CN101992049B - Method for preparing porous nano-hollow sphere by self-assembled organic micromolecule acid-base double components - Google Patents

Abstract

The invention provides a method for preparing porous nano hollow spheres by the self-assembly of organic small molecule acid-base two-component self-assembly, which is the organic small-molecule acid component and the organic small molecule of the organic small-molecule acid-base two-component self-assembly system Alkali components are dissolved in organic solvents respectively, after mixing the obtained acid component solution and alkali component solution, dilute with water, place at room temperature for 1-4 days or slowly add water to dilute under stirring state to obtain single-pore nanometer hollow ball. The method of the invention has the advantages of simple preparation process, controllable and stable shape and performance of the porous nanometer hollow sphere, and the prepared hollow nanometer sphere has a larger drug loading capacity than the non-porous hollow sphere.

Description

Method for preparing porous nano hollow spheres by self-assembly of organic small molecule acid-base two-component

technical field

The invention belongs to the field of chemistry and materials, and relates to the self-assembly of small organic molecules to prepare porous nano hollow spheres.

Background technique

Nano- or micro-hollow spheres have important applications in the loading and controlled release of drugs, cosmetics, inks, pigments, dyes, paints, chemical reagents, catalysts, etc., and have caused extensive research on pores. However, the hollow ball without holes is loaded and released only by the tiny gaps on the surface of the spherical shell, and the process is very slow. The micro-nano hollow spheres with holes on the surface can not only increase the speed of loading and releasing substances, but also increase the loading capacity and load nanoparticles, which has recently aroused great interest at home and abroad. Inorganic porous nano-hollow spheres are the earliest and most researched, because such hollow spheres are more effective catalysts or catalyst supports, and better photoelectric materials. Recently, there have been reports of some porous nanohollow spheres of organic polymers. Xia et al. prepared polystyrene single-hole hollow nanospheres by solvent swelling and liquid nitrogen freezing. These porous hollow spheres can be loaded with coumarin-6, bovine serum albumin, and superparamagnetic iron oxide nanoparticles, while the latter two substances cannot be loaded by hollow spheres without holes (Nature Materials 2005, 4, 671-675). Zhang et al. used polystyrene nanobead templates to synthesize single-hole polystyrene hollow nanospheres, which can absorb more TNT explosive molecules (Advanced Materials 2007, 19, 2370-2374). Zhang et al. also synthesized polystyrene single-hole hollow nanospheres by interface-induced emulsion polymerization (Chemistry Letters 2007, 36, 944-945). However, the preparation of these organic polymer porous nano-hollow spheres requires low-temperature freezing, complex processes such as polystyrene templates and gradient heating, and the preparation time is long, difficult and costly. Using small organic molecules to self-assemble organic micro-nano materials has the advantages of simple preparation and purification, easy functionalization, adjustable shape and performance, stable products, and simple processing. As a soft material (Soft Materials), it can be used in inorganic nanomaterials Synthetic templates, biomimetic materials, nanodevices and nanosensors, used for the storage, transportation, directional release, separation and purification of substances, used as microreactors and microreaction environments, etc., have received more and more attention. It has become a research hotspot and frontier in recent years. However, the self-assembly of hollow nanospheres with small organic molecules has not been reported.

Contents of the invention

The task of the present invention is to provide a method for preparing porous nano hollow spheres by the self-assembly of organic small molecule acid-base two components, which has the advantages of simple preparation process, controllable and stable shape and performance of porous nano hollow spheres, and the preparation of The porous hollow spheres have the advantages of greater drug loading than non-porous hollow spheres.

Realize the technical scheme of the present invention is:

The method for preparing porous nano-hollow spheres provided by the present invention includes the following steps:

Step (a): The organic small molecule acid component and the organic small molecule base component of the organic small molecule acid-base two-component self-assembly system are respectively dissolved in a water-soluble organic solvent, and the concentration range of the solution is 0.1mM-10000mM, and the The obtained acid component and base component solution are mixed to obtain a mixed solution, the molar ratio of the acid component and the base component in the mixed solution is 0.1:1-10:1, and the self-assembly of the organic small molecule acid-base two-component The small organic molecule acid component of system has structure shown in formula (I):

In the formula,

_R is H, thienyl, phenyl, naphthyl, phenylethynyl or styryl;

R ₂ and R ₃ are the same or different, respectively represent benzoyloxy, naphthoyloxy, acetoxy, hydroxyl, H, or collectively represent 1 or 2 π bonds;

In formula (I), the substituents R ₁ , R ₂ and R ₃ may specifically be:

When R ₁ =H, R ₂ =OCOPh, R ₃ =OCOPh; or

When R ₁ =2-thienyl, R ₂ =OCOPh, R ₃ =OCOPh; or

When R ₁ =phenylethynyl, R ₂ =OCOPh, R ₃ =OCOPh; or

When R ₁ =H, R ₂ =OH, R ₃ =OH or R ₁ =R ₂ =R ₃ =H; or

When R ₁ =H, R ₂ and R ₃ are together a π bond.

