CN109293703A - Compound as DNA decomposition agent - Google Patents
Compound as DNA decomposition agent Download PDFInfo
- Publication number
- CN109293703A CN109293703A CN201811055158.3A CN201811055158A CN109293703A CN 109293703 A CN109293703 A CN 109293703A CN 201811055158 A CN201811055158 A CN 201811055158A CN 109293703 A CN109293703 A CN 109293703A
- Authority
- CN
- China
- Prior art keywords
- decomposition agent
- dna
- compound
- dna decomposition
- reduction potential
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000000354 decomposition reaction Methods 0.000 title claims abstract description 35
- 150000001875 compounds Chemical class 0.000 title claims abstract description 9
- 239000000126 substance Substances 0.000 abstract description 23
- 238000005336 cracking Methods 0.000 abstract description 6
- 230000005284 excitation Effects 0.000 abstract description 3
- 239000003795 chemical substances by application Substances 0.000 description 36
- 238000000034 method Methods 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical group N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 229940041181 antineoplastic drug Drugs 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 229940075397 calomel Drugs 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000004020 conductor Substances 0.000 description 2
- ZOMNIUBKTOKEHS-UHFFFAOYSA-L dimercury dichloride Chemical compound Cl[Hg][Hg]Cl ZOMNIUBKTOKEHS-UHFFFAOYSA-L 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000005281 excited state Effects 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 230000033116 oxidation-reduction process Effects 0.000 description 2
- 229910052707 ruthenium Inorganic materials 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 101000702488 Rattus norvegicus High affinity cationic amino acid transporter 1 Proteins 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
Classifications
-
- 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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic System compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The present invention provides a kind of compound that can be used as DNA decomposition agent, and wherein the compound has the reduction potential of remote super existing most of chemical dna decomposition agents under light excitation, is capable of providing stronger cracking performance.
Description
Technical field
The present invention relates to biochemical fields, more particularly to a kind of new DNA decomposition agent.Further, the present invention provides
New DNA decomposition agent possibly be also used to prepare anti-tumor drug and/or Photoactivatable agents.
Background technique
Common DNA decomposition agent can be divided into two kinds: biological decomposition agent, such as nuclease and chemical cleavage agents (or chemistry
Nuclease).Generally, biological decomposition agent or improves on its basis if nuclease extracts from nature biotechnology body more.
For example, the EcoR I restriction endonuclease for restricted digestion separated from E.coli.The reaction item of common biological DNA decomposition agent
Part is more harsh and complicated, often removes and needs Mg2+Outside, it is also necessary to S- adenosine-L-Met, ATP etc., and its optimal reaction temperature
Degree is mostly at 37 DEG C or so.Further, since many biological source nucleases are polypeptide, it is easy to inactivate and lose DNA cutting or cracking is lived
Property.Last century the eighties, researcher have found that Ru (II) bipyridyl complex has the function of the DNA cracking of photoinduction for the first time.
Such DNA decomposition agent has a variety of potential applications: (1) for the specific cleavage to the certain sites DNA；(2) it is non-to be used as nucleic acid
Radioactive luminous or electrochemical luminescence marker, such as it is used as DNA " molecular light switch "；(3) synthesize to certain and gene
Mutation have related disorders, such as cancer disease, therapeutic agent.Chemical dna decomposition agent has biological DNA decomposition agent simultaneously
High degree of specificity, and the designability (or programmability) for allowing researcher to be pre-designed DNA cracking site, in DNA molecular
Photoswitch, structure probe, light probe, photodestruciton reagent, anti-tumor drug, Photoactivatable agents etc. are latent with huge application
Power.However, the application prospect of chemical dna decomposition agent depends on its cracking ability.The light of existing Ru (II) bipyridyl complex
Excite lower reduction potential lower, which has limited the practical applications of existing Ru (II) bipyridyl complex.
Summary of the invention
Main advantage of the invention is that it provides a kind of new chemical dna decomposition agent, has remote super existing chemical dna
The reduction potential of decomposition agent, wherein chemical dna decomposition agent following structural formula of the present invention:
Wherein the former theoretical reduction potential is 1.996V, and it is more than existing that the theoretical reduction potential of the latter, which is 1.965V,
Ru (II) bipyridyl complex reduction potential.In other words, the present invention provides a kind of chemistry with high cracking ability
DNA decomposition agent.Further, chemical dna decomposition agent of the present invention can be used as DNA photodestruciton reagent, anti-tumor drug and/or photosensitive
Change reagent.
