CN110305146A - A kind of chain schiff bases copper complex and its preparation method and application - Google Patents
A kind of chain schiff bases copper complex and its preparation method and application Download PDFInfo
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- CN110305146A CN110305146A CN201910646979.2A CN201910646979A CN110305146A CN 110305146 A CN110305146 A CN 110305146A CN 201910646979 A CN201910646979 A CN 201910646979A CN 110305146 A CN110305146 A CN 110305146A
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- 239000002262 Schiff base Substances 0.000 title claims abstract description 66
- -1 schiff bases copper complex Chemical class 0.000 title claims abstract description 64
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 239000003446 ligand Substances 0.000 claims abstract description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims abstract description 15
- 239000010949 copper Substances 0.000 claims abstract description 14
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims abstract description 12
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 150000004699 copper complex Chemical class 0.000 claims abstract description 7
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000000126 substance Substances 0.000 claims abstract description 6
- 230000009471 action Effects 0.000 claims abstract description 5
- 230000004962 physiological condition Effects 0.000 claims abstract description 4
- 238000013459 approach Methods 0.000 claims abstract description 3
- 238000003780 insertion Methods 0.000 claims abstract description 3
- 230000037431 insertion Effects 0.000 claims abstract description 3
- 239000007800 oxidant agent Substances 0.000 claims abstract description 3
- 241000894007 species Species 0.000 claims abstract description 3
- 238000006701 autoxidation reaction Methods 0.000 claims abstract 2
- 238000002224 dissection Methods 0.000 claims abstract 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- 229910001431 copper ion Inorganic materials 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 6
- 239000013078 crystal Substances 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- 150000003983 crown ethers Chemical class 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 239000012074 organic phase Substances 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 238000010898 silica gel chromatography Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims 1
- 239000000243 solution Substances 0.000 description 13
- 238000005520 cutting process Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 150000004753 Schiff bases Chemical class 0.000 description 8
- 230000008859 change Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 230000009182 swimming Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 150000004696 coordination complex Chemical class 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000002189 fluorescence spectrum Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 229910021645 metal ion Inorganic materials 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 230000000171 quenching effect Effects 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 238000000246 agarose gel electrophoresis Methods 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000001502 gel electrophoresis Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 239000002184 metal Chemical class 0.000 description 3
- 229910052751 metal Chemical class 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000005838 radical anions Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- OWRCNXZUPFZXOS-UHFFFAOYSA-N 1,3-diphenylguanidine Chemical compound C=1C=CC=CC=1NC(=N)NC1=CC=CC=C1 OWRCNXZUPFZXOS-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 230000008304 DNA mechanism Effects 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000001857 anti-mycotic effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000002543 antimycotic Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- UDSAIICHUKSCKT-UHFFFAOYSA-N bromophenol blue Chemical compound C1=C(Br)C(O)=C(Br)C=C1C1(C=2C=C(Br)C(O)=C(Br)C=2)C2=CC=CC=C2S(=O)(=O)O1 UDSAIICHUKSCKT-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 238000002447 crystallographic data Methods 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 125000001967 indiganyl group Chemical group [H][In]([H])[*] 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
- C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
- C07F1/08—Copper compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pyridine Compounds (AREA)
Abstract
A kind of chain schiff bases copper complex, chemical formula are [Cu3(L)2(OAc)6] n, wherein L is 2- (α-pyridomethoxy) benzaldehyde contracting open-chain crown ether schiff bases, and OAc is acetate；The copper complex is monoclinic system, the structure of P21/c space group, cell parameter are as follows: a=11.3853 (5), b=29.5211 (15), and c=8.1522 (4), α=90,β=110.7890 (10), Z=2, unit-cell volume V=2561.6 (2) 3.The preparation method of chain schiff bases copper complex, the synthesis including (1) ligand L；(2) synthesis of complex.There is the medium Insertion action being bonded between chain schiff bases copper complex and CT-DNA；Under the physiological condition that reductant-oxidant is not added, apparent dissection is shown to pBR322DNA；PBR322DNA can be broken by autoxidation approach, and main active specy is hydroxyl radical free radical.
Description
Technical field
The invention belongs to synthesising chemical technology fields, and in particular to a kind of chain schiff bases copper complex and preparation method thereof
And application.
