CN109232663B - Preparation method of ruthenium complex and application of ruthenium complex in HIV reverse transcriptase inhibition - Google Patents
Preparation method of ruthenium complex and application of ruthenium complex in HIV reverse transcriptase inhibition Download PDFInfo
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- 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 Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0046—Ruthenium compounds
- C07F15/0053—Ruthenium compounds without a metal-carbon linkage
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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Abstract
The invention belongs to the field of research and development of HIV inhibitors, and discloses a preparation method of a polypyridine ruthenium complex and application of the polypyridine ruthenium complex in HIV reverse transcriptase inhibition. The invention designs a novel synthesis method of the polypyridine ruthenium complex, and the obtained compound has high purity, high yield, good water solubility and excellent spectral property. The polypyridine ruthenium complex has the capability of selectively combining TAR regions on HIV RNA, can block the reverse transcription process of reverse transcriptase on the virus RNA, and inhibits the replication of the virus RNA. The polypyridine ruthenium complex is an HIV RNA selective binding reagent with high affinity and an HIV reverse transcriptase inhibitor with high activity, and is an HIV drug with great application potential.
Description
Technical Field
The invention belongs to the field of HIV reverse transcriptase inhibitors and HIV drug research and development, and particularly relates to a preparation method of a polypyridine ruthenium complex and application of the polypyridine ruthenium complex in HIV reverse transcriptase inhibition.
Background
AIDS is a disease seriously harming the healthy life of human beings. China reports that as many as 65.4 cases of HIV infectors and patients die 20.1 cases of death. The death number of AIDS is the first death number of infectious diseases in China. By inhibiting the reverse transcription of the viral RNA by the reverse transcriptase, the generation and diffusion of the virus can be controlled, so that the effects of treating and early preventing AIDS and other diseases which cannot be cured temporarily and are closely related to the reverse transcriptase and the viral RNA can be achieved (Science, 1992, 256, 1783-1790; Biochemistry, 2011, 50, 5042-5057). Therefore, hiv reverse transcriptase becomes the primary target of current anti-aids drug design (curr.
At present, reverse transcriptase inhibitors used in clinical applications as drugs are mainly classified into two categories, namely, "nucleoside reverse transcriptase inhibitors" and "non-nucleoside reverse transcriptase inhibitors". Nucleoside reverse transcriptase inhibitors are nucleoside analogs that compete with viral DNA formed by reverse transcription of viral RNA for binding to the reverse transcriptase, inhibiting viral replication to some extent. However, long-term administration of nucleoside reverse transcriptase inhibitors can cause serious toxic and side effects (such as bone marrow growth inhibition and the like) and obvious drug resistance, and face a deselected fate. Through large-scale activity screening of a large number of new compounds, small molecular compounds with different structures are successively discovered to show better reverse transcriptase inhibitory activity, and the small molecular compounds are called non-nucleoside reverse transcriptase inhibitors. Their affinity for the "enzyme-substrate" complex is higher than for the enzyme, and through interaction with reverse transcriptase a conformational change of the enzyme can be induced, which leads to a decrease in the affinity of the active site of the substrate. Since non-nucleoside reverse transcriptase inhibitors do not directly impair the function of the substrate binding region, they are less cytotoxic and can inhibit the activity of retroviruses at very low concentrations (chem. soc. rev., 2012, 41, 4657-4670).
TAR and RRE are two important functional regions of HIV RNA, and play a crucial role in the reverse transcription activity of the viral RNA (mol. cell biol., 1988, 8, 2555-2561). Recently, one aminothiazole compound showed better TAR RNA selectivity (chem. Eur.J., 2014, 20, 2071-2079; chem. Commun., 2010, 46, 6162-6164). The compound can eliminate the influence of DNA and tRNA, selectively combine with the U-A base pair part of TAR RNA, and inhibit the growth of HIV-1 strain without obvious influence on the growth of normal cells.
The structure of the polypyridine ruthenium complex is introduced into the thiazole compound, and the molecular structure is further designed and optimized, so that the polypyridine ruthenium complex which has good water solubility and spectral property and has an aminothiazole functional group with a specific recognition effect on HIV RNA is obtained, can be selectively combined with a TAR region of the HIV RNA, and can obviously inhibit the activity of HIV reverse transcriptase. The polypyridine ruthenium complex is not only a specific binding reagent of HIV RNA, but also a specific inhibitor of HIV reverse transcriptase, and is a potential high-activity AIDS specific drug.
