CN106467487A - A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer and preparation method thereof and the application in the sterilizing of light power - Google Patents

A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer and preparation method thereof and the application in the sterilizing of light power Download PDF

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CN106467487A
CN106467487A CN201510510732.XA CN201510510732A CN106467487A CN 106467487 A CN106467487 A CN 106467487A CN 201510510732 A CN201510510732 A CN 201510510732A CN 106467487 A CN106467487 A CN 106467487A
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formula
compound
photosensitizer
soluble cationic
water
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CN106467487B (en
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吴飞鹏
方艳艳
赵榆霞
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Technical Institute of Physics and Chemistry of CAS
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Abstract

The present invention discloses a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer and its synthetic method and the application in the sterilizing of light power.The photosensitizer molecule structure of the present invention is simple, have the chemical constitution of determination, and has suitable fat moisture proportioning, has the characteristics that fat water amphiphilic, and the reaction condition of its synthesis is gently it is easy to prepare and purify, simple to operate simultaneously.The photosensitizer of the present invention has higher biological photodynamic activity in 350～600nm wave-length coverage, can optionally light power inactivation of pathogenic microorganism and avoid damage to host cell and tissue as far as possible, there is broad spectrum antibacterial, in terms of light power sterilizing, there is application prospect well.

Description

A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer and preparation method thereof with light power Application in sterilizing
Technical field
The present invention relates to field of photodynamic.More particularly, to a kind of water-soluble cationic benzal The preparation method of cycloalkane ketone photosensitizer and its application in the sterilizing of light power.
Background technology
The discovery of antibiotic once made the mankind once think the epoch that will take leave of microorganism infection.But, with The commonly used and continuous upgrading of antibiotic, clinical bacteria infection is not controlled, therewith completely On the contrary, many pathogenic bacterium or conditioned pathogen, under the pressure of living environment, have made a variation and have effectively supported into having Imperial antibiotic kills the multi-drug resistant bacteria of resistance mechanism.It is high dead that the microbial infection of multidrug resistant leads to Rate and high medical care expenses make the work of anti-microbial infection be faced with acid test.2010, British Medical Periodical《Lancet》That announces carries the " super of " New Delhi metalloproteases -1 (NDM-1) " gene Antibacterial " almost can tolerate all of antibiotic, but the anti-infectives clinically commonly used at present and side Method is extremely limited to this para-infectious curative effect.Therefore, once the general drug resistance with regional infection ability occurs Bacterium infects, and consequence will be extremely serious.
Optical dynamic therapy (photodynamic therapy, PDT) is a kind of effect in light for utilization photosensitizer The active substance eliminating sick cell or antibacterial can be produced down, thus reaching the treatment meanss of therapeutic purposes.
, among research, in vitro study is proved the method can be effective for photodynamic therapy anti-microbial infection Combating microorganisms (inclusion fastbacteria), and natural and synthetic photosensitizer all can use.In the recent period, Demidova and Hamblin et al. is in " Photodynamic inactivation of Bacillus spores mediated by phenothiazinium dyes”,Appl Environ Microbiol,2005,vol.71, Also demonstrate that in the article of pp6918-6925, under the temperate condition that phenothiazines dyestuff exists, using red Light irradiation bacterial spore (having drug resistance to most of antibacterial) cultivating system can make bacillus cereuss inactivate. Jori G. et al. is in " Photodynamic therapy in the treatment of microbial infections: basic principles and perspective applications”,Lasers in Surgery and Medicine, Point out in the article of 2006, vol.38, pp468-481 under physiological ph, the such as fen of cationic photosensitizer Thiazine derivative, phthalocyanine derivates, derivatives of porphyrin can effectively lead to Gram-negative and gram sun Property antibacterial inactivation, in addition its yeast, funguses, mycoplasma and pathogenic protozoon are also had good light move Power curative effect.Compared with traditional antibiotic therapy, the sterilizing of light power has following main advantage:(1), wide General antimicrobial spectrum, all effective to antibacterial, funguses, virus, protozoon etc., multiple antibiotic resistant strain is equally had Effect；(2), optionally can kill pathogenic microorganism, and not damage host tissue；(3), it is not result in The drug resistance of bacterial strain；(4), the toxic and side effects of photosensitizer are little, and the damage to hepatic and renal function is little.
