CN107573365A - A kind of double copper complex dicopper complex4-amino-3s and preparation method with SOD enzyme activity - Google Patents
A kind of double copper complex dicopper complex4-amino-3s and preparation method with SOD enzyme activity Download PDFInfo
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- CN107573365A CN107573365A CN201710827895.XA CN201710827895A CN107573365A CN 107573365 A CN107573365 A CN 107573365A CN 201710827895 A CN201710827895 A CN 201710827895A CN 107573365 A CN107573365 A CN 107573365A
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Abstract
The invention discloses a kind of double copper complex dicopper complex4-amino-3s with SOD enzyme activity and preparation method thereof, the complex is by double the 1 of a tool isopropyl side arm, 4,7 7-triazacyclononane compounds are obtained as part and copper chloride in the organic solvents such as methanol by the solution-phase reaction of routine, and synthesized complex is a dicopper complex4-amino-3 [Cu2LCl4], the complex show it is more existing be based on Isosorbide-5-Nitrae, the more excellent superoxide anion (O of the SOD enzyme mimics of 7 7-triazacyclononane derivatives2 ‑) Scavenging activity.
Description
Technical field
The present invention relates to bioinorganic chemistry and study of pharmacy field, and in particular to a kind of double with SOD enzyme activity
Copper complex dicopper complex4-amino-3 and preparation method.
Background technology
When cellular respiration and it is metabolic when can produce O2-。、H2O2、OH。Etc. different types of active oxygen radical, these
Free radical can cause cellular damage when building up to higher concentration in vivo, and then trigger body aging and inflammation, fill again
Note damage or nerve degenerative diseases.Substantial amounts of result of study shows, is widely present one kind in vivo and is directed to super oxygen
Ion O2-。Important antioxidase, it have catalysis superoxide ion decompose function, by disproportionated reaction mistake in organism
The superoxide ion O2 of amount-。Decomposition and inversion is O2And H2O2, this antioxidant is named as superoxide dismutase, abbreviation SOD
Enzyme.
Currently with double Isosorbide-5-Nitraes, 7- 7-triazacyclononane derivatives prepare the research of superoxide dismutase manual simulation's thing
Abundant achievement is achieved, mainly with the non-substituted double Isosorbide-5-Nitraes of ring skeleton N atoms, 7- 7-triazacyclononane derivatives in research
Or ring skeleton N atoms are connected with double Isosorbide-5-Nitraes of coordinating pendant arms, 7- 7-triazacyclononane derivatives are as synthesized by macrocyclic ligand
Copper, manganese, nickel complex are as superoxide dismutase manual simulation's thing.
So far, using double Isosorbide-5-Nitraes, 7- 7-triazacyclononane derived ligands have synthesized the abundant SOD enzyme moulds of species
Intend thing, they have also shown certain enzymatic activity.But utilize the non-substituted double Isosorbide-5-Nitraes of skeleton N atoms, 7- 7-triazacyclononanes
The SOD enzyme mimics of derived ligand synthesis easily easily form inactive/weaker dimer species of activity under solution state；And
By being connected with double Isosorbide-5-Nitraes of coordinating pendant arms on skeleton N atoms, though the SOD enzyme mimics of 7- 7-triazacyclononanes derived ligand synthesis
Dimer can be so avoided the formation of by the space steric effect of side arm, but due to tradable coordination site around metal ion
Reduction and the steric hindrance of side arm itself, also resulting in the SOD enzyme activity of analogies reduces.
In summary, it is existing based on double Isosorbide-5-Nitraes, the enzymatic activity of the SOD enzyme mimics of 7- 7-triazacyclononane derived ligands
Larger gap still be present in the activity apart from natural SOD enzymes.
The content of the invention
The purpose of the present invention is that to solve the low problem of enzymatic activity of existing SOD enzyme mimics and provides a kind of tool
There are double copper complex dicopper complex4-amino-3s of SOD enzyme activity（Hereinafter referred to as " dicopper complex4-amino-3 [Cu2LCl4]”）And preparation side
Method.