Disclosure of Invention
The invention aims to provide a polypyridine ruthenium complex which has good water solubility and spectral property, specific HIV RNA recognition function and excellent HIV reverse transcriptase inhibition capability aiming at the research of AIDS drugs which are not overcome at present.
The second purpose of the invention is to provide a preparation method of the polypyridine ruthenium complex.
The third purpose of the invention is to provide the application of the polypyridine ruthenium complex in the preparation of HIV TAR RNA specific recognition.
The fourth purpose of the invention is to provide the application of the polypyridine ruthenium complex in preparation of HIV reverse transcriptase inhibition.
The above object of the present invention is achieved by the following technical solutions:
a ruthenium complex comprised of a cation and an anion, the cation having the formula I:
the ruthenium complexes of the invention are not limited to the type of anion, and anions conventional in the art can achieve the objects of the invention, especially anions of inorganic salts, such as PF6 －、ClO4 －、Cl－Etc., as a most preferred embodiment, the anion of the ruthenium complex of the present invention is PF6 －。
The preparation method of the ruthenium complex comprises the following steps:
s1, oxidizing 4,4 '-dimethyl-2, 2' -bipyridyl into aldehyde group substituted bipyridyl through selenium dioxide, oxidizing carboxyl group substituted bipyridyl through silver nitrate, and further condensing with an aminothiazole compound under the action of 1-hydroxy-7-azobenzotriazole (HOAt), 1-ethyl-carbonyldiimine hydrochloride (EDCI) and 4-Dimethylaminopyridine (DMAP) to obtain a bipyridyl ligand L1 containing an aminothiazole functional group, wherein the bipyridyl ligand L1 is shown as a formula II:
s2, reacting a compound 4,4 '-dimethyl-2, 2' -bipyridyl with bromoacetonitrile, bromobutyronitrile and bromohexanenitrile respectively under the action of lithium diisopropylamide to obtain a cyano-substituted bipyridyl compound, hydrolyzing with hydrochloric acid to generate a carboxyl-substituted bipyridyl compound, and further condensing with an aminothiazole compound under the action of 1-hydroxy-7-azobenzotriazol (HOAt), 1-ethyl-carbodiimide hydrochloride (EDCI) and 4-Dimethylaminopyridine (DMAP) to obtain bipyridyl ligands L2, L3 and L4 containing aminothiazole functional groups.
S3, the ligands L1-L4 are respectively mixed with a precursor compound cis- [ Ru (bpy)2Cl2]·2H2And (3) refluxing O in ethylene glycol, adding saturated aqueous solution of ammonium hexafluorophosphate after the reaction is finished, filtering the obtained precipitate, washing with anhydrous diethyl ether, drying under vacuum, carrying out neutral alumina column chromatography, and washing with acetonitrile to obtain the only red component, namely the polypyridine ruthenium complex Ru 1-Ru 4.
The invention has the following beneficial effects:
the invention provides a novel polypyridine ruthenium complex which can be used as an HIV RNA selective binding reagent and an HIV reverse transcriptase inhibitor. The synthesized polypyridine ruthenium complex has stable structure, good spectral property, good HIV RNA selective combination and HIV reverse transcriptase inhibiting capacity, and is a novel HIV reverse transcriptase inhibitor.
The application of the novel polypyridine ruthenium complex synthesized by the invention in HIV reverse transcriptase inhibitors has the following advantages: (1) the water solubility and the stability are good; (2) has positive charge, which is beneficial to the interaction with RNA with negative charge; (3) the probe has good spectral properties and can perform spectral response on RNA; (4) compared with aminothiazole organic compounds, the compound has stronger HIV reverse transcriptase inhibiting capability.