Background technique
Schiff bases is widely used in the fields such as the synthesis of pigment, dyestuff, catalyst, pharmaceutical intermediate, and schiff bases has packet
Include antimycotic, antibacterial, anti-malarial, antiproliferative, anti-inflammatory, antiviral and antipyretic etc. extensive bioactivity.Schiff bases is also good
Ligand, multiple tooth shape schiff bases and its metal complex have structure abundant, physical chemistry and catalytic performance, therefore in biology
It plays an important role in inorganic chemistry.Schiff base metal complex is usually by schiff bases and metal salt or organometallic
Close object and directly react preparation, the copper complex based on schiff base ligand structure in molecular probe, cell imaging, antibacterial, anti-swell
Bioactivity such as tumor etc. have a wide range of applications.Transient metal complex is had an effect because it can be pinpointed with DNA, in life
It is play an important role in object inorganic chemistry research.Transient metal complex is as DNA hybridization indicator or electroactive marker
In electrochemical DNA biosensor, DNA molecular photoswitch, DNA footprint reagent has in DNA break reagent and extremely widely answers
With.DNA is important life inhereditary material, is considered as pharmaceutically-active Major biological target in pharmaceutical research.
Using DNA as the Metal Drugs of target molecule, activity is made since certain base groups of metal ion and DNA are directly coordinated
It obtains DNA to be hindered in duplication and transcription, to inhibit the growth and division of certain sick cells, leads to its death.Cause
This, studies the interaction mechanism of metal complex and DNA, to exploitation and develops Metal Drugs important in inhibiting.
Summary of the invention
The purpose of the present invention is to provide a kind of chain schiff bases copper complexes and its preparation method and application, and the present invention is
It is achieved through the following technical solutions.
Chain schiff bases copper complex of the invention, chemical formula are [Cu3(L)2(OAc)6] n, wherein L is 2- (α-pyridine
Methoxyl group) benzaldehyde contracting open-chain crown ether schiff bases, OAc is acetate.The copper complex is monoclinic system, and P21/c is empty
Between group structure, cell parameter are as follows: a=11.3853 (5), b=29.5211 (15), c=8.1522 (4), α=90,β=110.7890 (10), Z=2, unit-cell volume V=2561.6 (2) 3, total is connected by acetate ion
One-dimensional catenary structure, copper ion have two kinds of coordination modes of pentacoordinate and hexa-coordinate respectively, wherein the coordination atom of pentacoordinate mode
It is all the O atom on acetate ion, the configuration of center copper ion is identical by two of four acetate ion bridgings
Tetragonal pyramid；And the coordination atom of hexa-coordinate mode is the N on O atom and two ligand pyridine groups on four acetate ions
Atom, the configuration of center copper ion are using two pyridine N atoms as the octahedron of the distortion of axis.
The preparation method of chain schiff bases copper complex of the invention includes the following steps:
(1) K is added into the acetonitrile solution of salicylide in the synthesis of ligand L2CO3, 2- chloromethyl pyridine hydrochloride is then added,
It is heated to reflux the h of 4 h~8.Reaction mixture after filtering, is extracted with dichloromethane, through silica gel column chromatography point after organic phase concentration
From ethers intermediate compound I is obtained, intermediate compound I is reacted to obtain ligand L, i.e. 2- (α-pyridine in acetonitrile solution with open-chain crown ether
Methoxyl group) benzaldehyde contracting open-chain crown ether schiff bases.
(2) ligand L and Cu (OAc) that the synthesis of complex synthesizes step (1)2·H2The room temperature in ethanol solution of O
Under the conditions of stir 30 min, after filtering, filtrate places solvent flashing at room temperature, be precipitated after 5-7 days blue crystal, as
[Cu3(L)2(OAc)6] n complex.
In above-mentioned steps (1), salicylide and K2CO3Molar ratio be 1:1.5~1:2.5.
In above-mentioned steps (1), the molar ratio of salicylide and 2- chloromethyl pyridine hydrochloride is 1:1~1.1:1.
In above-mentioned steps (1), the molar ratio of intermediate compound I and open-chain crown ether is 1:1~1:1.1.
In above-mentioned steps (2), ligand L and Cu (OAc)2·H2The molar ratio of O is 1:1~1:3.
The chain schiff bases copper complex prepared using the method for the present invention, by fluorescent quenching it is experimentally confirmed that the chain
There is the medium Insertion action being bonded between schiff bases copper complex and CT-DNA；It is through agarose gel electrophoresis it is demonstrated experimentally that described
Chain schiff bases copper complex shows significantly to cut and make under the physiological condition that reductant-oxidant is not added to pBR322DNA
With；Cutting mechanism experiment by introducing free radical scavenger shows that the chain schiff bases copper complex can be by from oxygen
Change approach is broken pBR322DNA, and main active specy is hydroxyl radical free radical.
