CN104478857B - A kind of 2-pyridine vinyl naphthalene imide fluorescent dendrimer and its preparation method and application - Google Patents

A kind of 2-pyridine vinyl naphthalene imide fluorescent dendrimer and its preparation method and application Download PDF

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CN104478857B
CN104478857B CN201410843638.1A CN201410843638A CN104478857B CN 104478857 B CN104478857 B CN 104478857B CN 201410843638 A CN201410843638 A CN 201410843638A CN 104478857 B CN104478857 B CN 104478857B
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fluorescent
dendrimer
vinyl naphthalene
vpn
pyridine
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CN104478857A (en
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钱鹰
胡秀东
孙京府
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Southeast University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
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    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
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    • C09B23/162—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing hetero atoms only nitrogen atoms
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    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
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    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
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    • C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
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    • C09K2211/1025—Heterocyclic compounds characterised by ligands
    • C09K2211/1029—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom
    • C09K2211/1033—Heterocyclic compounds characterised by ligands containing one nitrogen atom as the heteroatom with oxygen

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Abstract

The invention discloses a kind of 2 pyridine vinyl naphthalene imide fluorescent dendrimer PAMAM VPN, it is to connect 4 naphthalimide fluorogens with daiamid for skeleton.The invention also discloses its preparation method, under inert atmosphere, by 4 (2 pyridine vinyls) 1,8 naphthalene acid anhydrides and daiamid reflux in methanol and carry out anhydride ammonolysis reaction, again through decompression distillation, chromatography over CC, is recrystallized to give described 2 pyridine vinyl naphthalene acid imide dendrimers.PAMAM VPN is the fluorescent material of a kind of function admirable, has extremely important using value in fields such as fluorescent probe, fluorescent optical sensor, biological fluorescent labelling, living cells imagings.Fluorescence dendrimer of the present invention can be as bovine serum albumin fluorescent probe, sensitive pH fluorescent probe；There is aggregation-induced emission characteristic, can be as gathering induced luminescence material；Can be as fluorescent dye for live cell fluorescent imaging.

Description

A kind of 2-pyridine vinyl naphthalene imide fluorescent dendrimer and its preparation method and application
Technical field
The present invention relates to naphthalimide fluorescent molecule technical field, be specifically related to one with polyamide-amide skeleton even 2-pyridine vinyl naphthalene imide fluorescent dendrimer connect and its preparation method and application.
Background technology
Naphthalimide derivative has strong fluorescent emission, good light stability and chemical stability, higher Fluorescence quantum yield and bigger Stokes shift, at fluorescent probe, chemical sensor, bioluminescence mark The fields such as note have important application prospect, and relevant experiment and theoretical research receive significant attention.Document report at present Most naphthalimide derivatives in road have good fluorescence property in weak solution, but when state of aggregation by Result in non-radiative energy conversion in intermolecular interaction or formed and be unfavorable for the species of fluorescent emission, producing poly- The phenomenon of collection fluorescent quenching.
Summary of the invention
First purpose of the present invention is to provide a kind of 2-pyridine vinyl naphthalene imide fluorescent dendrimer (PAMAM-VPN)。
Second object of the present invention is to provide the system of above-mentioned 2-pyridine vinyl naphthalene imide fluorescent dendrimer Preparation Method.
Third object of the present invention is to provide answering of above-mentioned 2-pyridine vinyl naphthalene imide fluorescent dendrimer With.
The present invention is by the following technical solutions:
A kind of 2-pyridine vinyl naphthalene imide fluorescent dendrimer, it is made up of following structural formula:
The preparation method of above-mentioned 2-pyridine vinyl naphthalene imide fluorescent dendrimer, comprises the steps: inertia Under atmosphere, by 4-(2-pyridine vinyl)-1,8-naphthalene acid anhydride (VPN) and polyamide-amide (PAMAM) are at methanol Middle backflow carries out anhydride ammonolysis reaction, then through decompression distillation, chromatography over CC, is recrystallized to give described 2-pyridine Vinyl naphthalene acid imide dendrimer.
Above-mentioned 2-pyridine vinyl naphthalene imide fluorescent dendrimer is glimmering as bovine serum albumin fluorescent probe, pH Light probe or the application of aggregation inducing fluorescent material.
Above-mentioned 2-pyridine vinyl naphthalene imide fluorescent dendrimer as fluorescent dye in live cell fluorescent imaging In application.
Beneficial effects of the present invention:
The naphthalimide fluorescence dendrimer of the present invention is to be connected 4 naphthalimide fluorogens by polyamide-amide, Core centered by polyamide-amide, naphthalimide is interior layer unit, and pyridine is outer layer end group, obtains multi-arm naphthoyl Imines high-efficiency fluorescence molecule, is turned by the Photo-induced electron transfer between multi-arm naphthalimide and fluorescence resonance energy The fluorescence property of the sensitive regulatory molecule of shifter mechanism, has good aggregation-induced emission characteristic.The multi-arm of the present invention Naphthalimide fluorescence dendrimer is the fluorescent material of a kind of function admirable, fluorescent probe, fluorescent optical sensor, The fields such as biological fluorescent labelling, living cells imaging have extremely important using value.Tree-like point of fluorescence of the present invention Son can be as bovine serum albumin fluorescent probe, sensitive pH fluorescent probe；There is aggregation-induced emission characteristic, Can be as gathering induced luminescence material；Can be as fluorescent dye for live cell fluorescent imaging.
Accompanying drawing explanation
Fig. 1 is the Solid fluorescene spectrum of 2-pyridine vinyl naphthalene imide fluorescent dendrimer PAMAM-VPN.
Fig. 2 is PAMAM-VPN fluorescence intensity and fluorescence in different proportion water/oxolane mixed solution Quantum yield is with the changing trend diagram of water content.
Fig. 3 is the fluorescence intensity changing trend diagram at different pH of PAMAM-VPN.
Fig. 4 be PAMAM-VPN under the physiological condition that pH is 7.4 fluorescence intensity with bovine serum albumin BSA The changing trend diagram of concentration.
Detailed description of the invention
By the following examples the present invention is described in further detail:
A kind of 2-pyridine vinyl naphthalene imide fluorescent dendrimer, it is made up of following structural formula:
The preparation method of above-mentioned 2-pyridine vinyl naphthalene imide fluorescent dendrimer, comprises the steps: nitrogen Under atmosphere, by bromo-for 4-1,8-naphthalene acid anhydride and 2-vinyl-pyridin 4-(the 2-pyridine ethylene obtained by Heck reacts Base)-1,8-naphthalene acid anhydride (VPN) and polyamide-amide (PAMAM) be 4～5:1 to return in methanol in molar ratio Stream carries out anhydride ammonolysis reaction 20～30h, after through decompression distillation, chromatography over CC, be recrystallized to give described 2-pyridine vinyl naphthalene acid imide dendrimer, wherein, described anhydride ammonolysis reaction is carried out under agitation.
The PAMAM that following example relate to by literature method (Tomalia D A, Baker H, Dewald J, Hall M,Kallos G,Martin S,Roeck J,Ryder J,Smith P.Polymer Journal, 1985,17 (1), 117-132) prepare.
The preparation method of compound VPN is as follows:
Under conditions of nitrogen protection and anhydrous and oxygen-free, addition 4-bromo-1,8-naphthalene acid anhydride (1.00g, 3.61mmol), Palladium (0.04g, 0.18mmol), three o-methyl-phenyl-phosphorus (0.11g, 0.36mmol), potassium phosphate (0.38g, 1.81mmol), 2-vinyl-pyridin (0.42mL, 3.97mmol) and 10mL DMF, It is heated to 100 DEG C of backflow 12h, detects to determine that reaction completes with silica gel tlc.After reaction terminates, pour into In the water of 300mL, the luteotestaceous solid of sucking filtration, with the mixed liquor of dichloromethane and methanol as leacheate Carry out silica gel column chromatography separation, obtain glassy yellow acicular substance, yield 74%.
Analysis gained compound PVN:
1HNMR(300MHz,CDCl3): δ 8.81 (d, J=9.0Hz, 1H), 8.72～8.66 (m, 1H), 8.63 (t, J=15.0Hz, 1H), 8.13 (d, J=6.0Hz, 1H), 7.89 (t, J1=6.0Hz, J2=9.0Hz, 1H), 7.79 (t, J1=6.0Hz, J2=9.0Hz, 1H), 7.47 (d, J=9.0Hz, 1H), 7.41 (d, J=6.0Hz, 1H), 7.33～7.31 (m, 1H), 7.29～7.24 (m, 1H), 7.13～7.08 (m, 1H) .TOF-MS, m/z: 300.2[M-H]+；302.3[M+H]+
The compound VPN structural formula obtained is:
Embodiment 1
The preparation of 2-pyridine vinyl naphthalene imide fluorescent dendrimer PAMAM-VPN
Under nitrogen protection, in the 30mL methanol solution dissolved with VPN (0.51g, 1.70mmol), slowly The 20mL methanol solution of dropping PAMAM (0.20g, 0.39mmol), return stirring reaction at 60 DEG C 24h.Decompression distillation, chromatography over CC, recrystallization, obtain tree-like point of 2-pyridine vinyl naphthalene imide fluorescent Sub-PAMAM-VPN, fusing point 232～234 DEG C, productivity is 45%.
Synthetic route is as follows:
Analyze gained fluorescence dendrimer PAMAM-VPN
Proton nmr spectra1H NMR(CDCl3, 300MHz) and δ: 8.68～8.58 (m, 4H), 8.45～8.30 (m, 4H), 8.26 (d, J=6.0Hz, 4H), 8.22 (d, J=9.0Hz, 4H), 8.16 (d, J=6.0Hz, 4H), 7.76～7.68 (m, 8H), 7.61～7.53 (m, 4H), 7.49～7.43 (m, 4H), 7.37 (d, J=6.0Hz, 4H), 7.24～7.22 (m, 4H), 7.18 (d, J=15.0Hz, 2H), 7.07 (d, J=12.0Hz, 2H), 4.18～4.22 (m, 8H), 3.64～3.55 (m, 8H), 2.70～2.65 (m, 8H), 2.54～2.45 (m, 4H), 2.36～2.30 (m, 8H)
High resolution mass spectrum HRMS calcd for C98H85N14O12[M+H]+1649.6471, found 1649.6471
The fluorescence dendrimer structural formula obtained is:
PAMAM-VPN prepared by embodiment 1 is used for the performance test of embodiment 2～5.
Embodiment 2
The aggregation-induced emission character of PAMAM-VPN
Fig. 1 is the Solid fluorescene spectrum of PAMAM-VPN.In darkroom, the pressed powder of PAMAM-VPN exists Sending bright yellow fluorescence under uviol lamp, its solid state maximum emission wavelength is 533nm. PAMAM-VPN water soluble, in a length of 366nm of maximum absorption wave seen from pure water medium ultraviolet, maximum fluorescence Emission peak is positioned at 494nm, and fluorescence quantum yield is 4.42%.In oxolane, PAMAM-VPN's Ultraviolet and visible absorption peak is 363nm, and maximum fluorescence emission peak is 450nm, and fluorescence quantum yield is 10.35%. Fig. 2 is PAMAM-VPN fluorescence intensity and fluorescence in the water/oxolane mixed solution of different volumes ratio Quantum yield is with the changing trend diagram of water content.Show that PAMAM-VPN has aggregation-induced emission characteristic, Significant application value can be had as gathering induced luminescence material.
Embodiment 3
The PAMAM-VPN sensitive response to pH
Fig. 3 is the fluorescence intensity of PAMAM-VPN changing trend diagram under different pH.PAMAM-VPN Fluorescence intensity be gradually increased with pH value and substantially weaken.Show that PAMAM-VPN can be as sensitive pH Fluorescent probe.
Embodiment 4
The PAMAM-VPN detection to bovine serum albumin
As shown in Figure 4, the concentration keeping PAMAM-VPN under the physiological condition that pH is 7.4 is constant (concentration of PAMAM-VPN is 5.0 × 10-6Mol/L), along with the concentration of bovine serum albumin BSA increases, The fluorescence intensity of PAMAM-VPN gradually strengthens.Through experimental calculation PAMAM-VPN and bovine serum albumin Binding constant is 1.03 × 105.Show that PAMAM-VPN can be as sensitive Fluorescence Increasing type probe for cattle The detection of serum albumin BSA.
Embodiment 5
PAMAM-VPN is used for living cells imaging as fluorescent dye
Adding the Hela cell after PAMAM-VPN hatching can be clear under laser confocal fluorescence microscope Imaging, shows that PAMAM-VPN can be used for living cells imaging.PAMAM-VPN can be used for tumor-localizing, The key areas such as study of pharmacy and fluorescent microscopic imaging.
PAMAM-VPN has aggregation-induced emission characteristic, can be as gathering induced luminescence material； PAMAM-VPN can be as sensitive pH fluorescent probe and bovine serum albumin fluorescent probe； PAMAM-VPN can be as fluorescent dye for live cell fluorescent imaging.PAMAM-VPN is a kind of performance Excellent fluorescent material, in fields such as fluorescent probe, fluorescent optical sensor, biological fluorescent labelling, living cells imagings There is extremely important using value.

