CN108363901A - A kind of analogy method of pH response types block copolymer PAE-PEG loadings and release naphthalene molecule - Google Patents
A kind of analogy method of pH response types block copolymer PAE-PEG loadings and release naphthalene molecule Download PDFInfo
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- CN108363901A CN108363901A CN201810125755.2A CN201810125755A CN108363901A CN 108363901 A CN108363901 A CN 108363901A CN 201810125755 A CN201810125755 A CN 201810125755A CN 108363901 A CN108363901 A CN 108363901A
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Abstract
The invention discloses a kind of pH response types block copolymer PAE PEG to load the analogy method with release naphthalene molecule, it is the molecular model of method structure PAE PEG copolymers using Dissipative Particle Dynamics Simulation, naphthalene and water, to investigate under different pH environments PAE PEG copolymers to the loading and release behavior of naphthalene molecule.Then this method utilizes the methods of equilibrium configuration figure, radial distribution function to investigate influence of the pH value to PAE PEG polymer to naphthalene molecule loading and release behavior first by Materials Studio software building PEG PEA copolymer molecules, the mixed solution model of naphthalene molecule and hydrone.Analogy method of the present invention can explain that pH response type block copolymers load the behavioral mechanism with release naphthalene molecule from microcosmic angle, emulsified for efficient pH response types block copolymer PAE PEG and provide certain theoretical direction with the research being demulsified.
Description
Technical field
The present invention relates to the emulsifications of pH response type block copolymers and demulsification research field, and in particular to a kind of pH response types are embedding
Section copolymer p AE-PEG loads the analogy method with release naphthalene molecule.
Background technology
With the development of material science, the research and application of high molecular material are more and more extensive.Two or more knot
The copolymer of the structure polymer composition different from property, referred to as property block copolymer.It can design block copolymer as needed
Molecular weight, chemical constitution and composition.Since the different blocks of block copolymer have thermodynamics incompatibility, thus selecting
Structurally ordered clearly demarcated core-shell structure copolymer micella can be obtained by self assembly in property medium.The hydrophobic inner core of this kind of micella densification is used for
The loading of lyophobic dust, the solubility for the carrier that can be greatly improved.Hydrophilic outer shell layer as the protective layer between kernel and solution,
It avoids assembling mutually between micella, to the effect of playing stably, micella is enable to obtain longer cycle under various environmental conditions
Time.Polymer micelle is provided simultaneously with that grain size is small and surface area/volume ratio is big, the low and solubilized space of critical micelle concentration (CMC)
The advantages such as big.Therefore, because its excellent performance in a solvent, makes block copolymer can be used as a kind of efficient hydrophobicity delivering
Carrier tool is widely used in drug delivery system, gene therapy, mineralising template, the persuader etc. for manufacturing metallic colloid synthesis
Field.
The structure of amphipathic copolymer is transformed using pH sensitive groups to obtain the embedding short copolymer of pH response types.Due to
The type of pH sensitivities group is different, and pH response type copolymers are broadly divided into faintly acid polymer and alkalescent polymer two major classes.
The typical feature of pH response type copolymers is exactly to contain protonated group in polymer, and important parameter is pKa or pKb values.
Faintly acid polymer can protonate under the conditions of pH is less than its pKa value, can then be gone under the conditions of pH is higher than its pKa value
Protonation.And the protonated/deprotonated change of alkalescent polymer is then in contrast.Such as faintly acid polymer poly metering system
Sour (Poly (methacrylic acid), PMAA) contains carboxylic group, and receiving proton when pH is relatively low becomes hydrophobicity-
COOH provides proton in pH higher and becomes have hydrophilic-COO-；And alkalescent polymer such as polymethylacrylic acid diethyl
The property of base amine ethyl ester (po (N, N-diethylaminoethyl methacrylate), PDEA) is then just opposite.Therefore pH
Response type copolymer can change according to the acid condition of environment realizes that the loading of carrier is discharged with control, is usually used in loading drug point
Son increases its targeting to cancer cell, improves the transfer efficiency of drug and weakens the toxic side effect of drug, as delivering drug
The tool of molecule and be applied to medicinal chemistry arts.There is researcher using the technique study pH response type blocks of experiment at this stage
Copolymer loads hydrocarbon molecules and forms oil-in-water emulsion, and changing pH value makes release hydrocarbon point after copolymer pH group protons
Son makes water-oil phase detach.It is ground with the theory of release hydrocarbon molecule behavioral mechanism however, being loaded for pH response type block copolymers
Study carefully and is rarely reported.Therefore research pH response type block copolymers load the behavioral mechanism with release hydrocarbon molecules, for further investigation
The microstructure transformation and carrier releasing mechanism of the behavior of pH response type Self-Assembling of Block Copolymer, loading with release hydrocarbon molecules
Certain theoretical direction is provided, the research field of pH response type copolymers is made to be expanded to oilfield chemistry by medical chemistry.
