CN107365331B - A kind of different dual-nuclei structure model and the preparation method and application thereof - Google Patents
A kind of different dual-nuclei structure model and the preparation method and application thereof Download PDFInfo
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- CN107365331B CN107365331B CN201710651028.5A CN201710651028A CN107365331B CN 107365331 B CN107365331 B CN 107365331B CN 201710651028 A CN201710651028 A CN 201710651028A CN 107365331 B CN107365331 B CN 107365331B
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- dimethyl sulfoxide
- bipyridyl
- ruthenium complex
- platinum ruthenium
- tetrachloro
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- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 239000012327 Ruthenium complex Substances 0.000 claims abstract description 30
- CFQCIHVMOFOCGH-UHFFFAOYSA-N platinum ruthenium Chemical compound [Ru].[Pt] CFQCIHVMOFOCGH-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000003112 inhibitor Substances 0.000 claims abstract description 9
- 230000006919 peptide aggregation Effects 0.000 claims abstract description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 69
- 239000011734 sodium Substances 0.000 claims description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 14
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 13
- 229910052708 sodium Inorganic materials 0.000 claims description 13
- -1 bipyridyl dimethyl sulfoxide Chemical compound 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 11
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 10
- 229910052700 potassium Inorganic materials 0.000 claims description 10
- 239000011591 potassium Substances 0.000 claims description 10
- 235000019441 ethanol Nutrition 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 abstract description 11
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
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- 239000002245 particle Substances 0.000 description 5
- JADVWWSKYZXRGX-UHFFFAOYSA-M thioflavine T Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C1=[N+](C)C2=CC=C(C)C=C2S1 JADVWWSKYZXRGX-UHFFFAOYSA-M 0.000 description 5
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- CWVRJTMFETXNAD-FWCWNIRPSA-N 3-O-Caffeoylquinic acid Natural products O[C@H]1[C@@H](O)C[C@@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-FWCWNIRPSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
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- PZIRUHCJZBGLDY-UHFFFAOYSA-N Caffeoylquinic acid Natural products CC(CCC(=O)C(C)C1C(=O)CC2C3CC(O)C4CC(O)CCC4(C)C3CCC12C)C(=O)O PZIRUHCJZBGLDY-UHFFFAOYSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
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- 238000005481 NMR spectroscopy Methods 0.000 description 1
- CWVRJTMFETXNAD-KLZCAUPSSA-N Neochlorogenin-saeure Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)c(O)c2)[C@@H]1O)C(=O)O CWVRJTMFETXNAD-KLZCAUPSSA-N 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
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- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 1
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 1
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- 229940074393 chlorogenic acid Drugs 0.000 description 1
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- BMRSEYFENKXDIS-KLZCAUPSSA-N cis-3-O-p-coumaroylquinic acid Natural products O[C@H]1C[C@@](O)(C[C@@H](OC(=O)C=Cc2ccc(O)cc2)[C@@H]1O)C(=O)O BMRSEYFENKXDIS-KLZCAUPSSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
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- 150000002500 ions Chemical class 0.000 description 1
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- UPQNPBHYPACBSK-UHFFFAOYSA-N methylsulfinylmethane;sodium Chemical compound [Na].CS(C)=O UPQNPBHYPACBSK-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
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- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229960001285 quercetin Drugs 0.000 description 1
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- 238000012827 research and development Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- BIXNGBXQRRXPLM-UHFFFAOYSA-K ruthenium(3+);trichloride;hydrate Chemical class O.Cl[Ru](Cl)Cl BIXNGBXQRRXPLM-UHFFFAOYSA-K 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
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- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- ZTWIEIFKPFJRLV-UHFFFAOYSA-K trichlororuthenium;trihydrate Chemical compound O.O.O.Cl[Ru](Cl)Cl ZTWIEIFKPFJRLV-UHFFFAOYSA-K 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of bipyridyl-dimethyl sulfoxide platinum ruthenium complexes and the preparation method and application thereof.The bipyridyl-dimethyl sulfoxide platinum ruthenium complex chemical formula is Na { [RuCl4(DMSO‑S)](bpy)[Pt(DMSO‑S)Cl2]}；Its structural formula such as formula is shown in formula I.The bipyridyl-dimethyl sulfoxide platinum ruthenium complex synthetic method is simple, is a kind of good amyloid peptide aggregation inhibitor with the very strong ability for inhibiting amyloid peptide aggregation.