The beneficial effects of the present invention are, chain schiff bases copper complex structure novel of the invention, preparation method is simple
Reliably, product stability is good, preparation cost is low, and it has stronger bonding action to CT-DNA, has to pBR322DNA
Apparent cutting effect can be used as potential drug candidate.
Detailed description of the invention
Fig. 1 is the synthetic route chart of ligand L in the present invention.
Fig. 2 be the present invention in ligand L nuclear magnetic resonance (1H NMR) figure.
Fig. 3 be the present invention in ligand L nuclear magnetic resonance (13C NMR) figure.
Fig. 4 is chain schiff bases copper complex one-dimensional crystal structure chart prepared by the present invention.
Fig. 5 is the fluorescent quenching experimental result of chain schiff bases copper complex prepared by the present invention and EB competition.
Fig. 6 is concentration dependant cutting experiment result of the chain schiff bases copper complex prepared by the present invention to pBR322DNA.
Fig. 7 is mechanism cutting experiment result of the chain schiff bases copper complex prepared by the present invention to pBR322DNA.
Specific embodiment
The present invention is further specifically described below by embodiment.
Embodiment 1
Synthetic ligands L(2- (α-pyridomethoxy) benzaldehyde contracting open-chain crown ether schiff bases)
As shown in Figure 1, by 1 mL(10 mmol) salicylide dissolve in 60 mL acetonitriles, be added 2.52 g (18 mmol)
K2CO3, it stirs evenly, is heated to reflux the 2- chloromethyl pyridine hydrochloride for adding 1.87 g (11.5 mmol) after 40 min, after
Continuous to be heated to reflux 8 hours, reaction mixture after filtering, is extracted three times with 30 mL methylene chloride, with anhydrous after organic phase collection
Na2SO4It dries and filters, filtrate obtains yellow oily liquid after being evaporated in Rotary Evaporators, isolated through silica gel column chromatography
White 0.95 g of ethers intermediate compound I, yield 44.68%.
Take above-mentioned intermediate I0.682 g(20 mmol) it dissolves in 20 mL acetonitriles, 0.355 g(2.20 mmol) is right
Methylaniline dissolves in 12 mL acetonitriles, and open-chain crown ether acetonitrile solution is added dropwise under room temperature and stirring condition, and it is 2 small that the reaction was continued
32 mL water are added dropwise in Shi Hou, and yellow solid is precipitated, and mixture is filtered and is recrystallized to give 0.79 g ligand L with petroleum ether, produce
Rate 81.69%, fusing point: 63.7-64.5 DEG C.
Fig. 2,3 be respectively the nuclear magnetic resonance spectroscopy and carbon spectrum of ligand L.
FT-IR(KBr, ν/cm-1): 1621, 1592, 1506, 1488, 1434, 1246, 1109, 1052,
757.
1H NMR (500 MHz, CDCl3) d: 9.06 (s, 1H), 8.62 (m, 1H), 8.22-8.02 (dd, J=
8.0 Hz, J=1.5 Hz, 1H), 7.73-7.70 (td, J=7.5 Hz, J=1.5 Hz, 1H), 7.51-7.50 (d,J=8.0 Hz, 1H), 7.43-7.39 (m, 1H), 7.27-7.19 (m, 5H), 7.09-7.06 (t, J=7.5 Hz,
1H), 7.01-6.99 (d, J=8.5 Hz, 1H), 5.32 (s, 2H), 2.38 (s, 3H). 13C NMR (125
MHz, CDCl3): 158.2, 156.8, 155.5, 149.2, 137.0, 132.7, 129.7, 128.8, 127.9,
122.8, 121.5, 121.3, 121.2, 121.0, 112.6, 71.0, 21.0.
Embodiment 2
Chain schiff bases copper complex [Cu3(L)2(OAc)6]nPreparation
By the Cu (OAc) of 167 mg(0.8 mmol)2·H2O dissolves in 20 mL ethyl alcohol, 160mg (0.5 prepared by embodiment 1
Mmol) ligand L dissolves in Cu (OAc)2·H2In the ethanol solution of O, 30 min are stirred at room temperature, and after filtering, filtrate is put at room temperature
Slow solvent flashing is set, the crystal of blue is precipitated after 7 days, crystal is collected by filtration, yield: 40%.FT-IR (KBr,ν/cm-1):
1628, 1598, 1552, 1506, 1434, 1401, 1206, 1031, 758.
Complex is measured as monoclinic system, the structure of P21/c space group through X-ray single crystal diffraction, and total can be regarded as
The two-part 1D structure connected by acetate ion, as shown in Figure 4.Wherein there are two types of coordination modes for copper ion, divide
It is not pentacoordinate and hexa-coordinate mode, wherein the coordination atom of pentacoordinate mode is all the O atom on acetate ion, and six match
The coordination atom of bit pattern is the N atom on O atom and two ligand pyridine groups on four acetate ions.It is computed,τ
=0.0027, therefore the configuration of the copper ion of the pentacoordinate in complex is identical by two of four acetate ion bridgings
Tetragonal pyramid.And the configuration of the copper ion of hexa-coordinate is using two pyridine N atoms as the octahedron of the distortion of axis.Tables 1 and 2 difference
List complex crystallographic data and main bond distance's bond angle data.
Embodiment 3
Chain schiff bases copper complex [Cu3(L)2(OAc)6]nFluorescent quenching with EB-DNA is tested
By the way that the situation of change of the fluorescence intensity of chain schiff bases copper complex front and back solution, the i.e. change of fluorescence spectra is added
Change, it can be seen that the size of chain schiff bases copper complex and DNA binding ability.The method has high sensitivity, easy to operate
Many advantages, such as facilitating.After chain schiff bases copper complex and DNA combine, the existence form of DNA in the solution can change
Become, under excitation, the fluorescence intensity of electromagnetic radiation can also change.Chain schiff bases copper complex sheet of the invention
Body does not generate fluorescence, cannot use the interaction of direct fluorescence spectrum method for measuring chain schiff bases copper complex and DNA.Therefore it adopts
The fluorescence of EB-DNA conjugate is quenched with chain schiff bases copper complex, by the variation for studying EB-DNA conjugate fluorescence intensity
Come indirect determination complex and the combination degree of DNA.Specific steps are as follows:
Prepare EB(ethidium bromide) and CT-DNA mixed aqueous solution (EB concentration be 2.4 × 10-6 M, CT-DNA concentration are 4.8
×10-5) and chain schiff bases copper complex (concentration 10 M-3 M DMF/H)2O(V/V=1:1) solution.To quartz
2 mL EB-DNA solution are added in cuvette, scan corresponding fluorescence spectrum, then concentration gradient gradually increases complex
Concentration, and corresponding fluorescence spectrum is scanned, data are exported, maps and is fitted using origin software.
As a result as shown in figure 5, with chain schiff bases copper complex concentration increase, fluorescence intensity reduces gradually, according to
Classical fluorescent quenching is theoretical, with I0/ I (front and back fluorescence intensity ratio is added in chain schiff bases copper complex) is to chain schiff bases
The mapping of copper complex concentration, obtains straight line.According to equation KEB[EB]=Kapp[complex], KEB=1.0×107 M-1
([EB]=2.4 μM) calculates the apparent binding constants K of chain schiff bases copper complexappIt is 1.26 × 106, it is less than classical key
Close constant 107M-1, illustrate to be medium bonding action between chain schiff bases copper complex and DNA.
Embodiment 4
Chain schiff bases copper complex [Cu3(L)2(OAc)6]nTo the cutting experiment of pBR322DNA
Gel electrophoresis is primarily used to isolate and purify the substances such as DNA, is the molecular size range of researching DNA and the common hand of structure
Section.Agarose gel electrophoresis method is after being solidified at room temperature using agarose solution, Ago-Gel as supported matrix one
Kind is commonly used to separate and study the means of the large biological molecules substances such as nucleic acid.PBR322 Plasmid DNA is handled by active material
Afterwards, there are three types of common structure types.Form I: covalently closed circle super spirial plasmid；Form II: the open loop that sub-thread fracture generates
Incise type DNA；Form III: the linear DNA that bifilar fracture generates.There is agarose gel electrophoresis charge effect and molecular sieve to imitate
It answers, DNA has negative electrical charge because it is with phosphate group, mobile from cathode to anode in electrophoresis process.In suitable agarose
Under concentration, the rate travel of three kinds of forms are as follows: Form I > Form III > Form II.
The present embodiment studies the change of chain schiff bases copper complex at close under physiological condition (37 DEG C of constant temperature, pH=7.2)
Nuclease is learned, demonstrating influences chain schiff bases copper complex to the concentration dependant and mechanism of action of the cleavage activity of DNA.
Specific step is as follows:
(1) buffer is configured, wherein containing 18 mM NaCl and 50 mM Tris, is adjusted to pH=7.2 with hydrochloric acid.Suitable for electrophoresis reality
It tests.The Ago-Gel (EB containing 0.5 μ g/mL) for preparing 0.9%, uses TBE to delay liquid as electrode buffer solution, in reaction terminating
Bromophenol blue is added in agent and is used to refer to electrophoresis process.Basic step is that pBR322 DNA (0.1 μ g/ μ L) is added, a certain amount of
(chain schiff bases copper complex concentration is 0.05,0.15,0.35,0.50,0.65 to chain schiff bases copper complex solution
MM) and buffer, mixing are placed on constant temperature certain time in 37 °C of water-baths, and 2 μ L of terminate liquid is added, makes the final volume of reaction solution
20 μ L are maintained at, then by sample spot into agarose gel groove, carry out electricity under 120V constant-pressure conditions in TBE electrophoretic buffer
Swimming, is finally analyzed with UVITEC gel automated imaging analysis system and handles data.Complex is solidifying to the cutting of pBR322 DNA
Gel electrophoresis map is as shown in fig. 6, wherein swimming lane 0:DNA compares (3 h)；Swimming lane 1-5:DNA+ complex (0.05,0.15,
0.35, 0.50, 0.65 mM).It can be seen from the figure that with the increase of chain schiff bases copper complex concentration, chain Schiff
The Form II that the cutting of alkali copper complex generates has different degrees of increase, shows good concentration dependant, illustrates chain seat
The concentration of husband's alkali copper complex is strictly one of the active factor of its Chemistry Nuclease that influences.
(2) on the basis of above-mentioned steps (1), further study chain schiff bases copper complex cutting pBR322 DNA's
Mechanism.It is separately added into several possible inhibitor or promotor: singlet oxygen (1O2) inhibitor NaN3, singlet oxygen (1O2)
Diphenylguanidine2O, hydroxyl radical free radical (OH) quencher KI, super oxygen state radical anion (O2 •-) quencher SOD and metal ion
Chelating agent EDTA waits the influence to cleavage activity.Different inhibitor or promotor cut the DNA of chain schiff bases copper complex
Active gel electrophoresis spectrum is as shown in Figure 7.Wherein swimming lane 0:DNA compares (3h)；Swimming lane 1:DNA+ complex；Swimming lane 2-6:
DNA+ complex+inhibitor (0.25 mM NaN3, D2O, 0.1 M KI, 20 U/mL SOD, 0.5 mM EDTA).From figure
In as can be seen that be added NaN3, D2After O, SOD, the cleavage activity of chain schiff bases copper complex is not suppressed, can be excluded
Singlet oxygen (1O2) and super oxygen state radical anion (O2 •-) generation.And after KI is added, chain schiff bases copper complex is cut
It cuts activity obviously to be inhibited, illustrates the generation for having hydroxyl radical free radical in cutting process.Metal ion chelation agent EDTA, chain is added
Shape schiff bases copper complex cleavage activity has more apparent inhibition, illustrates that metal ion is generated in chain schiff bases copper complex
Take on key player during active.
Claims (9)
1. a kind of chain schiff bases copper complex, chemical formula is [Cu3(L)2(OAc)6] n, wherein L is 2- (α-pyridine methoxy
Base) benzaldehyde contracting open-chain crown ether schiff bases, OAc is acetate；The copper complex is monoclinic system, P21/c space group
Structure, cell parameter are as follows: a=11.3853 (5), b=29.5211 (15), c=8.1522 (4), α=90,β=
110.7890 (10), Z=2, unit-cell volume V=2561.6 (2) 3, total are one connected by acetate ion
Chain structure is tieed up, copper ion there are two kinds of coordination modes of pentacoordinate and hexa-coordinate respectively, and wherein the coordination atom of pentacoordinate mode is all
It is the O atom on acetate ion, the configuration of center copper ion is two identical four by four acetate ion bridgings
Side's cone；And the coordination atom of hexa-coordinate mode is N on O atom and two ligand pyridine groups on four acetate ions former
Son, the configuration of center copper ion are using two pyridine N atoms as the octahedron of the distortion of axis.