Drawings
FIG. 1 is a synthesis route of a polypyridine ruthenium complex Ru1 prepared by the invention;
FIG. 2 is a synthetic route of polypyridine ruthenium complexes Ru 2-Ru 4 prepared by the invention;
FIG. 3 is a gel electrophoresis diagram of an experiment of competitive binding of polypyridine ruthenium complex prepared in the present invention and tat protein to TAR RNA;
FIG. 4 is a data diagram of enzyme-linked immunosorbent assay for inhibiting HIV reverse transcriptase by the polypyridine ruthenium complex prepared in the invention;
FIG. 5 is a diagram of the UV-Vis spectral titration of the interaction between polypyridine ruthenium complex and DNA prepared by the present invention;
FIG. 6 is a graph of the UV-VIS spectrum titration of the interaction between polypyridine ruthenium complex and total RNA prepared in the present invention;
FIG. 7 is a diagram of the UV-VIS spectrum titration of the interaction between polypyridine ruthenium complex and tRNA prepared in the present invention;
FIG. 8 is a graph of UV-VIS titration of interaction of polypyridine ruthenium complex prepared in the present invention with poly (A) RNA.
Detailed Description
The invention is further described below with reference to the figures and the specific examples. The examples are given solely for the purpose of illustration and are not intended to limit the invention in any manner. Reagents, methods and equipment used in the present invention are conventional in the art and, unless otherwise specified, reagents and materials are commercially available.
EXAMPLE 1 preparation of polypyridyl ruthenium complexes
1. Preparation of polypyridine ruthenium complex Ru 1:
synthesized according to the route shown in FIG. 1.4, 4 '-dimethyl-2, 2' -bipyridine (1.5g, 8mmol) and selenium dioxide (887.68mg, 8mmol) were refluxed in 100ml of 1, 4-dioxane for 24 hours, cooled to room temperature, the black solid was filtered off, and the solvent was evaporated to give a white solid. The solid was dissolved with 100ml ethyl acetate with stirring, the insoluble material was filtered off, the filtrate was washed three times with 20ml 1.0M sodium carbonate solution, the organic phase was extracted three times with 50ml 0.3M sodium metabisulfite solution, the aqueous phases were combined, the pH was adjusted to 10 with sodium carbonate solution, extracted four times with 20ml chloroform, the organic phases were combined, dried over anhydrous sodium sulfate and the solvent was evaporated to give the crude product. The crude product is purified by column chromatographyEluting with petroleum ether/ethyl acetate (1:4) to obtain 398mg of aldehyde group-substituted bipyridine with a yield of 25%. Dissolving all the obtained aldehyde group substituted bipyridine in 20ml of ethanol, adding 4ml of silver nitrate aqueous solution, stirring, slowly adding 10ml of 1.0M sodium hydroxide aqueous solution, reacting for 15 hours at room temperature, evaporating the solvent, washing the solid with 4ml of 1.3M sodium hydroxide and 4ml of water for 2 times, extracting the combined filtrate with 10ml of chloroform for three times, adjusting the pH of the aqueous phase to 3.5 with 4M hydrochloric acid, filtering the generated white solid, and drying in vacuum to obtain 258mg of carboxyl group substituted bipyridine with the yield of 60%. The obtained carboxyl-substituted bipyridine (1.3mmol) was dissolved in 20ml of DMF, and aminothiazole compound (300mg, 1.3mmol), 1-hydroxy-7-azobenzotriazole (1.3mmol, 177mg), 4-dimethylaminopyridine (1.3mmol, 146mg), 1-ethyl-carbonyldiimine hydrochloride (1.3mmol,87mg) were added thereto, followed by stirring at room temperature for 6 hours, filtration of the resulting solid, washing with 25ml of water four times, and vacuum drying to obtain 457mg of an aminothiazole-functional group-substituted polypyridine ligand (L1) in a yield of 82%. The