CN101805362B - Porphyrin modified by diethylenetriamine pentaacetic acid gadolinium and preparation method and application thereof - Google Patents
Porphyrin modified by diethylenetriamine pentaacetic acid gadolinium and preparation method and application thereof Download PDFInfo
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- CN101805362B CN101805362B CN 201010135433 CN201010135433A CN101805362B CN 101805362 B CN101805362 B CN 101805362B CN 201010135433 CN201010135433 CN 201010135433 CN 201010135433 A CN201010135433 A CN 201010135433A CN 101805362 B CN101805362 B CN 101805362B
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Abstract
The invention discloses porphyrin modified by diethylenetriamine pentaacetic acid gadolinium and a preparation method and application thereof. The porphyrin modified by diethylenetriamine pentaacetic acid gadolinium has the following structure (I) shown in the specification of the invention. The porphyrin modified by diethylenetriamine pentaacetic acid gadolinium has favorable water solubility and higher biomagnetic effect. Through large quantity of grope by the inventor, the orphyrin modified by diethylenetriamine pentaacetic acid gadolinium has high enhancement in clinical MRI (Magnetic Resonance Imaging) and also stronger fluorescence quantum yield, strong fluorescent effect and wide application prospect and can be applied to the fields of nonlinear photoelectric materials, magnetic resonance imaging diagnosis, fluorescent molecular probes and the like. A preparation method of a porphyrin contrast agent modified by the diethylenetriamine pentaacetic acid gadolinium is concise and easy to operate.
Description
Technical field
The present invention relates to a kind of porphyrin, relate to a kind of porphyrin and Preparation method and use of modified by diethylenetriamine pentaacetic acid gadolinium particularly.
Background technology
Nuclear magnetic resonance radiography (MRI) technology has been widely used in the diagnosis of multiple disease, and more produce effects is really to cardiovascular disorder and tumour.The MRI contrast medium is one type of medicine that can strengthen healthy tissues and the contrast of pathological tissues magnetic resonance signal, show organ dysfunction and body fluid situation; The paramagnetic metal complex Gd (diethylene triaminepentaacetic acid(DTPA)) that uses as MR I contrast medium has better biocompatibility with human body, is widely used clinically.Found afterwards that the Gd-diethylene triaminepentaacetic acid(DTPA) also came with some shortcomings, the no specificity that distributes in, the body too fast as eliminating can not obviously be improved the MRI image comparison.Porphyrin can optionally be enriched in tumor tissues, has been used as photodynamic therapy and MR I diagnosis to tumour.TSPP (Mn) is a research porphyrin class contrast medium early
[2], make its Gd coordination compound research fewer owing to the cavity of porphyrin ring is limited.Simultaneously, porphyrin has good light, and oxygen and thermostability all have extensively and important use in a lot of fields.Especially the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium is extensive just day by day with its unique absorption and the application of fluorescent characteristic in biochemical analysis.Porphyrin is as extensive application such as photovaltaic material, photo-dynamical medicine, laser dyess in addition.How increasing its water-soluble and biocompatibility is to promote porphyrin in the biomedical sector key in application.At present method commonly used is to introduce sulfonic acid group through sulfonylation in this field, and waits and improve its solvability through introducing carboxyl.But the introducing or the introducing of sulfonic acid group that are carboxyl are to all few of raising of the biocompatibility of porphyrin.
Summary of the invention
The objective of the invention is to overcome the deficiency of prior art, provide to have high paramagneticly, have the porphyrin of the modified by diethylenetriamine pentaacetic acid gadolinium of excellent biological compatibility.
