (bottom) polarization microscope images of porous silica microspheres prepared according to an example of the invention, wherein the mass percentages of reactive liquid crystals are (a) 9.7% and (b) 19% (the same scale for multiple microscope images);

FIG. 9 is (a) parallel and (b) cross-polarization micrographs (the same scale for multiple micrographs) of porous silica prepared according to an example of the invention.

Detailed Description

In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present invention, however, it will be apparent to those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known structures and devices are shown in block diagram form. In this regard, the illustrated example embodiments are provided for purposes of illustration only and are not intended to be limiting of the invention. Therefore, it is intended that the scope of the invention be limited not by this detailed description, but rather by the claims appended hereto.

Abbreviations and molecular formulas as used herein are listed:

5 CB: 4-cyano-4' -pentylbiphenyl

RM 257: 2-methyl-1, 4-phenylene-bis [4- (3-acryloyloxypropoxy) benzoate ]

DMPAP: 2-bis-methoxy-2-phenyl ethanone

SPG film: shirasu Porous Glass membrane

SDS (sodium dodecyl sulfate): sodium dodecyl sulfate

As shown in fig. 1, the present invention discloses a porous silica microsphere having an internal structure and a pore channel arrangement in a ray-type conformation, that is, both the internal structure and the pore channel are arranged in a radial direction, thereby optically exhibiting ray-type optical anisotropy (maltese black cross). The particle size of the porous silicon dioxide microspheres is uniform and controllable, and the average particle size can be changed between 3 and 300 micrometers. More preferably, the average particle size may vary from 5 to 80 microns. Meanwhile, the specific surface area of the porous silicon dioxide microspheres can be 100-1000 m²Adjusting the ratio between the concentration and the concentration. More preferably, the specific surface area of the porous silica microspheres can be 100-500 m²Adjusting the ratio between the concentration and the concentration. The average pore diameter of the outer pore canal and the inner pore canal of the porous silicon dioxide microsphere is 1-100 nm. More preferably, the average pore diameter of the pore channel is 10-50 nm

In the embodiment of the present invention, the porous silica microspheres may be prepared by a method using functional polymer microspheres as a template, which comprises the following specific steps.

First, porous aminated polymer microsphere with internal structure of ray conformation and pore canal arrangement is prepared, which can show ray optical anisotropy. Meanwhile, a plurality of amino functional groups are connected to the surface and the interior of the aminated polymer microsphere, and the amino functional groups can further react with a silicon dioxide precursor to generate silicon dioxide. In an embodiment of the present invention, the step of preparing porous aminated polymeric microspheres further comprises: preparing porous functional polymer microspheres, wherein the functional polymer microspheres also have an internal structure with ray-type conformation and pore canal arrangement; the functional polymer microsphere is aminated, wherein an amination agent used in the amination reaction can be ethylenediamine or ammonia water, and the functional polymer microsphere has a functional group capable of reacting with the amination agent, so that the amino group can replace the original functional group, and a porous aminated polymer microsphere is further formed.

And then, adding a silicon dioxide precursor, wherein the silicon dioxide precursor can perform hydrolysis reaction on the surface and in the pore channel of the aminated polymer microsphere, so that silicon dioxide is generated on the surface and in the pore channel of the original aminated polymer microsphere, and the silicon dioxide/polymer composite microsphere is formed. The reaction may be carried out in water or a mixed solution of water, and in an embodiment of the present invention, a water/ethanol mixed solution or a water/isopropanol mixed solution is used. During the reaction, proper amount of organic alcohol, such as methanol, ethanol, isopropanol, glycol, etc. may be added to control the hydrolysis rate and to facilitate the formation of silica inside the pore canal of the polymer microsphere. The silica precursor may be a conventional silicon source such as orthosilicates (methyl orthosilicate, ethyl orthosilicate, etc.) or silanes (dodecyl trimethoxy silane, etc.). In the following examples, ethyl orthosilicate was used as a silica precursor.

And finally, calcining the silica/polymer composite microspheres to decompose and remove the polymer, thereby finally obtaining the porous silica microspheres. The produced silica microspheres retain the internal characteristics of the original functional polymer microspheres serving as templates, namely, the prepared porous silica microspheres also have the internal structure and the pore canal arrangement with radial conformation.

The prepared porous silica microspheres can be applied to chromatographic separation, and particularly can be used as a stationary phase of a chromatographic column. Because the porous silica microspheres have ordered internal structures and pore canal arrangements, when the porous silica microspheres are used as a stationary phase of a chromatographic column, the interaction between a separation substance and the stationary phase is regular, so that the separation time can be shortened, a mobile phase is saved, and the separation effect is improved.

Because the particle size and the pore distribution of the porous silica microspheres are determined by the functional polymer microspheres serving as the template, in order to obtain the porous silica microspheres meeting the requirements, in the embodiment of the invention, the functional polymer microspheres with controllable particle size and ordered pore channels are prepared by adopting a liquid crystal-assisted template polymerization method, and the method specifically comprises the following steps:

in the first step, reactive liquid crystals, non-reactive liquid crystals, comonomers and polymerization initiators are mixed in a certain proportion to form a uniform liquid crystal mixture. Among them, the reactive liquid crystal has a polymerizable chemical group and can react to form a polymer in the presence of a polymerization initiator, for example, an acrylate-based liquid crystal (RM257), a methacrylate-based liquid crystal (HCM062), an allyl-based liquid crystal (HCM126), and the like. The mass percentage of the reactive liquid crystal in the liquid crystal mixture can be adjusted between 5% and 40%. More preferably, the mass percentage can be adjusted between 5% and 25%. The non-reactive liquid crystal has no polymerizable chemical groups and does not polymerize further. The non-reactive liquid crystal comprises at least one nematic liquid crystal, such as the commonly used nematic liquid crystal 5CB or nematic mixed crystal E7. The comonomers have unsaturated bonds and can react with polymerizable chemical groups of the reactive liquid crystal to form a copolymeric compound. Meanwhile, the comonomer has functional groups reactive with the aminating agent, including epoxy, hydroxyl, carboxyl, ester and halogen groups. However, the present invention is not limited thereto, and may include other functional groups as required. In the following examples, glycidyl methacrylate containing epoxy groups was used as a comonomer. The molar ratio of the comonomer to the reactive liquid crystal is preferably 1:3 to 3: 1.