Claims (5)

1. a 2-pyridine vinyl naphthalene imide fluorescent dendrimer, it is characterised in that it is by following structural formula structure Become:
2. the preparation method of 2-pyridine vinyl naphthalene imide fluorescent dendrimer described in claim 1, it is special Levy and be, comprise the steps: under inert atmosphere, by 4-(2-pyridine vinyl)-1,8-naphthalene acid anhydride and polyamide- Amine refluxes in methanol and carries out anhydride ammonolysis reaction, then through decompression distillation, chromatography over CC, is recrystallized to give Described 2-pyridine vinyl naphthalene acid imide dendrimer.
3. described in claim 1,2-pyridine vinyl naphthalene imide fluorescent dendrimer is preparing bovine serum albumin Application in fluorescent probe or pH fluorescent probe reagent.
4. 2-pyridine vinyl naphthalene imide fluorescent dendrimer described in claim 1 is as aggregation inducing fluorescence The application of material.
5. 2-pyridine vinyl naphthalene imide fluorescent dendrimer described in claim 1 is preparing fluorescent dye examination Agent application in live cell fluorescent imaging.
CN201410843638.1A 2014-12-30 2014-12-30 A kind of 2-pyridine vinyl naphthalene imide fluorescent dendrimer and its preparation method and application Expired - Fee Related CN104478857B (en)

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