After completing step (a), proceed to the following step (b) or step (c) to obtain single-hole hollow nanospheres:

Step (b): Dilute the mixed solution obtained in step (a) with water so that the volume ratio of the organic solvent to water is 0.001:1-1000:1, and leave it at room temperature for 1-4 days to obtain single-hole hollow nanospheres;

Step (c): Slowly dilute the mixed solution obtained in step (a) with water, so that the volume ratio of the organic solvent to water is 0.001:1-1000:1, to obtain single-hole hollow nanospheres.

The organic small molecule acid components in the organic small molecule acid-base two-component self-assembly system described in the method of the present invention can be pure enantiomers, racemates or mesomers, and can also be each A mixture of isomers.

The organic small molecule base component in the described organic small molecule acid-base two-component self-assembly system is a commercially available organic base, such as 2-amino-1,2-diphenylethanol, 1,2-diphenylethanol, Phenyl-1,2-diaminoethane or phenylglycinol, other commercially available organic bases are not excluded, and the organic small molecule base component can be a pure enantiomer of an organic amine , racemate, mesoform or a mixture of various isomers, or a mixture of different types of organic amines.

The water-soluble organic solvent is ethanol, tetrahydrofuran, dioxane, acetone, acetonitrile or N,N-dimethylformamide and the like.

After completing step (a), proceed to the following step (b) or step (c) to obtain single-hole hollow nanospheres:

Step (b): Dilute the mixed solution of acid component and alkali component obtained in step (a) with water, the volume ratio of organic solvent to water is 0.001:1-1000:1, and leave it at room temperature for 1-4 days. Obtain single-hole hollow nanosphere;

Step (c): Slowly dilute the mixed solution of the acid component and the alkali component obtained in step (a) with water, and the volume ratio of the organic solvent to water is 0.001:1-1000:1 to obtain a single hole nano hollow spheres.

The synthesis method of the compound represented by formula (I) can be found in literature [Yan-Song Zheng, Yu-Jian Hu, J.Org.Chem.2009, 74, 5660-5663.].

The present invention has carried out FE-SEM electronic scanning and TEM transmission electron microscope detection to the single hole hollow nanosphere prepared by the method of the present invention, FE-SEM electronic scanning detection photo is shown in Fig. 1 and Fig. 2, and TEM transmission electron microscope detection photo is shown in Fig. 3 and Figure 4. It can be seen from the FE-SEM scanning electron photos of Fig. 1 and Fig. 2 that the diameter of the single-hole nano hollow sphere prepared by the method of the present invention is 60-800nm, and the diameter of the hole is 20-200nm. It can be seen from the TEM transmission electron microscope photos in Fig. 3 and Fig. 4 that the diameter of the hollow sphere is 100-300nm, and the diameter of the hole is 20-100nm, which is consistent with the FE-SEM photo. It shows that the method of the present invention has successfully produced hollow nanometer spheres.

The preparation process of the method of the present invention is simple, and the shape and performance of the hollow nanospheres with holes are controllable. The hollow nanospheres with holes prepared by the method of the present invention are placed for observation for one month, and the shape and performance of the hollow nanospheres with holes are found to be stable. The experiment proves that the porous nanometer hollow sphere prepared by the method of the present invention has a larger drug loading capacity than the non-porous hollow sphere.

Description of drawings

Fig. 1 is the FE-SEM photo of the porous nano-hollow spheres prepared by the inventive method;

Fig. 2 is another FE-SEM photo of the porous nano-hollow spheres prepared by the method of the present invention;

Fig. 3 is the TEM photo of the porous nano-hollow spheres prepared by the inventive method;

Fig. 4 is another TEM photograph of porous nano-hollow spheres prepared by the method of the present invention.

Detailed ways

Example 1

Mix 0.1 mL of 0.02M Ia (D-configuration, R ₁ =H or 2-thienyl, R ₂ =R ₃ =PhCOO) THF solution with 0.1 mL of 0.02M (1S,2S)-2-amino-1 , 2-diphenylethylenediamine THF solution is mixed, diluted with water to 2mL, the resulting suspension is non-porous nano-hollow spheres, which turn into single-hole nano-hollow spheres after being placed at room temperature for 1-4 days.

