CN104888225B - A kind of nano vesicle of covalent cross-linking and preparation method thereof - Google Patents

Abstract

A kind of covalently cross-linked nanovesicles, whose construction unit is based on sulfonated calix[4]arene, and triacetylene cationic surfactant as the guest, constructs a supramolecular assembly through host-guest interaction, and then builds a supramolecular assembly with A water-soluble azide compound cross-links the above-mentioned assembly to construct a covalently cross-linked nanovesicle; the preparation method is: 1) dissolving sulfonated calix[4]arene and a triynyl cationic surfactant in water and uniformly mixing to obtain a supramolecular Vesicle solution; 2) adding water-soluble azide compound, CuCl ₂ and sodium ascorbate to react at room temperature, passing the reacted cross-linked vesicle solution through a size exclusion column to obtain the target product. The advantages of the present invention are: the preparation method is simple, efficient, and low in cost; the prepared cross-linked nanovesicles have good stability, can realize depolymerization under the condition of HIO ₄ , thereby releasing the entrapped objects, and can stably protect the entrapped objects , which has broad application prospects in the protection of easily oxidized drugs and dyes prone to photobleaching.

Description

A kind of covalently cross-linked nanovesicle and its preparation method

【Technical field】

The invention belongs to the technical field of nano-supramolecular materials, in particular to a covalently cross-linked nano-vesicle and a preparation method thereof.

【Background technique】

Vesicles are ubiquitous building blocks in living organisms and are widely used in the fields of biology, chemistry, and materials science [(1) X. Zhang, S. Rehm, M. M. Safont-Sempere and F. Würthner, Nat. Chem., 2009, 1, 623-629; (2) A. Mueller and D.F.O`Brien, Chem. Rev., 2002, 102, 727-757; (3) D.M. Vriezema, M.C. Aragonès, J.A.A.W. Elemans, J.J.L.M. Cornelissen, A.E. Rowan and R.J.M. Nolte, Chem. Rev., 2005, 105, 1445-1489.]. In the past forty years, artificial vesicles have received extensive attention due to their structural diversity.

However, due to the influence of packing parameters, assembly conditions and other factors, not all surfactants can self-assemble into vesicles (N. Sakai, S. Matile. Nature Chem. 2009, 1, 599-600.). Liu Yu's research group first proposed the concept of calixarene-induced aggregation, and successfully constructed many calixarene-based binary supramolecular vesicles [(1) D.-S.Gou, Y.Liu, Acc.Chem .Res.2014,47,1925–1934; (2) D.-S.Guo, K.Wang, Y.-X.Wang, and Y.Liu, J.Am.Chem.Soc.,2012,134, 10244-10250; (3) K. Wang, D.-S. Guo, X. Wang, and Y. Liu, ACS Nano, 2011, 5, 2880–2894; (4) K. Wang, D.-S. Guo , and Y. Liu, Chem. Eur. J., 2010, 16, 8006-8011].

Vesicles constructed by supramolecular methods avoid complex chemical synthesis, but the resulting assemblies are often less stable than covalently synthesized vesicles. The "click" chemical reaction between terminal alkynes and azides has been effectively used to synthesize stable carbon nanotubes, covalent micelles, and other functional materials [(1) H.Li, F.Cheng, A.M.Duft, A. Adronov, J. Am. Chem. Soc., 2005, 127, 14518–14524; (2) S. Zhang, Y. Zhao, Macromolecules 2010, 43, 4020–4022; (3) H.-Q. Peng, Y .-Z. Chen, Y. Zhao, Q.-Z. Yang, L.-Z. Wu, C.-H. Tung, L.-P. Zhang, and Q.-X. Tong, Angew. Chem. Int. Ed. 2012, 51, 2088–2092]. The combination of supramolecular construction method and "click" chemical reaction can achieve the purpose of fast and simple construction of stable vesicles.

【Content of invention】

The purpose of the present invention is to provide a covalently cross-linked nanovesicle and its preparation method in view of the above-mentioned technical analysis and existing problems. The covalently cross-linked vesicles assembled by the supramolecules of the active agent are cross-linked by a water-soluble azide cross-linking agent, have good stability, and can depolymerize and release the encapsulated substance in the presence of periodic acid (HIO ₄ ); and the preparation The method is simple and efficient, and the amount of raw materials such as host, guest and cross-linking agent is small.

Technical scheme of the present invention:

A covalently cross-linked nanovesicle, the building block of which is based on sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) as the guest, constructs a superstructure through host-guest interaction. Molecular assembly, and then use water-soluble azide compound (WA) to cross-link the above-mentioned assembly to construct covalently cross-linked nanovesicles. The structure of the above-mentioned building unit is as follows:

A method for preparing the covalently cross-linked vesicles, the steps are as follows:

1) Dissolve sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) in water, sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) in Concentrations in water were 0.01mmol/L and 0.04mmol/L, and the supramolecular vesicle solution was obtained after uniform mixing;

2) Add cross-linking agent water-soluble azide compound (WA), catalyst CuCl and reducing agent _sodium ascorbate (SA) to the above-mentioned supramolecular vesicle solution to obtain a mixed solution, and the cross-linking agent water-soluble azide compound in the mixed solution (WA), the concentration of catalyst CuCl ₂ and reducing agent sodium ascorbate (SA) were 0.06mmol/L, 0.002mmol/L and 0.02mmol/L respectively, and the mixed solution was reacted at room temperature for 24h, and the cross-linked capsule after the reaction was The bubble solution was passed through a size exclusion column G50 column to prepare covalently cross-linked nanovesicles.

