CN102516606A - Preparation method of nitrogen oxide donor - quantum dots compound - Google Patents
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- CN102516606A CN102516606A CN2011103832716A CN201110383271A CN102516606A CN 102516606 A CN102516606 A CN 102516606A CN 2011103832716 A CN2011103832716 A CN 2011103832716A CN 201110383271 A CN201110383271 A CN 201110383271A CN 102516606 A CN102516606 A CN 102516606A
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Abstract
The invention relates to a nitrogen oxide donor-quantum dots compound and a preparation method thereof. The preparation method comprises the following steps that: chitosan or chitosan derivative with certain deacelation degree is dissolved in the water, metal salt solution and chalcogenide solution with appropriate quantity are sequentially added into the chitosan or the chitosan derivative solution under a room-temperature stirring condition, a compound of chitosan or the chitosan derivative and quantum dots is obtained by heating and backflowing, dialyzing, evaporating and drying the mixture solution, and then the compound is reacted with nitrogen oxide under a pressurizing condition to prepare a nitrogen oxide donor. Compared with the prior art, chitosan is adopted as a carrier for releasing the nitrogen oxide, quantum dots are adopted as a fluorescent probe for detecting the release of the nitrogen oxide, the nitrogen oxide can be stably released under the phycological environment, a function on detecting the release of the nitrogen oxide can be realized, the biocompatibility is good, no physiological toxicity exists, and a promising prospect can be realized on the diagnosis and treatment aspects of hypertension, heat diseases, respiratory diseases, sexual disorder and the like.
Description
Technical field
The invention belongs to the crossing domain of chemistry, biological and material, especially relate to and a kind ofly have the release nitrogen protoxide and survey nitric oxide donors of its release conditions function and preparation method thereof.
Background technology
Nitrogen protoxide (NO) is very important biological messenger molecule, and nitric oxide production shortage can cause dysfunction of organ, causes hypertension, heart trouble, respiratory system disease etc.Lack the various diseases that causes in order to treat nitrogen protoxide; People have designed and synthesized a variety of nitric oxide donors, and wherein nucleophilic nitric oxide donors diazeniumdiolate is nitric oxide donors-quantum dot mixture that a kind of in-situ investigation nitrogen protoxide of a kind of excellent property of growing up in recent years discharges.This type nucleophilic nitric oxide donors generally is that nucleophilic compound that contains secondary amine group and nitric oxide gas are made in the reaction of the molten thorn of polarity mesohigh, can be with the spontaneous release nitric oxide donors of different speed under physiological condition.In nucleophilic nitric oxide donors material, chitosan and verivate thereof receive much concern owing to its excellent biological compatibility and characteristics such as biodegradability and low cytotoxicity.There are some researches show that chitosan can stably discharge nitrogen protoxide as a kind of nucleophilic nitric oxide donors material under physiological environment.Semiconductor fluorescence quantum dot (QD) has the exciting light spectrum width, emmission spectrum is narrow, but advantage such as emission wavelength accuracy controlling, photochemical stability be good.Compare with traditional optical dye, quantum dot has special advantages at aspects such as fluorescent probe, biomarker, medicals diagnosis on disease.Singularity on the chitosan structure makes it to have effects such as complexing, absorption and IX with many ions, organism, biomolecules etc.Utilize chitosan and verivate thereof to combine, it is carried out modification to improve stability and the biocompatibility existing patent report (Chinese patent CN 101962450A, CN 1831080A) of quantum dot as fluorescent probe with quantum dot.
Though existing nitric oxide donors can stably discharge nitrogen protoxide, also has better biocompatibility, can't survey nitric oxide production release conditions.Realize the nitric oxide production fluorescence detection of discharge, must use fluorescent probe simultaneously, so just increased the difficulty of operation, and be unfavorable for the reduction of cost.Therefore, how to prepare and can stablize the release nitrogen protoxide, can realize fluorescence detection that nitrogen protoxide is discharged again, and the nitric oxide donors with good biocompatibility being a problem highly significant, also is the key technical problem that needs to be resolved hurrily.