Example 2

Mix 0.1 mL of 0.02M Ia (D-configuration, R ₁ =H or 2-thienyl, R ₂ =R ₃ =PhCOO) THF solution with 0.1 mL of 0.02M (1S,2S)-2-amino-1 After mixing 2-diphenylethylenediamine THF, slowly add 2 mL of water under stirring to obtain single-hole hollow nanospheres. Carry out FE-SEM electronic scanning and TEM transmission electron microscope detection to the obtained single hole nanometer hollow sphere, can see from the FE-SEM electron scanning photo of Fig. 1 and Fig. 2, the diameter of hollow sphere is 60-800nm, and the diameter of hole is 20-200nm. It can be seen from the TEM photos of Figure 3 and Figure 4 that the diameter of the hollow sphere is 100-300nm, and the diameter of the hole is 20-100nm, which is consistent with the FE-SEM photo.

Example 3

Mix 0.1 mL of 0.02M Ia (D-configuration, R ₁ =H or 2-thienyl, R ₂ =R ₃ =PhCOO) THF solution with 0.1 mL of 0.02M (1S,2S)-2-amino-1 , 2-diphenylethylenediamine, THF, and diluted with water to 2 mL to obtain a suspension. Prepare 2 parts of such suspensions. One part of the suspension is not placed. At this time, it is a non-porous nano-hollow sphere. Add naproxen directly and stir for 2 hours; the other part is left at room temperature for 4 days to transform into a single-hole nano-sphere. After hollowing out the spheres, add naproxen and stir for 2 hours. Fluorescence analysis was performed on the supernatants after centrifugation of the two samples, and it was found that the hollow nanospheres with holes were loaded with more than 50% more naproxen than the hollow nanospheres without holes.

Claims (4)

1. organic molecule acid and alkali double component self assembly prepares the method for porose nano-hollow ball, may further comprise the steps:

Step (a): in the organic molecule acid constituents and the water-soluble solubleness organic solvent of organic molecule alkaline constituents difference with organic molecule acid and alkali double component self-assembly system; The solution concentration scope is 0.1mM-10000mM; Acid constituents that obtains and the mixing of alkaline constituents solution are obtained mixed liquor, and the mol ratio of acid constituents and alkaline constituents is 0.1:1-10:1 in the mixed liquor;

Described organic molecule alkaline constituents is a 2-amino-1,2-diphenyl ethanol, 1,2-diphenyl-1, the sweet amine alcohol of 2-diaminoethanes or phenyl;

Described water-miscible organic solvent is ethanol, oxolane, dioxane, acetone, acetonitrile or N, dinethylformamide;

The organic molecule acid constituents of described organic molecule acid and alkali double component self-assembly system has structure shown in the formula (I):

In the formula,

R ₁Be H, thienyl, phenyl, naphthyl, phenylacetylene base, styryl;

R ₂, R ₃Identical or different, represent benzoyloxy, naphthalene formyloxy, acetoxyl group, hydroxyl, H respectively; Or be expressed as 1 or 2 π keys jointly;

And then carry out following steps (b) or step (c):

Step (b): with the mixed liquor dilute with water that step (a) obtains, the volume ratio that makes organic solvent and water is 0.001:1-1000:1, promptly obtains the single hole nano-hollow ball after 1-4 days in the room temperature held;

Step (c): with mixed liquor slow thin up under stirring that step (a) obtains, the volume ratio that makes organic solvent and water is 0.001:1-1000:1, promptly obtains the single hole nano-hollow ball.

2. preparation according to claim 1 contains the method for the organic nano hollow ball of hole, it is characterized in that, in formula (I)

Work as R ₁During=H, R ₂=OCOPh, R ₃=OCOPh;

Or

Work as R ₁During=2-thienyl, R ₂=OCOPh, R ₃=OCOPh;

Or

Work as R ₁During=phenylacetylene base, R ₂=OCOPh, R ₃=OCOPh;

Or

Work as R ₁During=H, R ₂=OH, R ₃=OH or R ₁=R ₂=R ₃=H;

Or

R ₁=H, R ₂And R ₃Common is the π key.

3. preparation according to claim 1 and 2 contains the method for the organic nano hollow ball of hole; It is characterized in that the organic molecule acid constituents in the described organic molecule acid and alkali double component self-assembly system is pure enantiomter, racemic modification, mesomer or various mixture of isomers.

4. preparation according to claim 1 contains the method for the organic nano hollow ball of hole; It is characterized in that; Described organic molecule alkaline constituents is a kind of pure enantiomter, racemic modification, mesomer or various mixture of isomers of organic amine, also can be the mixture of variety classes organic amine.

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