Description
Technical field
The invention belongs to technical field of function materials, and in particular to a kind of different Binuclear platinum ruthenium complex and preparation method thereof with
Using.
Background technique
With the development of biological medicine technology, it is found that the aggregation of more and more diseases and amyloid protein in vivo deposits
It is related, therefore more attention are received to the research of such amyloid diseases.Protein can pass through folding under normal circumstances
Certain higher structure is formed, to obtain distinctive physiological function.When the albumen normally folded is induced that wrong folding has occurred
When folded, it will assemble in vivo and gradually form amyloid deposition, and lose its physiological function.Many diseases all with this class process
Related, if alzheimer's disease is related with amyloid beta, Parkinson's disease is related with synapse nucleoprotein, Huntingdon disease and henry
The court of a feudal ruler albumen is related, and type II diabetes and people's amylin are related etc..Assembling fibrosis is the important of amyloid protein
Feature, therefore probe into how to inhibit the aggregation of amyloid protein be the key that capture related disease.
People's amylin (hIAPP) related with type II diabetes has very strong aggregation amyloid deposits
Ability is to be currently known strongest one of the albumen with amyloid deposition property.Under normal physiological condition, hIAPP monomer master
To exist in the form of random coil, and the hIAPP that lesion occurs will form the fiber containing a large amount of beta sheet structures.
The inhibitor of hIAPP generally comprises small molecule compound at present, transition metal ions, metal complex and certain
Small peptide.Wherein, micromolecular compound inhibitor is mainly based on Polyphenols, such as Quercetin, baicalein, caffeic acid and chlorogenic acid
Deng.In addition, armaticity organic molecule is for example Congo red, caffeic acid etc. also can effectively inhibit the amyloid deposition of hIAPP.And metal
The influence of ion pair islet amyloid polypeptide aggregation is also increasingly valued by people, this is also to study causing a disease for type II diabetes
Mechanism and its medicament research and development provide new thinking.
Some metal complexs are due to itself lower cytotoxicity, and its can pass through the characteristics such as blood-brain barrier, make it
Be able to biomedicine field rapidly develop.Cis-platinum is first successful anticancer Metal Drugs.And ruthenium complex is shown
Very high physiological activity and lower cytotoxicity are very potential Metal Drugs.
Ability of the ruthenium metal complex in terms of inhibiting amyloid polypeptide aggregation has been confirmed.As certain fragrant rutheniums are matched
Close object can with PrPC Neuropeptide P rP106-126 by coordination in conjunction with, inhibit the aggregation of polypeptide and reduction by polypeptide aggregation
Caused cytotoxicity.The ruthenium complex of some NAMI-A classes can also inhibit the aggregation of hIAPP by electrostatic interaction, be potential
Amyloid protein inhibitor.
It selects the aromatic molecules of appropriate configuration to connect two different metal centers, designs new different Binuclear platinum ruthenium complex conduct
The agglutination inhibitor of 4 amyloid is the important topic in protein configuration disease mechanism study and drug development.
Summary of the invention
It is bipyridyl-dimethyl sulfoxide of ligand that it is an object of the present invention to provide a kind of using bipyridyl and dimethyl sulfoxide
Platinum ruthenium complex, and the inhibitor research for the amyloidosis albumen such as be applied to people's amylin.
