CN108727605A - Hydrogen bond organic framework materials, preparation method and the application constructed based on condensed ring ligand - Google Patents
Hydrogen bond organic framework materials, preparation method and the application constructed based on condensed ring ligand Download PDFInfo
- Publication number
- CN108727605A CN108727605A CN201810220893.9A CN201810220893A CN108727605A CN 108727605 A CN108727605 A CN 108727605A CN 201810220893 A CN201810220893 A CN 201810220893A CN 108727605 A CN108727605 A CN 108727605A
- Authority
- CN
- China
- Prior art keywords
- condensed ring
- hydrogen bond
- organic framework
- ring ligand
- framework materials
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
- C08G83/008—Supramolecular polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention belongs to porous organic material fields, specifically disclose a kind of hydrogen bond organic framework materials, preparation method and application constructed based on condensed ring ligand.The material is constructed using condensed ring ligand as organic backbone using the synergistic effect of multiple hydrogen bonding and the π-π interaction forces of condensed ring ligand；The condensed ring ligand is selected from carboxylic more phenyl ring and is conjugated aromatic hydrocarbons, and the grain size of the material is 200 nanometers~50 microns.Such organic framework materials has the characteristics that high-specific surface area, permanent duct, high chemistry and thermal stability, the singlet oxygen that synthesis condition is mild, excellent generate ability, and the bright preparation method of material is simple, and operability is strong, can freely control the grain size of particle.The material has good bio-compatibility and lower bio-toxicity, after further compound anti-cancer medicine, has excellent composite chemical-photodynamic therapy ability, is demonstrated by out excellent treatment of cancer effect, cancer cell survival rate is low.
Description
Technical field
The invention belongs to porous organic material fields, are related to a kind of hydrogen bond organic frame material constructed based on condensed ring ligand
A kind of material, and in particular to hydrogen bond organic framework materials, preparation method and application constructed based on condensed ring ligand.
Background technology
Hydrogen bond organic framework materials (abbreviation HOFs), because it is with bigger serface, good recyclability and synthesis item
The mild feature of part shows excellent application prospect in fields such as gas storage/separation, proton conduction, but its stability is not
High characteristic limits the development of its application.
Cancer causes millions of people dead every year, increasing to the threat of human health.Chemotherapy is currently still most often
The cancer treatment method seen.However, the intrinsic limitation of chemotherapy, including bad side effect, undesirable pharmacokinetic
It learns and undesirable organism is distributed, these all force people to find compound therapy, such as chemistry-photodynamic therapy and change
- heat therapy, this has become the limitation for cracking single component, eliminates the available strategy for the treatment of of cancer.
Invention content
The present invention provides a kind of hydrogen bond organic framework materials constructed based on condensed ring ligand, the material use multiple hydrogen bonding and
The synergistic effect of the π-π interaction forces of condensed ring ligand, solves that previous hydrogen bond organic framework materials stability is poor, cannot keep
The problem of permanent duct, and make the material that there is very excellent chemically and thermally stability, and can be real in acidic environment
The reparation of existing crystalline state and specific surface area.
The hydrogen bond organic framework materials constructed based on condensed ring ligand are utilized using condensed ring ligand as organic backbone
Hydrogen bond organic framework materials made of the synergistic effect of the π-π interaction forces of multiple hydrogen bonding and condensed ring ligand is constructed.
According to the present invention, a kind of hydrogen bond organic framework materials, it includes condensed ring ligand, the condensed ring ligand is selected from optionally quilt
The aromatic compound for including conjugated structure of 1,2 or more carboxyl substitution, such as by 1,2,3,4,5,6,7,8,9,10
Or more carboxyl substitution the aromatic compound for including conjugated structure；Wherein, the aromatic compound for including conjugated structure
May include：Such as containing being conjugated the aromatic hydrocarbons formed by 2~60 phenyl ring；It is conjugated the heteroaryl sweetening treatment formed by 2~60 heteroaromatics
Close object；Or the heteroaryl sweetening treatment formed is conjugated by least one phenyl ring (such as 1~60) and at least one (such as 1~60) heteroaromatic
Close object；
Preferably, described 1~60 mean can be 1~60 in arbitrary integer, such as can be 1,2,3,4,5,6,7,
8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29 or 30；Described 2~60
Mean can be 2~60 in arbitrary integer, such as can be 2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,
17,18,19,20,21,22,23,24,25,26,27,28,29 or 30；
As example, the aromatic compound comprising conjugated structure can by 2~30, such as 2~10 (such as 2,
3,4,5,6,7,8,9 or 10) phenyl ring formed conjugation aromatic hydrocarbons, the example can be naphthalene, anthracene, Fu, pyrene, etc.；
The heteroaromatic can be containing 1,2,3,4 or 5 selected from nitrogen, oxygen, heteroatomic the 5 of sulphur, 6,7,8,9 or 10 yuan
Heteroaromatic；
The conjugation can be condensed or realized by way of chemical key connection；
Embodiment according to the present invention, the condensed ring ligand can be selected from the structure being shown below：
For example, the condensed ring ligand can be selected from Isosorbide-5-Nitrae-naphthalenedicarboxylic acid, 9,10- anthracenes dioctyl phthalate, 1,3,6,8- tetra- (to carboxyl
Phenyl) pyrene etc..