Second purpose of the present invention provides the preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
The 3rd purpose of the present invention provides the purposes of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Technical scheme of the present invention is summarized as follows:
The porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium has following structure (I):
Wherein M is H, Fe, Mn, Cu, Zn, Co, Pt or Mg;
R1＝-X-Y；
R2=-X-Y ,-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R3=-X-Y ,-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R4=-X-Y ,-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
N=2,3,4,5 or 6;
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with porphyrin compound (II), diethylene-triamine pentaacetic acid dicyclo acid anhydride, triethylamine is dissolved in the organic solvent; 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room reaction 12-36h; Add entry, leave standstill, treat that deposition is separated out fully after; Successively with the washing of methylene dichloride, ethanolic soln, recrystallization obtains the pure article of the porphyrin compound that diethylene-triamine pentaacetic acid modifies; Said organic solvent is DMSO 99.8MIN., N, dinethylformamide or pyridine;
(2) porphyrin compound of diethylene-triamine pentaacetic acid modification is soluble in water, add Gadolinium trichloride, regulate the pH value to 7-8, stirring reaction 12-30h under the room temperature adopts ethanol/ether to carry out recrystallization, obtains the porphyrin (I) of modified by diethylenetriamine pentaacetic acid gadolinium;
The structural formula of said porphyrin compound (II) is:
Wherein M is H, Fe, Mn, Cu, Zn, Co, Pt or Mg;
R1＝-X-H；
R2=-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R3=-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R4=-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
N=2,3,4,5 or 6.
Said step (1) is preferably: with the porphyrin compound (II) of 0.2-0.5g, and the diethylene-triamine pentaacetic acid dicyclo acid anhydride of 0.50-3.0g, the triethylamine of 0.2.0-2.0mL is dissolved in the organic solvent of 10-30ml; 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room reaction 12-36h; Add 10-40ml water, leave standstill, treat that deposition is separated out fully after; Successively with the washing of methylene dichloride, ethanolic soln, recrystallization obtains the pure article of the porphyrin compound that diethylene-triamine pentaacetic acid modifies; Said organic solvent is DMSO 99.8MIN., N, dinethylformamide or pyridine.
Said step (2) is preferably: the porphyrin compound that the diethylene-triamine pentaacetic acid of 0.2-0.8g is modified is dissolved in the 10-50ml water; The Gadolinium trichloride that adds 0.1-1.0g; Regulate the pH value to 7-8; Stirring reaction 12-30h under the room temperature, the employing volume ratio is that ethanol/ether of 1: 1 carries out recrystallization, obtains the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
The porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium is in the preparation contrast Material Injection Protocols.
The porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium is in the application of preparation fluorescent probe.
The porphyrin good water solubility of modified by diethylenetriamine pentaacetic acid gadolinium of the present invention, and have higher relaxation effect, the porphyrin of each modified by diethylenetriamine pentaacetic acid gadolinium of the present invention gropes in a large number that through the contriver very high enhancement can be arranged in the clinical MRI imaging; Has stronger fluorescence quantum yield simultaneously; Very strong fluorescent effect is arranged in the fluorescence imaging, have broad application prospects, can be applicable to the nonlinear optical electric material; The diagnosis of mr imaging, fields such as fluorescent molecular probe.The succinct easy handling of preparation method of the porphyrin contrast medium of modified by diethylenetriamine pentaacetic acid gadolinium of the present invention.
Description of drawings
Fig. 1 is the uv-spectrogram of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium of the present invention;
Fig. 2 is the mass spectrum of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium of the present invention;
Fig. 3 is the infrared spectrum of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium of the present invention;
Fig. 4 is the porphyrin contrast medium (performance in the body) of modified by diethylenetriamine pentaacetic acid gadolinium;
Fig. 5 is the porphyrin contrast medium (external performance) of modified by diethylenetriamine pentaacetic acid gadolinium;
Fig. 6 is the porphyrin fluorescent probe (external fluorescence) of modified by diethylenetriamine pentaacetic acid gadolinium;
Fig. 7 is the porphyrin fluorescent probe (fluorescence in the body) of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment
Below in conjunction with specific embodiment the present invention is further described.Following embodiment just is used for the present invention is described but does not limit the present invention.
(1) with 0.2g 5,10,15,20-four-[right-aminophenyl] porphyrin, 1.4g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 1.0ml is dissolved in the DMSO 99.8MIN. of 15ml, 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 12h.After reaction finishes, add 30mL water, leave standstill, separate out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
(2) take by weighing the porphyrin compound that the 0.6g diethylenetriamine pentaacetic acid modifies and be dissolved in the 50ml water, add the 0.54g Gadolinium trichloride, transfer pH to 7.0-8.0, induction stirring 12h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, structure is: (I)
Wherein: X is H for
M
The uv-spectrogram of the porphyrin of product modified by diethylenetriamine pentaacetic acid gadolinium is seen Fig. 1, and mass spectrum is seen Fig. 2 ([M-1]
-4=697.34), infrared spectrum is seen Fig. 3.