The bipyridyl-dimethyl sulfoxide platinum ruthenium complex chemical formula is Na { [RuCl4(DMSO-S)](bpy)[Pt
(DMSO-S)Cl2]}；Its structural formula such as formula is shown in formula I:
The bipyridyl-dimethyl sulfoxide platinum ruthenium complex preparation method, includes the following steps:
Tetrachloro bipyridyl dimethyl sulfoxide is closed into ruthenic acid sodium (Na [trans-RuCl4(DMSO) (bpy)]) it is water-soluble
Liquid and trichlorine dimethyl sulfoxide close potassium platinate (K [PtCl3(DMSO)] aqueous solution) is mixed, then room temperature (10-30
DEG C) stirring 1-3h after, be added excess ethyl alcohol, (10-20 hours) are stood overnight at 2-5 DEG C, are dried in vacuo after being spin-dried for solvent,
Obtain target product yellow solid bipyridyl-dimethyl sulfoxide platinum ruthenium complex.
Wherein, tetrachloro bipyridyl dimethyl sulfoxide closes ruthenic acid sodium and trichlorine dimethyl sulfoxide closes mole of potassium platinate
Than for 1:1.The stirring is stirred using magnetic stirring apparatus.
The additional amount of the ethyl alcohol is the aqueous solution and trichlorine two that tetrachloro bipyridyl dimethyl sulfoxide closes ruthenic acid sodium
Methyl sulfoxide closes twice or more of the total volume of the aqueous solution of potassium platinate.
The tetrachloro bipyridyl dimethyl sulfoxide conjunction ruthenic acid sodium can refer to literature method and be prepared, and specific method is such as
Under:
1) three hydrate ruthenium trichlorides are dissolved in after being heated to reflux 3-6h in ethyl alcohol, obtain dark green solution.Filtering, by filtrate
It is spin-dried for the 3/10-1/10 of original volume, hydrochloric acid and dimethyl sulfoxide is added, be warming up to 70-100 DEG C, stir 10-30min.Drop
It filters, is dried in vacuo after adding diethyl ether, obtain two dimethyl sulfoxide tetrachloro of a hydrogen, two dimethyl sulfoxide and close ruthenium；
2) mixing for two dimethyl sulfoxide tetrachloro of a hydrogen, two dimethyl sulfoxide conjunction ruthenium being dissolved in second alcohol and water is molten
In liquid.The sodium chloride being dissolved in water is added, agitation and filtration is washed with cold acetone and ether, is dried in vacuo, is obtained Chinese red
Two dimethyl sulfoxide of solid tetrachloro closes ruthenic acid sodium；
3) two dimethyl sulfoxide of tetrachloro conjunction ruthenic acid sodium is dissolved in dimethyl sulfoxide, is stirred for that Isosorbide-5-Nitrae is added '-connection pyrrole
The acetone soln of pyridine.It filters after 2-4h is stirred at room temperature, is washed with cold acetone and ether, be dried in vacuo, obtain Chinese red
Solid tetrachloro bipyridyl dimethyl sulfoxide closes ruthenic acid sodium.
The trichlorine dimethyl sulfoxide conjunction potassium platinate can also refer to literature method and be prepared, and the specific method is as follows:
Platinous Potassium Chloride is soluble in water, dimethyl sulfoxide is added, 2-4h is stirred, by a small amount of white needle-like crystals of generation
Filtering, mother liquor rotary evaporation start until crystallizing, and filter after cooling solution, obtain yellow solid trichlorine dimethyl sulfoxide and close platinum
Sour potassium.
It is a further object to provide the applications of above-mentioned bipyridyl-dimethyl sulfoxide platinum ruthenium complex.
The bipyridyl-dimethyl sulfoxide platinum ruthenium complex is in terms of the aggregation inhibition of 4 amyloid, especially in people's pancreas islet
The aggregation of 4 amyloid inhibits aspect to have obvious action.It can be used for preparing the agglutination inhibitor of 4 amyloid, especially people
The agglutination inhibitor of islet amyloid sample peptide (hIAPP).
Present invention has an advantage that
The present invention passes through aromatic ligand Isosorbide-5-Nitrae '-bipyridyl and platinum ruthenium metal reaction obtain novel different Binuclear platinum ruthenium complex,
And preparation is simple for the complex.The different Binuclear platinum ruthenium complex is in the aggregation inhibition side of people's islet amyloid sample peptide
Face has obvious action.