The covalently cross-linked vesicles are based on nanovesicles assembled by sulfonated calix[4]arenes and triacetylene cationic surfactants. In the presence of water-soluble cross-linking agents and reaction catalysts, supramolecular vesicles based covalently cross-linked vesicles. Compared with non-crosslinked nanovesicles, it has the advantage of being more stable, and at the same time, in the presence of HIO ₄ , crosslinked nanovesicles can also depolymerize, thereby releasing the entrapped substance.

The advantages of the present invention are: the covalently cross-linked vesicles are assembled based on sulfonated calix[4]arene and triynyl cationic surfactant supramolecularly and cross-linked by a water-soluble azide cross-linking agent, the preparation method is simple and efficient, The amount of raw materials such as host, guest and cross-linking agent is small; the cross-linked nanovesicles have good stability, and can be depolymerized in the presence of periodic acid to release the encapsulated substances; the cross-linked nanovesicles can stably protect It has broad application prospects in the protection of easily oxidized drugs and dyes prone to photobleaching.

【Description of drawings】

Figure 1 is a schematic diagram of the construction process of the covalently cross-linked nanovesicles.

Fig. 2 is a graph showing the critical aggregation concentration of triynyl cationic surfactants in the presence of sulfonated calix[4]arene.

Fig. 3 is a dynamic light scattering diagram of supramolecular nanovesicles assembled with sulfonated calix[4]arene and triacetylene cationic surfactant supramolecularly.

Fig. 4 is a high-resolution transmission electron microscope image of supramolecular nanovesicles assembled by sulfonated calix[4]arene and triynyl cationic surfactant supramolecularly.

Fig. 5 is a UV absorption spectrum change graph of covalently cross-linked vesicles constructed by hydroxysafflower yellow A (HSYA)-loaded sulfonated calix[4]arene and triynyl cationic surfactant.

Figure 6 shows the oxidative depolymerization of hydroxysafflower yellow A (HSYA)-supported sulfonated calix[4]arenes and triacetylene cationic surfactants to construct covalently cross-linked vesicles with HIO ₄ and without HIO ₄ The ultraviolet absorption spectrum at 402nm of the agent changes with the dialysis time.

Fig. 7 is a diagram showing the change of UV absorption spectrum at 402nm of covalently cross-linked vesicles constructed by sulfonated calix[4]arene loaded with hydroxysafflower yellow A (HSYA) and triacetylene cationic surfactant with dialysis time.

【detailed description】

Example:

A covalently cross-linked nanovesicle, the building block of which is based on sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) as the guest, constructs a superstructure through host-guest interaction. Molecular assembly, and then use water-soluble azide compound (WA) to cross-link the above-mentioned assembly to construct covalently cross-linked nanovesicles. The structure of the above-mentioned building unit is as follows:

Its preparation method steps are as follows:

1) Dissolve sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) in water, sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) in The concentrations in water were 0.01mmol/L and 0.04mmol/L respectively, and the supramolecular vesicle solution was obtained after uniform mixing. The construction process of the non-covalent supramolecular vesicles is shown in Figure 1;

2) Add cross-linking agent water-soluble azide compound (WA), catalyst CuCl and reducing agent _sodium ascorbate (SA) to the above-mentioned supramolecular vesicle solution to obtain a mixed solution, and the cross-linking agent water-soluble azide compound in the mixed solution (WA), the concentration of catalyst CuCl ₂ and reducing agent sodium ascorbate (SA) were 0.06mmol/L, 0.002mmol/L and 0.02mmol/L respectively, and the mixed solution was reacted at room temperature for 24h, and the cross-linked capsule after the reaction was The bubble solution was passed through a size exclusion column G50 column to prepare covalently cross-linked nanovesicles.

Detection and analysis of the covalently cross-linked nanovesicles:

1) The particle size and morphology of the covalently cross-linked nanovesicles

Firstly, the critical aggregation concentration of the supramolecular assembly in the solution is determined by measuring the light transmittance of the solution. Figure 2 shows the critical aggregation concentration diagram of the triacetylene cationic surfactant under the condition of sulfonated calix[4]arene, as shown in the figure The critical aggregation concentration is 0.013mmol/L. That is to say, when the concentration of immobilized SC4A is 0.01mmol/L, when the concentration of TPA is greater than 0.013mmol/L, there will be obvious aggregates. Therefore, when we construct supramolecular vesicles, the concentrations of host and guest are respectively 0.01mmol/L, 0.04mmol/L, which is the isoelectric point of the system, was tested. Then it was characterized by dynamic light scattering and high-resolution transmission electron microscopy: Figure 3 is the dynamic light scattering diagram of the supramolecular nanovesicles assembled by sulfonated calix[4]arene and triynyl cationic surfactant supramolecular, as shown in As shown, the particle size distribution of nanoparticles is very uniform, which is 229nm; Figure 4 shows the covalent nanovesicles assembled and cross-linked by sulfonated calix[4]arene and triynyl cationic surfactant supramolecular high-resolution transmission electron Microscope image demonstrating cross-linked vesicles as spherical hollow particles in solution.

2) Loading experiment verification of the covalently cross-linked nanovesicles

Fig. 5 is a covalently cross-linked vesicle UV absorption spectrum change graph of sulfonated calix[4]arene loaded with hydroxysafflower yellow A (HSYA) and a triacetylene cationic surfactant. The specific implementation method is as follows:

Dissolve sulfonated calix[4]arene (SC4A), hydroxysafflower yellow A (HSYA), and triacetylene cationic surfactant (TPA) in water in sequence, and mix thoroughly and uniformly to obtain hydroxysafflower yellow A (HSYA ) loaded supramolecular vesicle solution of sulfonated calix[4]arene and triynyl cationic surfactant, add water-soluble azide compound (WA), CuCl ₂ and sodium ascorbate (SA) to the solution, room temperature React for 24 hours to obtain a crude solution of covalently cross-linked vesicles, and then pass the solution through a size exclusion column (G50 column) to collect a solution with a nanometer particle size, which is pure hydroxysafflower yellow A (HSYA) Loaded covalently cross-linked vesicle solution, in which the concentrations of HSYA, TPA, WA, CuCl ₂ and SA are 0.01mmol/L, 0.04mmol/L, 0.06mmol/L, 0.002mmol/L, 0.02mmol/L .

As shown in Figure 5, the successful loading of hydroxysafflor yellow A by the covalently cross-linked vesicles was confirmed by the change of UV absorption spectrum.

3) Experimental verification of the loading stability of the covalently cross-linked nanovesicles:

Figure 6 shows the oxidative depolymerization of hydroxysafflower yellow A (HSYA)-supported sulfonated calix[4]arenes and triacetylene cationic surfactants to construct covalently cross-linked vesicles with HIO ₄ and without HIO ₄ The ultraviolet absorption spectrum at 402nm of the agent changes with the dialysis time. 402nm is the characteristic absorption peak of hydroxysafflor yellow A. The information on the stability of the cross-linked vesicle loading can be obtained by detecting the change of the ultraviolet absorption at this place with the dialysis time. As shown in Figure 6, when 10 times the cross-linking dose of HIO ₄ is added to the cross-linked nanovesicles, the structure of the covalently cross-linked vesicles can be destroyed, and the encapsulated substances can be released. After dialysis for 60 minutes, the depolymerized covalent vesicles can be observed The vesicles had released more than 30% of the loaded material, while the undamaged covalently cross-linked vesicles released only 10% of the loaded material, demonstrating the loading stability of the covalently cross-linked nanovesicles. Figure 7 is a graph of the UV absorption spectrum at 402nm of covalently crosslinked vesicles constructed by hydroxysafflower yellow A (HSYA)-loaded sulfonated calix[4]arenes and triacetylene cationic surfactants as a function of dialysis time, as shown in FIG. As shown in Fig. 240 min of dialysis, the release of the cross-linked nanovesicles to the entrapped substance reached 30%, which also proved the loading stability of the covalently cross-linked nanovesicles.

Claims (2)

1. A covalently cross-linked nanovesicle, characterized in that: the building block is based on sulfonated calix [4] arene (SC4A), and the triacetylenic cationic surfactant (TPA) is the object, through the host- The guest-guest interaction constructs supramolecular assemblies, and then cross-links the above-mentioned assemblies with water-soluble azide compounds (WA) to construct covalently cross-linked nanovesicles. The structure of the above-mentioned building units is as follows: 2. A method for preparing covalently cross-linked nanovesicles as claimed in claim 1, characterized in that the steps are as follows: 1) Dissolve sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) in water, sulfonated calix[4]arene (SC4A) and triacetylene cationic surfactant (TPA) in Concentrations in water were 0.01mmol/L and 0.04mmol/L, and the supramolecular vesicle solution was obtained after uniform mixing; 2) Add cross-linking agent water-soluble azide compound (WA), catalyst CuCl and reducing agent _sodium ascorbate (SA) to the above-mentioned supramolecular vesicle solution to obtain a mixed solution, and the cross-linking agent water-soluble azide compound in the mixed solution (WA), the concentration of catalyst CuCl ₂ and reducing agent sodium ascorbate (SA) were 0.06mmol/L, 0.002mmol/L and 0.02mmol/L respectively, and the mixed solution was reacted at room temperature for 24h, and the cross-linked capsule after the reaction was The bubble solution was passed through a size exclusion column G50 column to prepare covalently cross-linked nanovesicles.