Wherein, the hydrogen bond organic framework materials, grain size are 200 nanometers~50 microns；Preferably, grain size 200
Nanometer~30 microns；It is highly preferred that its grain size is 200 nanometers~5 microns；According to exemplary embodiment of the subject disclosure, grain
Diameter can be 200 nanometers, 500 nanometers, 1 micron, 10 microns, 15 microns.
Embodiment according to the present invention, the hydrogen bond organic framework materials have using condensed ring ligand as organic backbone
Multi-pore channel structure.
According to exemplary embodiment of the subject disclosure, the specific surface area of the hydrogen bond organic framework materials is 1000~2400
Between meters squared per gram, such as between 2000~2200 meters squared per grams.
The present invention also provides the preparation method of above-mentioned hydrogen bond organic framework materials, this method includes：Using recrystallization method, to
Poor solvent is added in the solution of condensed ring ligand, through being sufficiently stirred, stand, centrifuge, clean, obtains constructing based on condensed ring ligand
Hydrogen bond organic framework materials.
Method produced according to the present invention, the solvent in the solution of the condensed ring ligand are the solvent that can dissolve condensed ring ligand,
Preferably good solvent, for example, can be in n,N-Dimethylformamide, n,N-dimethylacetamide, dimethyl sulfoxide at least one
Kind；
The solution concentration of the condensed ring ligand be less than condensed ring ligand saturated solution concentration, such as can be 2~10 milligrams/
Milliliter, such as 6.67 mg/mls.
The poor solvent can be methanol, ethyl alcohol, acetone, tetrahydrofuran, chloroform, deionized water, acetonitrile, 1,4-
At least one of dioxane, ethyl acetate；Preferably, the poor solvent is methanol, ethyl alcohol, acetone, deionized water, second
At least one of acetoacetic ester.
The volume ratio of the solution of the poor solvent and condensed ring ligand is 1:1 or more；Preferably, volume ratio can be (1~
8):1；According to exemplary embodiment of the subject disclosure, the volume ratio can be 4:1.
Method produced according to the present invention, it is described to stand to stand 3~48 hours at room temperature, it is preferable that it is small to stand 3~24
When；According to exemplary embodiment of the subject disclosure, 12 hours are stood；
The centrifugation is high speed centrifugation；Preferably, centrifugal rotational speed is between 10000~20000 revs/min；For example, with
12000 revs/min of speed centrifuges 3 minutes.
The present invention also provides the preparation method of the hydrogen bond organic framework materials of micro/nano level, this method includes：Using weight
Crystallisation is added poor solvent under stirring condition into the solution of condensed ring ligand and obtains micro/nano level after centrifugation, cleaning and be based on
The hydrogen bond organic framework materials that condensed ring ligand is constructed.
According to the present invention, the preparation method of the hydrogen bond organic framework materials of the micro/nano level, this method specifically includes：It adopts
With recrystallization method, deionized water or ethyl acetate is added under stirring condition into the solution of condensed ring ligand, when being kept stirring one section
Between after, add ethyl alcohol, high speed centrifugation, after being cleaned multiple times, obtaining the hydrogen bond that micro/nano level is constructed based on condensed ring ligand has machine frame
Frame material.
Method produced according to the present invention, the solvent in the solution of the condensed ring ligand are the solvent that can dissolve condensed ring ligand,
Preferably good solvent, for example, can be in n,N-Dimethylformamide, n,N-dimethylacetamide, dimethyl sulfoxide at least one
Kind；
The solution concentration of the condensed ring ligand be less than condensed ring ligand saturated solution concentration, such as can be 2~10 milligrams/
Milliliter, such as 6.67 mg/mls.
Method produced according to the present invention, solution, deionized water or the ethyl acetate of the condensed ring ligand, the volume ratio of ethyl alcohol
Can be 3~6:10~40:10~40；Such as can be 3:20:15~20；Illustratively, volume ratio can be 3:20:18,
3:20:16.66。
Described stirring a period of time is stirring 5~20 minutes；Such as it stirs 5 minutes, 10 minutes, 15 minutes；
The ultracentrifugal rotating speed is between 10000~20000 revs/min；Such as with 12000 revs/min of speed
Centrifuge 15min；
It is described to be cleaned multiple times to be cleaned 3~5 times with ethyl alcohol and acetone respectively；Such as first cleaned 4 times with ethyl alcohol, then use acetone
Cleaning 4 times.
The grain size of method produced according to the present invention, the micro/nano level material is 200 nanometers~10 microns.
A kind of pharmaceutical composition, including above-mentioned hydrogen bond organic framework materials and the drug for being carried on the material.
The present invention also provides the application of above-mentioned hydrogen bond organic framework materials in medicine preparation.Preferably, by anticarcinogen
Object is supported in material, realizes photodynamics-chemotherapy synergistic treatment.
Preferably, the drug is anticancer drug.
Preferably, the anticancer drug can be adriamycin, camptothecine, cis-platinum etc. or one kind in their derivative or
It is a variety of.