Detailed description of the invention
Fig. 1 is bipyridyl-dimethyl sulfoxide platinum ruthenium complex infrared spectrogram in embodiment 1；
Fig. 2 is the thioflavine that bipyridyl-dimethyl sulfoxide platinum ruthenium complex inhibits people's islet amyloid sample peptide aggregation in embodiment 2
T fluorescence analysis figure, wherein abscissa is wavelength, unit: nm；Ordinate is fluorescence intensity.The fluorescence that solid line represents hIAPP is strong
Degree, dotted line represent the fluorescence intensity of hIAPP after 0.5 times of concentration complex of addition, and dotted line represents hIAPP after addition equivalent complex
Fluorescence intensity, pecked line represent be added 10 times of concentration complexs after hIAPP fluorescence intensity.
Fig. 3 is the dynamic optical that bipyridyl-dimethyl sulfoxide platinum ruthenium complex inhibits people's islet amyloid sample peptide aggregation in embodiment 3
Scattering analysis figure, wherein abscissa is particle size, unit: nm；Ordinate is particle diameter distribution relative intensity percentage.Solid line generation
The particle diameter distribution of table hIAPP, dotted line represent the particle diameter distribution of hIAPP after addition equivalent complex, and it is dense that dotted line represents 10 times of addition
The particle diameter distribution of hIAPP after degree complex.
Fig. 4 is the atomic force that bipyridyl-dimethyl sulfoxide platinum ruthenium complex inhibits people's islet amyloid sample peptide aggregation in embodiment 4
Microscope figure, wherein scale item is 5 μm.A is independent hIAPP shape appearance figure, and B is the hIAPP pattern being added after 0.5 times of complex
Figure, C are the hIAPP shape appearance figure being added after equivalent complex, and D is the hIAPP shape appearance figure being added after 10 times of concentration complexs.
Specific embodiment
Method of the invention is illustrated below by specific embodiment, but the present invention is not limited thereto, it is all at this
Any modifications, equivalent replacements, and improvements etc. done within the spirit and principle of invention, should be included in protection model of the invention
Within enclosing.
Experimental method used in following embodiments is conventional method unless otherwise specified.
The materials, reagents and the like used in the following examples is commercially available unless otherwise specified.
Embodiment 1
1) tri- hydrate ruthenium trichloride of 0.1g, which is dissolved in 10mL ethyl alcohol, is heated to reflux 3h, obtains dark green solution.Filtering, will filter
Liquid is spin-dried for the 1/10 of original volume.37% hydrochloric acid of 0.1mL and 0.2mL dimethyl sulfoxide is added, is warming up to 80 DEG C, stirring
10min.It filters, is dried in vacuo after ether is added dropwise, obtain two dimethyl sulfoxide tetrachloro of a hydrogen, two dimethyl sulfoxide and close ruthenium.
Mono- hydrogen of 1.12g, two dimethyl sulfoxide tetrachloro, two dimethyl sulfoxide conjunction ruthenium is dissolved in the mixed of 50mL ethyl alcohol and 0.7mL water
It closes in solution.Stirring is added thereto after 175mg sodium chloride is dissolved into 0.5mL water, agitation and filtration, with cold acetone and ether
Washing, vacuum drying obtain two dimethyl sulfoxide of Chinese red solid tetrachloro and close ruthenic acid sodium.
Two dimethyl sulfoxide of 0.135g tetrachloro closes ruthenic acid sodium and is dissolved in 2mL dimethyl sulfoxide, then by 0.25g Isosorbide-5-Nitrae '-
Stirring is added thereto after bipyridyl is dissolved in 5mL acetone.It filters after 3h is stirred at room temperature, is washed with cold acetone and ether
It washs, then is dried in vacuo, obtain red orange solid tetrachloro bipyridyl dimethyl sulfoxide and close ruthenic acid sodium.