Invention content
The purpose of the present invention is to provide a kind of pH response types block copolymer PAE-PEG to load the mould with release naphthalene molecule
Quasi- method, this method can explain that pH response type block copolymers load the behavioral mechanism with release naphthalene molecule from microcosmic angle,
It is emulsified for efficient pH response type polymers PAE-PEG and provides certain theoretical direction with the research being demulsified.
Its technical solution includes：
A kind of analogy method of copolymer p AE-PEG loadings and release naphthalene molecule, includes the following steps successively：
A builds initial model,
It is total using Bead Tpyes, the Mesomolecule tools builds PAE-PEG in Materials Studio softwares
Polymers molecule, naphthalene molecule, hydrone change-NH- and-NH in PAE-PEG strands+ 2Ratio simulating different pH
Value, and field of force distribution and preliminary optimization are carried out to each molecule；
Utilize Mesostructrue tools build model boxes；By copolymer molecule, naphthalene molecule, the water after preliminary optimization
Structure mixed solution model in model box is added in molecule at random；
B calculated equilibrium configurations,
It is excellent that Dissipative Particle Dynamics are carried out to the mixed solution model described in step a using Mesocite Tools modules
Change, then Dissipative Particle Dynamics Simulation is carried out to the model after optimization, obtains equilibrium configuration；
C comprehensive analysis,
According to the trail file of the equilibrium configuration obtained in step b, analysis model equilibrium configuration figure；Utilize Mesocite
The poly- β amino esters of Tools moulds Analysis tool analysis copolymer hydrophobic segment in the block, hydrophilic segment polyethylene glycol and naphthalene molecule
Radial distribution function, specific deployment analysis copolymer p AE-PEG loads the behavior with release naphthalene molecule.
Compared with prior art, the direct advantageous effects brought are above-mentioned technical proposal：
PAE-PEG copolymers are investigated with the method for simulation and load and discharge naphthalene molecule, need not expend a large amount of experiment material
Material and experimental facilities, reduce cost, save the time, have efficient advantage.
As a preferred solution of the present invention, above-mentioned copolymer is pH response type block copolymers.
Compared with prior art, the present invention provides a kind of pH response types PAE-PEG copolymers to load and release naphthalene molecule
Analogy method, it be Dissipative Particle Dynamics method change solution ph, to investigate PAE-PEG under different pH environments
Copolymer loads the behavior with release naphthalene molecule.First by building mixed solution model calculated equilibrium configuration, secondly using flat
The methods of configuration picture, radial distribution function investigation pH value that weighs load naphthalene molecule in PAE-PEG polymer the shadow with release behavior
It rings.
Analogy method calculating of the present invention is quick, easy to implement, and result of calculation is accurate, matches with experimental result；It can be more
The deficiency for mending laboratory facilities explains the mechanism that polymer and surfactant interact, HPAM- surface-actives from microcosmic angle
Agent compound system gas-liquid interface Quality Research provides certain theoretical direction.
Description of the drawings
The present invention will be further described below in conjunction with the accompanying drawings：
Fig. 1-Fig. 3 is poly- β amino esters-polyethylene glycol, naphthalene, molecular structure water formula and coarseness pearl criteria for classifying figure；
Fig. 4-Fig. 7 is poly- β amino esters-peg molecule initial configuration figure under different pH environments；
Fig. 8 is mixed solution (PAE-PEG, naphthalene, the H under different pH environment2O) initial configuration figure；
Fig. 9 is the radial distribution of hydrophobic segment (PAE), hydrophilic segment (PEG) and naphthalene molecule in mixed solution equilibrium configuration
Curve graph.