The present invention also provides a kind of regeneration methods of the hydrogen bond organic framework materials, including use at sour (such as concentrated hydrochloric acid)
Manage the hydrogen bond organic framework materials 12~60 hours, such as 24~48 hours.Preferably, the processing is to be soaked or dipped.
The beneficial effects of the invention are as follows：
The present invention obtains matching based on condensed ring using the synergistic effect of multiple hydrogen bonding and the π-π interaction forces of condensed ring ligand
The hydrogen bond organic framework materials that body is constructed, such organic framework materials have high-specific surface area, permanent duct, high chemistry steady with heat
It qualitative, the features such as synthesis condition is mild, excellent singlet oxygen generates ability, solves previous hydrogen bond organic framework materials and stablizes
Property is poor, cannot keep the problem of permanent duct.And the bright preparation method of material is simple, operability is strong, can freely control particle
Grain size, minimum can reach 200 nanometers.
The material has good bio-compatibility and lower bio-toxicity, after further compound anti-cancer medicine,
With excellent composite chemical-photodynamic therapy ability, it is excellent that the two coordinative role makes hydrogen bond organic framework materials show
Treatment of cancer effect, cancer cell survival rate is low.
Description of the drawings
Fig. 1 is the structural schematic diagram of hydrogen bond organic framework materials of the present invention, wherein：Hole in intermediate cylindrical representative structure
Road.
Fig. 2 is the molecular formula for the condensed ring ligand that can be used for preparing hydrogen bond organic backbone that the present invention enumerates.
Fig. 3 is the hydrogen bond organic framework materials and meter based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene prepared by embodiment 1
Calculate the XRD comparison diagrams that simulation obtains.
Fig. 4 be embodiment 1 prepare the hydrogen bond organic framework materials based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene
By the N of varying environment treated 77K2Absorption.
Fig. 5 be embodiment 1 prepare the hydrogen bond organic framework materials based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene
By varying environment treated XRD comparison diagrams.
Fig. 6 be embodiment 1 prepare the hydrogen bond organic framework materials based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene
The N of 77K after being repaired in treatment of different temperature and acidic environment2Absorption.
Fig. 7 be embodiment 1 prepare the hydrogen bond organic framework materials based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene
XRD comparison diagrams after treatment of different temperature.
Fig. 8, which is the various sizes of hydrogen bond based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene prepared by embodiment 3, machine frame
SEM figure (the scales in a of frame material：1 micron；Scale in b：300 nanometers；Scale in c and d：100 nanometers).
Fig. 9 is the SEM figures for the hydrogen bond organic framework materials that load prepared by embodiment 5 has adriamycin.
Figure 10 is the singlet oxygen generation detection figure of embodiment 1, embodiment 3,5 sample of embodiment.
Figure 11 is the vitro cytotoxicity test for the hydrogen bond organic framework materials that load prepared by embodiment 5 has adriamycin
Figure.
Figure 12 is that the cell in vitro photodynamics for the hydrogen bond organic framework materials that load prepared by embodiment 5 has adriamycin is treated
Imitate test chart.
Specific implementation mode
Material of the present invention and its preparation method and application is done further specifically below in conjunction with specific embodiment
It is bright.It should be appreciated that the following example is merely illustrative the ground description and interpretation present invention, and it is not necessarily to be construed as protecting the present invention
The limitation of range.In the range of all technologies realized based on the above of the present invention are encompassed by the present invention is directed to protect.
Unless otherwise indicated, the raw materials and reagents used in following embodiment are commercial goods, or can be by
It is prepared by perception method.
Part device information is as follows：
X-ray diffractometer：Rigaku Miniflex 600；
Full-automatic specific surface and lacunarity analysis instrument：The ASAP 2020 and ASAP 2460 of Merck & Co., Inc；
Scanning electron microscope：Japan Electronics JSM6700-F；
Ultraviolet-uisible spectrophotometer：Shimadzu UV-2550.
Embodiment 1 is based on the hydrogen bond organic framework materials of 1,3,6,8- tetra- (to carboxyl phenyl) pyrene
The preparation process of hydrogen bond organic framework materials based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene：
By 10 milligram 1,3,6,8- tetra- are dissolved in (to carboxyl phenyl) in 1.5 milliliters of n,N-Dimethylformamide, wait matching
It after body is completely dissolved, is added to solution in 6 milliliters of methanol solution, stirs 1 minute, sample is stood 12 at room temperature later
Hour.It is centrifuged 3 minutes with 12000 revs/min of speed, is continuously cleaned 3 times with acetone later, obtain being based on 1,3,6,8- tetra-
The hydrogen bond organic framework materials of (to carboxyl phenyl) pyrene.The material has high-specific surface area：According to Brunauuer-Emmett-
Teller formula are calculated as 2122 meters squared per grams, 1.7 nanometers of aperture.
After above each material proportion equivalent is expanded, the material can be still obtained.
Embodiment 2 is based on naphthalene, En, Fu, hydrogen bond organic framework materials
It is identical as embodiment based on naphthalene, En, Fu, the preparation process of hydrogen bond organic framework materials, raw material need to only be replaced
It is changed to particular compound shown in Fig. 2.