The present invention is achieved through the following technical solutions above-mentioned purpose：
Dicopper complex4-amino-3 [Cu2LCl4], it is in double macrocyclic ligand Isosorbide-5-Nitraes-two [4,7- bis- based on tool isopropyl side arm（Isopropyl
Base）- Isosorbide-5-Nitrae, 7- 7-triazacyclononane -1- methyl] benzene（L）（Hereinafter referred to as " double macrocyclic ligand L "）The double-core copper prepared is matched somebody with somebody
Compound [Cu2LCl4]。
Dicopper complex4-amino-3 [Cu2LCl4], its preparation method comprises the following steps：
The first step, by double macrocyclic ligand L and copper chloride according to 1:2 mol ratio is added in methanol, resulting solution back flow reaction,
Produce green precipitate；
Second step, reaction are filtered under diminished pressure after terminating, wash precipitation with methanol, spontaneously dry at room temperature, it is in green powder to obtain
Product is dicopper complex4-amino-3 [Cu2LCl4]。
Dicopper complex4-amino-3 [Cu2LCl4], double macrocyclic ligand L synthesis step includes needed for its preparation：
The first step, by [Isosorbide-5-Nitrae, the 7- 7-triazacyclononane -1- methyl] benzene of Isosorbide-5-Nitrae-two and 2- N-Propyl Bromides according to 1：4~1：8 mol ratio
It is mixed in anhydrous acetonitrile；
Second step, add Anhydrous potassium carbonate solid, reactant mixture heating response under nitrogen protection；
3rd step, reaction are depressurized after terminating and filtered, and are collected filtrate, are removed acetonitrile, obtain buff grease；
4th step, the grease is dissolved with distilled water, is extracted with chloroform, merge chloroform phase, removed through drying, filtering, decompression molten
Double macrocyclic ligand L are obtained after agent.
Beneficial effect is：Because isopropyl noncoordinating on part can effectively prevent inactive/weak active dimer
Formation, while ensure that metal active centres nearby have enough commutative coordination sites and are used to combine superoxide anion,
So that the dicopper complex4-amino-3 [Cu2LCl4] there is excellent SOD enzyme activity.
Brief description of the drawings
Fig. 1 is dicopper complex4-amino-3 [Cu in the present invention2LCl4] molecular structure；
Fig. 2 is the synthetic route schematic diagram of double macrocyclic ligand L in the present invention；
Fig. 3 is dicopper complex4-amino-3 [Cu in the present invention2LCl4] influence schematic diagram of the concentration to NBT rates of reduction；
Fig. 4 is in the present inventionV 0/V cat -1To dicopper complex4-amino-3 [Cu2LCl4] concentration map.
Description of reference numerals is as follows：
V 0Expression is not added with dicopper complex4-amino-3 [Cu2LCl4] when NBT rate of reduction；V catRepresent the double-core copper of addition various concentrations
Complex [Cu2LCl4] when NBT rate of reduction.
Embodiment
The invention will be further described below in conjunction with the accompanying drawings：
（One）Double macrocyclic ligand L synthesis（Fig. 2）, its synthetic method is as follows：
50 mL anhydrous acetonitriles, 2 g potassium carbonate, 1.16 g Isosorbide-5-Nitraes-two [Isosorbide-5-Nitrae, 7- are sequentially added in 250 mL three-neck flask
7-triazacyclononane -1- methyl] benzene and 1.59 ~ 3.18 g 2- N-Propyl Bromides, resulting mixed liquor is under nitrogen protection in 80
DEG C heating response 24 hours；Decompression filters, and collects filtrate, removes acetonitrile under reduced pressure, obtain buff grease；Add 25 mL distillations
Water dissolves grease, uses chloroform（3×50 mL）Extraction, merge chloroform phase, dry half an hour through anhydrous magnesium sulfate, steamed with rotation
Send out instrument and remove solvent, obtain double macrocyclic ligands of yellow（L）.
Yield:1.26 g, yield：74%.Elementary analysis C32H60N6：Theoretical value C 72.67, H 11.44, N
15.89；Calculated value：C 72.64, H 11.40, N 15.95%.Infrared spectrum (KBr, cm –1)：3473(s), 2948(s),
2840(m), 1652(s), 1463(s), 1362(m), 1158(s), 829(w), 711(m).Electrospray ionization mass spectrum：m/z =
529.6 [L + H]+。
（Two）Dicopper complex4-amino-3 [Cu2LCl4] preparation
Dicopper complex4-amino-3 [Cu2LCl4] it is by double Isosorbide-5-Nitraes of a tool isopropyl side arm, 7- 7-triazacyclononane compound conducts
Part is obtained with copper chloride in the organic solvents such as methanol by the solution-phase reaction of routine, and concrete operations are as follows：
53 mg Isosorbide-5-Nitraes-two [4,7- bis- are added into 50 mL round-bottomed flasks（Isopropyl）- Isosorbide-5-Nitrae, 7- 7-triazacyclononane -1- first
Base] benzene（L）As part, the first that 5 mL are dissolved with 34 mg Copper dichloride dihydrates is added dropwise into flask by dropping funel
Alcoholic solution；Mixed solution produced green precipitate in 80 DEG C of back flow reactions 3 hours in course of reaction；Reaction is cooled to room after terminating
Temperature, it is filtered under diminished pressure, and uses methanol（3×5 mL）Washing precipitation, spontaneously dries, obtains dicopper complex4-amino-3 [Cu at room temperature2LCl4]
Be in green powder product.