total amount of L1(1.06mmol) obtained was reacted with the compound cis- [ Ru (bpy)2Cl2]·2H2O (442mg, 0.85mmol) is refluxed for 8 hours under the protection of 20ml of ethylene glycol and argon, cooled to room temperature, 10ml of saturated ammonium hexafluorophosphate aqueous solution is added, the obtained orange precipitate is filtered, washed once with 15ml of water, washed three times with 30ml of anhydrous ether, and dried in vacuum to obtain a crude product. The crude product was chromatographed on a neutral alumina column with acetonitrile eluting the only orange component to give the target polypyridine complex Ru1 in 616mg yield at 64%.1H-NMR(300MHz,DMSO-d6):(ppm)12.28(s,1H),10.79(s,1H),9.21(d,J＝1.4Hz,1H),8.95–8.79(m,5H),8.41(t,J＝1.9Hz,1H),8.20(ddt,J＝7.9,6.5,1.8Hz,4H),7.99–7.85(m,2H),7.85–7.66(m,5H),7.66–7.48(m,7H),7.49–7.38(m,2H),2.58(s,3H),2.18(s,3H)。ESI-MS[CH3CN，m/z]421.6 (theoretical value: 421.5, [ M-2 PF)6]2+)。
2. Preparation of polypyridine ruthenium complex Ru 2:
synthesized according to the route shown in FIG. 2. Into a flame-dried flask were charged previously dried 4,4 '-dimethyl-2, 2' -bipyridine (3.0mmol, 552.7mg) and 20ml of anhydrous tetrahydrofuran at-78 deg.C1.8ml of 2.0M lithium diisopropylamide was slowly added, and the reactor was sealed and allowed to react at-78 ℃ for 1 hour. Bromoacetonitrile (3.6mmol,431.8mg) dissolved in 5ml of anhydrous tetrahydrofuran was slowly added to the reaction by syringe, the reactor was slowly returned to room temperature, and after 12 hours of further reaction, 20ml of water was added to quench the reaction. The reaction solution is neutralized by dilute hydrochloric acid, extracted by 50ml ethyl acetate for three times, organic phases are combined, washed by saturated saline solution, dried by anhydrous sodium sulfate, evaporated to remove the solvent, and the obtained crude product is subjected to column chromatography by silica gel, and the main components are washed by ethyl acetate/petroleum ether (1:2) to obtain the cyano-containing bipyridine. This was added to 6ml of concentrated hydrochloric acid and refluxed for 12 hours, cooled to room temperature, adjusted to pH 4.5 with sodium hydroxide, extracted three times with 50ml of chloroform, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain 393mg of bipyridine containing carboxyl group. Further, this was dissolved in 20ml of DMF, and aminothiazole compound (454mg, 1.95mmol), 1-hydroxy-7-azobenzotriazole (272mg, 2mmol), 4-dimethylaminopyridine (224mg, 2.0mmol) and 1-ethyl-carbonyldiimine hydrochloride (384mg, 2.0mmol) were added thereto and stirred at room temperature for 12 hours. The precipitate was filtered, washed three times with 25ml of water, and dried in vacuo to give 670mg of an aminothiazole-functional group-substituted polypyridine ligand (L2), in a total yield of 49% in three steps. Ligand L2(667mg 1.46mmol) was reacted with the compound cis- [ Ru (bpy)2Cl2]·2H2And refluxing O (632mg, 1.22mmol) for 8 hours under the protection of 20ml of ethylene glycol and argon, cooling to room temperature, adding 10ml of saturated ammonium hexafluorophosphate aqueous solution, filtering the obtained orange precipitate, washing the orange precipitate once with 15ml of water, washing the orange precipitate three times with 30ml of anhydrous ether, and drying in vacuum to obtain a crude product. The crude product was chromatographed on a neutral alumina column with acetonitrile eluting the only orange component to give the target polypyridine complex Ru2 in 864mg yield 61%.1H-NMR(300MHz,DMSO-d6):(ppm)12.24(s,1H),10.03(s,1H),8.92–8.75(m,6H),8.71(d,J＝7.9Hz,1H),8.28–8.02(m,5H),7.71(dt,J＝13.3,6.2Hz,4H),7.52(tq,J＝20.0,6.1Hz,12H),7.36(d,J＝8.3Hz,4H),3.14(t,J＝7.3Hz,2H),2.83(d,J＝7.6Hz,2H),2.17(s,3H)。ESI-MS[CH3CN，m/z]435.6 (theoretical value: 435.6, [ M-2 PF)6]2+)。
3. Preparation of polypyridine ruthenium complex Ru 3:
the preparation steps are the same as those of the preparation of a polypyridine ruthenium complex Ru2, and are different in that bromoacetonitrile in the polypyridine ruthenium complex Ru2 is replaced by bromobutyronitrile (3.6mmol,533mg) to obtain the polypyridine ligand (L3)626mg, and the total yield of the three steps is 43%. Further with the compound cis- [ Ru (bpy)2Cl2]·2H2O (572mg, 1.1mmol) gave the desired polypyridine complex Ru3 in a yield of 706mg and 54%.1H-NMR(300MHz,DMSO-d6):(ppm)12.22(s,1H),9.96(s,1H),8.82(d,J＝8.2Hz,4H),8.75(d,J＝7.6Hz,2H),8.23(s,1H),8.15(t,J＝7.7Hz,4H),7.83–7.62(m,4H),7.54(q,J＝5.7Hz,7H),7.48–7.20(m,5H),2.82(t,J＝7.7Hz,2H),2.39(t,J＝7.6Hz,2H),2.17(s,3H),1.73(m,4H)。ESI-MS[CH3CN，m/z]449.6 (theoretical value: 449.6, [ M-2PF ]6]2+)。
4. Preparation of polypyridine ruthenium complex Ru 4:
the preparation process is the same as that of the polypyridine ruthenium complex Ru2, and is different from the preparation process in that bromoacetonitrile is replaced by bromohexanenitrile (3.6mmol,630mg) to obtain the polypyridine ligand (L4)585mg, and the total yield of the three steps is 38%. Further with the compound cis- [ Ru (bpy)2Cl2]·2H2O (494mg, 0.95mmol) gave the desired polypyridine complex Ru4 in 531mg yield, 46%.1H-NMR(300MHz,DMSO-d6):(ppm)12.24(s,1H),9.93(s,1H),8.82(d,J＝8.3Hz,4H),8.76(s,1H),8.71(s,1H),8.25(s,1H),8.15(t,J＝7.9Hz,4H),7.79–7.64(m,4H),7.64–7.43(m,8H),7.43–7.22(m,4H),2.76(d,J＝8.1Hz,2H),2.33(t,J＝7.2Hz,2H),2.16(s,3H),1.64(d,J＝23.9Hz,4H),1.38(s,4H)。ESI-MS[CH3CN，m/z]463.6 (theoretical value: 463.6, [ M-2 PF)6]2+)。
Example 2 electrophoresis experiment of identifying TAR RNA of HIV by polypyridyl ruthenium complex
Adding polypyridine ruthenium complexes with different concentrations into an AIDS virus TAR RNA (Shanghai biological) and TAR binding protein tat (Shanghai Qiangyao biological) system with a ratio of 1:1, carrying out polyacrylamide Gel electrophoresis experiments, carrying out 4S Gel Red staining, and carrying out Gel imaging on FluorChemFC 3. As shown in fig. 3, as the concentration of polypyridyl ruthenium complex increases, TAR RNA bound to tat protein gradually decreases and eventually disappears completely, indicating that ruthenium complex competes with tat for binding to the same site. The binding capacity of the complex to TAR RNA is sequentially Ru1> Ru2> Ru3> Ru4, which shows that the binding capacity of the complex to TAR RNA is reduced as the distance between a TAR RNA recognition group and the center of a ruthenium complex (the length of a connecting chain) is increased. On the other hand, the ruthenium complex Ru1 showed a stronger ability to bind TAR RNA than the tat protein, indicating that the action of a molecule with an enhanced electronegative RNA containing two positively charged ruthenium coordination centers.
Example 3 enzyme-linked immunosorbent assay for inhibiting HIV reverse transcriptase by polypyridyl ruthenium complex
The inhibitory activity of the polypyridine ruthenium complex prepared by the invention on the recombinant HIV-1 AIDS Reverse Transcriptase is experimentally determined by adopting a Roche kit (Reverse Transcriptase Assay, colorimetric) based on an enzyme-linked immunosorbent Assay, and the absorption value of 405nm is recorded (the absorption value of 490nm is taken as reference). Through single exponential curve fitting, the concentration (IC) of the polypyridine ruthenium complex Ru 1-Ru 4 for inhibiting the activity of half of HIV reverse transcriptase50) Are respectively 2.38, 5.42, 5.87 and 8.20 mu M and are obviously higher than the aminothiazole compound without connecting ruthenium complex. Therefore, the polypyridine ruthenium complex prepared by the invention has high HIV reverse transcriptase inhibition activity and is a potential drug for diseases such as AIDS and the like closely related to reverse transcriptase.