2. the preparation method of chain schiff bases copper complex described in claim 1, includes the following steps:
(1) K is added into the acetonitrile solution of salicylide in the synthesis of ligand L2CO3, 2- chloromethyl pyridine hydrochloride is then added, adds
The heat reflux h of 4 h~8, reaction mixture after filtering, are extracted with dichloromethane, and separate after organic phase concentration through silica gel column chromatography
Ethers intermediate compound I is obtained, intermediate compound I is reacted to obtain ligand L, i.e. 2- (α-pyridine first in acetonitrile solution with open-chain crown ether
Oxygroup) benzaldehyde contracting open-chain crown ether schiff bases；
(2) ligand L and Cu (OAc) that the synthesis of complex synthesizes step (1)2·H2The room temperature condition in ethanol solution of O
30 min of lower stirring, after filtering, filtrate places solvent flashing at room temperature, and the crystal of blue, as [Cu are precipitated after 5-7 days3
(L)2(OAc)6] n complex.
3. the preparation method of chain schiff bases copper complex according to claim 2, which is characterized in that the salicylide with
K2CO3Molar ratio be 1:1.5~1:2.5.
4. the preparation method of chain schiff bases copper complex according to claim 2, which is characterized in that the salicylide with
The molar ratio of 2- chloromethyl pyridine hydrochloride is 1:1~1.1:1.
5. the preparation method of chain schiff bases copper complex according to claim 2, which is characterized in that the intermediate compound I
Molar ratio with open-chain crown ether is 1:1~1:1.1.
6. the preparation method of chain schiff bases copper complex according to claim 2, which is characterized in that the ligand L with
Cu(OAc)2·H2The molar ratio of O is 1:1~1:3.
7. there is the medium Insertion action being bonded between chain schiff bases copper complex described in claim 1 and CT-DNA.
8. chain schiff bases copper complex described in claim 1 is under the physiological condition that reductant-oxidant is not added, right
PBR322DNA shows apparent dissection.
9. chain schiff bases copper complex described in claim 1 can be broken pBR322DNA, Er Qiezhu by autoxidation approach
The active specy wanted is hydroxyl radical free radical.
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| CN113801100A (en) * | 2021-10-26 | 2021-12-17 | 四川省产品质量监督检验检测院 | Tetranuclear copper complex and preparation method and application thereof |
| CN113817175A (en) * | 2021-10-18 | 2021-12-21 | 安阳工学院 | Preparation method and application of one-dimensional chain-like Schiff base Mn-based coordination polymer |
| CN114702441A (en) * | 2022-05-12 | 2022-07-05 | 山西农业大学 | Cuprous complex with anti-tumor activity and preparation method and application thereof |
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| CN102060864A (en) * | 2010-12-29 | 2011-05-18 | 河南中医学院 | Salicylide schiff's base and transition metal compound and preparation method thereof |
| WO2012011875A1 (en) * | 2010-07-21 | 2012-01-26 | Republic Polytechnic | Compounds for photodynamic therapy |
| CN107827914A (en) * | 2017-11-24 | 2018-03-23 | 山西大学 | A kind of copper schiff bases complex and its preparation method and application |
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| WO2012011875A1 (en) * | 2010-07-21 | 2012-01-26 | Republic Polytechnic | Compounds for photodynamic therapy |
| CN102060864A (en) * | 2010-12-29 | 2011-05-18 | 河南中医学院 | Salicylide schiff's base and transition metal compound and preparation method thereof |
| CN107827914A (en) * | 2017-11-24 | 2018-03-23 | 山西大学 | A kind of copper schiff bases complex and its preparation method and application |
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| CN113817175A (en) * | 2021-10-18 | 2021-12-21 | 安阳工学院 | Preparation method and application of one-dimensional chain-like Schiff base Mn-based coordination polymer |
| CN113817175B (en) * | 2021-10-18 | 2022-09-16 | 安阳工学院 | Preparation method and application of one-dimensional chain-like Schiff base Mn-based coordination polymer |
| CN113801100A (en) * | 2021-10-26 | 2021-12-17 | 四川省产品质量监督检验检测院 | Tetranuclear copper complex and preparation method and application thereof |
| CN114702441A (en) * | 2022-05-12 | 2022-07-05 | 山西农业大学 | Cuprous complex with anti-tumor activity and preparation method and application thereof |
| CN114702441B (en) * | 2022-05-12 | 2023-04-14 | 山西农业大学 | Cuprous complex with anti-tumor activity and preparation method and application thereof |
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