2) 250mg Platinous Potassium Chloride is dissolved in 2.5mL water, 0.0436mL dimethyl sulfoxide is added, stir 3h.It will generate
A small amount of white needle-like crystals filtering, mother liquor rotary evaporation until crystallization start.It is filtered after cooling solution, obtains yellow solid three
Chlorodimethyl sulfoxide closes potassium platinate.
3) 0.1g tetrachloro bipyridyl dimethyl sulfoxide conjunction ruthenic acid sodium is dissolved in 2mL water, then by 0.084g tri-
Chlorodimethyl sulfoxide, which closes potassium platinate and is dissolved in after 2mL water to stir, to be added thereto.After stirring 1h in room temperature, excess ethyl alcohol is added
(50ml), at 4 DEG C overnight.It is dried in vacuo after being spin-dried for solvent, obtains yellow bipyridyl-dimethyl sulfoxide platinum ruthenium complex Na
{[RuCl4(DMSO-S)](bpy)[Pt(DMSO-S)Cl2], shown in molecular structure Formulas I.
By obtained bipyridyl-dimethyl sulfoxide platinum ruthenium complex Na { [RuCl4(DMSO-S)](bpy)[Pt(DMSO-S)
Cl2] elemental analysis is carried out, result is as follows: C14H20Cl6NaN2O2Pt RuS2: calculated value (%): C19.8, N3.32,
H2.37；Experiment value (%): C20.21, N3.45, H2.42.
By obtained bipyridyl-dimethyl sulfoxide platinum ruthenium complex Na { [RuCl4(DMSO-S)](bpy)[Pt(DMSO-S)
Cl2] IR Characterization (such as Fig. 1) is carried out, characteristic peak (cm-1) it is as follows: 814,1026,1084,1113,1224.7,1313.4,
1415.6,1614.3,2920,3012.7,3566.
By obtained bipyridyl-dimethyl sulfoxide platinum ruthenium complex Na { [RuCl4(DMSO-S)](bpy)Pt(DMSO-S)
Cl2] progress nuclear magnetic resonance characterization, characteristic peak (1H, ppm) as follows: -12.33 (br, Me2SO-S), -1.12 (H2,6, bpy),
6.04(H3,5, bpy), 6.25 (H3’,5’, bpy), 7.62 (H2’,6’, bpy), 3.44 (6H, Me2SO-S)。
Embodiment 2
The fluorescence intensity change of 4 amyloid after complex effect is detected by thioflavin T fluorometric method.By 100 μ L, 5 μM of people
(wherein the molar ratio of complex and hIAPP are 0.5:1's, 1:1,10:1) for islet amyloid sample peptide hIAPP solution and various concentration
Bipyridyl-dimethyl sulfoxide platinum ruthenium complex co-incubation 72h at 37 DEG C.It separately weighs suitable thioflavine T and is dissolved in phosphoric acid buffer
In solution, concentration 10mM.Equivalent thioflavine T is added in each albumen miscible fluid, makes the concentration of thioflavine T in final system
Control is at 20 μM.Sample is fitted into the quartzy fluorescence pond of 1cm, excitation wavelength 432nm, measurement range is set as 450-
650nm, scanning voltage 700V, excitation and transmite slit are 10nm, measure the fluorescence intensity change of the sample at 485nm.
As complex concentration ratio increases, the fluorescence intensity of 4 amyloid has different degrees of reduction, as shown in Figure 2.
Embodiment 3
The change of size of 4 amyloid after complex effect is detected by dynamic light scattering experiment.By 100 μ L, 5 μM of people's pancreases
The bipyridyl-two of island 4 amyloid hIAPP solution and various concentration (wherein the molar ratio of complex and hIAPP are 1:1,10:1)
Then first sulfoxide platinum ruthenium complex co-incubation 72h at 37 DEG C is centrifuged 15min under 12,000rpm revolving speed and is precipitated with removing,
Transfer supernatant is measured into sample cell.With complex concentration than increasing, 4 amyloid partial size has different degrees of reduction,
As shown in Figure 3.