3 micro/nano level of embodiment is based on the hydrogen bond organic framework materials of 1,3,6,8- tetra- (to carboxyl phenyl) pyrene
Nanoscale is based on the preparation process of the hydrogen bond organic framework materials of 1,3,6,8- tetra- (to carboxyl phenyl) pyrene：By 10 millis
Gram 1,3,6,8- tetra- (to carboxyl phenyl) pyrenes are dissolved in 1.5 milliliters of n,N-Dimethylformamide, after waiting for that ligand is completely dissolved,
10 milliliters of deionized water is added to solution under 1000 revs/min of mixing speed, and is kept stirring 5 minutes.Add again later
Enter 9 milliliters of ethyl alcohol, and centrifuged 15 minutes with 12000 revs/min of speed, is continuously respectively cleaned 4 times, obtained with ethyl alcohol, acetone
The hydrogen bond organic framework materials based on pyrene that grain size is 200 nanometers (see Fig. 8 d).
By changing reaction time and the condition of synthesis, can obtain from micron order to the nano level hydrogen bond organic frame
Material：
According to 2 preparation method of embodiment, deionized water is changed into ethyl acetate, it is 10 microns based on 1,3 to obtain grain size,
The hydrogen bond organic framework materials (see Fig. 8 a) of 6,8- tetra- (to carboxyl phenyl) pyrene；
According to 2 preparation method of embodiment, after mixing time is extended for 15min, it is 1 micron based on 1,3 to obtain grain size,
The hydrogen bond organic framework materials (see Fig. 8 b) of 6,8- tetra- (to carboxyl phenyl) pyrene；
According to 2 preparation method of embodiment, after mixing time is extended for 10min, it is 500 nanometers based on 1 to obtain grain size,
The hydrogen bond organic framework materials (see Fig. 8 c) of 3,6,8- tetra- (to carboxyl phenyl) pyrene.
4 micro/nano level of embodiment is based on naphthalene, En, Fu, hydrogen bond organic framework materials
Nanoscale is same as Example 2 based on naphthalene, En, Fu, the preparation process of hydrogen bond organic framework materials, only need by
Raw material replaces with particular compound shown in Fig. 2, and amount of alcohol added replaces with 8.33 milliliters, you can it is 200 nanometers to obtain grain size
Based on naphthalene, En, Fu, etc. hydrogen bond organic framework materials.
It (such as uses the poor solvent of opposite low pole instead by the reaction time and condition of changing synthesis and extends the reaction time
Can obtain the material of relative diameter bigger), it can obtain from micron order to the nano level hydrogen bond organic framework materials.
Embodiment 5
Load has hydrogen bond organic framework materials of the nanoscale based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene of adriamycin
It prepares：
The hydrogen bond that the nanoscale that 5 milligrams of embodiments 2 are prepared is based on 1,3,6,8- tetra- (to carboxyl phenyl) pyrene is organic
Frame material is added in the aqueous solution of 2.5 milliliters of adriamycin, and the aqueous solution of adriamycin contains the dilute of 0.001 mol/L
Hydrochloric acid.It is later that the solution containing material is 2 minutes ultrasonic in ultrasonic machine, it is put into shaking table later and is shaken with 240 revs/min of speed
It is 1 hour dynamic, it is centrifuged 15 minutes with 12000 revs/min of speed, is continuously cleaned 2 times with acetone later, obtaining load has adriamycin
Nanoscale hydrogen bond organic framework materials.
As seen in Figure 9：It has loaded the hydrogen bond organic framework materials after adriamycin and has still maintained its basic pattern,
Illustrate that it has good stability.
The performance detection of the hydrogen bond organic framework materials prepared in 6 embodiment 1 of embodiment
Fig. 3 is the XRD comparison diagrams that hydrogen bond organic framework materials prepared by embodiment 1 are obtained with calculating simulation.
Test condition：Hydrogen bond organic framework materials drying prepared by embodiment 1, uses Rigaku under normal temperature condition
Miniflex 600 carries out the test of Powder XRD pattern, and it is compared with the XRD spectrum result that simulation obtains is computed
It is right.
Test result：Show that embodiment 1 prepares the XRD diffraction maximums of sample and is computed the result height that simulation obtains to intend
It closes.
Fig. 4 is the hydrogen bond organic framework materials that prepare of embodiment 1 through varying environment treated nitrogen adsorption figure.
Test condition：Acetone-exchanged is used before 1 sample test of embodiment 6 times, it is 8 hours every time, Celsius using 90 later
Degree vacuum drying 6 hours, then carries out 77K N2The test of absorption.
Test result：Show that 1 sample of embodiment impregnates in deionized water, concentrated hydrochloric acid, 0.1M dilute hydrochloric acid, methanol or acetone
117 days, or impregnated 10 days in boiling water, significant change does not occur for adsorption curve, illustrates that structure still maintains stable at this time,
The hydrogen bond organic framework materials have excellent chemistry and thermal stability.
Fig. 5 is the hydrogen bond organic framework materials that prepare of embodiment 1 through varying environment treated XRD spectrum.Test result
Show：Show that 1 sample of embodiment impregnates 117 days in deionized water, concentrated hydrochloric acid, 0.1M dilute hydrochloric acid, methanol or acetone, Huo Zhe
It is impregnated 10 days in boiling water, the XRD diffraction maximums of sample do not change, illustrate that sample structure still maintains stable.The hydrogen bond is organic
Frame material has excellent chemistry and thermal stability.