Yield：62 mg, yield：76%.Elementary analysis C32H60Cl4Cu2N6：Theoretical value C 48.24, H 7.54, N
10.55%；Calculated value C 48.18, H 7.46, N 10.61%.Infrared spectrum (KBr, cm –1)：3485(s), 2935(s),
2851(m), 1642(s), 1458(s), 1369(m), 1165(s), 827(w), 719(m).Electrospray ionization mass spectrum：m/z =
363.1 [Cu2LCl2] + 。
Resulting dicopper complex4-amino-3 [Cu2LCl4], two Cu (II) ions are in by copper complex skeleton nitrogen-atoms
And in the coordination sphere that forms of two chlorions, noncoordinating isopropyl can effectively prevent inactive/weak active two on part
The formation of aggressiveness, and the commutative coordination site that metal active centres are nearby occupied by chlorion can be used for combining superoxide ion, it is right
SOD enzyme activity is presented in complex to play a crucial role.
（Three）Dicopper complex4-amino-3 [Cu2LCl4] SOD enzyme activity test
Reaction in-situ is occurred by xanthine (XO) and xanthine oxidase (XOD) and produces O2 •-, use NBT
(NBT) it is used as superoxide anion（O2 •-）Indicator, indirect determination dicopper complex4-amino-3 [Cu2LCl4] SOD enzyme activity.Because
NBT can be by O2 •-Reduction generates blue formazans.When adding SOD enzymes or its analogies, they can compete O with NBT2 •-And
Make O2 •-Generation disproportionated reaction.The maximal ultraviolet visible absorbance of formazan adds dicopper complex4-amino-3 [Cu at 550 nm2LCl4] before
Absorbance of the spectrophotometry xanthine xanthine oxidase-NBT compound systems at 550 nm is used afterwards, can measure NBT
Rate of reduction（The generating rate of Ji formazans）So that it is determined that dicopper complex4-amino-3 [Cu2LCl4] catalysis O2 •-Disproportionated reaction occurs
Speed constant andIC 50（IC 50Value is required dicopper complex4-amino-3 [the Cu when percentage of suppression NBT reduction is 50%2LCl4] it is dense
Degree）.
Specific implementation step is as follows：
Concentration is respectively configured as 3 × 10 using 10 mM PB cushioning liquid-4 M dicopper complex4-amino-3 [Cu2LCl4]、2.5×10-3 M NBT and 1.0 × 10-3 M xanthine (XD) storing solution, and with 10 mM PB cushioning liquid by xanthine oxidase
(XOD) 21 μ L/mL are diluted to.μ L of xanthine storing solution 100, the μ L of NBT storing solutions 200 and 10 mM PB are pipetted with liquid-transfering gun
The mL of buffer solution 1.7, and well mixed (cumulative volume of mixed solution is 2 mL, wherein including 250 μm of ol by above-mentioned three kinds of solution
NBT and 50 μm of ol xanthine), appropriate xanthine oxidase is added, after the dosage for determining xanthine oxidase, into system
Add isometric but various concentrations dicopper complex4-amino-3 [Cu2LCl4] solution, at 25 DEG C, made with 10 mM PB cushioning liquid
For reference solution, absorbance of each system at 550 nm is observed using ultraviolet-visual spectrometer, sets the change of absorbance
Change value is 0.024/min, and each system of continuous monitoring is in 10 min internal absorbance situations of change, each concentration system parallel determination
Three groups of data, with the dicopper complex4-amino-3 [Cu containing various concentrations2LCl4] the absorbance of system scatter diagram is made to the time, obtain
6 straight lines as shown in Figure 3 are obtained, the slope of gained straight line is the rate of reduction of NBT under different condition.V 0Expression is not added with double
Core copper complex [Cu2LCl4] when NBT rate of reduction,V catRepresent the dicopper complex4-amino-3 [Cu of addition various concentrations2LCl4]
When NBT rate of reduction.
From the figure 3, it may be seen that as the dicopper complex4-amino-3 [Cu containing various concentrations in system2LCl4] when, with formazan at 550 nm
Absorbance be plotted against time the straight slope of gained and change significantly, and with dicopper complex4-amino-3 [Cu2LCl4] concentration
The slope of increase respective straight also becomes smaller, illustrates that the complex can show SOD enzyme activity, can be catalyzed O2 •-It is disproportionated
Reaction is so as to effectively suppression NBT reduction.
WithV 0/V cat -1To dicopper complex4-amino-3 [Cu2LCl4] concentration make scatter diagram, obtain accompanying drawing 4, linear fit obtains
Straight slope beK cat/K NBT[NBT], whereinK NBTIt is NBT by O2 •-The reaction rate constant of reduction,K NBT = 5.88×104
Mol/ (Ls), by straight slope withK catRelation calculate and add dicopper complex4-amino-3 [Cu2LCl4] after reaction rate it is normal
NumberK cat,IC 50For in Fig. 3V 0/V cat -1Corresponding dicopper complex4-amino-3 [Cu when=12LCl4] concentration values.
Obtained by Fig. 3IC 50For 0.074 M,K cat = 2×108 Mol/ (Ls), dicopper complex4-amino-3 [Cu2LCl4] urge
Change disproportionation O2 •-Process close to diffusion control, the SOD enzyme activity of the complex is about as much as under equal experiment condition naturally
The 20% of Cu, Zn-SOD enzymatic activity（IC 50For 0.015 M,K cat = 109 mol/(L·s)）, be at present it is existing be based on Isosorbide-5-Nitrae,
The most excellent a kind of compound of enzymatic activity in the SOD enzyme mimics of 7- 7-triazacyclononane derived ligands.
Claims (3)
1. a kind of double copper complex dicopper complex4-amino-3s with SOD enzyme activity, the complex comprise at least following molecule
Structure：
,
Two Cu (II) ions are in the coordination sphere that is made up of copper complex skeleton nitrogen-atoms and two chlorions.
2. a kind of double copper complex dicopper complex4-amino-3s with SOD enzyme activity, its preparation method comprise the following steps：
The first step, by double macrocyclic ligand L and copper chloride according to 1:2 mol ratio is added in methanol, resulting solution back flow reaction,
Produce green precipitate；
Second step, reaction are filtered under diminished pressure after terminating, wash precipitation with methanol, spontaneously dry at room temperature, it is in green powder to obtain
Product is double copper complex dicopper complex4-amino-3s.
3. the complex according to required by claim 2, described double macrocyclic ligand L synthesis step includes：
The first step, by [Isosorbide-5-Nitrae, the 7- 7-triazacyclononane -1- methyl] benzene of Isosorbide-5-Nitrae-two and 2- N-Propyl Bromides according to 1：4~1：8 mol ratio
It is mixed in anhydrous acetonitrile；
Second step, add Anhydrous potassium carbonate solid, reactant mixture heating response under nitrogen protection；
3rd step, reaction are depressurized after terminating and filtered, and are collected filtrate, are removed acetonitrile, obtain buff grease；
4th step, the grease is dissolved with distilled water, is extracted with chloroform, merge chloroform phase, removed through drying, filtering, decompression molten
Double macrocyclic ligand L are obtained after agent.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108586499A (en) * | 2018-07-27 | 2018-09-28 | 河南中医药大学 | A kind of azacyclo- transition metal copper complex of imidazole ring-containing and its preparation method and application |
| CN108822300A (en) * | 2018-05-17 | 2018-11-16 | 陕西科技大学 | The copper coordination polymer and its preparation method and application of nitrogenous oxidative function group |
| CN114230583A (en) * | 2021-12-09 | 2022-03-25 | 江苏海洋大学 | Binuclear copper complex with biological activity, preparation method and application |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106674256A (en) * | 2016-12-15 | 2017-05-17 | 天津师范大学 | Oxalic acid bridged binuclear copper complex as well as preparation method and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106674256A (en) * | 2016-12-15 | 2017-05-17 | 天津师范大学 | Oxalic acid bridged binuclear copper complex as well as preparation method and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| MAHAPATRA, SAMIRAN ET AL.: "Binucleating Ligand Structural Effects on (μ-Peroxo)- and Bis(μ-oxo)dicopper Complex Formation and Decay: Competition between Arene Hydroxylation and Aliphatic C-H Bond Activation", 《 INORGANIC CHEMISTRY》 * |
| MAHAPATRA, SAMIRAN ET AL.: "Tuning the structure and reactivity of the [Cu2(μ-O)2]2+ core: characterization of a new bis(μ-oxo)dicopper complex stabilized by a sterically hindered dinucleating bis(triazacyclononane) ligand", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION IN ENGLISH》 * |
| WANG HONG-JUN: "Crystal Structures of Dinuclear Copper(Ⅱ) Complexesof bis (1,4,7-triazacyclononane) Ligands Containing Rigid Bridging Groups", 《结构化学》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108822300A (en) * | 2018-05-17 | 2018-11-16 | 陕西科技大学 | The copper coordination polymer and its preparation method and application of nitrogenous oxidative function group |
| CN108586499A (en) * | 2018-07-27 | 2018-09-28 | 河南中医药大学 | A kind of azacyclo- transition metal copper complex of imidazole ring-containing and its preparation method and application |
| CN114230583A (en) * | 2021-12-09 | 2022-03-25 | 江苏海洋大学 | Binuclear copper complex with biological activity, preparation method and application |
| CN114230583B (en) * | 2021-12-09 | 2023-09-08 | 江苏海洋大学 | Binuclear copper complex with bioactivity, preparation method and application |
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