Embodiment 4
Atomic force microscope morphology characterization.By obtained bipyridyl-dimethyl sulfoxide platinum ruthenium complex Na { [RuCl4(DMSO-
S)](bpy)[Pt(DMSO-S)Cl2] be dissolved in DMSO as mother liquor；People's islet amyloid sample peptide that configuration concentration is 50 μM
HIAPP solution takes appropriate complex mother liquor to be added in polypeptide solution, and making the two (complex: hIAPP) molar ratio is respectively 0.5:
1,1:1 and 10:1, in 37 DEG C of culture 72h.Use H2It is 0.5mL that O, which is diluted to liquor capacity, and final peptide concentration control is at 5 μM.With
The syringe pipette samples 5-10 μ L drop of 1mL is tested after sample natural air drying on silicon wafer.Atomic force microscope uses
Tapping mode measures, sweep speed 1Hz, and scanning road number is 512.With complex concentration than increasing, 4 amyloid shape
Looks become bulk fine fibre by netted fiber, dotted oligomer, and it is most of exist with monomer, as shown in Figure 4.
Herein using bipyridyl be ligand prepare bipyridyl-dimethyl sulfoxide platinum ruthenium complex, synthetic method is simple, have compared with
The ability of strong inhibition amyloid peptide aggregation, is a kind of good amyloid peptide aggregation inhibitor.
The foregoing is only a preferred embodiment of the present invention, but scope of protection of the present invention is not limited thereto,
In the technical scope disclosed by the present invention, any changes or substitutions that can be easily thought of by anyone skilled in the art,
It should be covered by the protection scope of the present invention.Therefore, protection scope of the present invention answers the protection model with claim
Subject to enclosing.
Claims (6)
1. a kind of bipyridyl-dimethyl sulfoxide platinum ruthenium complex, structural formula are shown in formula I:
2. bipyridyl described in claim 1-dimethyl sulfoxide platinum ruthenium complex preparation method, includes the following steps:
Tetrachloro bipyridyl dimethyl sulfoxide is closed to the aqueous solution of ruthenic acid sodium and the water of trichlorine dimethyl sulfoxide conjunction potassium platinate
Solution is mixed, after 1-3h then is stirred at room temperature, be added ethyl alcohol, 2-5 DEG C placement 10-20 hours, carried out after being spin-dried for solvent
It is dry, obtain bipyridyl-dimethyl sulfoxide platinum ruthenium complex.
3. according to the method described in claim 2, it is characterized by: the tetrachloro bipyridyl dimethyl sulfoxide closes ruthenic acid sodium
The molar ratio for closing potassium platinate with trichlorine dimethyl sulfoxide is 1:1.
4. according to the method in claim 2 or 3, it is characterised in that: the additional amount of the ethyl alcohol is tetrachloro bipyridyl
Dimethyl sulfoxide closes the aqueous solution of ruthenic acid sodium and trichlorine dimethyl sulfoxide close twice of total volume of aqueous solution of potassium platinate with
On.
5. the method according to any one of Claims 2 or 3, it is characterised in that: the drying is vacuum drying.
6. bipyridyl described in claim 1-dimethyl sulfoxide platinum ruthenium complex is in preparation people's islet amyloid sample peptide aggregation inhibitor
In application.
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| Binuclear ruthenium complexes inhibit the fibril formation of human islet amyloid polypeptide;Gehui Gong等,;《RSC Adv.》;20170327;18512-18522页 * |
| Hetero-multinuclear Ruthenium(III)/Platinum(II) Complexes That Potentially Exhibit Both Antimetastatic and Antineoplastic Properties;Craig M. Anderson等,;《Inorg. Chem.》;20121114;12917-12924页 * |
| Inhibition of Aβ42 Peptide Aggregation by a Binuclear Ruthenium(II)-Platinum(II) Complex: Potential for Multimetal Organometallics as Anti-amyloid Agents;Amit Kumar等,;《ACS Chem. Neurosci.》;20100823;691-701页 * |
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