Fig. 6 is that hydrogen bond organic framework materials prepared by embodiment 1 are repaired in by treatment of different temperature and acidic environment
The N of 77K afterwards2Absorption figure.
Test condition：Hydrogen bond organic framework materials prepared by embodiment 1 are taken the photograph 90 degrees Celsius, 120 degrees Celsius, 150 respectively
Vacuum activating 6 hours under family name's degree, 180 degrees Celsius and 210 degrees celsius, later use Merck & Co., Inc ASAP2020 and
ASAP2460 adsorption instruments carry out the characterization of 77K nitrogen adsorptions.Later, by vacuum activating under 210 degrees celsius 6 hours should
Hydrogen bond organic framework materials take part to be impregnated 1 day using concentrated hydrochloric acid, and another part is prepared as the method that raw material uses embodiment 1
The regenerated hydrogen bond organic framework materials, and ASAP2020 the and ASAP2460 adsorption instruments for being used for Merck & Co., Inc respectively carry out
The characterization of 77K nitrogen adsorptions.
Test result：Show 1 sample of embodiment vacuum activating 6 hours under 90 degrees Celsius, 120 degrees celsius respectively,
Apparent variation does not occur for its adsorption curve, illustrates that it illustrates that sample structure still maintains stable.1 sample of embodiment exists respectively
150 degrees Celsius, 180 degrees Celsius, after 6 hours, the adsorbance of adsorption curve is substantially reduced vacuum activating under 210 degrees celsius,
Illustrate at such a temperature, material skeleton will appear certain variation, and the sample after high-temperature activation is impregnated 1 in concentrated hydrochloric acid later
It, adsorption curve has restored reset condition again, illustrates that it has restored original state in concentrated hydrochloric acid condition lower skeleton, has
Self-healing characteristic.Meanwhile preparing the hydrogen bond organic framework material, adsorption curve using the sample after high-temperature activation as raw material
It is almost the same with original adsorption curve, illustrate that the skeleton of the two is almost the same, illustrates the good reproducibility of the material.
Fig. 7 is the hydrogen bond organic framework materials of the preparation of embodiment 1 in the XRD spectrum after treatment of different temperature.Test
The result shows that：After being repaired in by high-temperature process or acidic environment, the Powder XRD pattern of the hydrogen bond organic framework materials
It is consistent with simulation Powder XRD pattern, illustrate that the material still remains good skeleton structure, crystal structure does not occur apparent
Phase transformation.
The singlet oxygen of the hydrogen bond organic framework materials prepared in 7 embodiment 1,3 and 5 of embodiment generates performance
Test condition：By 1.92 milligrams of 1 samples of embodiment, 3 sample of embodiment, 5 sample of embodiment, it is added separately to 15 millis
In the acetonitrile solution for rising 9, the 10- diphenylanthrancenes for 0.32 mg/ml for being oxygenated operation through 30 minutes, in the irradiation of xenon lamp
Under, test detection agent 9, the uv-vis spectra of 10- diphenylanthrancenes.
Test result：1 sample of embodiment, 3 sample of embodiment and 5 sample of embodiment all have excellent as seen in Figure 10
Good singlet oxygen generates rate, and is preferred with embodiment 3 and 5 properties of sample of embodiment, and 1 sample of embodiment takes second place.
The load prepared in 8 embodiment 5 of embodiment has the vitro cytotoxicity of the hydrogen bond organic framework materials of adriamycin to survey
Examination
Test condition：Hela cells 1640 medium cultures of Gibco RPMI, are inoculated in 96 holes and are incubated overnight, carefully
After born of the same parents' bed board 12h, 1 mcg/ml, 10 mcg/ml embodiment, 5 sample treatment are used respectively 24 hours, after removing treatment fluid,
It is tested again with MTT, control group is tested using 5 sample of Doxorubicin solution alternative embodiment of various concentration.
Test result：No light as seen in Figure 11 is not added under sample condition, and cell all has good work
Property, but after different samples is added, the cell survival rate that the experimental group of anticancer drugs, doxorubicin is added is decreased obviously, when
Doxorubicin concentration reach 10 mcg/mls when, the cell survival rate of experimental group only only has 10%, and in same concentration conditions
Under, the cell survival rate of the experimental group of 5 sample of 3 sample of embodiment and embodiment is significantly higher, and 5 sample of embodiment is especially added
The cell survival rate of experimental group can reach 75% under conditions of sample concentration reaches 10 mcg/ml, such experiment
As a result illustrate that 5 sample of embodiment has lower cytotoxicity.
The load prepared in 9 embodiment 5 of embodiment has the cell in vitro light power of the hydrogen bond organic framework materials of adriamycin
Learn curative effect test
Test condition：Hela cells 1640 medium cultures of Gibco RPMI, are inoculated in 96 holes and are incubated overnight, carefully
After born of the same parents' bed board 12 hours, use 1 mcg/ml, 10 mcg/mls, 20 mcg/ml embodiment, 5 sample treatment 24 small respectively
When, it is irradiated 30 minutes with 400 nanometer lasers after removing treatment fluid, then tested with MTT, control group uses the adriamycin of various concentration
Solution, unsupported 5 sample of material alternative embodiment are tested.