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with 0.5g 5-(4-aminophenyl)-10,15,20-phenyl porphyrin, 1.2g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 0.5ml is dissolved in the 20mL pyridine, 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 36h.After reaction finishes, add 30mLH
2O separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization, the porphyrin compound modified of diethylenetriamine pentaacetic acid;
(2) claim that the porphyrin compound that the 0.3g diethylenetriamine pentaacetic acid is modified is dissolved in the 30ml water, add the 0.29g Gadolinium trichloride, transfer pH to 7.0-8.0, induction stirring 20h.Steam and remove 8mL water, pour reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration obtains the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, and structure is: (I)
Wherein: X is H for
M.
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with 0.5g 5,10-two (4-aminophenyl)-15,20-phenylbenzene porphyrin, 2.0g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 2.0ml are dissolved among N, the dinethylformamide 30mL, 4, under the catalysis of 4-Dimethylamino pyridine, stir 36h under the room temperature.After reaction finishes, add 30mLH
2O separates out product, suction filtration, and with 6ml washed with dichloromethane 3 times, 10ml washing with alcohol 3 times, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
(2) take by weighing the porphyrin compound that the 0.6g diethylenetriamine pentaacetic acid modifies and be dissolved in the 50ml water, add the 0.68g Gadolinium trichloride, transfer pH to 7.0-8.0, induction stirring reaction 30h.Steam and remove 10mL water, pour reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, structure is: (I)
Wherein: X is H for
M.
Embodiment 4
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with 0.350g 5,10,15-three (4-aminophenyl)-20-phenyl porphyrin, 1.4g diethylenetriamine pentaacetic acid dicyclo acid anhydride (1.9 * 10
-3Mol), the triethylamine of 2.0ml is dissolved in the 20mL DMSO 99.8MIN., 4, and under the catalysis of 4-Dimethylamino pyridine, stirring at room 24h.After reaction finishes, add 40mLH
2O separates out product, and suction filtration obtains bullion.With 5ml washed with dichloromethane 3 times, 5ml washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
(2) take by weighing the porphyrin compound that the 0.6g diethylenetriamine pentaacetic acid modifies and be dissolved in the 50ml water, add the 0.86g Gadolinium trichloride, transfer pH to 7.0-8.0, induction stirring, reaction 30h.Steam and remove 10mL water, pour reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, structure is: (I)
Wherein: X is H for
M.
Embodiment 5
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with 0.4g 5,10,15,20-four-[4-aminophenyl] porphyrin (Cu); 1.8g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 2.0ml are dissolved in the 10mL DMSO 99.8MIN., 4, under the catalysis of 4-Dimethylamino pyridine; Stirring at room 12h adds 30mL water, separates out product.Suction filtration obtains bullion.With 5ml washed with dichloromethane 3 times, 5ml washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
(2) take by weighing the porphyrin compound that the 0.6g diethylenetriamine pentaacetic acid modifies and be dissolved in the 30ml water, add the 0.78g Gadolinium trichloride, transfer pH to 7.0-8.0, induction stirring, reaction 12h steams and removes 5mL water, pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, structure is: (I)
Wherein: X is Cu for
M.
Embodiment 6
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 0.2ml is dissolved in the 20mL pyridine, and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=2; M is Fe
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.1g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 7
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 0.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=5; M is Mg;
(2) take by weighing the porphyrin compound 0.8g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 1.0g, transfer pH to 8.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 8
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 0.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=6; M is Zn;
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.5g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 9
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 0.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=3; M is Co;
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.6g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 10
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 1.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=4; M is Pt;
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.1g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 11
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 1.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=4; M is Mn
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.1g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 12
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 1.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=4; M is Cu;
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.1g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 13
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 1.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=4; M is H;
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.1g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 14
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium comprises the steps:
(1) with the porphyrin compound (II) of 0.4g, 2.5g diethylenetriamine pentaacetic acid dicyclo acid anhydride, the triethylamine of 1.2ml is dissolved in the 20mL DMSO 99.8MIN., and 4, under the catalysis of 4-Dimethylamino pyridine, stirring at room 14h adds 10mL water, separates out product.Suction filtration obtains bullion.With washed with dichloromethane 3 times, washing with alcohol 3 times, drying, recrystallization obtains the porphyrin compound that diethylenetriamine pentaacetic acid is modified;
The porphyrin compound of present embodiment (II), wherein
n=4; M is Pt;
(2) take by weighing the porphyrin compound 0.2g that diethylenetriamine pentaacetic acid modifies and be dissolved in the 20ml water, add Gadolinium trichloride 0.4g, transfer pH to 7.0, induction stirring, reaction 15h pours reaction solution into 30mL (CH
3CH
2OH: (CH
3CH
2)
2O=1: 1) separate out product in the mixed solution, suction filtration, the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
Embodiment 15
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5,10,15,20-four-[right-hydroxy phenyl] porphyrin, other are with embodiment 1.