Do not see as yet at present chitosan or chitosan derivatives are combined the mixture of formation and the related patent U.S. Patent No. report of nitric oxide gas prepared in reaction nitric oxide donors with quantum dot.
Summary of the invention
The object of the invention is exactly to provide a kind of simple to operate for the defective that overcomes above-mentioned prior art existence; Cost is lower; Product can stably discharge nitrogen protoxide under physiological environment; And can survey nitric oxide production release conditions effectively, good biocompatibility is in the preparation method that the nitric oxide donors-quantum dot mixture of good prospects for application is arranged aspect the diagnosis of hypertension, heart trouble, respiratory system disease, sexual dysfunction etc. and the treatment.
The object of the invention can be realized through following technical scheme: the preparation method of nitric oxide donors-quantum dot mixture is characterized in that this method may further comprise the steps:
(1) at room temperature the certain amount of chitosan or derivatives thereof is dissolved in the deionized water, makes the chitosan or the chitosan derivatives aqueous solution that concentration is 2-12mg/ml;
(2) at the metal-salt precursor aqueous solution that in the chitosan that step (1) makes or the chitosan derivatives aqueous solution, adds 0.0002-0.01mol/L under stirring at room or the ultra-sonic oscillation condition; Stirred 6-15 hour, and obtained the metal ion complex solution of chitosan or chitosan derivatives;
(3) gained metal ion complex solution is placed reactor drum; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add chalcogenide solution; The mol ratio of the sulfur family element in metallic element in the metal ion complex and the chalcogenide solution is controlled at 1: 3-3: between 1, obtain the colloidal solution of homogeneous transparent;
(4) with above-mentioned colloidal solution under nitrogen protection and agitation condition; In 80-100 ℃ temperature refluxed 2-4 hour; Dialysed in deionized water 2-5 days with dialysis tubing in the cooling back fast; In Rotary Evaporators, concentrate then, obtain the mixture of stable chitosan or chitosan derivatives and quantum dot again through lyophilize;
(5) in 25-45 ℃ autoclave, the mixture of above-mentioned chitosan or chitosan derivatives and quantum dot is added in the absolute methanol solution of sodium methylate, the mass ratio of chitosan or chitosan derivatives and sodium methylate is controlled at 1: 1-1: 3; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 50-120psi, after stirring reaction 5-9 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Described chitosan or derivatives thereof is one or more in water-soluble chitosan with different deacetylations, CMS, the chitosan quaternary ammonium salt, and viscosity-average molecular weight is 2-80 ten thousand.
The deacetylation of described chitosan or derivatives thereof is 45%-60%.
Described metal-salt precursor is Cadmium chloride fine powder, cadmium acetate, zinc chloride or zinc acetate.
Described chalcogenide is sodium hydrogen selenide, sodium hydrogen telluride or sodium sulphite.
Described dialysis tubing is the dialysis tubing with molecular weight cut-off.
The speed of the described stirring at room of step (2) is 200-800r/min, and the speed of the described high-speed stirring of step (3) is 800-2000r/min, and the speed of the described stirring of step (4) is 100-500r/min.
The described quick cooling of step (4) be meant at the 1-10min internal cooling to room temperature.
The present invention is a template with the chitosan or derivatives thereof molecular chain of aqueous phase; Obtain the mixture of chitosan or derivatives thereof and fluorescence quantum through original position synthetic method, but the nitric oxide donors-quantum dot mixture that again this mixture is discharged with nitric oxide gas prepared in reaction in-situ investigation nitrogen protoxide under pressurized conditions.Quantum dot combines through complexing action with the chitosan or derivatives thereof, thereby the chitosan or derivatives thereof combines with nitrogen protoxide with nitrogen protoxide generation nucleophilic reaction through contained parahelium group.Preparing method of the present invention is simple to operate; Cost is lower; Product can stably discharge nitrogen protoxide under physiological environment; And can survey nitric oxide production release conditions effectively, good biocompatibility is having good prospects for application aspect the diagnosis of hypertension, heart trouble, respiratory system disease, sexual dysfunction etc. and the treatment.
Compared with prior art, the present invention has the following advantages and effect:
1. the preparation method is simple, and consumption of organic solvent is few;
2. the good biocompatibility of nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide for preparing discharges, stability is high, and the nitrogen protoxide releasing effect is good;
3. have the function that the fluorescence detection nitrogen protoxide discharges, fluorescence efficiency is high, and Effect on Detecting is good.
Description of drawings
Fig. 1 is the preparation process synoptic diagram of the nitric oxide donors-quantum dot mixture of in-situ investigation nitrogen protoxide release of the present invention;
Fig. 2 is the transmission electron microscope photo of the nitric oxide donors-quantum dot mixture of in-situ investigation nitrogen protoxide release of the present invention.
Embodiment
Below in conjunction with accompanying drawing and specific embodiment the present invention is elaborated.
Embodiment 1
As shown in Figure 1; The preparation process synoptic diagram of the nitric oxide donors-quantum dot mixture that discharges for in-situ investigation nitrogen protoxide of the present invention; At room temperature with molecular weight be 80,000, deacetylation is that 58% chitosan is dissolved in the deionized water, makes the chitosan aqueous solution that concentration is 3mg/ml; In this chitosan aqueous solution, adding concentration under the stirring at room condition is the Cadmium chloride fine powder aqueous solution of 0.005mol/L, stirs 8 hours, obtains the cadmium ion complex solution of chitosan; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add the aqueous solution that contains with the equimolar sodium hydrogen selenide of Cadmium chloride fine powder, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition; In 90 ℃ temperature refluxed 2.5 hours; Fast to use molecular weight cut-off be that 1.8 ten thousand dialysis tubing dialyse in deionized water 3 days in the cooling back, concentrated in Rotary Evaporators then, obtains the stable chitosan and the mixture of CdSe quantum dots through lyophilize again; In temperature is 40 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.5; The earlier logical nitrogen of autoclave is vacuumized again, feed nitric oxide gas then, keep pressure 80psi; Behind the stirring reaction 6 days; Blow away unreacted nitric oxide gas with nitrogen, product is filtered, in succession with anhydrous methanol and ether washing; Vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges, and the transmission electron microscope photo of this mixture is as shown in Figure 2.
Embodiment 2
At room temperature with molecular weight be 100,000, deacetylation is that 60% chitosan is dissolved in the deionized water, makes the chitosan aqueous solution that concentration is 3.5mg/ml; In this chitosan aqueous solution, adding concentration under the stirring at room condition is the cadmium acetate aqueous solution of 0.005mol/L, stirs 10 hours, obtains the cadmium ion complex solution of chitosan; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add the aqueous solution that contains with the equimolar sodium hydrogen telluride of cadmium acetate, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition; In 85 ℃ temperature refluxed 3 hours; Fast to use molecular weight cut-off be that 1.5 ten thousand dialysis tubing dialyse in deionized water 4 days in the cooling back, concentrated in Rotary Evaporators then, obtains the stable chitosan and the mixture of cadmium telluride quantum dot through lyophilize again; In temperature is 30 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.5; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 80psi, stirring reaction is after 8 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Embodiment 3
At room temperature with molecular weight be 50,000, deacetylation is that 60% chitosan is dissolved in the deionized water, makes the chitosan aqueous solution that concentration is 5mg/ml; In this chitosan aqueous solution, adding concentration under the stirring at room condition is the cadmium acetate aqueous solution of 0.0008mol/L, stirs 10 hours, obtains the cadmium ion complex solution of chitosan; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add the aqueous solution that contains with the equimolar sodium hydrogen telluride of cadmium acetate, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition; In 85 ℃ temperature refluxed 3 hours; Fast to use molecular weight cut-off be that 1.5 ten thousand dialysis tubing dialyse in deionized water 4 days in the cooling back, concentrated in Rotary Evaporators then, obtains the stable chitosan and the mixture of cadmium telluride quantum dot through lyophilize again; In temperature is 30 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.5; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 80psi, stirring reaction is after 7 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