Test result：Different experiments group only has 65% under the illumination condition for being added without sample as seen in Figure 12
Cell survival rate, this is damage of the light to cell.And be added under illumination condition different samples can be found that be added it is identical
In the experimental group of concentration samples, be added 5 sample of embodiment experimental group compare be added 3 sample of embodiment experimental group it is thin
Born of the same parents' survival rate is substantially reduced, or even can be approached under conditions of sample addition concentration reaches 10 mcg/ml and only be added Ah mould
The experimental group of element, this illustrates that 5 sample of embodiment has good treatment of cancer effect.
More than, embodiments of the present invention are illustrated.But the present invention is not limited to the above embodiments.It is all
Within the spirit and principles in the present invention, any modification, equivalent substitution, improvement and etc. done should be included in the guarantor of the present invention
Within the scope of shield.
Claims (10)
1. a kind of hydrogen bond organic framework materials, it includes condensed ring ligand, the condensed ring ligand is selected from optionally by 1,2 or more
The aromatic compound for including conjugated structure of a carboxyl substitution, such as taken by 1,2,3,4,5,6,7,8,9,10 or more carboxyls
The aromatic compound for including conjugated structure in generation；Wherein, the aromatic compound comprising conjugated structure may include：Such as containing
It is conjugated the aromatic hydrocarbons formed by 2~60 phenyl ring；It is conjugated the heteroaryl aroma compounds formed by 2~60 heteroaromatics；Or by least one
Phenyl ring (such as 1~60) and at least one (such as 1~60) heteroaromatic are conjugated the heteroaryl aroma compounds to be formed；
The aromatic compound comprising conjugated structure can be by 2~30, such as 2~10 (such as 2,3,4,5,6,7,8,9
Or 10) phenyl ring formed conjugation aromatic hydrocarbons, the example can be naphthalene, anthracene, Fu, pyrene, etc.；
The conjugation can be condensed or realized by way of chemical key connection；
Preferably, the condensed ring ligand can be selected from the structure being shown below：
For example, the condensed ring ligand can be selected from Isosorbide-5-Nitrae-naphthalenedicarboxylic acid, 9,10- anthracenes dioctyl phthalate, 1,3,6,8- tetra- (to carboxyl benzene
Base) pyrene etc..
2. hydrogen bond organic framework materials according to claim 1, which is characterized in that the grain size of the material is 200 nanometers
~50 microns；Preferably, grain size is 200 nanometers~30 microns；It is highly preferred that its grain size is 200 nanometers~5 microns.
3. the preparation method of hydrogen bond organic framework materials according to claim 1 or 2, which is characterized in that this method includes：
Using recrystallization method, poor solvent is added into the solution of condensed ring ligand, through being sufficiently stirred, standing, centrifuge, clean, obtains base
In the hydrogen bond organic framework materials that condensed ring ligand is constructed.
4. preparation method according to claim 3, which is characterized in that the solvent in the solution of the condensed ring ligand is solvable
Solve the solvent of condensed ring ligand, preferably good solvent, for example, can be selected from n,N-Dimethylformamide, n,N-dimethylacetamide,
At least one of dimethyl sulfoxide；Preferably, the solution of the condensed ring ligand it is a concentration of less than condensed ring ligand saturated solution
Concentration.
5. preparation method according to claim 3 or 4, which is characterized in that the poor solvent can be selected from methanol, second
At least one of alcohol, acetone, tetrahydrofuran, chloroform, deionized water, acetonitrile, 1,4- dioxane, ethyl acetate；It is excellent
Selection of land, the poor solvent can be selected from least one of methanol, ethyl alcohol, acetone, deionized water, ethyl acetate；
The volume ratio of the solution of the poor solvent and condensed ring ligand is 1:1 or more；Preferably, volume ratio can be (1~8):
1。
6. according to claim 3~5 any one of them preparation method, which is characterized in that described to stand to stand 3 at room temperature
~48 hours, it is preferable that stand 3~24 hours；
The centrifugation is high speed centrifugation；Preferably, centrifugal rotational speed is between 10000~20000 revs/min.
7. the preparation method of hydrogen bond organic framework materials according to claim 1 or 2, which is characterized in that this method includes：
Using recrystallization method, poor solvent is added under stirring condition into the solution of condensed ring ligand and is obtained micro-nano after centrifugation, cleaning
The hydrogen bond organic framework materials that grade is constructed based on condensed ring ligand；
Preferably, the method includes：Using recrystallization method, deionized water is added into the solution of condensed ring ligand under stirring condition
Or ethyl acetate, continue to be kept stirring, add ethyl alcohol, high speed centrifugation after being cleaned multiple times, is obtained micro/nano level and matched based on condensed ring
The hydrogen bond organic framework materials that body is constructed.