Embodiment 16
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5-[right-hydroxy phenyl]-10,15,20 phenyl porphyrins, other are with embodiment 1.
Embodiment 17
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5,10-[right-hydroxy phenyl]-15,20-phenyl porphyrin, other are with embodiment 1.
Embodiment 18
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5,10,15,20-four-[right-hydroxy ethoxy formyl radical phenyl] porphyrin, other are with embodiment 1.
Embodiment 19
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5,15-four-[right-hydroxy ethoxy formyl radical phenyl]-10,20-phenyl porphyrin, other are with embodiment 1.
Embodiment 20
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5-[right-ammonia ethoxy acetyl phenyl]-10,15,20-phenyl porphyrin, other are with embodiment 1.
Embodiment 21
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5-[right-the ammonia ethoxyl phenenyl]-10,15,20-phenyl porphyrin, other are with embodiment 1.
Embodiment 22
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5-[right-the hydroxyethylamino phenyl]-10,15,20-phenyl porphyrin, other are with embodiment 1.
Embodiment 23
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5,10-[right-the hydroxyethylamino phenyl]-15,20-phenyl porphyrin, other are with embodiment 1.
Embodiment 24
The preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, the porphyrin compound (II) in the step (1) is 5,10-[right-the aminoethyl aminophenyl]-15,20-phenyl porphyrin, other are with embodiment 1.
Embodiment 25
The porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium is in the preparation contrast Material Injection Protocols.
With 5,10,15,20-four-[right-aminophenyl] porphyrin is that the porphyrin compound of the modified by diethylenetriamine pentaacetic acid gadolinium that obtains of raw material is an example, with D
2O is a solvent, and the solution of preparation series concentration 1mmol/L, 0.5mmol/L, 0.1mmol/L, 0.01mmol/L under the 400M NMR, records its relaxation time (T
1), i.e. 1/T
1Relation such as Fig. 4 with concentration; With saline water preparation 1mmol/L contrast medium, under mr imaging appearance, intravenous injection 200ul obtains it and is image signal and strengthens and see Fig. 5 in the mouse body, and the mark position is a tumor locus among the figure.
Embodiment 26
The porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium is as the application of fluorescent probe at the living body fluorescent imaging
With 5,10,15,20-four-[right-aminophenyl] porphyrin is that the porphyrin compound of the modified by diethylenetriamine pentaacetic acid gadolinium that obtains of raw material is an example, and compound concentration is the 10-5mmol/L aqueous solution, as excitation wavelength, measures its emmission spectrum such as Fig. 6 with 420nm; With the saline water compound concentration is the aqueous solution of 1mmol/L; Tail vein injection 200ul is in the mouse body, and scanning is the light source activation wavelength with 465nm under the living body fluorescent imager; Gather the fluorescence imaging picture with 700nm for the fluorescent emission wavelength, obtain its fluorescence imaging enhancing and see Fig. 7.