In a second step, the liquid crystal mixture is emulsified to form liquid crystal droplets dispersed in the continuous phase, wherein the liquid crystal droplets comprise a reactive liquid crystal, a non-reactive liquid crystal, a comonomer and a polymerization initiator. In an embodiment of the invention, the continuous phase is water or a water-miscible solution. The method of emulsification may include stirring, shaking, ultrasonic method, membrane emulsification and the like. In the embodiment of the invention, in order to better control the particle size and distribution of the liquid crystal droplets, the liquid crystal mixture is passed through a membrane emulsification device into a continuous phase by adopting a membrane emulsification mode to form monodisperse liquid crystal droplets. The principle of the membrane emulsification device is shown in fig. 2, which mainly utilizes the dispersion technology based on membrane emulsification to realize the preparation of monodisperse liquid crystal droplets. The specific operation is as follows: the liquid crystal mixture as a disperse phase slowly passes through an inorganic membrane with micropores, liquid crystal droplets are formed after the liquid crystal mixture is extruded from the micropores of the inorganic membrane and are dispersed in a continuous phase, so that a dispersion system taking the liquid crystal droplets as the disperse phase is formed, the size of the liquid crystal droplets can be controlled by the pore size of the micropores of the inorganic membrane, and finally, the particle size of the prepared functional polymer microspheres with porous structures is controlled. In the following examples, a membrane emulsification apparatus using an SPG membrane having micropores was selected to precisely control the size of liquid crystal droplets. The continuous phase contains a liquid crystal conformation modifier which can make the liquid crystal molecules (including reactive liquid crystal and non-reactive liquid crystal) in the liquid crystal microdroplets regularly arranged. In embodiments of the invention, the liquid crystal conformation change agent causes liquid crystal molecules in the liquid crystal droplets to align in a radial direction of the liquid crystal droplets to form a radial-type conformation. The liquid crystal conformation change agent can be an ionic surfactant, such as SDS; or inorganic salts such as sodium iodide, sodium perchlorate.

And thirdly, polymerizing the reactive liquid crystal in the liquid crystal microdroplets to form intermediate microspheres containing non-reactive liquid crystal which does not participate in polymerization. Before polymerization, the liquid crystal molecules in the liquid crystal microdroplets are regularly arranged due to the presence of the liquid crystal conformation change agent, so that the internal structure of the formed intermediate microspheres substantially maintains the regular arrangement before reaction after polymerization. The polymerization may be photopolymerization, thermal polymerization or radiation polymerization. In an embodiment of the present invention, the polymerization mode is preferably photopolymerization.

And fourthly, removing the non-reactive liquid crystal which does not participate in the polymerization to further form the functional polymer microspheres with regular internal structures and pore channel arrangement. Since the non-reactive liquid crystal does not participate in the polymerization reaction, micropores are formed in the interior of the polymer microsphere after the non-reactive liquid crystal is removed, and the distribution of the micropores is influenced by the previous arrangement of the liquid crystal molecules and tends to be regularly arranged. Meanwhile, the polymer microsphere reserves functional groups in the comonomer, so that the functional groups are uniformly distributed on the surface and in the pore channel of the polymer microsphere.

The structure, optical activity and preparation method of the silica microspheres of the present invention will be described in detail with reference to specific examples. In the embodiment of the present invention, the specific surface area and the internal pore size of the prepared silica microspheres may be measured by a conventional BET specific surface area test method. In the following examples, the BET test was carried out using a BeckmanCoulter specific surface analyzer SA 3100.

In the following examples, the general procedure for forming a homogeneous liquid crystal mixture is: mixing reactive liquid crystal, non-reactive liquid crystal, comonomer and polymerization initiator in proportion, heating the mixture to a temperature above the clearing point of the mixed liquid crystal until the mixture becomes a uniform solution, fully vibrating the solution to mix the solution uniformly, and then slowly cooling the solution to room temperature to form a liquid crystal mixture. When photopolymerization is used, the solution must be kept in the dark while slowly cooling, since the photoinitiator is sensitive to light.

The general steps for forming functional polymeric microspheres are: at a certain speed, the uniform liquid crystal mixture slowly and smoothly passes through an SPG film emulsifying device to be dispersed into a continuous phase containing the liquid crystal conformation change agent, the stirring speed of the continuous phase is 300r/min, and finally, an emulsion containing liquid crystal microdroplets with uniform sizes is formed. The emulsion containing the liquid crystal microdroplets is placed under a 365nm UV light source for curing polymerization, and the radiation intensity is 2.5mW/cm²The polymerization time is 30 minutes, and the system needs to be stirred continuously in the polymerization process. And washing the polymer by using an ethanol solution for three times after polymerization, and centrifuging to remove supernatant to obtain the polymer microsphere with unreacted substances removed.