8. preparation method according to claim 7, which is characterized in that
Solvent in the solution of the condensed ring ligand is the solvent that can dissolve condensed ring ligand, preferably good solvent, such as can be selected
From at least one of N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide；
The solution concentration of the condensed ring ligand is less than the concentration of condensed ring ligand saturated solution, such as can be 2~10 milligrams/milli
It rises；
Solution, deionized water or the ethyl acetate of the condensed ring ligand, the volume ratio of ethyl alcohol can be 3~6:10~40:10~
40；
It is stirring 5~20 minutes to continue the time being kept stirring；
The ultracentrifugal rotating speed is between 10000~20000 revs/min；
It is described to be cleaned multiple times to be cleaned 3~5 times with ethyl alcohol and acetone respectively；
The grain size of the micro/nano level material is 200 nanometers~10 microns.
9. a kind of pharmaceutical composition, including hydrogen bond organic framework materials as claimed in claim 1 or 2 and the medicine for being carried on the material
Object；
Preferably, the application of hydrogen bond organic framework materials as claimed in claim 1 or 2 in medicine preparation, the drug can be with
It is one or more in anticancer drug, such as adriamycin, camptothecine, cis-platinum etc. or their derivative.
10. the regeneration method of hydrogen bond organic framework materials described in claims 1 or 2, including use sour (such as concentrated hydrochloric acid) processing institute
State hydrogen bond organic framework materials 12 hours or more, such as 24~48 hours；
Preferably, the processing is to be soaked or dipped.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810220893.9A CN108727605B (en) | 2018-03-16 | 2018-03-16 | Hydrogen bond organic framework material constructed based on condensed ring ligand, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810220893.9A CN108727605B (en) | 2018-03-16 | 2018-03-16 | Hydrogen bond organic framework material constructed based on condensed ring ligand, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108727605A true CN108727605A (en) | 2018-11-02 |
| CN108727605B CN108727605B (en) | 2020-12-29 |
Family
ID=63940831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810220893.9A Active CN108727605B (en) | 2018-03-16 | 2018-03-16 | Hydrogen bond organic framework material constructed based on condensed ring ligand, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108727605B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110706936A (en) * | 2019-10-24 | 2020-01-17 | 陈丰 | Polypyrrole-phosphorus molybdenum oxide supercapacitor material and preparation method thereof |
| CN110790944A (en) * | 2019-11-14 | 2020-02-14 | 中国人民解放军国防科技大学 | Method for preparing zirconium metal organic framework nanotube |
| CN112920794A (en) * | 2021-02-05 | 2021-06-08 | 浙江师范大学 | Hydrogen bond organic framework composite luminescent material and preparation method thereof |
| CN113388127A (en) * | 2021-06-09 | 2021-09-14 | 上海大学 | Triphenylene group-containing hydrogen bond organic framework compound and preparation method thereof |
| CN114230804A (en) * | 2021-12-22 | 2022-03-25 | 云南大学 | Copper peroxide/hydrogen bond organic framework nano material, probe thereof and kit for detecting lipocalin-2 |
| CN114262444A (en) * | 2021-12-20 | 2022-04-01 | 中国科学院化学研究所 | Carbon dioxide-induced nanopore hydrogen bond organic framework material and preparation method and application thereof |
| CN114276552A (en) * | 2020-09-28 | 2022-04-05 | 中国科学院福建物质结构研究所 | Carboxylic acid monomer based anionic hydrogen bond organic frame material, preparation method and application thereof |
| WO2024082366A1 (en) * | 2022-10-18 | 2024-04-25 | 苏州科技大学 | Hydrogen bond organic framework nanocomposite material, and preparation method therefor and use thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902498A (en) * | 2016-06-03 | 2016-08-31 | 复旦大学 | Nano drug delivery system inhibiting multidrug resistance breast cancer growth and preparation method and application thereof |
-
2018
- 2018-03-16 CN CN201810220893.9A patent/CN108727605B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105902498A (en) * | 2016-06-03 | 2016-08-31 | 复旦大学 | Nano drug delivery system inhibiting multidrug resistance breast cancer growth and preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| ICHIRO HISAKI等: "Hexaazatriphenylene-Based Hydrogen-Bonded Organic Framework with Permanent Porosity and Single-Crystallinity", 《CHEMISTRY A EUROPEAN JOURNAL》 * |
| 董丽红等: "《两亲分子在纳米技术领域中的应用》", 31 October 2013, 吉林大学出版社 * |
| 赵临襄等: "《化学制药工艺学（第四版）》", 31 August 2015, 中国医药科技出版社 * |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110706936B (en) * | 2019-10-24 | 2021-05-14 | 绍兴市梓昂新材料有限公司 | Polypyrrole-phosphorus molybdenum oxide supercapacitor material and preparation method thereof |
| CN110706936A (en) * | 2019-10-24 | 2020-01-17 | 陈丰 | Polypyrrole-phosphorus molybdenum oxide supercapacitor material and preparation method thereof |
| CN110790944A (en) * | 2019-11-14 | 2020-02-14 | 中国人民解放军国防科技大学 | Method for preparing zirconium metal organic framework nanotube |
| CN114276552B (en) * | 2020-09-28 | 2023-03-28 | 中国科学院福建物质结构研究所 | Carboxylic acid monomer based anionic hydrogen bond organic frame material, preparation method and application thereof |