EXAMPLE 4 interaction of the Complex with nucleic acids
Weighing appropriate amount of calf thymus DNA, dissolving in buffer solution, performing ultrasonic oscillation for 15 min, performing suction filtration, diluting the filtrate as required, and measuring absorbance values at 260nm and 280 nm. A. the260/A280In the range of 1.8 to 1.9, it was found to be substantially free of protein and RNA. Three different RNA solutions of total RNA, yeast tRNA and poly (A) RNA are prepared by a reference DNA solution preparation method. The exact nucleic acid concentration was calculated from the molar extinction coefficient corresponding to the characteristic absorption peak of each. Ultraviolet spectrum titration charts of interaction of polypyridine ruthenium complexes Ru 1-Ru 4 with calf thymus DNA (figure 5), total RNA (figure 6) and yeast tRNA (figure 7) are unknownThe color reduction or red shift is realized, and the action modes of the complexes Ru 1-Ru 4 and three nucleic acids containing conjugated double-chain structures such as calf thymus DNA, total RNA and yeast tRNA are probably through electrostatic action, hydrogen bond action and the like, but not through the mode of inserting base pairs. For single-stranded poly (A) RNA, the complex Ru1 produces obvious spectral response, and Ru1 has specific recognition effect on the single-stranded RNA. On the other hand, there was no significant spectral change between Ru 2-Ru 4 and single-stranded poly (A) RNA before and after the interaction. This is because Ru1 has a pi-orbital conjugated structure, and can efficiently transfer changes in electrons and molecular orbitals at a hydrogen bonding site to ruthenium at a coordination center, thereby causing a significant change in a ligand-to-metal charge transfer transition (MLCT). However, although Ru2 to Ru4 may have such a recognition effect, since the connecting chain is an aliphatic chain, the energy level changes of the electron and molecular orbitals before and after hydrogen bonding cannot be efficiently transmitted as in the case of the structure of conjugated pi orbitals, and thus the spectrum shows no significant change.
Therefore, the polypyridine ruthenium complex prepared by the invention is a specific RNA binding reagent, can identify a site on TAR RNA of the HIV, which is bound with tat protein, can efficiently inhibit the activity of HIV reverse transcriptase, and is a potential high-activity drug molecule for diseases such as AIDS and the like related to the reverse transcriptase at present.
Claims (6)
1. A polypyridine ruthenium complex is composed of a cation part and an anion part, and is characterized in that the structural formula of the cation part is shown as a formula I:
2. the polypyridine ruthenium complex according to claim 1, wherein the anion is an inorganic salt ion.
3. The ruthenium polypyridine complex of claim 2, wherein the inorganic salt ion is PF6 －，ClO4 －Or Cl－。
4. The process for producing a polypyridine ruthenium complex according to claim 1, which comprises the steps of:
s1, oxidizing 4,4 '-dimethyl-2, 2' -bipyridyl into aldehyde group substituted bipyridyl through selenium dioxide, oxidizing carboxyl group substituted bipyridyl through silver nitrate, and further condensing with an aminothiazole compound under the action of 1-hydroxy-7-azobenzotriazole (HOAt), 1-ethyl-carbonyldiimine hydrochloride (EDCI) and 4-Dimethylaminopyridine (DMAP) to obtain a bipyridyl ligand L1 containing an aminothiazole functional group, wherein the bipyridyl ligand L1 is shown as a formula II:
s2, reacting a compound 4,4 '-dimethyl-2, 2' -bipyridyl with bromoacetonitrile, bromobutyronitrile and bromohexanenitrile respectively under the action of lithium diisopropylamide to obtain a cyano-substituted bipyridyl compound, hydrolyzing with hydrochloric acid to generate a carboxyl-substituted bipyridyl compound, and further condensing with an aminothiazole compound under the action of 1-hydroxy-7-azobenzotriazol (HOAt), 1-ethyl-carbodiimide hydrochloride (EDCI) and 4-Dimethylaminopyridine (DMAP) to obtain bipyridyl ligands L2, L3 and L4 containing aminothiazole functional groups, wherein the bipyridyl ligands are shown in formula II;
s3, the ligands L1-L4 are respectively mixed with a precursor compound cis- [ Ru (bpy)2Cl2]·2H2And (3) refluxing O in ethylene glycol, adding saturated aqueous solution of ammonium hexafluorophosphate after the reaction is finished, filtering the obtained precipitate, washing with anhydrous diethyl ether, drying in vacuum, carrying out neutral alumina column chromatography, and washing with acetonitrile to obtain the only red component, namely the polypyridine ruthenium complex.
5. The use of polypyridine ruthenium complex as claimed in claim 1 in preparing AIDS virus TAR RNA selective recognition reagent.
6. Use of the polypyridine ruthenium complex in claim 1 in the preparation of HIV reverse transcriptase inhibitor.
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