Specific implementation mode
The present invention proposes a kind of analogy method of pH response types block copolymer PAE-PEG loadings and release naphthalene molecule,
In order to keep advantages of the present invention, technical solution clearer, clear, the present invention is done specifically with reference to specific embodiment
It is bright.
The poly- β amino esters of main chemical-polyethylene glycol (PAE-PEG) and naphthalene selected by the present invention can pass through business
Channel is commercially available.
It is for pH response type block copolymers are poly- β amino esters-polyethylene glycol PAE-PEG by copolymer below, to this
Invention is described further.
Embodiment 1：
PH response type PAE-PEG copolymers load the analogy method with release naphthalene molecule, specifically include following steps：
Step 1, structure molecular structure,
According to the related experiment and theory literature of the poly- β amino esters-polyethylene glycol of pH response type copolymers, poly- β amino is obtained
Ester-polyethylene glycol, naphthalene, molecular structure water formula, according to molecule segment hydrophobe type to poly- β amino esters-polyethylene glycol, naphthalene, water
Molecular structural formula carries out coarseness pearl division, and poly- β amino esters-polyethylene glycol, naphthalene, molecular structure water formula and coarseness pearl are drawn
Minute mark standard is shown in Fig. 1, Fig. 2 and Fig. 3, n=9 in Fig. 1, and coarseness hydrone pearl includes 8 hydrones in m=1, Fig. 3；Secondly,
According to the coarseness pearl criteria for classifying, Bead Tpyes, Mesomolecule tools in Materials Studio softwares are utilized
PAE-PEG copolymer molecules, naphthalene molecule, hydrone are built ,-NH- (PAE) in poly- β amino esters-peg molecule chain is changed
With-NH2 +The ratio of (PAEH) carries out field of force distribution and preliminary optimization to simulate different pH value to each molecule.
Poly- β amino esters-peg molecule initial configuration is shown in Fig. 4, Fig. 5 under different pH environments, wherein pH=7 in Fig. 4
(PAE：PAEH=5：0), pH=5.0 (PAE in Fig. 5：PAEH=0：5)；
Step 2, structure initial model,
Utilize Mesostructrue Template module construction model boxes；Secondly, Mesostructrue modules are utilized
By after optimization poly- β amino esters-peg molecule, naphthalene molecule, hydrone is according to 8%：2%：90% concentration ratio is random
It is added in model box and builds mixed solution initial configuration, model box sizeEach coarseness pearl
Average quality is 432amu, and radius isPearl number density ρ=3 in box, truncation radius is between coarseness pearlMixed solution (PAE-PEG, naphthalene, H under different pH environment2O) initial configuration is shown in Fig. 6, AE-PEG points of copolymer p
Son, naphthalene molecule, hydrone are randomly dispersed in model box；
Step 3 calculates mixed solution equilibrium configuration,
Dissipative Particle Dynamics optimization (Geometry is carried out to mixed solution model using Mesocite Tools modules
Optimization), Dissipative Particle Dynamics Simulation (Dissipative Particle then are carried out to the model after optimization again
Dynamics)；
Mixed solution model Dissipative Particle Dynamics Optimal Parameters：The field of force selects compass, Van der Waals interaction to use
Atom Based methods calculate, and Coulomb interactions is calculated using Ewald methods, and optimization method selects Smart
Minimization, optimization step number are 5000 steps；
Mixed solution model Dissipative Particle Dynamics Simulation parameter：The meter of molecular dynamics simulation is carried out using NVT assemblages
It calculates, temperature chooses 298K, truncation radius selectionSimulated time is 300000ps, time step 860fs, every 1000
Step one frame of output, Dissipation Parameters (dissipation strength) are 4.5, and dissipation radius (dissipation radius) is
1.0, mass scale (Mass scale) is 432amu, and repelling force parameter between coarseness pearl is shown in Table 1；
Table 1
Mixed solution equilibrium configuration figure under different pH environments is shown in Fig. 7, Fig. 8, pH=7 (PAE in Fig. 7：PAEH=5：
0), pH=5.0 (PAE in Fig. 8：PAEH=0：5)；It is seen that naphthalene molecule is located inside copolymer molecule, copolymer dress
Carry naphthalene molecule；As pH value reduces, copolymer molecule and naphthalene molecular position change, and copolymer discharges naphthalene molecule；
Step 4, comprehensive analysis,
According to the trail file of mixed solution equilibrium configuration, Mesocite Tools moulds Analysis tools in the block are utilized
Analyze the poly- β amino esters (PAE) of copolymer hydrophobic segment, hydrophilic segment polyethylene glycol (PEG) and naphthalene molecule radial distribution function,
Hydrophobic segment (PAE), hydrophilic segment (PEG) surrounding naphthalene molecule amount are calculated, further analyzes pH value to PAE-PEG polymer pair
Fig. 9 is shown in the influence that naphthalene molecule loads with release behavior.