| CN114276552A (en) * | 2020-09-28 | 2022-04-05 | 中国科学院福建物质结构研究所 | Carboxylic acid monomer based anionic hydrogen bond organic frame material, preparation method and application thereof |
| CN112920794B (en) * | 2021-02-05 | 2022-08-23 | 浙江师范大学 | Hydrogen bond organic framework composite luminescent material and preparation method thereof |
| CN112920794A (en) * | 2021-02-05 | 2021-06-08 | 浙江师范大学 | Hydrogen bond organic framework composite luminescent material and preparation method thereof |
| CN113388127A (en) * | 2021-06-09 | 2021-09-14 | 上海大学 | Triphenylene group-containing hydrogen bond organic framework compound and preparation method thereof |
| CN114262444A (en) * | 2021-12-20 | 2022-04-01 | 中国科学院化学研究所 | Carbon dioxide-induced nanopore hydrogen bond organic framework material and preparation method and application thereof |
| CN114262444B (en) * | 2021-12-20 | 2022-08-30 | 中国科学院化学研究所 | Carbon dioxide-induced nanopore hydrogen bond organic framework material and preparation method and application thereof |
| CN114230804B (en) * | 2021-12-22 | 2022-08-30 | 云南大学 | Copper peroxide/hydrogen bond organic framework nano material, probe thereof and kit for detecting lipocalin-2 |
| CN114230804A (en) * | 2021-12-22 | 2022-03-25 | 云南大学 | Copper peroxide/hydrogen bond organic framework nano material, probe thereof and kit for detecting lipocalin-2 |
| WO2024082366A1 (en) * | 2022-10-18 | 2024-04-25 | 苏州科技大学 | Hydrogen bond organic framework nanocomposite material, and preparation method therefor and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108727605B (en) | 2020-12-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108727605A (en) | Hydrogen bond organic framework materials, preparation method and the application constructed based on condensed ring ligand | |
| Yang et al. | Green synthesis of β-cyclodextrin metal–organic frameworks and the adsorption of quercetin and emodin | |
| Zhao et al. | Uniform mesoporous carbon as a carrier for poorly water soluble drug and its cytotoxicity study | |
| Li et al. | Microwave-assisted synthesis of UIO-66 and its adsorption performance towards dyes | |
| Li et al. | Fabrication of a covalent organic framework and its gold nanoparticle hybrids as stable mimetic peroxidase for sensitive and selective colorimetric detection of mercury in water samples | |
| Ben et al. | Polymer‐Supported and Free‐Standing Metal–Organic Framework Membrane | |
| Hua et al. | Hierarchically porous organic cages | |
| CN107151329A (en) | The fast synthesis method of cyclodextrin-metal-organic framework materials | |
| Yu et al. | Porphyrin-based covalent organic framework coated stainless steel fiber for solid-phase microextraction of polycyclic aromatic hydrocarbons in water and soil samples | |
| Dong et al. | Modular design of solar-thermal nanofluidics for advanced desalination membranes | |
| CN110586052B (en) | Preparation and application of magnetic composite porous network adsorption material | |
| CN105879704A (en) | Preparation method and application of mixed matrix membrane containing zeolite imidazolate framework material | |
| Hamedi et al. | A γ-cyclodextrin-based metal–organic framework (γ-CD-MOF): A review of recent advances for drug delivery application | |
| Kim et al. | Surface coating of MOF layers on the nanocrystals of other MOFs using nanoparticle mediated nucleation for the efficient removal of formaldehyde | |
| CN110201652A (en) | A kind of preparation method of the Carbon Nanotubes/Chitosan hydrogel with three-dimensional net structure | |
| Zhou et al. | Magnetic amino-functionalized metal-organic frameworks as a novel solid support in ionic liquids-based effervescent tablets for efficient extraction of polycyclic aromatic hydrocarbons in milks | |
| Yang et al. | Investigating two distinct dummy templates molecularly imprinted polymers as paclitaxel adsorbent in synthesis system and releaser in biological samples | |
| Li et al. | Cannabidiol/hydroxypropyl-β-cyclodextrin inclusion complex: Structure analysis, release behavior, permeability, and bioactivity under in vitro digestion | |
| Perovic et al. | Mesoporous carbon materials with enantioselective surface obtained by nanocasting for selective adsorption of chiral molecules from solution and the gas phase | |
| Wang et al. | Polysiloxane assisted fabrication of chiral crystal sponge coated capillary column for chiral gas chromatographic separation | |
| Tan et al. | Design and synthesis of hollow Ce/Zr-UiO-66 nanoreactors for synergistic and efficient catalysis | |
| Zhao et al. | Hierarchical Porous Nanocellulose Aerogels Loaded with Metal–Organic Framework Particles for the Adsorption Application of Heterocyclic Aromatic Amines | |
| Liu et al. | Simple synthesis of magnetic porous organic cages for adsorption of triphenylmethane dyes in aquatic products | |
| Ghasemi et al. | Bacteria-templated ZIF-8 embedded in polyacrylonitrile nanofibers as a novel sorbent for thin film microextraction of benzoylurea insecticides | |
| Zhang et al. | Synthesis of a magnetic micelle molecularly imprinted polymers to selective adsorption of rutin from Sophora japonica |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |