CN110204733B - Alpha-mannose modified donor-receptor type biopolymer material and preparation method and application thereof - Google Patents
Alpha-mannose modified donor-receptor type biopolymer material and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides an alpha-mannose modified donor-acceptor type conjugated polymer and a preparation method thereof, and the polymer with better photophysical property and wider fluorescence emission spectrum range is obtained by introducing different donor units and acceptor units. The polymer can be combined with the lectin capable of specifically recognizing the alpha-mannose on the surfaces of pathogenic bacteria in a targeted manner, the types and the quantity of the lectin capable of recognizing the alpha-mannose on the surfaces of different types of pathogenic bacteria are different, the binding capacity of the polymer and the different types of pathogenic bacteria are different, and the aggregation states of the polymer on the surfaces of the different types of pathogenic bacteria are different, so that the fluorescence resonance energy transfer efficiency from a donor unit to an acceptor unit of the polymer is different, and the different types of pathogenic bacteria can be distinguished and detected by monitoring the change of the fluorescence color of the polymer. The rapid visual pathogenic bacteria distinguishing method has potential application value in the aspects of food safety, clinical diagnosis, environmental monitoring and the like.
Description
Technical Field
The invention belongs to the field of functional polymers, and relates to an alpha-mannose modified donor-receptor type biopolymer material, and a preparation method and application thereof.
Background
In recent years, the problem of infection by pathogenic bacteria such as bacteria and fungi has become a global public health safety problem. Bacterial and fungal infections, as the main cause of pathogenic infections, often have extremely serious consequences and can even endanger the life of the patient, leading to increased mortality in patients [ Molecules,2009,14(2):586 597 ]. Pathogenic bacteria are responsible for the infection of humans with food-borne diseases, syphilis and tuberculosis, and half of these infections are caused by pathogenic E.coli [ J.Clin.Microbiol.,1999,37(6): 2024-; environ, health Perspectrum, 1982,43(FEB):9-19 ]. In clinical practice, Polymicrobial infections caused by a variety of pathogenic bacteria are prevalent in patients, and therefore differential detection of pathogenic bacteria is important for the treatment of these diseases [ polymeric diseases.2002 ]. The traditional blood culture method is usually used clinically for identifying pathogen infection, but the method is long in time consumption and unstable in sensitivity, thereby influencing the application efficiency of the method in early diagnosis [ J.Clin.Microbiol.,1995,33(4): 978-981; j. Infect, 2008,57(4): 307-. In order to develop more effective pathogenic bacteria detection technology, researchers establish methods such as PCR (polymerase chain reaction) method based on specific nucleic acid probes, immunological method for detecting pathogenic bacteria antigens, DNA microarray method, biosensing method and the like to perform differential detection on pathogenic bacteria [ biosens. Bioelctron, 2007,22(7):1205-1217 ]. However, these methods have high detection cost, complicated preparation process and harsh requirements on instruments, thereby limiting the large-scale application thereof.
In 2000, sialic acid and mannose were first modified to the end of Polythiophene (PT) by the Baek research group of the Lorentberg Kelly national laboratory, university of California, USA, and detection of influenza virus and E.coli (E.coli) was achieved by monitoring changes in the degree of polymer conjugation under ligand-receptor specific binding [ coli. bioconjugate chem.,2000,11(6):777-788 ]. Subsequently, this recognition and detection method using the specific interaction of ligand-receptor has been rapidly developed, and researchers have achieved rapid and highly sensitive detection of e.coli using α -mannose and trimannose modified poly-p-phenylene vinylene (PPE), α -mannose modified polyfluorene (PFP) containing polyethylene glycol (PEG) side chain, and α -mannose modified neutral water-soluble oligomer, respectively [ j.am.chem.soc.,2004,126(41): 13343-13346; macromolecules,2008,41(20): 7316-; j. Mater. chem.,2010,20(7):1312-1316 ]. In addition, based on the high-sensitive signal response characteristic of Polydiacetylene (PDA), a targeting identification system related to PDA is also used for detecting pathogenic bacteria. Subsequently, the Wang research group at Ohio State university, USA, utilizing the property of Gal- α -1,4-Gal disaccharide functionalized PDA to be able to specifically bind Shiga toxin B subunit in liquid phase, achieved specific detection of Shiga toxin-producing E.coli (E.coli O157) by monitoring the color change of the solution [ Bioorg.Med.chem.Lett.,2008,18(2):700- "703 ]. Liquid phase PDA sensors have some instability and in order to overcome this disadvantage researchers have developed solid phase PDA sensing systems. The Korean institute of science and technology Park research group designed and developed Streptavidin (STA) -functionalized PDA solid-phase chip, and utilized the system to realize specific detection of Chlamydia trachomatis [ Small,2008,4(10): 1778-.
However, the existing alpha-mannose modified polymer material is only used for detecting specific pathogenic bacteria, and can not realize the differential detection of different pathogenic bacteria.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides an alpha-mannose modified donor-receptor type biopolymer material and application thereof, which can realize visual distinguishing detection of different pathogenic bacteria.
The invention is realized by the following technical scheme:
an alpha-mannose modified donor-receptor biopolymer material, the structural formula of which is shown in formula I or formula II:
in the formula I and the formula II, m and n are respectively an integer of 1-10 ten thousand independently; k is an integer between 0 and 30; a. the1、A2、A3、A6、A7And A8Each independently is O, N or an S atom; a. the4Is a C or N atom; a. the5S, O, N or a C atom; r is H atom, F atom or CN group; r1、R2、R3、R4、R5And R6Each independently is a H atom, a F atom or a linear or branched alkyl group having 1 to 20 carbon atoms.
Preferably, it is any one of the following polymers a to H:
the synthesis method of the alpha-mannose modified donor-receptor type biopolymer material is characterized by comprising the following steps:
(1) synthesis of conjugated polymers
Etherifying the 2,5-dibromo hydroquinone derivative and the compound 1 under the action of a first alkaline substance and an additive to obtain a compound 2; performing Li-Br exchange on the compound 2 and a lithium reagent to obtain an intermediate phenyl lithium, and further reacting the intermediate phenyl lithium with pinacol isopropyl borate to obtain a compound 3;
carrying out Pd-catalyzed Suzuki coupling reaction on the compounds 2,3 and 4 to obtain a donor-receptor type conjugated polymer P1; or alkylating 2, 7-dibromofluorene and the compound 1 under the action of a second basic substance to obtain a compound 5, and carrying out Suzuki coupling reaction on the compounds 3,4 and 5 under the catalysis of a Pd catalyst to obtain a donor-acceptor type conjugated polymer P2;
(2) modification of targeting groups
Reacting 1,2,3,4, 6-pentaacetyl-alpha-mannose with alkynyl or cyano compound under the action of Lewis acid to obtain a compound 6;
carrying out SN2 substitution reaction on a donor-receptor type conjugated polymer P1 and an azidation reagent to obtain an azidated polymer P1-1, carrying out Click reaction on the polymer P1-1 and a compound 6 under the catalysis of a metal catalyst to obtain a polymer P1-2 with an acetyl mannose terminal, and further removing acetyl protection to obtain a compound shown in the formula I;
or, carrying out SN2 substitution reaction on the donor-receptor type conjugated polymer P2 and an azidation reagent to obtain an azidated polymer P2-1, further carrying out Click reaction on the polymer P2-1 and a compound 6 under the catalysis of a metal catalyst to obtain a polymer P2-2 with an acetyl mannose terminal, and further carrying out deacetylation protection to obtain a compound shown in a formula II;
preferably, in the step (1), the first basic substance is one of potassium carbonate, potassium hydroxide and KHMDS, the additive is one of 18-crown 6, dibenzo 18-crown 6 and aza 18-crown 6, and the lithium reagent is one of n-butyllithium, t-butyllithium and metallic lithium.
Preferably, in the step (1), the second basic substance is one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide and potassium tert-butoxide.
Preferably, in step (1), the Pd catalyst is palladium acetate, tetrakis (triphenylphosphine) palladium, dichlorobis (triphenylphosphine) palladium or (1,1' -bis (diphenylphosphino) ferrocene) dichloropalladium.
Preferably, in the step (2), the Lewis acid is aluminum trichloride, titanium tetrachloride, stannic chloride, zinc chloride, bismuth trichloride or silver trifluoromethanesulfonate; the azide reagent is sodium azide, potassium azide or TMSN3And TsN3One or more of them.
Preferably, in the step (2), the metal catalyst is a copper-based catalyst, a rhodium-based catalyst, a ruthenium-based catalyst, a palladium-based catalyst or an iron-based catalyst.
Preferably, in the step (2), the reagent used for deacetylation protection is one or more of sodium methoxide, sodium ethoxide and sodium tert-butoxide.
The alpha-mannose modified donor-receptor type biopolymer material is applied to detection and differentiation of different pathogenic bacteria.
Compared with the prior art, the invention has the following beneficial technical effects:
the invention designs and synthesizes a series of alpha-mannose modified donor-receptor type conjugated polymers, and obtains the polymers with better photophysical properties and wider fluorescence emission spectrum range by introducing different donor units and receptor units. The polymer can be combined with the lectin capable of specifically recognizing the alpha-mannose on the surfaces of pathogenic bacteria in a targeted manner, the types and the quantity of the lectin capable of recognizing the alpha-mannose on the surfaces of different types of pathogenic bacteria are different, the binding capacity of the polymer and the different types of pathogenic bacteria are different, and the aggregation states of the polymer on the surfaces of the different types of pathogenic bacteria are different, so that the fluorescence resonance energy transfer efficiency from a donor unit to an acceptor unit of the polymer is different, and the different types of pathogenic bacteria can be distinguished and detected by monitoring the change of the fluorescence color of the polymer. The method has the advantages of simplicity, convenience, rapidness, visualization and the like, and does not involve any complicated instrument, virulent dye and expensive labeled primer. It is believed that the rapid visual pathogenic bacteria distinguishing method can show potential application value in food safety, clinical diagnosis, environmental monitoring and the like.
The invention obtains a polymer framework through Suzuki coupling reaction preparation, and obtains a series of donor-acceptor type biological high molecular materials through alpha-mannose modification of a side chain through click chemistry.
The microbial detection method based on the functional material has the advantages of simplicity, rapidness, visual naked eyes, no need of any complex instrument, use of a virulent dye and an expensive marking primer and the like, and has the characteristics of rapidness, convenience and low cost compared with the conventional microbial detection method of pathogenic bacteria and the like.
Drawings
FIG. 1 shows the fluorescence emission spectrum of the polymer A obtained in example 4 after normalization.
FIG. 2 is a normalized fluorescence emission spectrum of the polymer C obtained in example 6.
FIG. 3 is a graph showing the results of pathogenic bacterium discrimination detection using the polymer H obtained in example 11.
Detailed Description
The present invention will now be described in further detail with reference to specific examples, which are intended to be illustrative, but not limiting, of the invention.
Example 1: synthesis of phenyl units
(1) Preparation of 14,14' - ((2,5-dibromo-1,4-phenylene) bis (oxy)) bis (1-brono-3, 6,9, 12-tetroxa-tetracan) (B-1):
2, 5-dibromozene-1, 4-diol (1.0eq,10mmol,2.68g) and 1, 14-dibromoo-3, 6,9, 12-tetraoxatetaracane (5eq,50mmol,18.2g) were dissolved in 80mL tetrahydrofuran, potassium hydroxide (3.0eq,30mmol,1.68g) and dibenzo 18-crown 6(200mg) were added and reacted at room temperature to reflux temperature until the starting material disappeared, 50mL water was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. The solvent is dried by spinning to obtain the compound B-1.1HNMR(400MHz,CDCl3,δ):7.21(s,2H),4.42(t,4H,J＝4.4Hz),3.90(t,4H,J＝3.6Hz),3.74(t,4H,J＝4.4Hz),3.60-3.20(m,28H).C26H42Br4O10:calcd.C37.43,H5.07；found C 37.48,H 5.04.
(2) Preparation of 2,2' - (2,5-bis ((14-bromo-3,6,9, 12-tetraoxatadecyl) oxy) -1,4-phenylene) bis (4,4,5, 5-tetramethy-1, 3,2-dioxaborolane) (B-2):
after compound B-1(1.0eq,10mmol,8.34g) was dissolved in 50mL of tetrahydrofuran and n-butyllithium (2.4eq,24mmol,2.5M in hex,10mL) was added dropwise under nitrogen protection at-78 ℃ and reacted at this temperature for 1-2h, 2-isopropoxy-4,4,5, 5-tetramethylol-1, 3,2-dioxaborolane (2.2eq,22mmol,4.09g,4.5mL) was added and slowly warmed to room temperature, 50mL of saturated ammonium chloride solution was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. After the solvent is dried by spinning, ethanol is recrystallized to obtain a compound B-2.1H NMR(400MHz,CDCl3,δ):6.88(s,2H),4.35(t,4H,J＝4.4Hz),3.92(t,4H,J＝3.6Hz),3.76(t,4H,J＝4.4Hz),3.62-3.26(m,28H),1.15(s,24H).C38H66B2Br2O14:calcd.C 49.16,H 7.17；found C 49.22,H7.14.
(3) Preparation of 20,20' - ((2,5-dibromo-3,6-dimethyl-1,4-phenylene) bis (oxy)) bis (1-bromo-3,6,9,12,15, 18-hexaoxaicosine) (B-3):
2,5-dibromo-3,6-dimethylbenzene-1,4-diol (1.0eq,1.0mmol,296mg) and 1,20-dibromo-3,6,9,12,15, 18-hexaoxacosicane (5eq,5.0mmol,2.26g) were dissolved in 10mL of dichloromethane, potassium carbonate (3.0eq,3.0mmol,414mg) and 18 crown 6(0.1eq,0.1mmol,26.4mg) were added and reacted at room temperature to reflux temperature until the raw materials disappeared, 50mL of water was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. The solvent is dried by spinning to obtain the compound B-3.1H NMR(400MHz,CDCl3,δ):4.35(t,4H,J＝4.4Hz),3.85(t,4H,J＝3.6Hz),3.70(t,4H,J＝4.4Hz),3.55-3.14(m,44H),2.27(s,6H).C36H62Br4O14:calcd.C 41.64,H 6.02；found C 41.71,H 6.09.
(4) Preparation of 2,2' - (2,5-bis ((20-bromo-3,6,9,12,15,18-hexaoxaicosyl) oxy) -3,6-dimethyl-1,4-phenylene) bis (4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (B-4):
compound B-3(1.0eq,0.5mmol,505mg) was dissolved in 10mL tetrahydrofuran, n-butyllithium (2.4eq,1.2mmol,2.5M in hex, 0.5mL) was added dropwise under nitrogen protection at-78 deg.C, and after reaction at this temperature for 1.5h, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.2eq,1.1mmol,205mg,0.23mL) was added and slowly warmed to room temperature, 15mL of saturated ammonium chloride solution was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. After the solvent is dried by spinning, the compound B-4 is obtained by ethanol recrystallization.1H NMR(400MHz,CDCl3,δ):4.33(t,4H,J＝4.4Hz),3.93(t,4H,J＝3.6Hz),3.76(t,4H,J＝4.4Hz),3.61-3.22(m,44H),2.31(s,6H),1.17(s,24H).C48H86B2Br2O18:calcd.C 50.90,H 7.65；found C 50.97,H 7.59.
(5) Preparation of 26,26' - ((2,5-dibromo-1,4-phenylene) bis (sulphanediyl) bis (1-bromo-3,6,9,12,15,18,21, 24-octaoxacoxsacane) (B-5):
2, 5-dibromobenzozene-1, 4-dithiol (1.0eq,10mmol,3.00g) and 1, 26-dibromoo-3, 6,9,12,15,18,21, 24-octaoxazacosane (5eq,50mmol,27.0g) were dissolved in 10mL of dichloromethane, KHMDS (3.0eq,30mmol,1.0M,30mL) and aza 18 crown 6(200mg) were added and reacted at room temperature to reflux temperature until the starting material disappeared, 50mL of water was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. The solvent is dried by spinning to obtain the compound B-5.1H NMR(400MHz,CDCl3,δ):7.18(s,2H),3.92(t,4H,J＝3.6Hz),3.78(t,4H,J＝4.4Hz),3.76-3.28(m,60H),3.22(t,4H,J＝4.4Hz).C42H74Br4O16S2:calcd.C 41.39,H 6.12；found C 41.45,H 6.19.
(6) Preparation of 2,2' - (2,5-bis ((26-bromo-3,6,9,12,15,18,21, 24-octaoxahexosyl) thio) -1,4-phenylene) bis (4,4,5, 5-tetramethy-1, 3,2-dioxaborolane) (B-6):
compound B-5(1.0eq,0.2mmol,244mg) was dissolved in 15mL tetrahydrofuran, lithium metal (10eq,2.0mmol,14mg) was added under nitrogen at room temperature, the mixture was reacted at 45 ℃ for 1.5h, 2-isopopoxy-4, 4,5, 5-tetramethylol-1, 3,2-dioxaborolane (2.2eq,0.44mmol,82mg,0.10mL) was added and slowly warmed to room temperature, 5mL of saturated ammonium chloride solution was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. After the solvent is dried by spinning, the compound B-6 is obtained by ethanol recrystallization.1H NMR(400MHz,CDCl3,δ):7.21(s,2H),3.90(t,4H,J＝3.6Hz),3.77(t,4H,J＝4.4Hz),3.78-3.20(m,60H),3.27(t,4H,J＝4.4Hz),1.29(s,24H).C54H98B2Br2O20S2:calcd.C 49.40,H 7.52；found C 49.52,H 7.61.
(7) Preparation of 20,20' - ((2,5-dibromo-3,6-dimethyl-1,4-phenylene) bis (oxy)) bis (1-bromo-3,6,9,12,15, 18-hexaoxaicosine) (B-7):
2, 5-dibromozene-1, 4-diamine (1.0eq,1.0mmol,2.66g) and 1, 20-dibromoo-3, 6,9,12,15, 18-hexaoxacor (5eq,5.0mmol,2.26g) were dissolved in 10mL of acetone, KHMDS (3.0eq,3.0mmol,1.0M,3.0mL) and aza 18 crown 6(30mg) were added and reacted at room temperature to reflux temperature until the starting material disappeared, 50mL of water was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. The solvent is dried by spinning to obtain the compound B-3.1H NMR(400MHz,CDCl3,δ):9.15(b,2H),6.71(s,2H),3.88(t,4H,J＝3.6Hz),3.69(t,4H,J＝4.4Hz),3.78-3.20(m,48H).C34H60Br4N2O12:calcd.C 40.49,H 6.60,N 2.78；found C 40.54,H 6.66,N 2.74.
(8) Preparation of N1, N4-bis (20-bromo-3,6,9,12,15, 18-hexaoxacor) -2,5-bis (4,4,5,5-tetra-methyl-1,3,2-dioxaborolan-2-yl) bezene-1, 4-diamine (B-8):
after compound B-7(1.0eq,0.2mmol,202mg) was dissolved in 6mL of tetrahydrofuran and t-butyllithium (4.4eq,0.88mmol,1.6M, 0.55mL) was added dropwise under nitrogen protection at-78 ℃ and reacted at this temperature for 1.5h, 2-isopropoxy-4,4,5, 5-tetramethylol-1, 3,2-dioxaborolane (2.2eq,0.44mmol,82mg,0.1mL) was added and slowly warmed to room temperature, the reaction was quenched by addition of 5mL of saturated ammonium chloride solution, extracted with ethyl acetate, and the organic phases were combined and dried over anhydrous sodium sulfate. After the solvent is dried by spinning, the compound B-8 is obtained by ethanol recrystallization.1H NMR(400MHz,CDCl3,δ):8.94(b,2H),6.47(s,2H),3.85(t,4H,J＝3.6Hz),3.65(t,4H,J＝4.4Hz),3.82-3.30(m,48H),1.12(s,24H).C46H84B2Br2N2O16:calcd.C 50.11,H 7.68,N 2.54；found C 50.17,H 7.71,N 2.51.
Example 2: synthesis of fluorenyl units
(1) Preparation of 20,20' - (2, 7-dibromo-9H-fluoroene-9, 9-diyl) bis (1-bromo-3,6,9,12,15, 18-hex-aoxaicosan) (F-1):
2, 7-dibromo-9H-fluoroene (1.0eq,10mmol,3.24g) and 1,20-dibromo-3,6,9,12,15, 18-hexaoxaicosine (5eq,50mmol,22.6g) were dissolved in 80mL of acetone, potassium tert-butoxide (3.0eq,30mmol,3.4g) and tetrabutylammonium bromide (0.2eq,2mmol,644mg) were added, and after the reaction was carried out at room temperature to reflux temperature until the starting material disappeared, 50mL of water was added to quench the reaction, ethyl acetate was extracted, and the organic phases were combined and dried over anhydrous sodium sulfate. The solvent was spin-dried to give compound F-1.1H NMR(400MHz,CDCl3,δ):7.83(d,2H,J＝8.4Hz),7.75(s,2H),7.39(d,2H,J＝8.0Hz),3.97(t,4H,J＝3.6Hz),3.71-3.16(m,48H)2.13(t,4H,J＝4.4Hz).C41H62Br4O12:calcd.C 46.17,H 5.86；found C 46.21,H 5.89.
(2) Preparation of 26,26' - (2, 7-dibromo-9H-fluoroene-9, 9-diyl) bis (1-bromo-3,6,9,12,15,18,21, 24-octaoxacoxsacine) (F-2):
2, 7-dibromo-9H-fluoroene (1.0eq,10mmol,3.24g) and 1,20-dibromo-3,6,9,12,15, 18-hexaoxaicosine (5eq,50mmol,27.0g) were dissolved in 100mL of acetone, potassium hydroxide (3.0eq,30mmol,1.68g) and tetrabutylammonium bromide (0.2eq,2mmol,644mg) were added, and after reaction at room temperature to reflux temperature until the starting material disappeared, 50mL of water was added to quench the reaction, ethyl acetate was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. And (4) spin-drying the solvent to obtain the compound F-2.1H NMR(400MHz,CDCl3,δ):7.79(d,2H,J＝8.4Hz),7.69(s,2H),7.55(d,2H,J＝8.0Hz),3.93(t,4H,J＝3.6Hz),3.71-3.16(m,64H)2.11(t,4H,J＝4.4Hz).C49H78Br4O16:calcd.C 47.36,H 6.33；found C 47.42,H 6.38.
Example 3: synthesis of alpha-mannosyl units
(1) Preparation of (2R,3R,4S,5S,6S) -2- (acetoxymethyl) -6- (prop-2-yn-1-yloxy) tetrahydro-2H-pyran-3,4,5-triyl triacetate (G-1):
1,2,3,4, 6-pentaacetyl-alpha-mannose (1.0eq,10mmol,3.90g) and propargyl alcohol (1.3eq,13mmol,729mg) were dissolved in 20mL of chloroform, tin tetrachloride (1.0eq,10mmol,2.61g) was added and reacted at-20 ℃ to room temperature under nitrogen protection until the starting material disappeared, 50mL of saturated aqueous ammonium chloride solution was added to quench the reaction, chloroform was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. And (4) carrying out column chromatography purification after spin-drying the solvent to obtain the compound G-1.1H NMR(400MHz,CDCl3,δ):5.48(dd,1H,J＝3.4,1.4Hz),5.37(dd,1H,J＝10.9,3.4Hz),5.34(d,1H,J＝3.6Hz),5.19(dd,1H,J＝10.9,3.7Hz),4.28(dd,2H,J＝2.4,1.0Hz),4.27(m,1H),4.13–4.10(m,2H),2.47(t,1H,J＝2.4Hz),2.16,2.09,2.06,1.99(4s,12H).C17H22O10:calcd.C 52.85,H 5.74；found C 52.89,H 5.76.
(2) Preparation of (2R,3R,4S,5S,6S) -2- (acetoxymethyl) -6- (cyanomethyl) tetrahydro-2H-pyran-3,4, 5-trieyl triacetate (G-2):
1,2,3,4, 6-pentaacetyl-alpha-mannose (1.0eq,10mmol,3.90g) and 2-hydroxyacenitrilide (1.3eq,13mmol,742mg) were dissolved in 20mL1, 2-dichloroethane, titanium tetrachloride (1.0eq,10mmol,1.89g) was added and the reaction was carried out under nitrogen protection at-20 ℃ to room temperature until the starting material disappeared, 50mL saturated aqueous ammonium chloride solution was added to quench the reaction, chloroform was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. And (4) carrying out column chromatography purification after spin-drying the solvent to obtain the compound G-2.1H NMR(400MHz,CDCl3,δ):5.67(dd,1H,J＝3.4,1.4Hz),5.43(dd,1H,J＝10.9,3.4Hz),5.39(d,1H,J＝3.6Hz),5.25(dd,1H,J＝10.9,3.7Hz),4.62-4.54(m,2H),4.35(dd,2H,J＝2.4,1.0Hz),4.31(m,1H),2.56(t,1H,J＝2.4Hz),2.19,2.11,2.08,2.03(4s,12H).C16H21NO10:calcd.C 49.61,H 5.64,N 3.62；found C 49.66,H 5.69,N 3.67.
(3) Preparation of (2R,3R,4S,5S,6R) -2- (acetoxymethyl) -6- ((cyanomethyl) thio) tetrahydro-2H-pyran-3,4, 5-trienyl triacetate (G-3):
1,2,3,4, 6-pentaacetyl-alpha-mannose (1.0eq,10mmol,3.90g) and 2-mercaptoacetonitrile (1.3eq,13mmol,950mg) were dissolved in 20mL of chloroform, bismuth trichloride (1.0eq,10mmol,3.15g) was added and the reaction was carried out under nitrogen protection at-20 ℃ to room temperature until the starting material disappeared, 50mL of saturated aqueous ammonium chloride solution was added to quench the reaction, chloroform extraction was carried out, the organic phases were combined and dried over anhydrous sodium sulfate. And (4) carrying out column chromatography purification after spin-drying the solvent to obtain the compound G-3.1H NMR(400MHz,CDCl3,δ):5.51(dd,1H,J＝3.4,1.4Hz),5.29(dd,1H,J＝10.9,3.4Hz),5.13(d,1H,J＝3.6Hz),4.73(dd,1H,J＝10.9,3.7Hz),4.22-4.18(m,2H),4.02(dd,2H,J＝2.4,1.0Hz),3.68(m,1H),3.09(t,1H,J＝2.4Hz),2.21,2.13,2.10,2.03(4s,12H).C16H21NO9S:calcd.C 47.64,H 5.25,N 3.47；found C 47.69,H 5.28,N 3.43.
(4) Preparation of (2R,3R,4S,5S,6S) -2- (acetoxymethyl) -6- (prop-2-yn-1-ylamino) tetrahydro-2H-pyran-3,4,5-triyl triacetate (G-4):
1,2,3,4, 6-pentaacetyl-alpha-mannose (1.0eq,10mmol,3.90g) and propargylamine (1.3eq,13mmol,716mg) were dissolved in 20mL of dichloromethane, zinc chloride (1.0eq,10mmol,1.36g) was added and reacted at-20 ℃ to room temperature under nitrogen protection until the starting material disappeared, 50mL of saturated aqueous ammonium chloride solution was added to quench the reaction, chloroform was extracted, the organic phases were combined and dried over anhydrous sodium sulfate. And (4) carrying out column chromatography purification after spin-drying the solvent to obtain the compound G-4.1H NMR(400MHz,CDCl3,δ):5.27(dd,1H,J＝9.0,4.0Hz),5.16(t,1H,J＝9.4,9.4Hz),5.05-4.87(m,2H),4.15(dd,1H,J＝12.0,3.3Hz),4.03(m,2H),3.72(ddd,1H,J＝9.2,5.0,3.3Hz),3.31(d,2H,J＝4.0Hz),2.99(s,1H),1.98,1.94,1.91,1.89(4s,12H).C17H23NO9:calcd.C 52.98,H 6.02,N 3.63；found C 53.01,H 6.04,N 3.61.
(5) Preparation of (2R,3R,4S,5S,6S) -2- (acetoxymethyl) -6- ((cyanomethyl) amino) tetrahydro-2H-pyran-3,4, 5-trienyl triacetate (G-5):
1,2,3,4, 6-pentaacetyl-alpha-mannose (1.0eq,10mmol,3.90g) and 2-hydroxyacenitritrile (1.3eq,13mmol,729mg) were dissolved in 20mL of chloroform, after addition of silver triflate (1.0eq,10mmol,2.57g) under nitrogen protection, reaction was carried out at-20 ℃ to room temperature until the starting material disappeared, 50mL of saturated aqueous ammonium chloride solution was added to quench the reaction, chloroform extraction was carried out, the organic phases were combined and dried over anhydrous sodium sulfate. And (4) carrying out column chromatography purification after spin-drying the solvent to obtain the compound G-5.1H NMR(400MHz,CDCl3,δ):5.46(dd,1H,J＝9.4,3.6Hz),5.22(t,1H,J＝9.4,9.4Hz),5.12-4.93(m,2H),4.22(dd,1H,J＝12.0,3.3Hz),4.14(m,2H),3.83(m,1H),3.62(d,2H,J＝3.6Hz),2.02,1.96,1.94,1.92(4s,12H).C16H22N2O9:calcd.C 49.74,H 5.74,N 7.25；found C 49.77,H 5.75,N 7.23.
Example 4: synthesis of Polymer of formula A
In N2Under protection, 3.0mmol of boric acid derivative B-2, 1.5mmol of bromobenzene derivative B-1 and 1.5mmol of benzothiadiazole derivative S-1 were added to a vacuum-dried three-necked flask, dissolved in 15mL of toluene and charged with N2After bubbling for 0.5h, 0.03eq of Pd (dba) was added2Catalyst, 2M potassium carbonate solution is added and aeration is continued for 0.5h, then the reaction is heated for 48 h. After the reaction was completed, it was cooled to room temperature and 30mL of water was added to quench the reaction, and the aqueous phase was extracted with chloroform and the organic phases were combined and dried over anhydrous magnesium sulfate. The polymer intermediate with the end being bromine can be obtained by secondary sedimentation after the Soxhlet extraction. This was dissolved in DMF, 10eq of sodium azide was added and reacted at rt for 30 h. Dissolving with chloroform, washing with water, drying, filtering, and settling in methanol to obtain the desired polymer intermediate P-A.
Dissolving the polymer intermediate P-A into tetrahydrofuran, adding 10eq of alphｃA-mannosyl unit and 0.2eq of cuprous iodide as ｃA catalyst, and reacting for 20h under the protection of nitrogen. Spin-drying the solvent, adding into methanol/sodium methoxide system to remove acetyl protection, adjusting pH to 4-5, and extracting the reaction solution with chloroform-methanol system. The organic phases were combined, dried over anhydrous sodium sulfate and the solvent was spin dried. And dialyzing to remove metal ions and small molecular compounds to obtain the target polymer A.1H NMR(400MHz,DMSO-d6,δ):8.10(s,2H),7.73(s,6H),7.12-6.93(m,10H),5.45(b,6H),4.87-4.62(br,20H),4.47(s,12H),4.32-4.19(m,12H),3.92-2.15(m,132H)。
Example 5: synthesis of Polymer of formula B
In N2The desired polymer intermediate P-B was obtained by the remaining procedure of reference example 4 using palladium acetate as a catalyst by adding 3.0mmol of the boronic acid derivative B-4, 1.5mmol of the bromobenzene derivative B-7 and 1.5mmol of the benzothiadiazole derivative S-2 to the vacuum dried three-necked flask under protection.
The polymer intermediate P-B was dissolved in toluene, 10eq of alpha-mannosyl units and 0.2eq of catalyst Cp RuCl (PPh) were added3) And reacting for 30 hours under the protection of nitrogen. Spin-drying the solvent, adding into ethanol/sodium ethoxide system to remove acetyl protection, adjusting pH to 8-9, and extracting with chloroform-methanol system. The organic phases were combined, dried over anhydrous sodium sulfate and the solvent was spin dried. And (4) dialyzing to remove metal ions and small molecular compounds to obtain the target polymer B.1H NMR(400MHz,DMSO-d6,δ):7.95(s,6H),7.33(s,4H),6.82(s,2H),5.51(b,6H),4.90-4.60(br,20H),4.52(s,12H),4.41-4.36(m,12H),3.90-2.10(m,180H),2.32-2.15(m,12H)。
Example 6: synthesis of Polymer of formula C
In N2Under protection, 3.0mmol of boric acid derivative B-6, 1.5mmol of bromobenzene derivative B-5 and 1.5mmol of benzothiadiazole derivative S-3 are added into a vacuum-dried three-neck flask, dichlorobis (triphenylphosphine) palladium is used as a catalyst, and TMSN is added3The remaining operations, referred to example 4, for the azidation reagent and rhodium acetate as the catalyst for the Click reaction yielded the desired polymer C.1H NMR(400MHz,DMSO-d6,δ):7.78(s,6H),7.42-7.03(m,8H),5.39(b,6H),4.96-4.72(br,20H),4.29-4.13(m,12H),4.05(s,12H),3.96-2.10(m,228H)。
Example 7: synthesis of Polymer of formula D
In N2Under protection, 3.0mmol of boric acid derivative B-8, 1.5mmol of bromobenzene derivative B-7 and 1.5mmol of benzothiadiazole derivative S-4 were added to a vacuum-dried three-necked flask using TsN3The remaining operations, referred to example 5, for the azidation reagent and ferrous chloride as the click reaction catalyst gave the desired polymer D.1H NMR(400MHz,DMSO-d6,δ):9.16(br,6H),7.02-6.85(m,8H),6.22(br,6H),4.76(m,6H),4.96-4.72(br,20H),3.96-2.10(m,204H)。
Example 8: synthesis of Polymer of formula E
In N2The desired polymer E was obtained by conducting the rest of the procedure of reference example 5 using (1,1' -bis (diphenylphosphino) ferrocene) dichloropalladium as a catalyst by adding 3.0mmol of the boronic acid derivative B-4, 1.5mmol of the bromobenzene derivative B-5 and 1.5mmol of the benzothiadiazole derivative S-4 to a vacuum-dried three-necked flask under protection.1H NMR(400MHz,DMSO-d6,δ):8.12(s,2H),7.32-7.21(m,2H),6.91(s,2H),6.31(br,6H),4.81(m,6H),4.91-4.66(br,20H),4.11-2.54(m,204H),2.35-2.20(m,12H)。
Example 9: synthesis of Polymer of formula F
In N2The desired polymer F was obtained by adding 3.0mmol of the boronic acid derivative B-6, 1.5mmol of the bromofluorene derivative F-1 and 1.5mmol of the benzothiadiazole derivative S-2 to a vacuum-dried three-necked flask with a deacetylation protecting system of t-butanol/sodium t-butoxide under protection in accordance with example 4.1H NMR(400MHz,DMSO-d6,δ):8.10-7.31(m,20H),5.43(m,6H),4.81-4.54(m,30H),4.11-2.54(m,240H)。
Example 10: synthesis of Polymer of formula G
In N2The desired polymer G was obtained by the remaining operations with reference to example 4, while adding 3.0mmol of the boric acid derivative B-8, 1.5mmol of the bromofluorene derivative F-2 and 1.5mmol of the benzothiadiazole derivative S-5 to a vacuum-dried three-necked flask under protection.1H NMR(400MHz,DMSO-d6,δ):8.91(br,4H),8.09-7.31(m,12H),6.78-6.62(m,2H),4.63(m,6H),4.89-4.64(m,30H),3.94-2.54(m,174H)。
Example 11: synthesis of Polymer of formula H
In N2The desired polymer H was obtained by the rest of the procedure of reference example 5 by adding 3.0mmol of the boric acid derivative B-4, 1.5mmol of the bromofluorene derivative F-1 and 1.5mmol of the benzothiadiazole derivative S-3 to a vacuum-dried three-necked flask under protection.1H NMR(400MHz,DMSO-d6,δ):8.12-7.35(m,6H),6.85(s,2H),6.36(br,6H),4.89-4.64(m,30H),3.94-2.54(m,198H),2.42-2.30(m,12H)。
FIG. 1 shows the fluorescence emission spectrum of the polymer A obtained in example 4 after normalization. FIG. 2 is a normalized fluorescence emission spectrum of the polymer C obtained in example 6. The fluorescence emission spectrum range of the polymer C is widened due to the introduction of electron-withdrawing groups F and CN into the acceptor unit of the polymer C.
FIG. 3 is a graph showing the results of pathogenic bacterium discrimination detection using the polymer H obtained in example 11. As the types and the quantity of the agglutinin contained on the surfaces of the strains E.coli, S.aureus and C.albicans are different, the polymer H shows different aggregation states when being combined with the strains respectively, and the effect of fluorescence resonance energy transfer to an acceptor unit is different, the polymer H emits fluorescence (E.coli, pink; S.aureus, purple; C.albicans, blue-purple) with different colors after being aggregated on the surfaces of different strains, thereby realizing the visual detection of different types of pathogenic bacteria.
Claims (10)
1. An alpha-mannose modified donor-receptor biopolymer material, characterized in that the structural formula is shown as formula I or formula II:
in the formulas I and II, m and n are respectively independent integers of 1-10 ten thousand; k is an integer between 0 and 30; a. the1、A2、A3、A6、A7And A8Each independently is O, N or an S atom; a. the4Is a C or N atom; a. the5S, O, N or a C atom; r is H atom, F atom or CN group; r1、R2、R3、R4、R5And R6Each independently is H atom, F atom or C1-20 straight chain or branched chain alkyl;
2. the α -mannose-modified donor-receptor biopolymer material according to claim 1, characterized in that it is any one of the following polymers a to H:
3. the method for synthesizing an α -mannose-modified donor-receptor type biopolymer material according to any one of claims 1 to 2, comprising the steps of:
(1) synthesis of conjugated polymers
Etherifying the 2,5-dibromo hydroquinone derivative and the compound 1 under the action of a first alkaline substance and an additive to obtain a compound 2; performing Li-Br exchange on the compound 2 and a lithium reagent to obtain an intermediate phenyl lithium, and further reacting the intermediate phenyl lithium with pinacol isopropyl borate to obtain a compound 3;
carrying out Pd-catalyzed Suzuki coupling reaction on the compounds 2,3 and 4 to obtain a donor-receptor type conjugated polymer P1; or alkylating 2, 7-dibromofluorene and the compound 1 under the action of a second basic substance to obtain a compound 5, and carrying out Suzuki coupling reaction on the compounds 3,4 and 5 under the catalysis of a Pd catalyst to obtain a donor-acceptor type conjugated polymer P2;
(2) modification of targeting groups
Reacting 1,2,3,4, 6-pentaacetyl-alpha-mannose with alkynyl or cyano compound under the action of Lewis acid to obtain a compound 6;
carrying out SN2 substitution reaction on a donor-receptor type conjugated polymer P1 and an azidation reagent to obtain an azidated polymer P1-1, carrying out Click reaction on the polymer P1-1 and a compound 6 under the catalysis of a metal catalyst to obtain a polymer P1-2 with an acetyl mannose terminal, and further removing acetyl protection to obtain a compound shown in the formula I;
or, carrying out SN2 substitution reaction on the donor-receptor type conjugated polymer P2 and an azidation reagent to obtain an azidated polymer P2-1, further carrying out Click reaction on the polymer P2-1 and a compound 6 under the catalysis of a metal catalyst to obtain a polymer P2-2 with an acetyl mannose terminal, and further carrying out deacetylation protection to obtain a compound shown in a formula II;
in the step (1), the additive is one of 18-crown 6, dibenzo 18-crown 6 and aza 18-crown 6.
4. The method for synthesizing α -mannose-modified donor-receptor-type biopolymer material according to claim 3, wherein in the step (1), the first basic substance is one of potassium carbonate, potassium hydroxide and KHMDS, and the lithium reagent is one of n-butyllithium, t-butyllithium and metallic lithium.
5. The method for synthesizing α -mannose-modified donor-receptor type biopolymer material according to claim 3, wherein in step (1), the second basic substance is one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium methoxide, sodium ethoxide and potassium tert-butoxide.
6. The method for synthesizing an α -mannose-modified donor-acceptor-type biopolymer material according to claim 3, wherein in the step (1), the Pd catalyst is palladium acetate, tetrakis (triphenylphosphine) palladium, dichlorobis (triphenylphosphine) palladium, or (1,1' -bis (diphenylphosphino) ferrocene) dichloropalladium.
7. The method for synthesizing α -mannose-modified donor-acceptor-type biopolymer material according to claim 3, wherein in the step (2), Lewis acid is aluminum trichloride, titanium tetrachloride, tin tetrachloride, zinc chloride, bismuth trichloride, or silver trifluoromethanesulfonate;the azide reagent is sodium azide, potassium azide or TMSN3And TsN3One or more of them.
8. The method for synthesizing α -mannose-modified donor-acceptor-type biopolymer material according to claim 3, wherein in the step (2), the metal catalyst is copper-based catalyst, rhodium-based catalyst, ruthenium-based catalyst, palladium-based catalyst, or iron-based catalyst.
9. The method for synthesizing α -mannose-modified donor-receptor biopolymer material according to claim 3, wherein in step (2), the deacetylation protection reagent is one or more of sodium methoxide, sodium ethoxide and sodium tert-butoxide.
10. Use of the α -mannose-modified donor-receptor biopolymer material of any one of claims 1-2 in the preparation of a reagent for detecting and distinguishing between different species of pathogenic bacteria.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010075514A1 (en) * | 2008-12-23 | 2010-07-01 | Michigan Technological University | Fluorescent conjugated polymers with a bodipy-based backbone and uses thereof |
| CN101907556A (en) * | 2010-07-19 | 2010-12-08 | 湖南大学 | Method for detecting the colon bacillus by combining magnetic nanoparticle enrichment with bi-color flow cytometry |
| KR101069697B1 (en) * | 2010-04-06 | 2011-10-05 | 충남대학교산학협력단 | Mannose-modified water-soluble hyperbranched conjugated polymer and fluorescent lectin sensor containing the same |
| CN104031108A (en) * | 2014-06-04 | 2014-09-10 | 陕西师范大学 | Fluorescent compound and preparation method thereof, as well as method for preparing sensing film by using fluorescent compound and application thereof |
| CN105175691A (en) * | 2015-09-17 | 2015-12-23 | 南京邮电大学 | Conjugated polymer semiconductor materials based on thienoarylindole unit and preparation method thereof, and application of conjugated polymer semiconductor materials in high-efficiency polymer solar cells. |
| CN108578711A (en) * | 2018-04-04 | 2018-09-28 | 哈尔滨医科大学 | A kind of acetylation sugar ester-mPEG2000-DSPE conjugate and the preparation method and application thereof |
| CN108752569A (en) * | 2018-06-07 | 2018-11-06 | 南方科技大学 | A kind of amboceptor type polymer and its preparation method and application |
-
2019
- 2019-05-28 CN CN201910453563.9A patent/CN110204733B/en active Active
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010075514A1 (en) * | 2008-12-23 | 2010-07-01 | Michigan Technological University | Fluorescent conjugated polymers with a bodipy-based backbone and uses thereof |
| KR101069697B1 (en) * | 2010-04-06 | 2011-10-05 | 충남대학교산학협력단 | Mannose-modified water-soluble hyperbranched conjugated polymer and fluorescent lectin sensor containing the same |
| CN101907556A (en) * | 2010-07-19 | 2010-12-08 | 湖南大学 | Method for detecting the colon bacillus by combining magnetic nanoparticle enrichment with bi-color flow cytometry |
| CN104031108A (en) * | 2014-06-04 | 2014-09-10 | 陕西师范大学 | Fluorescent compound and preparation method thereof, as well as method for preparing sensing film by using fluorescent compound and application thereof |
| CN105175691A (en) * | 2015-09-17 | 2015-12-23 | 南京邮电大学 | Conjugated polymer semiconductor materials based on thienoarylindole unit and preparation method thereof, and application of conjugated polymer semiconductor materials in high-efficiency polymer solar cells. |
| CN105175691B (en) * | 2015-09-17 | 2018-10-02 | 南京邮电大学 | Conjugated polymer semi-conducting material, preparation and its high-efficiency polymer solar cell application of the one kind based on thieno (hetero) aryl indole unit |
| CN108578711A (en) * | 2018-04-04 | 2018-09-28 | 哈尔滨医科大学 | A kind of acetylation sugar ester-mPEG2000-DSPE conjugate and the preparation method and application thereof |
| CN108752569A (en) * | 2018-06-07 | 2018-11-06 | 南方科技大学 | A kind of amboceptor type polymer and its preparation method and application |
Non-Patent Citations (4)
| Title |
|---|
| A Simple Mannose-Coated Poly (p-Phenylene Ethynylene) for Qualitative Bacterial Capturing;Tsakama, M et al;《MOLECULES》;20180816;第23卷(第8期);第2056（1-10）页 * |
| A-Synthesis, characterization and detection of Concanavalin A based on a mannose-substituted conjugated polymer through aggregation-enhanced FRET;Wang, LY et al;《SENSORS AND ACTUATORS B-CHEMICAL》;20160127;第229卷;第47-56页 * |
| Triphenylamine-based fluorescent conjugated glycopolymers: Synthesis, characterization and interactions with lectins;Chen, Q et al;《POLYMER》;20090504;第50卷(第13期);第2830-2835页 * |
| 基于水溶性共轭聚合物的多色荧光体系的构建及生物医学应用;王凤燕等;《中国科学：化学》;20151120;第45卷(第11期);第1102-1111页 * |
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