It uses for reference the prior art and can be realized in the part that do not addressed in the present invention.
On the basis of above-mentioned pH response types copolymer p AE-PEG, those skilled in the art can also use the method for the present invention
The behavior for being loaded to study other pH response type copolymers and discharging other hydrocarbon molecules.
It should be noted that any equivalent way that those skilled in the art are made under the introduction of this specification, or
Obvious variant should all be within the scope of the present invention.
Claims (2)
1. a kind of copolymer p AE-PEG loads the analogy method with release naphthalene molecule, which is characterized in that include following step successively
Suddenly：
A builds initial model,
Utilize Bead Tpyes, the Mesomolecule tools build PAE-PEG copolymers in Materials Studio softwares
Molecule, naphthalene molecule, hydrone change-NH- and-NH in PAE-PEG strands+ 2Ratio to simulate different pH value, and
Field of force distribution and preliminary optimization are carried out to each molecule；
Utilize Mesostructrue tools build model boxes；By copolymer molecule, naphthalene molecule, the hydrone after preliminary optimization
Random be added in model box builds mixed solution model；
B calculated equilibrium configurations,
Dissipative Particle Dynamics optimization is carried out to the mixed solution model described in step a using Mesocite Tools modules, then
Dissipative Particle Dynamics Simulation is carried out to the model after optimization, obtains equilibrium configuration；
C comprehensive analysis,
According to the trail file of the equilibrium configuration obtained in step b, analysis model equilibrium configuration figure；Utilize Mesocite Tools
The diameter of the poly- β amino esters of mould Analysis tool analysis copolymer hydrophobic segment in the block, hydrophilic segment polyethylene glycol and naphthalene molecule
To distribution function, specific deployment analysis copolymer p AE-PEG loads the behavior with release naphthalene molecule.
2. a kind of copolymer p AE-PEG according to claim 1 loads the analogy method with release naphthalene molecule, feature exists
In：The copolymer is pH response type block copolymers.
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Cited By (3)
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| CN110767273A (en) * | 2019-10-30 | 2020-02-07 | 华南理工大学 | Simulation method for self-assembly behavior of rigid block copolymer solution |
| CN112778490A (en) * | 2020-12-31 | 2021-05-11 | 深圳飞扬兴业科技有限公司 | Waterborne polyurethane and preparation method thereof |
| CN113144213A (en) * | 2021-03-23 | 2021-07-23 | 西安交通大学医学院第一附属医院 | Nano-drug for multi-stage pH response gene-drug co-delivery, preparation method and application thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110767273A (en) * | 2019-10-30 | 2020-02-07 | 华南理工大学 | Simulation method for self-assembly behavior of rigid block copolymer solution |
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| CN113144213A (en) * | 2021-03-23 | 2021-07-23 | 西安交通大学医学院第一附属医院 | Nano-drug for multi-stage pH response gene-drug co-delivery, preparation method and application thereof |
| CN113144213B (en) * | 2021-03-23 | 2023-04-07 | 西安交通大学医学院第一附属医院 | Nano-drug for multi-stage pH response gene-drug co-delivery, preparation method and application thereof |
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Application publication date: 20180803 |