At room temperature with molecular weight be 300,000, deacetylation is that 45% CMS is dissolved in the deionized water, making concentration is the carboxymethyl chitosan sugar aqueous solution of 5mg/ml; In this carboxymethyl chitosan sugar aqueous solution, adding concentration under the stirring at room condition is the cadmium acetate aqueous solution of 0.00lmol/L, stirs 8 hours, obtains the cadmium ion complex solution of CMS; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add the aqueous solution that contains with the equimolar sodium hydrogen telluride of cadmium acetate, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition; In 95 ℃ temperature refluxed 2 hours; Fast to use molecular weight cut-off be that 1.5 ten thousand dialysis tubing dialyse in deionized water 5 days in the cooling back, concentrated in Rotary Evaporators then, obtains the stable CMS and the mixture of cadmium telluride quantum dot through lyophilize again; In temperature is 25 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.2; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 90psi, stirring reaction is after 6 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Embodiment 5
At room temperature with molecular weight be 250,000, deacetylation is that 50% chitosan quaternary ammonium salt is dissolved in the deionized water, making concentration is the chitosan quaternary ammonium salt brine solution of 5mg/ml; In this chitosan quaternary ammonium salt brine solution, adding concentration under the stirring at room condition is the Cadmium chloride fine powder aqueous solution of 0.005mol/L, stirs 11 hours, obtains the cadmium ion complex solution of chitosan quaternary ammonium salt; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add the aqueous solution that contains with the equimolar sodium hydrogen selenide of Cadmium chloride fine powder, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition; In 85 ℃ temperature refluxed 3.5 hours; Fast to use molecular weight cut-off be that 1.2 ten thousand dialysis tubing dialyse in deionized water 5 days in the cooling back, concentrated in Rotary Evaporators then, obtains the stable chitosan quaternary ammonium salt and the mixture of CdSe quantum dots through lyophilize again; In temperature is 30 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.3; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 100psi, stirring reaction is after 5 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Embodiment 6
At room temperature with molecular weight be 420,000, deacetylation is that 50% chitosan quaternary ammonium salt is dissolved in the deionized water, making concentration is the chitosan quaternary ammonium salt brine solution of 4mg/ml; Under stirring at room (speed of stirring at room is 200r/min) condition, in this chitosan quaternary ammonium salt brine solution, adding concentration is the zinc acetate aqueous solution of 0.003mol/L, stirs 10 hours, obtains the zine ion complex solution of chitosan quaternary ammonium salt; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring (speed of high-speed stirring is 800r/min) condition, add the aqueous solution that contains with the equimolar sodium sulphite of zinc acetate, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition (speed of stirring is 100r/min); In 90 ℃ temperature refluxed 3 hours; Fast to use molecular weight cut-off be that 1.8 ten thousand dialysis tubing dialyse in deionized water 4 days in the cooling back, concentrated in Rotary Evaporators then, obtains the mixture of stable chitosan quaternary ammonium salt and zinc sulphide quantum dot again through lyophilize; In temperature is 25 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.6; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 100psi, stirring reaction is after 5 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Embodiment 7
At room temperature with molecular weight be 50,000, deacetylation is that 58% chitosan is dissolved in the deionized water, makes the chitosan aqueous solution that concentration is 2.5mg/ml; In this chitosan aqueous solution, adding concentration under the room temperature ultrasonic oscillating condition is the 0.001mol/L solder(ing)acid, stirs 12 hours, obtains the zine ion complex solution of chitosan; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add the aqueous solution that contains with the equimolar sodium sulphite of zinc chloride, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition; In 95 ℃ temperature refluxed 2 hours; Fast to use molecular weight cut-off be that 20,000 dialysis tubing dialyse in deionized water 3 days in the cooling back, concentrated in Rotary Evaporators then, obtains the mixture of stable chitosan and zinc sulphide quantum dot again through lyophilize; In temperature is 30 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.4; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 100psi, stirring reaction is after 5 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Embodiment 8
At room temperature with molecular weight be 120,000, deacetylation is that 60% chitosan is dissolved in the deionized water, makes the chitosan aqueous solution that concentration is 2.5mg/ml; In this chitosan aqueous solution, adding concentration under the room temperature ultrasonic oscillating condition is the zinc acetate aqueous solution of 0.005mol/L, stirs 9 hours, obtains the zine ion complex solution of chitosan; Gained solution is placed there-necked flask; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add the aqueous solution that contains with the equimolar sodium sulphite of zinc acetate, obtain the colloidal solution of homogeneous transparent, continue under nitrogen protection and agitation condition; In 85 ℃ temperature refluxed 4 hours; Fast to use molecular weight cut-off be that 1.5 ten thousand dialysis tubing dialyse in deionized water 4 days in the cooling back, concentrated in Rotary Evaporators then, obtains the mixture of stable chitosan and zinc sulphide quantum dot again through lyophilize; In temperature is 25 ℃ autoclave, above-mentioned mixture is added in the absolute methanol solution of sodium methylate, the mass ratio of mixture and sodium methylate was controlled at 1: 1.8; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 80psi, stirring reaction is after 10 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Embodiment 9
The preparation method of nitric oxide donors-quantum dot mixture, this method may further comprise the steps:
(1) at room temperature with viscosity-average molecular weight be 20,000, deacetylation is that 60% water-soluble chitosan is dissolved in the deionized water, makes the chitosan aqueous solution that concentration is 2mg/ml;
(2) at the Cadmium chloride fine powder aqueous solution that in the chitosan aqueous solution that step (1) makes, adds 0.0002mol/L under the stirring at room condition, stirred 6 hours, the speed of stirring at room is 800r/min, obtains the metal ion complex solution of chitosan;
(3) gained metal ion complex solution is placed reactor drum; Sealing and logical nitrogen protection; Under room temperature high-speed stirring (speed of high-speed stirring is 2000r/min) condition, add sodium hydrogen selenide solution; The mol ratio of the sulfur family element in cadmium element in the metal ion complex and the sodium hydrogen selenide solution is controlled between 1: 3, obtains the colloidal solution of homogeneous transparent;
(4) with above-mentioned colloidal solution under nitrogen protection and agitation condition (speed of stirring is 500r/min); In 80 ℃ temperature refluxed 2 hours; In deionized water, dialysed 2 days with dialysis tubing after 1min internal cooling to the room temperature with molecular weight cut-off; In Rotary Evaporators, concentrate then, obtain the stable chitosan and the mixture of quantum dot through lyophilize again;
(5) in 25 ℃ autoclave, the mixture of above-mentioned chitosan and quantum dot is added in the absolute methanol solution of sodium methylate, the mass ratio of chitosan and sodium methylate was controlled at 1: 1; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 50psi, stirring reaction is after 5 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Embodiment 10
The preparation method of nitric oxide donors-quantum dot mixture, this method may further comprise the steps:
(1) at room temperature with viscosity-average molecular weight be 800,000, deacetylation is that 60% chitosan quaternary ammonium salt is dissolved in the deionized water, making concentration is the chitosan quaternary ammonium salt brine solution of 12mg/ml;
(2) at the zinc acetate aqueous solution that in the chitosan quaternary ammonium salt brine solution that step (1) makes, adds 0.01mol/L under the ultra-sonic oscillation condition, stirred 15 hours, obtain the metal ion complex solution of chitosan quaternary ammonium salt;
(3) gained metal ion complex solution is placed reactor drum; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add sodium sulfide solution; The zinc element in the metal ion complex and the mol ratio of the sulfur family element in the sodium sulfide solution are controlled between 3: 1, obtain the colloidal solution of homogeneous transparent;