Specific embodiment
According to present pre-ferred embodiments, the present invention provides a kind of chemical dna decomposition agent, with following structural formula:
Wherein the theoretical reduction potential of structural formula I is 1.996V, and the theoretical reduction potential of formula II is 1.965V, super
Cross the reduction potential of existing Ru (II) bipyridyl complex.In other words, the chemistry of structure of the invention Formulas I and formula II
DNA decomposition agent all has high DNA photodestruciton ability.Further, the chemical dna of structure of the invention Formulas I and formula II cracks
Agent can be employed as DNA photodestruciton reagent, anti-tumor drug and/or Photoactivatable agents.
Following examples are used to illustrate the present invention the reduction potential of the chemical dna decomposition agent of structural formula I and formula II
And its calculation method.It will be appreciated by those skilled in the art which kind of method to detect or calculate the reduction of chemical dna decomposition agent using
Potential, and be not meant to limit the scope of the invention.It will be apparent for a person skilled in the art that there are other detections or meters
Calculation method determines the reduction potential of chemical dna decomposition agent of the present invention.
Example 1: the reduction potential of the chemical dna decomposition agent with structural formula I and its calculating
Using UB3LYP method, ruthenium atom uses LanL2DZ base group, and other atoms use 6-31G (d) base group, optimize
To the compound with structural formula I.To this compound, the data in solution using continuous polarity conductor model (CPCM) and are write from memory
Recognize parameter to be calculated.Optimize obtained triplet molecule, the minimum triplet excited state (T1) as molecule.In liquid phase
Gibbs free energy is calculated using CPCM model by single-point.For the thermodynamic data of excitation state complex, using list
The method that point calculates obtains.All calculate uses 09 program bag of Gaussian (Revision is D.01).
Based on thermodynamic cycle principle, following proposal 1 is taken, calculates the reduction of the chemical dna decomposition agent with structural formula I
Potential, wherein the standard oxidationreduction potential of the chemical dna decomposition agent with structural formula I can relative to standard mercury electrode (SCE)
To be obtained with following equations (1).The gibbs free energy change value of standard hydrogen electrode (SHE)EV, is equivalent to down
State the gibbs free energy change value of equation (8).Because standard calomel electrode is -0.2412V, SCE relative to the current potential of hydrogen electrode
Gibbs free energy change value(the free energy variate for being equivalent to following equations (9)) is by standard hydrogen electricity
The gibbs free energy change value of pole is obtained plus 0.2412eV:
Scheme 1: thermodynamic cycle method calculates the redox potential in solution:
Wherein,
ΔGo(2)=Go[Ru(tap)2tanp](n+1)+(aq)-Go[Ru(tap)2tanp](n+1)+(gas) (6)
ΔGo(1)=Go[Ru(tap)2tanp]n+(aq)-Go[Ru(tap)2tanp]n+(gas) (7)
Wherein, all relevant free energy variates are calculated at the standard conditions.Such as: temperature 298.15K, pressure
Power is 1 standard atmospheric pressure, and solution is 1mol/L (water is solvent)；Gas is 298.15K, 1 standard atmospheric pressure.Structural formula
Such as table 1 of data required for the reduction potential of the chemical dna decomposition agent of I:
Table 1:
The reduction potential for the chemical dna decomposition agent with structural formula I being wherein calculated is 1.966V.
Example 2: the reduction potential of the chemical dna decomposition agent with formula II and its calculating
Using UB3LYP method, ruthenium atom uses LanL2DZ base group, and other atoms use 6-31G (d) base group, optimize
To the compound with formula II.To this compound, the data in solution using continuous polarity conductor model (CPCM) and are write from memory
Recognize parameter to be calculated.Optimize obtained triplet molecule, the minimum triplet excited state (T1) as molecule.In liquid phase
Gibbs free energy is calculated using CPCM model by single-point.For the thermodynamic data of excitation state complex, using list
The method that point calculates obtains.All calculate uses 09 program bag of Gaussian (Revision is D.01).
