CN106083897A - Imidazopyridine rhodamine salicylide Cu-like ion ratio fluorescent probe and application thereof - Google Patents
Imidazopyridine rhodamine salicylide Cu-like ion ratio fluorescent probe and application thereof Download PDFInfo
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- CN106083897A CN106083897A CN201610347019.2A CN201610347019A CN106083897A CN 106083897 A CN106083897 A CN 106083897A CN 201610347019 A CN201610347019 A CN 201610347019A CN 106083897 A CN106083897 A CN 106083897A
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- rhodamine
- salicylide
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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
- G01N21/6428—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes"
- G01N21/643—Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" non-biological material
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Abstract
The invention discloses a kind of imidazo [1,5 a] pyridine rhodamine salicylide Cu-like ion ratio fluorescent probe and application thereof, described probe is imidazo [1,5 a] pyridine substituted rhodamine salicylide, and its chemical structural formula is as the formula (1).The fluorescence probe of the present invention in ethanol solution to Cu2+Have fluorescence selectivity, higher sensitivity and stronger other ion interference abilities anti-of uniqueness, there is huge application prospect.
Description
Technical field
The present invention relates to organic molecule fluorescence probe field, particularly relate to a kind of Cu2+Ratio fluorescent probe imidazo [1,
5-a] pyridine substituted rhodamine salicylide and application thereof.
Background technology
Rhodamine fluorescent dyes is launched because of it and absorbs all in visible region, and molar extinction coefficient is big, photostability
Height, fluorescence quantum yield is high, convieniently synthesized etc., and the fluorescence being widely used in after structural modification carrying out detecting metal ion is visited
Pin or the research of chemical sensor.
Cu2+Be in human body after iron, zinc the 3rd abundant transition metal.It plays in many physiology courses
Very important role, the minimizing of copper content is likely to result in anemic disorders.Cu2+Can participate in internal enzyme reaction, enzyme is transcribed and one
A little oxidation-reduction processes, are also in pressure closely related with the physiological reaction under fear simultaneously with people.If internal Cu2+Metabolism not
Normally, then various disease may be caused, such as Menkes syndrome, familial amyotrophic disease, Wilson syndrome, alzheimer '
Mos disease etc..As Cu in human body2+Too high levels, can produce huge toxic action to organism again.Therefore, to Copper in Body from
Qualitative and the quantitative detection of son becomes the field that chemists in recent years are paid special attention to.But, current copper ion probe is several
All single signals strengthen or attenuated type probe, have the Ratiometric fluorescent probe of two or more signal response change
Very few.
Content of the invention
For the deficiencies in the prior art, the problem that the present invention solves is to provide the Cu of a kind of two signals response change2+Ratio
The substituted rhodamine salicylide of rate fluorescence probe imidazo [1,5-a] pyridine and application thereof.
The technical scheme is that a kind of imidazo [1,5-a] pyridine substituted rhodamine bigcatkin willow aldehydes Cu2+Ratio is glimmering
Light probe, its chemical structural formula as the formula (1):
Present invention additionally comprises imidazo [1,5-a] pyridine substituted rhodamine bigcatkin willow aldehydes Cu2+Answering of ratio fluorescent probe
With, formula (1) compound in ethanol solution to Cu2+There is the fluorescence selectivity of uniqueness.
Present invention additionally comprises imidazo [1,5-a] pyridine substituted rhodamine bigcatkin willow aldehydes Cu2+The conjunction of ratio fluorescent probe
One-tenth method, in ethanol solution, by imidazo [1,5-a] pyridine-rhodamine hydrazides and salicylide according to 1:1 ingredient proportion,
80 degree of lower back flow reaction 3-7 hours, obtain the substituted rhodamine salicylide of imidazo [1,5-a] pyridine.
The ethanol solution of the preparation substituted rhodamine salicylide of imidazo [1,5-a] pyridine, is separately added into quantitative
MgCl2, CaCl2, AlCl3, SnCl2·2H2O,PbSO4, CrCl3·6H2O, MnCl2·4H2O, FeCl3·6H2O,
CoCl2·6H2O, NiCl2·6H2O, PdCl2, HgCl2, ZnCl2, CuCl2·2H2O, CdCl2·2H2O, AgNO3Second
Alcoholic solution, is tested the selectivity studied to different metal ion by fluorescence spectrum, surveys its fluorescence emission spectrum Strength Changes
Discovery: imidazo of the present invention [1,5-a] pyridine substituted rhodamine salicylide i.e. formula (1) compound is to Cu2+There is uniqueness
Fluorescence selectivity, as shown in Figure 1.It is gradually added into Cu2+To 1 equivalent, compound 1 fluorescence intensity at 465nm substantially reduces, with
When, at 585nm, fluorescence intensity is remarkably reinforced, as shown in Figure 2.Therefore, the substituted rhodamine bigcatkin willow of imidazo [1,5-a] pyridine
Aldehyde is as Cu2+Ratio fluorescent probe has huge application.