Claims (6)
1. the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium, its characteristic has following structure (I):
Wherein M is H, Fe, Mn, Cu, Zn, Co, Pt or Mg;
R1＝-X-Y；
R2=-X-Y ,-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R3=-X-Y ,-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R4=-X-Y ,-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
N=2,3,4,5 or 6;
2. the preparation method of the porphyrin of claim 1 modified by diethylenetriamine pentaacetic acid gadolinium is characterized in that comprising the steps:
(1) with porphyrin compound (II), diethylene-triamine pentaacetic acid dicyclo acid anhydride, triethylamine is dissolved in the organic solvent; Under the catalysis of 4-Dimethylamino pyridine, stirring at room reaction 12-36h adds entry; Leave standstill, treat that deposition is separated out fully after, wash with methylene dichloride, ethanolic soln successively; Recrystallization obtains the pure article of the porphyrin compound that diethylene-triamine pentaacetic acid modifies; Said organic solvent is DMSO 99.8MIN., N, dinethylformamide or pyridine;
(2) porphyrin compound of diethylene-triamine pentaacetic acid modification is soluble in water, add Gadolinium trichloride, regulate the pH value to 7-8, stirring reaction 12-30h under the room temperature adopts ethanol/ether to carry out recrystallization, obtains the porphyrin (I) of modified by diethylenetriamine pentaacetic acid gadolinium;
The structural formula of said porphyrin compound (II) is:
Wherein M is H, Fe, Mn, Cu, Zn, Co, Pt or Mg;
R1＝-X-H；
R2=-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R3=-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
R4=-X-H ,-H ,-OCH
3,-CH
3Or-COOH;
N=2,3,4,5 or 6.
3. the preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium according to claim 2 is characterized in that said step
(1) be: with the porphyrin compound (II) of 0.2-0.5g, the diethylene-triamine pentaacetic acid dicyclo acid anhydride of 0.50-3.0g, the triethylamine of 0.2-2.0mL is dissolved in the organic solvent of 10-30ml; Under the catalysis of 4-Dimethylamino pyridine, stirring at room reaction 12-36h adds 10-40ml water; Leave standstill, treat that deposition is separated out fully after, wash with methylene dichloride, ethanolic soln successively; Recrystallization obtains the pure article of the porphyrin compound that diethylene-triamine pentaacetic acid modifies; Said organic solvent is DMSO 99.8MIN., N, dinethylformamide or pyridine.
4. the preparation method of the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium according to claim 2; It is characterized in that said step (2) is: the porphyrin compound that the diethylene-triamine pentaacetic acid of 0.2-0.8g is modified is dissolved in the 10-50ml water; The Gadolinium trichloride that adds 0.1-1.0g is regulated the pH value to 7-8, stirring reaction 12-30h under the room temperature; The employing volume ratio is that ethanol/ether of 1: 1 carries out recrystallization, obtains the porphyrin of modified by diethylenetriamine pentaacetic acid gadolinium.
5. the porphyrin of the modified by diethylenetriamine pentaacetic acid gadolinium of claim 1 is in the preparation contrast Material Injection Protocols.
6. the porphyrin of the modified by diethylenetriamine pentaacetic acid gadolinium of claim 1 is in the application of preparation fluorescent probe.
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| CN102499924B (en) * | 2011-11-23 | 2013-07-24 | 中国医学科学院生物医学工程研究所 | Application of porphyrin modified by diethylene triamine pentaacetic acid or ethylene diamine tetraacetic acid or ethylene diamine tetraacetic acid |
| CN102408745B (en) * | 2011-11-25 | 2014-06-18 | 北京科技大学 | Asymmetrical dye molecule adopting tetraphenylporphin as core, and preparation method thereof |
| CN103143013B (en) * | 2013-01-04 | 2015-03-04 | 中国医学科学院生物医学工程研究所 | Photosensitive medicinal preparation containing amino poly-carboxylic acid modification tetraphenylporphyrin compound and purpose thereof |
| CN103242411A (en) * | 2013-05-28 | 2013-08-14 | 中国医学科学院生物医学工程研究所 | Preparation method and application of novel cholalic acid-porphyrin conjugate |
| CN107880061B (en) * | 2016-09-30 | 2019-11-01 | 中国科学院武汉物理与数学研究所 | A kind of multi-functional cave kind-porphyrin compound and its synthetic method and application |
| CN108314695B (en) * | 2018-01-04 | 2020-06-16 | 南京邮电大学 | Preparation and application of heterogeneous dual-core metal complex |
| CN111004623B (en) * | 2019-12-20 | 2023-07-18 | 河北科技大学 | Porphyrin fluorescent material and preparation method thereof |
| CN113583011A (en) * | 2021-08-31 | 2021-11-02 | 安徽清科瑞洁新材料有限公司 | Water-soluble porphyrin carboxylate and preparation method and application thereof |
| CN113735884B (en) * | 2021-09-22 | 2022-05-17 | 同济大学 | Porphyrin covalent connection molybdenum disulfide nonlinear nano hybrid material and preparation and application thereof |
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