Based on thermodynamic cycle principle, following proposal 2 is taken, calculates going back for the chemical dna decomposition agent with formula II
Former potential, wherein the standard oxidationreduction potential of the chemical dna decomposition agent with formula II is relative to standard mercury electrode
(SCE) it can be obtained with following equations (1).The gibbs free energy change value of standard hydrogen electrode (SHE) Phase
When in the gibbs free energy change value of following equations (8).Because standard calomel electrode relative to the current potential of hydrogen electrode is-
The gibbs free energy change value of 0.2412V, SCE(the free energy variate for being equivalent to following equations (9))
It is to be obtained by the gibbs free energy change value of standard hydrogen electrode plus 0.2412eV:
Scheme 2: thermodynamic cycle method calculates the redox potential in solution:
Wherein,
ΔGo(2)=Go[Ru(dcp)2phhat](n+1)+(aq)-Go[Ru(dcp)2phhat](n+1)+(gas) (6)
ΔGo(1)=Go[Ru(tap)2phhat]n+(aq)-Go[Ru(dcp)2phhat]n+(gas) (7)
Wherein, all relevant free energy variates are calculated at the standard conditions.Such as: temperature 298.15K, pressure
Power is 1 standard atmospheric pressure, and solution is 1mol/L (water is solvent)；Gas is 298.15K, 1 standard atmospheric pressure.Structural formula
Such as table 2 of data required for the reduction potential of the chemical dna decomposition agent of II:
Table 2:
The reduction potential for the chemical dna decomposition agent with formula II being wherein calculated is 1.965V.
Claims (1)
1. a kind of compound as DNA decomposition agent, which is characterized in that have following structure general formula:
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810500023 | 2018-05-15 | ||
| CN2018105000222 | 2018-05-15 | ||
| CN201810500022 | 2018-05-15 | ||
| CN2018105000237 | 2018-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109293703A true CN109293703A (en) | 2019-02-01 |
Family
ID=65166521
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811055158.3A Pending CN109293703A (en) | 2018-05-15 | 2018-09-07 | Compound as DNA decomposition agent |
| CN201811055157.9A Pending CN109456364A (en) | 2018-05-15 | 2018-09-07 | Compound as DNA decomposition agent |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811055157.9A Pending CN109456364A (en) | 2018-05-15 | 2018-09-07 | Compound as DNA decomposition agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN109293703A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012028874A1 (en) * | 2010-09-01 | 2012-03-08 | University Of Sheffield | Cytotoxic luminescent metal complexes |
| CN105884833A (en) * | 2014-12-24 | 2016-08-24 | 江南大学 | Preparation method and antineoplastic activity of novel ruthenium complex containing 4,4'-dibromo-2,2'-dipyridyl |
| CN105884834A (en) * | 2014-12-24 | 2016-08-24 | 江南大学 | Preparation method of novel Ru(II) complex containing benzoxazole imidazo[1,10]phenanthroline and light cracking activity thereof |
-
2018
- 2018-09-07 CN CN201811055158.3A patent/CN109293703A/en active Pending
- 2018-09-07 CN CN201811055157.9A patent/CN109456364A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012028874A1 (en) * | 2010-09-01 | 2012-03-08 | University Of Sheffield | Cytotoxic luminescent metal complexes |
| CN105884833A (en) * | 2014-12-24 | 2016-08-24 | 江南大学 | Preparation method and antineoplastic activity of novel ruthenium complex containing 4,4'-dibromo-2,2'-dipyridyl |
| CN105884834A (en) * | 2014-12-24 | 2016-08-24 | 江南大学 | Preparation method of novel Ru(II) complex containing benzoxazole imidazo[1,10]phenanthroline and light cracking activity thereof |
Non-Patent Citations (3)
| Title |
|---|
| TI-FANG MIAO等: ""Theoretical studies on DNA-photocleavage efficiencies of Ru(II) polypyridyl complexes", 《DALTON TRANS.》 * |
| TI-FANG MIAO等: "Theoretical Studies on DNA-Photocleavage Efficiency and Mechanism of Functionalized Ru(II) Polypyridyl Complexes", 《J. PHYS. CHEM. A》 * |
| 张建夫等: "Ｒu(Ⅱ) 多吡啶配合物DNA光裂解性质的密度泛函研究", 《原子与分子物理学》 * |
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| Publication number | Publication date |
|---|---|
| CN109456364A (en) | 2019-03-12 |
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Application publication date: 20190201 |