(4) with above-mentioned colloidal solution under nitrogen protection and agitation condition; In 100 ℃ temperature refluxed 4 hours; In deionized water, dialysed 5 days with dialysis tubing after 10min internal cooling to the room temperature with molecular weight cut-off; In Rotary Evaporators, concentrate then, obtain the stable chitosan quaternary ammonium salt and the mixture of quantum dot through lyophilize again;
(5) in 45 ℃ autoclave, the mixture of above-mentioned chitosan quaternary ammonium salt and quantum dot is added in the absolute methanol solution of sodium methylate, the mass ratio of chitosan quaternary ammonium salt and sodium methylate was controlled at 1: 3; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 120psi, stirring reaction is after 9 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
Claims (8)
1. the preparation method of nitric oxide donors-quantum dot mixture is characterized in that, this method may further comprise the steps:
(1) at room temperature the certain amount of chitosan or derivatives thereof is dissolved in the deionized water, makes the chitosan or the chitosan derivatives aqueous solution that concentration is 2-12mg/ml;
(2) at the metal-salt precursor aqueous solution that in the chitosan that step (1) makes or the chitosan derivatives aqueous solution, adds 0.0002-0.01mol/L under stirring at room or the ultra-sonic oscillation condition; Stirred 6-15 hour, and obtained the metal ion complex solution of chitosan or chitosan derivatives;
(3) gained metal ion complex solution is placed reactor drum; Sealing and logical nitrogen protection; Under room temperature high-speed stirring condition, add chalcogenide solution; The mol ratio of the sulfur family element in metallic element in the metal ion complex and the chalcogenide solution is controlled at 1: 3-3: between 1, obtain the colloidal solution of homogeneous transparent;
(4) with above-mentioned colloidal solution under nitrogen protection and agitation condition; In 80-100 ℃ temperature refluxed 2-4 hour; Dialysed in deionized water 2-5 days with dialysis tubing in the cooling back fast; In Rotary Evaporators, concentrate then, obtain the mixture of stable chitosan or chitosan derivatives and quantum dot again through lyophilize;
(5) in 25-45 ℃ autoclave, the mixture of above-mentioned chitosan or chitosan derivatives and quantum dot is added in the absolute methanol solution of sodium methylate, the mass ratio of chitosan or chitosan derivatives and sodium methylate is controlled at 1: 1-1: 3; The earlier logical nitrogen of autoclave is vacuumized again; Feed nitric oxide gas then, keep pressure 50-120psi, after stirring reaction 5-9 days; Blow away unreacted nitric oxide gas with nitrogen; Product is filtered, and with anhydrous methanol and ether washing, vacuum-drying at room temperature obtains nitric oxide donors-quantum dot mixture that the in-situ investigation nitrogen protoxide discharges in succession.
2. the preparation method of nitric oxide donors according to claim 1-quantum dot mixture; It is characterized in that; Described chitosan or derivatives thereof is one or more in water-soluble chitosan with different deacetylations, CMS, the chitosan quaternary ammonium salt, and viscosity-average molecular weight is 2-80 ten thousand.
3. the preparation method of nitric oxide donors according to claim 2-quantum dot mixture is characterized in that, the deacetylation of described chitosan or derivatives thereof is 45%-60%.
4. the preparation method of nitric oxide donors according to claim 1-quantum dot mixture is characterized in that, described metal-salt precursor is Cadmium chloride fine powder, cadmium acetate, zinc chloride or zinc acetate.
5. the preparation method of nitric oxide donors according to claim 1-quantum dot mixture is characterized in that, described chalcogenide is sodium hydrogen selenide, sodium hydrogen telluride or sodium sulphite.
6. the preparation method of nitric oxide donors according to claim 1-quantum dot mixture is characterized in that, described dialysis tubing is the dialysis tubing with molecular weight cut-off.
7. the preparation method of nitric oxide donors according to claim 1-quantum dot mixture; It is characterized in that; The speed of the described stirring at room of step (2) is 200-800r/min; The speed of the described high-speed stirring of step (3) is 800-2000r/min, and the speed of the described stirring of step (4) is 100-500r/min.
8. the preparation method of nitric oxide donors according to claim 1-quantum dot mixture is characterized in that, the described quick cooling of step (4) be meant at the 1-10min internal cooling to room temperature.
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| CN104449673A (en) * | 2014-11-25 | 2015-03-25 | 上海交通大学 | Preparation method of necklace-shaped nitric oxide fluorescent macromolecule probe |
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