The invention provides a kind of imidazo [1,5-a] pyridine substituted rhodamine bigcatkin willow aldehydes Cu2+Ratio fluorescent probe,
Experiment proves that formula (1) compound of the present invention can be with Cu2+In ethanol solution, stoichiometrically ratio 1:1 reaction, was reacting
Cheng Zhong, due to rhodamine salicylide and copper ion effect, carbon-to-nitrogen double bon ruptures, then hydrolysis, so that donor imidazo
[1,5-a] pyridine transmits with acceptor rhodamine generation energy, causes compound 1 fluorescence intensity at 465nm substantially to reduce, with
When, at 585nm, fluorescence intensity is remarkably reinforced.Thus susceptible of proof formula of the present invention (1) compound in ethanol solution to Cu2+
Have fluorescence selectivity, higher sensitivity and stronger other ion interference abilities anti-of uniqueness, there is huge application prospect.
Brief description
Fig. 1: formula (1) compound (10-5M) ethanol solution adds the fluorescence intensity after the different metal ion of equivalent
Change ratio bar graphs, in Fig. 1 ordinate be light intensity at 585nm with 465nm at the ratio of light intensity.
Fig. 2: formula (1) compound (10-5M) ethanol solution carries out Cu2+Fluorescence titration figure.In figure, intensity is light
By force, Wavelength is wavelength, and eq is multiple.
Fig. 3: formula (1) compound (10-5And the Cu of equivalent M)2+The ethanol solution coexisting adds other gold of equivalent
The change block diagram of fluorescence intensity ratio after genus ion.
Detailed description of the invention
Embodiment 1: the synthetic schemes of formula (1) compound is shown below:
Concrete synthesis step is as follows:
It is sequentially added into 0.704g(1.0 mmol in 50 mL round-bottomed flasks) imidazo [1,5-a] pyridine rhodamine hydrazides,
0.122g(1.0 mmol) salicylide, 20 mL absolute ethyl alcohols, 80 degree of lower back flow reaction 3-6 hours.After TLC detection reaction completes,
Reduced pressure concentration, column chromatography obtains 0.707g pale solid, productivity 89.0%.
Nuclear magnetic resonance hydrogen spectruming determining:1H NMR(400 MHz, CDCl3): δ 11.03 (s, 1H), 8.43 (s, 1H), 7.95
(m, 1H), 7.72 (dd, J = 4.0 Hz, 8.0 Hz, 1H), 7.55-7.41 (m, 5H), 7.10-7.01 (m,
3H), 6.70-6.67 (m, 2H), 6.56 (m, 2H), 6.46 (d, J = 12.0 Hz, 1H), 6.42 (d, J =
4.0 Hz, 1H), 6.31 (dd, J = 2.8 Hz, 8.0 Hz, 1H), 3.82 (s, 4H), 3.34 (q, J =
8.0 Hz, 4H), 3.28 (s, 4H), 2.96 (d, J = 4.0 Hz, 4H), 1.82 (m, 2H), 1.62 (s,
2H), 1.44 (m, 2H), 1.17 (t, J = 8.0 Hz, 6H), 0.97 (t, J = 8.0 Hz, 3H)。
Embodiment 2:
To formula (1) compound (10-5M) ethanol solution is separately added into the Mg of 2 equivalents2+, Ca2+, Al3+,Sn2+, Pb2+,
Cr3+, Mn2+, Fe3+, Co2+,Ni2+,Zn2+,Cd2+,Pd2+,Hg2+And Ag+After, survey it strong in 465nm and 585nm fluorescent emission
Degree ratio change discovery: formula (1) compound is to Cu2+There is the fluorescence selectivity of uniqueness, add the Cu of 1 equivalent2+After, compound 1 exists
At 465nm, fluorescence intensity substantially reduces, and meanwhile, at 585nm, fluorescence intensity is remarkably reinforced, I585/I465 =3.35, such as Fig. 2 institute
Show.
Embodiment 3:
In formula (1) compound (10-5The Cu of M) and 1 equivalent2+Ethanol solution in be separately added into the Mg of 2 equivalents2+, Ca2+, Al3+,
Sn2+, Pb2+,Cr3+, Mn2+, Fe3+, Co2+,Ni2+,Zn2+,Cd2+,Pd2+,Hg2+And Ag+After, survey it glimmering at 465nm and 585nm
Light emissive porwer ratio change discovery: formula (1) compound has stronger antijamming capability to other ions, as shown in Figure 3.
Claims (2)
1. imidazo [1,5-a] pyridine-rhodamine bigcatkin willow aldehydes Cu2+Ratio fluorescent probe, it is characterised in that: it is imidazoles
And the substituted rhodamine salicylide of [1,5-a] pyridine, its chemical structural formula as the formula (1):
Formula (1) compound in ethanol solution to Cu2+There is the fluorescence selectivity of uniqueness.
