CN108409710A - Conjugate oligomeric thiophene compound, preparation method and its antimicrobial application - Google Patents
Conjugate oligomeric thiophene compound, preparation method and its antimicrobial application Download PDFInfo
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Abstract
The invention discloses conjugate oligomeric thiophene compound and preparation method, the structural formula such as (I) of the compound is shown：Wherein, A is amine groups, and general formula is A=(CH2)aN(R)b(CH3)m, wherein：The integer that a is 2~6, R=methyl or ethyl, b=2, m=0 or 1.In the structural formula of the compound, when m=0, Compound nomenclature is OTT 1, passes sequentially through substitution reaction as raw material using p OTT and is prepared into OTT 1.In the structural formula of the compound, when m=1, Compound nomenclature is OTT 2, is that raw material prepares OTT 2 by methylation reaction with OTT 1.Above-mentioned conjugate oligomeric thiophene compound can be used as photosensitizer application during photoinduction is antimicrobial.Prepared by the asymmetric conjugate oligo-thiophenes compound that the present invention synthesizes is easy, of low cost, short preparation period, antimicrobial the used light source wide spectrum of its light power, including ultraviolet light and visible light, light intensity wide coverage, actually use it is more convenient, have excellent antibacterial effect.
Description
Technical field
The present invention relates to the preparation of conjugation thiophene compound and applied technical fields, and in particular to a kind of conjugate oligomeric thiophene
Close object, preparation method and its antimicrobial application.
Background technology
Oligo-thiophenes class compound (English abbreviation " OTT ") is a kind of mutual with ortho position C -- C single bond with multiple thienos
The oligomeric compounds of the high conjugated degree of connection, usually the thiophene conjugated structure there are three tools or more.Due to its conjugated degree
Higher, optical property is unique, is most frequently used conjugated material, especially in organic electronic device and molectronics
In be widely used.Therefore, the modification of oligo-thiophenes molecular structure is also one of research field the most active, structural modification packet
The extension for including conjugated system derives the research to two-dimensional structure and other kinds of novel topology from linear material.One
Aspect, the diversification modification of thiophene-structure have benefited from the maturation of thiophene chemistry, and the method for modifying of nuclear structure is various, another party
Face and most important aspect are that the system is that noble metal especially palladium chtalyst is coupled the ideal mould to form Pi-conjugated systems
Block.The research driving force of conjugation thiophene is its excellent electronics property and outstanding physicochemical characteristics.Under normal conditions,
Multiple valence states of sulphur are all very stable in thiophene, meanwhile, the characterization method for being conjugated thiophene derivant is also varied.Sulphur in thiophene
Atom high intensifies, and good stabilization is played to conjugated system, while assigning oligo-thiophenes system electronic again and preferably flowing
Dynamic property.In addition to this, thiophene-based oligomer is also easy to happen Supramolecular self assembly, and can be assembled in the surface of solids.Cause
This, convenient for preparing the monolayer thiophene film (SAMs) of the surface of solids.Due to the unique electronics of oligo-thiophenes, optics, and
Its redox characteristic, oligo-thiophenes class compound cause great research interest, are the key that organic and molectronics material
One of material, in Organic Light Emitting Diode, chemical sensor and biosensor etc. are widely used in fields.(Handbook of
Oligo-and Polythiophenes；Fichou,D.,Ed.；WileyVCH:Weinheim,1999；Metal Catalyzed
Cross-Coupling Reactions；Diedrich,F.,Stang,P.J.,Eds.；Wiley-VCH:Weinheim,
1998and 2006；Electronic Materials:The Oligomer Approach；Mullen,K.,Wegner,G.,
Eds.；Wiley-VCH:Weinheim,1998).
In self assembly field, Advincula et al. has synthesized a kind of water-soluble oligo-thiophenes, and design feature is point
Sub- skeleton contains 6 thiphene rings, and the end quaternary amine of a length of 6 carbon of chain has symmetrically been modified at skeleton both ends, corresponds to anion
For bromine, by absorption spectrum, fluorescence spectrum and AFM are the study found that the molecule can generate self assembly in THF/ aqueous systems.So
And Advincula et al. do not study further its bioactivity or to Ecotoxicology (Locklin,；Youk,et al.,
Langmuir,2002,18,877–883；Xia；Locklin,et al.,Langmuir,2002,18,955–957).
Light power antibacterial field, the Whitten groups of University of New Mexico of the U.S., the Schanze groups of University of Florida, in
Gongwu research institute of state Zhou Zhijun groups have then done more in-depth study to oligomerization phenylacetylene (OPE) class compound.By right
OPE shows that cytotoxicity can be generated to gram-positive bacteria and Gram-negative bacteria under ultraviolet irradiation condition.Research is also sent out
Existing, although the end quaternary amine EO-OPE ratios OPE without the modification of intermediate phenyl ring is water-soluble weaker, cytotoxicity is but more
By force.In addition, all OPE are to the Gram-positive mushroom toxin order of magnitude at least one greatly.Further dark toxicity mechanism study discovery,
EO-OPE molecules are very big to the morphological disruption of cell, and M-OPE does not cause the breakage of cell then under the conditions of respective concentration, phase
Answer cell dark toxicity relatively low.Recently, Zhou Zhijun et al. has found, neutral OPE molecule displays go out the cytotoxicity of remote super positive electricity OPE,
Even visible light can generate direct cytotoxicity under the conditions of shining.Mechanism study thinks that neutral OPE has preferably intracellular
Change ability, therefore, singlet oxygen isoreactivity oxygen radical can more directly contribute cytotoxicity.And the internalization capability of cell with
The electrical relationship of OPE is close, although more electrostatic charge improves its dissolubility, but reduces cell internalizing ability, thus, greatly
Its cytotoxic capacity (Zhou, Corbitt, et al., J.Phy.Chem.Lett., 2010,1,3207-3212 are reduced greatly；
Tang,Corbitt,et al.,Langmuir,2011,27(8),4956-4962；Wang,Tang,et al.,Langmuir,
2010,26(15),12509-12514；Dimitri,Ji,et al.,Langmuir,2012,28(31),11286-11290；
Wang,Zhou,et al.,ACS Applied Materials and Interfaces,2017,9,7964-7971；Zhou Zhi
Army, king wait quietly, Chinese patent, CN 104151174B；Zhou Zhijun, king wait quietly, Chinese patent, CN 104140372B).
In light power antibacterial field, professor's Tang Yanli group of Shaanxi Normal University completes a pionerring research, the group
Team synthesizes three polythiophenevinylenand quaternary amines, which is starting material by 2- iodothiophens, and target point is obtained by the reaction synthesis of 6 steps
Son.By absorption spectrum, it can be seen that, which has stronger absorption in visible-range, indicates that the molecule can absorb visible light
And be further excited and generate singlet oxygen, to generate bio-toxicity.Follow-up study finds that three polythiophenevinylenand quaternary amines exist
Under illumination to Staphylococcus aureus can reach 60ng/ml kill 99.9% bacterium ability, even if in the dark the compound if table
Reveal excellent antibacterial effect.It can be seen that three polythiophenevinylenand quaternary amines under the conditions of light activated, can generate activity freely
Base, the strong oxidizing properties active specy such as singlet oxygen, and toxicity is generated to microorganisms such as bacteriums.It is worth noting that the molecule is thin
Cellular toxicity but less (Tang Yanli, Zhao Qi, Chinese patent, CN 105001193B；Zhao, Li, et al., ACS Applied
Materials and Interfaces,2016,8,1019-1024).However, above-mentioned three polythiophenevinylenands quaternary amine synthesized
Journey needs to use palladium catalyst, and cost is higher, and synthesis control condition is stringent, and synthesis difficulty is very big, and yield is relatively low, difficult
In industrial applications.
In conclusion existing smooth power antimicrobial compound has the following disadvantages：
(1), existing smooth power antimicrobial compound antibacterial effect is poor, is mainly manifested on the one hand：Broad spectrum activity is poor, often
Kind compound can only generate toxic effect to specific strain, if certain compound is only to Gram-negative bacteria or gram sun
Property bacterium is worked, and can not play the role of anti-Gram-negative bacteria and positive bacteria simultaneously；On the other hand, under the same terms, reach
The light power antibacterial effect of setting, needs the concentration containing antimicrobial compound higher, and cost increases；
(2), since industrial applications need simple enough synthesis step, requirement at low cost and high yield, and it is existing
Light power antimicrobial compound preparation process in need to use expensive catalyst, consumptive material is more, of high cost, and difficulty is big, synthesis step
It is rapid more, it is unsuitable for industrialized production and application.
(3), further, since existing smooth power antimicrobial compound needs to use ultraviolet light as light source, to human body mostly
There is certain injury, the selection of light source is subject to certain restrictions.
Invention content
The technical problem to be solved by the present invention is to：Existing smooth power antimicrobial compound production cost is high, and uses light
Source wavelength is short, is unfavorable for industrial applications, and the present invention provides the conjugate oligomeric thiophene compound to solve the above problems, preparation sides
Method and its antimicrobial application.
The present invention is achieved through the following technical solutions：
The structural formula such as (I) of conjugate oligomeric thiophene compound, the compound is shown：
Wherein, A is amine groups, and general formula is A=- (CH2)aN(R)b(CH3)m, wherein：The integer that a is 2~6, R=methyl
Or ethyl, b=2, m=0 or 1.
Preferably, in the structural formula of the compound, when m=0, Compound nomenclature OTT-1 is described to prepare OTT-1's
Reaction equation is such as shown in (II)：
Wherein, the general formula of X is X=- (CH2)aN(R)b(CH3)m, wherein：The integer that a is 2~6, R=methyl or ethyl, b
=2, m=0；OTT-1 is prepared by the substitution reaction with alcohol using p-OTT as raw material.
Preferably, the method for preparing OTT-1 is specially：
Sodium hydride and Isosorbide-5-Nitrae-dioxane are added in reaction bulb, are stirred in ice-water bath by Step1, under inert gas shielding,
Corresponding hydramine is added in reaction bulb, is stirred to react at room temperature；
Then one kind in p-OTT raw materials and copper powder, cuprous salt, lithium chloride is added in Step2 into reaction bulb successively
Or more than one, by reaction system in water pump lower pumping displacement gas repetitive operation, inert gas shielding, in light protected environment reaction plus
Heat is warming up to 80~120 DEG C, and constant temperature stirring 10~stop heating afterwards for 24 hours is cooled to room temperature；
Step3, pad diatomite filtering, is washed with dichloromethane and methanol mixed solution, collects all filtrates, decompression rotation
It is dry；Residue purifies to obtain yellow solid through silica gel column chromatography, wherein eluent is using the mixed of ethyl acetate, methanol and triethylamine
Close solution.
Preferably, the p-OTT prepares reaction equation such as shown in (III)：
The substitution reaction on the ground p-OTT is prepared by substitution reaction using three thiophene a as raw material.
Preferably, the method for preparing p-OTT is specially：
Three thiophene a are dissolved in n,N-Dimethylformamide, under inert gas shielding, stir under room temperature by Step1
After setting time, N-iodosuccinimide is added under ice-water bath in batches；
Step2 is stirred to react setting time under room temperature；
Reaction solution is added drop-wise in ice water by Step3 while stirring, and a large amount of solids are precipitated, and filtering, filter cake uses water, two successively
Chloromethanes washs, and collects filter cake, and decompression is spin-dried for obtaining p-OTT finished products.
Preferably, the chemical constitution of the middle hydramine such as (IV) is shown：
Wherein, the integers of n=1~5.
Preferably, the cuprous salt be protochloride logical, protobromide ketone, cuprous iodide any of which or more than one
The mixture of arbitrary proportion.
Preferably, in the structural formula of the compound, when m=1, Compound nomenclature OTT-2 is described to prepare OTT-2's
Reaction equation is such as shown in (V)：
Wherein, the general formula of Y is Y=- (CH2)aN(R)b(CH3)m, wherein：The integer that a is 2~6, R=methyl or ethyl, b
=2, m=1；OTT-2 is prepared by methylation reaction using OTT-1 as raw material.
Preferably, the method for preparing the OTT-2 is specially：
Weigh Compound OTT-1 is added in eggplant-shape bottle, adds organic solvent, is added iodomethane, is stirred at room temperature
Reaction, is spin-dried for solvent under decompression, obtains faint yellow solid OTT-2.The organic solvent be methylene chloride/methanol, tetrahydrofuran/
Methanol or dichloromethane/tetrahydrofuran/methanol.
Above-mentioned conjugate oligomeric thiophene compound is in visible or UV light-induced antimicrobial answering as photosensitizer in the process
With.
The microorganism is Escherichia coli or Staphylococcus aureus.Used in the photo induced processes optical source wavelength for
300nm~800nm, light intensity 3mw/cm2~200mw/cm2。
The present invention has the advantage that and advantageous effect：
Prepared by the asymmetric conjugate oligo-thiophenes compound that the present invention synthesizes is easy, of low cost, short preparation period, and light is dynamic
It resists Institute of Micro-biology strenuously and uses light source wide spectrum, including ultraviolet light and visible light, light intensity wide coverage, actual use is more convenient,
With excellent antibacterial effect.Specifically：
(1) synthesis of OTT-1 provided by the invention, OTT-2 are simple, compare the phenylacetylene and thiophene of current light power antibacterial
More than required 6 step of synthesis of acetylene, this synthesis only needs 2~3 steps, and gross production rate will be far above corresponding phenylacetylene and thiophene
The synthesis of pheno acetylene；
(2) OTT light power antibacterial effect provided by the invention protrudes, and is shown under the conditions of visible light shines in various degree
Antibacterial activity, under similarity condition, the cytotoxin of OTT-1 is significantly larger than OTT-2.And in the dark, the bacterial poison of two kinds of OTT
Property be much smaller than illumination condition.
(3) cytotoxin of end branch sulfur-containing compound is better than oxygenatedchemicals in the present invention.It can be seen that this hair
Bright so-called novel antibacterial material OTT is simpler than the synthesis of similar compound, yield higher, and antibacterial effect is suitable or more prominent
Go out.
Description of the drawings
Attached drawing described herein is used for providing further understanding the embodiment of the present invention, constitutes one of the application
Point, do not constitute the restriction to the embodiment of the present invention.In the accompanying drawings：
Fig. 1 is the reaction equation for preparing asymmetric conjugate oligo-thiophenes compound that the embodiment of the present invention 1 provides.
Specific implementation mode
To make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiment and attached drawing, to this
Invention is described in further detail, and exemplary embodiment of the invention and its explanation are only used for explaining the present invention, do not make
For limitation of the invention.
Embodiment 1
The synthesis of compound p-OTT：Three thiophene a (1mmol, 248mg) are dissolved in dry n,N-Dimethylformamide
In (5ml), under nitrogen protection, after stirring 10min under room temperature, divide trisection every the N- iodos of 5 minutes one deciles of addition
After being stirred to react 1h, reaction solution is added drop-wise in ice water while stirring for succinimide (2mmol, 447mg), is precipitated a large amount of solid
Body, filtering, filter cake are washed with water twice, washed once with dichloromethane, collect filter cake, and decompression is spin-dried for obtaining faint yellow solid
0.47gp-OTT, yield：91%.Reaction is as shown in formula (III)：
Embodiment 2
The synthesis of compound OTT-1 (OC2)：By NaH (7.2mmol, 288mg) and Isosorbide-5-Nitrae-dioxane (steaming, 20ml) again
Be added it is dry after reaction bulb in, 10min is stirred in ice-water bath, under nitrogen protection, by 2- (dimethylamino) -1- ethyl alcohol
(6.4mmol, 760 μ L) be added reaction bulb in, at room temperature stir 40min after, successively into reaction bulb be added copper powder (0.8mmol,
51mg), cuprous iodide (3.2mmol, 609mg), lithium chloride (6.4mmol, 271mg), p-OTT (1.6mmol, 800mg).It will be anti-
Answer system in water pump lower pumping substitution gas repetitive operation four times, nitrogen protection, in light protected environment reaction be heated to 105
DEG C, constant temperature stirs 22h, stops heating, is cooled to room temperature, pad diatomite filtering, with methylene chloride/methanol (9:1) solution washs
Four times, each 20ml, merge and collect all filtrates, decompression is spin-dried for, and residue purifies (ethyl acetate/methanol/tri- through silica gel column chromatography
Ethamine=93：5：2(v:v:V) yellow solid 220mg OTT-1 (OC2), yield) are obtained：35%.Reaction is as shown in formula (VI)：
Embodiment 3
The synthesis of compound OTT-1 (OC4)：By NaH (7.2mmol, 288mg) and n,N-Dimethylformamide (steam again,
20ml) be added it is dry after reaction bulb in, 10min is stirred in ice-water bath, under nitrogen protection, by 4- (dimethylamino)-n-butyl alcohol
(6.4mmol, 754mg) be added reaction bulb in, at room temperature stir 40min after, successively into reaction bulb be added copper powder (0.8mmol,
51mg), cuprous iodide (3.2mmol, 609mg), lithium chloride (6.4mmol, 271mg), p-OTT (1.6mmol, 800mg).It will be anti-
Answer system in water pump lower pumping displacement gas repetitive operation four times, nitrogen protection, in light protected environment reaction be heated to 105 DEG C,
Constant temperature stirs 36h, stops heating, is cooled to room temperature, pad diatomite filtering, with methylene chloride/methanol (9:1) solution washing four
Secondary, each 20ml merges and collects all filtrates, and decompression is spin-dried for, and residue purifies the (second of ethyl acetate/methanol/tri- through silica gel column chromatography
Amine=93：5：2(v:v:V) yellow solid 189mg OTT-1 (OC4), yield) are obtained：25%.Reaction is as shown in formula (VII)：
Embodiment 4
The synthesis of compound OTT-2 (OC2)：Weigh Compound OTT-1 (OC2) (1mmol, 423mg) is dissolved in dichloromethane
In alkane and methanol (each 5ml), iodomethane (426mg, 3mmol) is being added, after reacting at room temperature 6h, is generating a large amount of precipitations, filters, use
Eluent methylene chloride obtains faint yellow solid 699mg.Yield：99%.Reaction is as shown in formula (VIII)：
Embodiment 5
The synthesis of compound OTT-2 (OC4)：Weigh Compound OTT-1 (OC4) (1mmol, 479mg) is dissolved in tetrahydrochysene furan
It mutters in methanol (each 5ml), iodomethane (426mg, 3mmol) is being added, after reacting at room temperature 6h, generate a large amount of precipitations, filter, use
Eluent methylene chloride obtains faint yellow solid 755mg.Yield：99%.Reaction is as shown in formula (IX)：
Next coming in order test the toxicity of compound OTT-1, OTT-2 to bacterium under illumination and non-illumination condition, investigationization
Close the influences of the factors to above-mentioned various Ecotoxicologies such as concentration, the light application time of object OTT-1, OTT-2.
Embodiment 6
OTT-1 (OC2) is to Escherichia coli toxicity：Escherichia coli (ATCC 25922) are cultivated in general culture solution at 37 DEG C
18h, centrifuge bacterium solution, and supernatant is outwelled, after the saline solution that suitable 0.9% sterilized is added, mix in an oscillator
It closes uniformly, centrifuges again, outwell supernatant and bacterium is uniformly suspended in 1ml's after same water-washing process carries out three times
In 0.9% saline solution sterilized, and it is spare that its OD600 is adjusted to 1.0.
1mg compounds OTT-1 (OC2) is dissolved in 1mlDMSO (dimethyl sulfoxide (DMSO)), 100 μ l dilutions, 0.9% food is taken
It is spare that brine is diluted to 1ml.Prepare the centrifuge tube after the sterilizing of 8 1.5ml capacity, number 1,2,3,4,5,6,7,8.
(1) 400 μ l0.9% saline solutions, OTT-1 (OC2) final concentration of 0 is added in above-mentioned centrifuge tube 1,2 respectively；
395 μ l0.9% saline solutions and 5 μ l dilution OTT-1 (OC2) solution, OTT-1 (OC2) final concentration are added in (2) 3,4
For 1 μ g/ml；
385 μ l0.9% saline solutions and 15 μ l dilution OTT-1 (OC2) solution, OTT-1 (OC2) final concentration are added in (3) 5,6
For 3 μ g/ml；
355 μ l0.9% saline solutions and 45 μ l dilution OTT-1 (OC2) solution, OTT-1 (OC2) final concentration are added in (4) 7,8
For 9 μ g/ml.
1min is shaken, OTT-1 (OC2) solution of uniform dissolution is obtained.It is added respectively to above-mentioned 1~No. 8 centrifuge tube again
100 μ l OD600 are 1.0 bacterium solution, and shake 1min on the oscillator.Centrifuge tube 1,3,5,7 is taken to preserve in darkroom and simultaneously
Timing；Centrifuge tube 2,4,6,8 is taken to be placed in visible light (90mw/cm2) under, and timing simultaneously.After 30min or 1h, 1~No. 8 is taken out
Sample after diluting 180,000 times with 0.9% saline solution, takes 100 μ l drops on solid medium, being used in combination spreader to smear uniform postposition
10~15h is cultivated in 37 DEG C of incubator, calculates bacterial plaque number, by calculating depositing for bacterium with the quantitative comparison of 1, No. 2 pipes
Motility rate.
Test result：
(1) non-illumination condition：Compound OTT-1 (OC2) is right by the reference with non-illumination condition under non-illumination condition
Than finding, in concentration 1 μ g/ml, 3 μ g/ml, 9 μ g/ml, no matter the preservation of 30min or 1h, be not observed apparent thin
Cellular toxicity, Survival probability of bacteria with mutually should refer to be consistent；
(2) visible light illumination condition：OTT-1 (OC2) shows the cytotoxin completely different with non-illumination condition.Illumination
Under the conditions of 30min, Survival probability of bacteria is 45% in 1 μ g/ml systems, and Survival probability of bacteria is in 3 μ g/ml and 9 μ g/ml systems
0%；When light application time extends to 1h, the OTT-1 (OC2) of 1 μ g/ml and its concentrations above observes that Survival probability of bacteria is 0%.
Embodiment 7
OTT-1 (OC2) is to Staphylococcus aureus toxicity：Staphylococcus aureus (ATCC 25923) is 37 in general culture solution
18h, centrifuge bacterium solution are cultivated at DEG C, and outwells supernatant, after the saline solution that suitable 0.9% sterilized is added, are being shaken
It swings in device and is uniformly mixed, centrifuge again, outwell supernatant and be uniformly suspended in bacterium after same water-washing process carries out three times
In 0.9% saline solution to sterilize of 1ml, and it is spare that its OD600 is adjusted to 1.0.
1mg compounds OTT-1 (OC2) is dissolved in 1mlDMSO, takes 10 μ l with 0.9% saline solution to be diluted to 1ml standby
With.Prepare the centrifuge tube after the sterilizing of 8 1.5ml capacity, number 1,2,3,4,5,6,7,8.
(1) 400 μ l0.9% saline solutions, OTT-1 (OC2) final concentration of 0 is added in above-mentioned centrifuge tube 1,2 respectively；
395 μ l0.9% saline solutions and 5 μ l dilution OTT-1 (OC2) solution, OTT-1 (OC2) final concentration are added in (2) 3,4
For 0.1 μ g/ml；
385 μ l0.9% saline solutions and 15 μ l dilution OTT-1 (OC2) solution, OTT-1 (OC2) final concentration are added in (3) 5,6
For 0.3 μ g/ml；
355 μ l0.9% saline solutions and 45 μ l dilution OTT-1 (OC2) solution (OTT-1 (OC2) final concentrations are added in (4) 7,8
For 0.9 μ g/ml.
1min is shaken, OTT-1 (OC2) solution of uniform dissolution is obtained.Add respectively into above-mentioned 1~No. 8 centrifuge tube again
Enter 100 μ l OD600 and be 1.0 bacterium solution, and shakes 1min on the oscillator.Centrifuge tube 1,3,5,7 is taken to preserve into darkroom and same
When timing；It takes centrifuge tube 2,4,6,8 to be placed under visible light to be irradiated, and timing simultaneously.After 30min or 1h, 1~No. 8 is taken out
Sample after diluting 180,000 times with 0.9% saline solution, takes 100 μ l drops on solid medium, being used in combination spreader to smear uniform postposition
10~15h is cultivated in 37 DEG C of incubator, calculates bacterial plaque number, by calculating depositing for bacterium with the quantitative comparison of 1, No. 2 pipes
Motility rate.
Test result：
(1) non-illumination condition：Compound OTT-1 (OC2) is right by the reference with non-illumination condition under non-illumination condition
Than finding, in concentration 0.1 μ g/ml, 0.3 μ g/ml, 0.9 μ g/ml, no matter the preservation of 30min or 1h, be not observed thin
Mushroom toxin, Survival probability of bacteria with mutually should refer to be consistent；
(2) under visible light illumination condition, OTT-1 (OC2) shows the cytotoxin completely different with non-illumination condition.
Under the conditions of illumination 30min, 0.1 μ g/ml OTT-1 (OC2) are not observed 99.9% bacterial death, and 0.3 μ g/ml and 0.9 μ
G/ml systems then observe that Survival probability of bacteria is 0%.
Embodiment 8
OTT-2 (OC2) is to Escherichia coli toxotest：Escherichia coli culture, processing procedure and sample processing procedure
It is identical as with embodiment 6.
Test result：
(1) non-illumination condition：Compound OTT-2 (OC2) is right by the reference with non-illumination condition under non-illumination condition
Than finding, in concentration 1 μ g/ml, 3 μ g/ml, 9 μ g/ml, 30min and 1h without cytotoxin, Survival probability of bacteria with mutually should refer to
It is consistent；
(2) under visible light illumination condition, OTT-2 (OC2) shows the cytotoxin completely different with non-illumination condition.
Under the conditions of illumination 30min, 1 μ g/ml OTT-2 (OC2) observe 5% bacterial death, and 3 μ g/ml and 9 μ g/ml bacterial death rates
Respectively reach 16% and 56%.
Embodiment 9
OTT-2 (OC2) is to Staphylococcus aureus toxotest：Staphylococcus aureus culture, processing procedure and sample
Processing procedure is identical as with embodiment 7.
Test result：
(1) non-illumination condition：Compound OTT-2 (OC2) is right by the reference with non-illumination condition under non-illumination condition
Than finding, in 0.1 μ g/ml of concentration, 0.3 μ g/ml, 0.9 μ g/ml, 30min and 1h is without cytotoxin, Survival probability of bacteria and phase
It should refer to be consistent；
(2) under visible light illumination condition, OTT-2 (OC2) shows the cytotoxin completely different with non-illumination condition.
Under the conditions of illumination 30min, 0.1 μ g/ml OTT-2 (OC2) observe 5% bacterial death, and the bacterial death rate of 0.3 μ g/ml is
12%, 0.9 μ g/ml systems then observe that bacterial death rate is 15%；When the time extending to 1h, the bacterial death of respective concentration
Rate is respectively 8%, 21% and 38%.
Above-described specific implementation mode has carried out further the purpose of the present invention, technical solution and advantageous effect
It is described in detail, it should be understood that the foregoing is merely the specific implementation mode of the present invention, is not intended to limit the present invention
Protection domain, all within the spirits and principles of the present invention, any modification, equivalent substitution, improvement and etc. done should all include
Within protection scope of the present invention.
Claims (10)
1. conjugate oligomeric thiophene compound, which is characterized in that the structural formula of the compound is such as shown in (I)：
Wherein, A is amine groups, and general formula is A=- (CH2)aN(R)b(CH3)m, wherein：The integer that a is 2~6, R=methyl or second
Base, b=2, m=0 or 1.
2. the preparation method of conjugate oligomeric thiophene compound according to claim 1, which is characterized in that the compound
In structural formula, when m=0, Compound nomenclature OTT-1, the reaction equation for preparing OTT-1 is such as shown in (II)：
Wherein, the general formula of X is X=- (CH2)aN(R)b(CH3)m, wherein：The integer that a is 2~6, R=methyl or ethyl, b=2, m
=0；OTT-1 is prepared by the substitution reaction with alcohol using p-OTT as raw material.
3. the preparation method of conjugate oligomeric thiophene compound according to claim 2, which is characterized in that prepare OTT-1's
Method is specially：
Sodium hydride and Isosorbide-5-Nitrae-dioxane are added in reaction bulb, are stirred in ice-water bath, under inert gas shielding, by phase by Step1
The hydramine answered is added in reaction bulb, is stirred to react at room temperature；
Then p-OTT raw materials and one kind in copper powder, cuprous salt, lithium chloride or one is added in Step2 into reaction bulb successively
Kind or more, by reaction system in water pump lower pumping displacement gas repetitive operation, inert gas shielding, in light protected environment reaction heating rise
To 80~120 DEG C, constant temperature stirring 10~stop heating afterwards for 24 hours is cooled to room temperature temperature；
Step3, pad diatomite filtering, is washed with dichloromethane and methanol mixed solution, collects all filtrates, decompression is spin-dried for；It is residual
Slag purifies to obtain yellow solid through silica gel column chromatography, wherein eluent is molten using the mixing of ethyl acetate, methanol and triethylamine
Liquid.
4. the preparation method of conjugate oligomeric thiophene compound according to claim 2, which is characterized in that the p-OTT's
It is shown to prepare reaction equation such as (III)：
The substitution reaction on the ground p-OTT is prepared by substitution reaction using three thiophene a as raw material.
5. the preparation method of conjugate oligomeric thiophene compound according to claim 4, which is characterized in that the preparation p-
The method of OTT is specially：
Three thiophene a are dissolved in n,N-Dimethylformamide by Step1, under inert gas shielding, stirring setting under room temperature
After time, N-iodosuccinimide is added under ice-water bath in batches；
Step2 is stirred to react setting time under room temperature；
Reaction solution is added drop-wise in ice water by Step3 while stirring, and a large amount of solids are precipitated, and filtering, filter cake uses water, dichloromethane successively
Alkane washs, and collects filter cake, and decompression is spin-dried for obtaining p-OTT finished products.
6. the preparation method of conjugate oligomeric thiophene compound according to claim 3, which is characterized in that the middle hydramine
Chemical constitution is such as shown in (IV)：
Wherein, the integers of n=1~5.
7. the preparation method of conjugate oligomeric thiophene compound according to claim 3, which is characterized in that the cuprous salt is
Protochloride is logical, protobromide ketone, cuprous iodide any of which or more than one arbitrary proportion mixture.
8. the preparation method of conjugate oligomeric thiophene compound according to claim 1, which is characterized in that the compound
In structural formula, when m=1, Compound nomenclature OTT-2, the reaction equation for preparing OTT-2 is such as shown in (V)：
Wherein, the general formula of Y is Y=- (CH2)aN(R)b(CH3)m, wherein：The integer that a is 2~6, R=methyl or ethyl, b=2, m
=1；OTT-2 is prepared by methylation reaction using OTT-1 as raw material.
9. the preparation method of conjugate oligomeric thiophene compound according to claim 8, which is characterized in that prepare the OTT-
2 method is specially：
Weigh Compound OTT-1 is added in eggplant-shape bottle, adds organic solvent, is added iodomethane, is stirred to react at room temperature,
It is spin-dried for solvent under decompression, obtains faint yellow solid OTT-2.
10. based on claim 1 to 9 any one of them conjugate oligomeric thiophene compound in visible or UV light-induced anti-micro- life
Application during object as photosensitizer.
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| CN105001193A (en) * | 2015-07-15 | 2015-10-28 | 陕西师范大学 | Cationic water-soluble oligothiophene acetylene compound, and preparation method and application thereof |
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| CN115300523A (en) * | 2021-05-07 | 2022-11-08 | 大立精准有限公司 | Use of conductive polymer material |
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