2. the synthesis side of imidazo described in claim 1 [1,5-a] pyridine-rhodamine bigcatkin willow aldehydes Cu2+ ratio fluorescent probe
Method, it is characterised in that: in ethanol solution, imidazo [1,5-a] pyridine-rhodamine hydrazides is fed intake according to 1:1 with salicylide
Ratio, back flow reaction 3-7 hour under 80 degree, obtain the substituted rhodamine salicylide of imidazo [1,5-a] pyridine.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107501285A (en) * | 2017-09-08 | 2017-12-22 | 中国地质大学（武汉） | A kind of water-soluble rhodamine base ionic liquid probe of bimetallic ion selectivity Division identification and preparation method, application |
| CN108219773A (en) * | 2016-12-23 | 2018-06-29 | 泰山医学院 | Pyridine [1,2-a] and benzimidizole derivatives class Hg2+Ratio fluorescent probe and its application |
| CN108219772A (en) * | 2016-12-23 | 2018-06-29 | 泰山医学院 | Imidazoles [1,5-a] and pyridine derived species Hg2+Ratio fluorescent probe and its application |
| CN108299427A (en) * | 2018-03-22 | 2018-07-20 | 泰山医学院 | Imidazopyridine Ben Bing oxadiazole class cysteine ratio fluorescent probes and its application |
| CN108484644A (en) * | 2018-05-23 | 2018-09-04 | 泰山医学院 | The rhodamine hydrazides Cu of pyrazolo [1,5-a] pyridine substitution2+Ratiometric fluorescent probe and its application |
| CN109781678A (en) * | 2017-11-14 | 2019-05-21 | 泰山医学院 | A kind of preparation and application of the ratio fluorescent probe detected applied to hypochlorous acid in mitochondria |
| CN110498794A (en) * | 2018-05-18 | 2019-11-26 | 泰山医学院 | The pyridine derived species Pd of imidazo [1,2-a]2+Fluorescence probe and its application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105524079A (en) * | 2016-02-04 | 2016-04-27 | 泰山医学院 | Ratio-type pH fluorescence probe for water-soluble locating lysosome as well as preparation method, application and test method of ratio-type pH fluorescence probe |
-
2016
- 2016-05-24 CN CN201610347019.2A patent/CN106083897B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105524079A (en) * | 2016-02-04 | 2016-04-27 | 泰山医学院 | Ratio-type pH fluorescence probe for water-soluble locating lysosome as well as preparation method, application and test method of ratio-type pH fluorescence probe |
Non-Patent Citations (3)
| Title |
|---|
| JINGHUI CHENG ET AL.: "Fluorescent metal ion chemosensors via cation exchange reactions of complexes, quantum dots,and metal–organic frameworks", 《ANALYST》 * |
| JIUSI JIA ET AL.: "Mesoporous silica doped with a chemosensor based on phosphorescent copper(I) complex: Synthesis, characterization, photophysical property, and sensing behavior towards molecular oxygen", 《SYNTHETIC METALS》 * |
| TAO LIU ET AL.: "Enhancing Detection Sensitivity of Responsive Microgel-Based Cu(II) Chemosensors via Thermo-Induced Volume Phase Transitions", 《CHEM.MATER.》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108219773A (en) * | 2016-12-23 | 2018-06-29 | 泰山医学院 | Pyridine [1,2-a] and benzimidizole derivatives class Hg2+Ratio fluorescent probe and its application |
| CN108219772A (en) * | 2016-12-23 | 2018-06-29 | 泰山医学院 | Imidazoles [1,5-a] and pyridine derived species Hg2+Ratio fluorescent probe and its application |
| CN107501285A (en) * | 2017-09-08 | 2017-12-22 | 中国地质大学（武汉） | A kind of water-soluble rhodamine base ionic liquid probe of bimetallic ion selectivity Division identification and preparation method, application |
| CN109781678A (en) * | 2017-11-14 | 2019-05-21 | 泰山医学院 | A kind of preparation and application of the ratio fluorescent probe detected applied to hypochlorous acid in mitochondria |
| CN109781678B (en) * | 2017-11-14 | 2022-03-18 | 山东第一医科大学(山东省医学科学院) | Preparation and application of ratiometric fluorescent probe applied to intramitochondrial hypochlorous acid detection |
| CN108299427A (en) * | 2018-03-22 | 2018-07-20 | 泰山医学院 | Imidazopyridine Ben Bing oxadiazole class cysteine ratio fluorescent probes and its application |
| CN110498794A (en) * | 2018-05-18 | 2019-11-26 | 泰山医学院 | The pyridine derived species Pd of imidazo [1,2-a]2+Fluorescence probe and its application |
| CN110498794B (en) * | 2018-05-18 | 2022-02-01 | 山东第一医科大学(山东省医学科学院) | Imidazo [1,2-a ] pyridine derivative Pd2+ fluorescent probe and application thereof |
| CN108484644A (en) * | 2018-05-23 | 2018-09-04 | 泰山医学院 | The rhodamine hydrazides Cu of pyrazolo [1,5-a] pyridine substitution2+Ratiometric fluorescent probe and its application |
| CN108484644B (en) * | 2018-05-23 | 2019-06-21 | 泰山医学院 | The rhodamine hydrazides Cu that pyrazolo [1,5-a] pyridine replaces2+Ratiometric fluorescent probe and its application |
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