PDT is dropped to the damage of host cell and tissue by the effective inactivation realizing pathogenic microorganism simultaneously Low be light power inactivation of pathogenic microorganism desired result.Friedberg et al. is in " Antibody-Targeted Photolysis:Bacteriocidal Effects of Sn(IV)Chlorin e6-Dextran-Monoclonal Antibody Conjugates”,Annals of the New York Academy of Sciences,1991, The side of the chemical molecular that targeting thalline is connected on antibacterial is proposed in the article of vol.66, pp383-393 Method, achieves preferable effect.But, such method can make the broad spectrum activity of antibacterial significantly reduce.Cause This, realize the selective more dominant strategy of PDT and still need to explore.Early-stage Study shows, mammalian cell membrane There is significant difference with the composition of the cell membrane of microorganism and structure, wherein, microbial cell film outer layer is in Elecrtonegativity, and the intimate electric neutrality of mammalian cell membrane outer layer.Based on above feature, design, synthesis exists Electropositive photosensitizer (cation photosensitizer) is assumed for the choosing realizing the inactivation of light power under physiological ph Selecting property is most important.In addition, cation photosensitizer is except inactivateing the micro- life of cause of disease using reactive oxygen species Beyond the region of objective existence, can also be by upsetting and interrupting the orderly membrane structure of microorganism to play antibacterial effect.Due to The special antibacterial mechanisms of cation photosensitizer, therefore, it is considered to have broad-spectrum antibacterial property.
At present existing clinic optical dynamic therapy photosensitizer such as hematoporphyrin derivative HpD, photofrin, Verteporfin etc., these photosensitizer all have that different degrees of active princlple is unclear, biological internal absorption Metabolic mechanism is indefinite, the problems such as metabolism is poor.And it is used for the photosensitizer phenothiazines in clinical practice stage Dyestuff methylene blue (methylene blue, MB), easily forms dimer in bacterium surface, has a strong impact on The efficiency of light power inactivation.
Based on problem above, need design, synthesize that some chemical constitutions are clear and definite, dissolubility is good and to cause of disease Microorganism has the novel photosensitive agent of effective lethal effect.
Content of the invention
It is an object of the present invention to provide a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer. Such photosensitizer has the chemical constitution of determination and molecular structure is simple, and in water, dissolubility is good, has Suitable fat moisture proportioning, and have in 350～600nm wave-length coverage and absorb more by force, under light source irradiates Quickly reactive oxygen species can be produced, can be used for the sterilizing of light power.
Second object of the present invention is to provide a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer Preparation method.Provide one kind can light power selective inactivation pathogenic microorganism and do not damage host cell Water-soluble cationic benzal cycloalkane ketone photosensitizer mentality of designing.The method is simple to operate, reaction Mild condition, purge process simplicity, product purity can reach the feature of medicine requirement.
Third object of the present invention is to provide a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer Purposes.
For reaching above-mentioned first purpose, the present invention adopts following technical proposals：
A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer it is characterised in that include have as follows The compound of formula C1, C2 or C3 structure：
Wherein：
R2, R3And R4Identical or different, R2、R3And R4Selected from methyl, ethyl, propyl group, isopropyl, Normal-butyl, isobutyl group, the tert-butyl group or-(CH2)n-R1X；Preferably, R2, R3And R4Selected from methyl, second Base or-(CH2)n-R1X；
R5And R6Identical or different, R5And R6Selected from N or P；Preferably, R5And R6For N；
X is anion Cl-、Br-Or I-；
N=1,2,3 or 4；Preferably, n is 1 or 2；
N1 and n2=0,1,2,3 or 4；Preferably, n1 and n2 is 0,1 or 2；
R1For quaternary ammonium salt cationic；Preferably, R1It is selected from
A is selected from N or P；Preferably, A is N；
A1, A2And A3Identical or different, A1、A2And A3Selected from methyl, ethyl, propyl group, isopropyl, Normal-butyl, isobutyl group, the tert-butyl group or phenyl；Preferably, A1, A2And A3Selected from methyl, ethyl or benzene Base；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
For reaching above-mentioned second purpose, a kind of present invention water-soluble cationic benzal cycloalkane ketone is photosensitive The preparation method of agent, the compound with formula C1 structure includes following synthesis step：
1) after phosphorus pentachloride being reacted with dimethylformamide, then with formula Q1 compound
Reaction, collects and obtains formula Q2 intermediate product
2) under the conditions of the base catalyst of ethanol-dichloromethane solution, willIn gained formula Q2 Between product reaction, collect obtain formula Q3 intermediate product,
3) under the conditions of the base catalyst of ethanol-dichloromethane solution, by gained formula Q3 intermediate product With formula Q4 compound
Reaction；
Or, under the conditions of the base catalyst of ethanol-dichloromethane solution, willWith gained formula Q2 Compound reacts；
Collect the formula Q5 intermediate product obtaining
4) under the conditions of solvent is for dimethylformamide (DMF), by gained formula Q5 intermediate product with Tertiary amine or nitrogen heterocyclic reaction, collect the compound obtaining formula C1 structure；
Wherein：
N3 and n4 is identical or different, n3, n4=1,2,3 or 4；Preferably, n3, n4 are 1 or 2；
N5 and n6 is identical or different, n5, n6=1,2,3 or 4；Preferably, n5 and n6 be 1 or 2；
B1And B2Identical or different, B1And B2Selected from-H ,-OH ,-Cl ,-Br or-I；
B3Selected from N or P；Preferably, B3For N；
B4、B5Selected from-H ,-Cl ,-Br or-I；B4、B5Identical or different, but at least one be selected from-Cl, - Br or-I；
B6Selected from N or P；Preferably, B6For N；
B7And B8Selected from-H ,-Cl ,-Br or-I；B7And B8Identical or different, but at least one choosing From-Cl ,-Br or-I；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
Preferably, there is the synthesis step 2 of the compound of formula C1 structure), 3) described in base catalysis Agent is Lithium hydrate, sodium hydroxide, potassium hydroxide, natrium carbonicum calcinatum, Anhydrous potassium carbonate, pyridine or hexahydro The combination of one or more of pyridine.
For reaching above-mentioned second purpose, a kind of present invention water-soluble cationic benzal cycloalkane ketone is photosensitive The preparation method of agent, the compound with formula C2 structure includes following synthesis step：
1) after phosphorus pentachloride being reacted with dimethylformamide, then with formula S1 compound
Reaction, collects and obtains formula S2 intermediate product
2) under the conditions of the base catalyst of ethanol-dichloromethane solution, willIn gained formula S2 Between product reaction, collect obtain formula S3 intermediate product
3) under the conditions of the base catalyst of ethanol-dichloromethane solution, by gained formula S3 intermediate product With formula Q2 compound
Reaction；
Or, under the conditions of the base catalyst of ethanol-dichloromethane solution, by gained formula S2 chemical combination Thing and formula Q3 compound
Reaction, collects the formula S4 intermediate product obtaining
4) under the conditions of solvent is for dimethylformamide (DMF), by gained formula S4 intermediate product with Tertiary amine or nitrogen heterocyclic reaction, collect the compound obtaining formula C2 structure；
Wherein：
N1=0,1,2,3 or 4；Preferably, n1 is 0,1 or 2；
N3 and n4 is identical or different, n3, n4=1,2,3 or 4；Preferably, n3, n4 are 1 or 2；
D1Selected from-H ,-OH ,-Cl ,-Br or-I；
D2Selected from-H ,-Cl ,-Br or-I；
B3Selected from N or P；Preferably, B3For N；
B4、B5Selected from-H ,-Cl ,-Br or-I；B4、B5Identical or different, but at least one be selected from-Cl, - Br or-I；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
Preferably, there is the synthesis step 2 of the compound of formula C2 structure), 3) described in base catalysis Agent is Lithium hydrate, sodium hydroxide, potassium hydroxide, natrium carbonicum calcinatum, Anhydrous potassium carbonate, pyridine or hexahydro The combination of one or more of pyridine.
For reaching above-mentioned second purpose, a kind of present invention water-soluble cationic benzal cycloalkane ketone is photosensitive The preparation method of agent, the compound with formula C3 structure includes following synthesis step：
1) by formula S3 compound
With formula S5 compound
React under the conditions of the base catalyst of ethanol-dichloromethane solution；
Or, by formula S2
With formulaReact under the conditions of the base catalyst of ethanol-dichloromethane solution；
Collection obtains formula T1 intermediate product
2) under the conditions of solvent is for dimethylformamide (DMF), by gained formula T1 intermediate product with Tertiary amine or nitrogen heterocyclic reaction, collect the compound obtaining formula C3 structure；
Wherein：
N1=0,1,2,3 or 4；Preferably, n1 is 0,1 or 2；
N2=0,1,2,3 or 4；Preferably, n2 is 0,1 or 2；
D2Selected from-H ,-Cl ,-Br or-I；
D3Selected from-H ,-Cl ,-Br or-I；D3And D2Identical or different, but at least one be selected from-Cl, - Br or-I；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
Preferably, there is the synthesis step 1 of the compound of formula C3 structure) described in base catalyst be Lithium hydrate, sodium hydroxide, potassium hydroxide, natrium carbonicum calcinatum, Anhydrous potassium carbonate, pyridine or hexahydropyridine One or more of combination.
For reaching above-mentioned 3rd purpose, the water-soluble cationic benzal cycloalkane ketone photosensitizer of the present invention should Used in light power inactivation of bacterial, funguses and virus.
Preferably, described antibacterial includes the gram positive bacteria according to Gram’s staining classification and gram-negative Property bacterium；It is highly preferred that described gram positive bacteria includes staphylococcus aureuses, streptococcus, the double ball of pneumonia Bacterium, anthrax bacillus, diphtheria corynebacterium or clostridium tetani；Described gram negative bacteria includes escherichia coli, dysentery Shigella, Bacillus typhi, Bacillus proteuss or bordetella pertussis.
Preferably, described funguses include mycete, yeast, Candida albicans, medicated beer mother bacterium, monascuses Element, candida mycoderma, Aspergillus flavus, geotrichum candidum or antibiotic bacteria.
Preferably, described virus include according to host types classification bacterial viruses, plant viruses, zoosis Poison；Preferably, described bacterial viruses include phage；Preferably, described plant viruses include Tobacco mosaic Virus；Preferably, described animal viruss include HIV, smallpox virus, hepatitis A virus, hepatitis B Virus or rubella viruses.
The water-soluble cationic benzal cycloalkane ketone photosensitizer of the present invention is applied in light power inactivation of bacterial, true The mechanism of bacterium and virus is cationic antimicrobial mechanism, and between cation photosensitizer and thalline, special electrostatic is mutual Effect, thus interrupt and upset the pith that antibacterial membrane structure is in its antibacterial mechanisms.
Beneficial effects of the present invention are as follows：
1. the water-soluble cationic benzal cycloalkane ketone photosensitizer structure in the present invention is simple, molecular weight is little, There is the chemical constitution of determination it is easy to preparation, purification and modifying further, meet the basic of clinical application Require.
2. the water-soluble cationic benzal cycloalkane ketone photosensitizer in the present invention has the spy of fat water parents Point, its fat moisture proportioning disclosure satisfy that the use requirement of clinical optical dynamic therapy.
3. the synthetic method of the water-soluble cationic benzal cycloalkane ketone photosensitizer in the present invention has operation Simply, the feature that product yield is high, purity is high, can high-volume synthesize.
4. the water-soluble cationic benzal cycloalkane ketone photosensitizer in the present invention is in 350～600nm wavelength Scope has higher biological photodynamic activity, has as photo-dynamical medicine inactivation of pathogenic microorganism aspect Good application prospect.
5. the water-soluble cationic benzal cycloalkane ketone photosensitizer in the present invention is capable of antibacterial, funguses With viral effective light inactivation, there is broad spectrum antibacterial, supplement benzal cycloalkane ketone antibacterial field very Big blank.
6. the water-soluble cationic benzal cycloalkane ketone photosensitizer in the present invention can optionally inactivate disease Pathogenic microorganism and reduce the damage to host cell as far as possible, this effect is strong demonstrate such Cation photosensitizer is applied to the bright outlook of clinic.
Brief description
Below in conjunction with the accompanying drawings the specific embodiment of the present invention is described in further detail.
Fig. 1 illustrates that in embodiment 1, photosensitizer C1-1 is in dimethylformamide (DMF) and phosphate-buffered salt Absorption spectrum in solution (PBS) buffer.
In the presence of Fig. 2 illustrates photosensitizer C1-1 in embodiment 1,1,3- dimethyl isobenzofuran (DPBF) Absorbance in DMF down ratio in time.
Fig. 3 illustrates absorption spectrum in DMF and PBS for the photosensitizer C1-2 in embodiment 7.
In the presence of Fig. 4 illustrates photosensitizer C1-2 in embodiment 7, absorbance in DMF for the DPBF with The down ratio of time.
Fig. 5 illustrates absorption spectrum in DMF and PBS for the photosensitizer C1-3 in embodiment 12.
In the presence of Fig. 6 illustrates photosensitizer C1-3 in embodiment 12, absorbance in DMF for the DPBF with The down ratio of time.
Fig. 7 illustrates that light power inactivation staphylococcus aureuses, colibacillary bacterium plate photosensitizer concentration are illustrated Figure.
Fig. 8 illustrates the experimental result of embodiment 40：The photosensitizer being obtained in embodiment 2 goes out for light power The experiment of staphylococcus aureuses alive.
Fig. 9 illustrates the experimental result of embodiment 41：The photosensitizer being obtained in embodiment 2 goes out for light power Colibacillary experiment alive.
Figure 10 illustrates the experimental result of embodiment 42：The photosensitizer being obtained in embodiment 2 is used for light power The experiment of inactivation Candida albicans.
Figure 11 illustrates the experimental result of embodiment 43：The photosensitizer being obtained in embodiment 8 is used for light power The experiment of inactivation staphylococcus aureuses.
Figure 12 illustrates the experimental result of embodiment 44：The photosensitizer being obtained in embodiment 8 is used for light power The experiment of colibacillus deactivating.
Figure 13 illustrates the experimental result of embodiment 45：The photosensitizer being obtained in embodiment 8 is used for light power The experiment of inactivation Candida albicanss.
Figure 14 illustrates the experimental result of embodiment 46：The photosensitizer being obtained in embodiment 13 is used for observing carefully Born of the same parents absorb the experiment of cation photosensitizer.
Specific embodiment
In order to be illustrated more clearly that the present invention, with reference to preferred embodiments and drawings, the present invention is done into one The explanation of step.In accompanying drawing, similar part is indicated with identical reference.Those skilled in the art It should be appreciated that following specifically described content is illustrative and be not restrictive, should not be limited with this Protection scope of the present invention.
Embodiment 1
A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer, its synthetic method is as follows：
(I) preparation of midbody compound Q2-1：
It is slowly added to 52.06 grams of (0.25mol) phosphorus pentachlorides in the DMF of the 150mL of ice bath cooling, Continue ice bath after 30 minutes, then be stirred at room temperature 15 minutes.It is slowly added to N- ethyl-N- in above-mentioned system 20 grams of hydroxyethylaniline (0.12mol), after 45 DEG C of temperature control stirs 12 hours, recovers to room temperature and uses carbon Sour hydrogen sodium solution neutralization reaction liquid.Reactant liquor is extracted three times with dichloromethane, dichloromethane extract water Add anhydrous magnesium sulfate to be dried after being washed till neutrality, remove dichloromethane through filtration, revolving, obtain 24.9 grams Corresponding intermediate product Q2-1 (yield 98%).
(II) preparation of midbody compound Q3-1：
10.58 grams of (0.05mol) Q2-1 of addition in 100 milliliters of there-necked flasks, 3.52 gram (0.05 Mol) cyclobutanone, 40 milliliters of dichloromethane and 20 milliliters of ethanol, stirring is disposable after so that it is uniformly dissolved Add 0.03 gram of sodium hydroxide, react 10 hours at 20 DEG C, reactant liquor removes solvent through revolving and obtains slightly Product, obtains 5.9 grams of (yield 44%) orange solids Q3-1 with chromatographic column separating-purifying.
(III) preparation of midbody compound Q5-1：
2.4 grams of (0.01mol) Q3-1,1.8 grams (0.01mol) is added in 100 milliliters of there-necked flasks Commercially available 4- (N, N- lignocaine) benzaldehyde, 40 milliliters of dichloromethane and 10 milliliters of ethanol, stirring Disposably add 0.06 gram of sodium hydroxide after so that it is uniformly dissolved, stir 12 hours under room temperature, remove through revolving Go solvent to obtain crude product, obtain 1.5 grams of Q5-1 solid (yield 35%) with chromatographic column separating-purifying.
(IV) preparation of target product C1-1：
0.23 gram of (0.5mmol) Q5-1 of addition in 100 milliliters of there-necked flasks, 1.96 grams of pyridines, 10 milliliters of DMF, stirring makes it be uniformly dissolved 100 DEG C of reactions of post-heating 12 hours.Question response system is cold But, to after room temperature, obtain 80 milligrams of C1-1 solid (yield 30%) using re crystallization from toluene.HR-MS(ESI): [M]+:Calcd for[C31H36N3O]+466.2852；found 466.2861.
(V) use the phosphate buffer of pH value 7.4 (referred to as：PBS) detect that target is photosensitive Dissolubility in aqueous systems for the agent C1-1,25 DEG C of its dissolubility are more than 4mg/mL；By target photosensitizer C1-1 is dissolved in DMF and PBS respectively, tests its absorption spectrum it was demonstrated that photosensitizer C1-1 Have compared with strong absworption peak in 350～600nm wave-length coverage, see Fig. 1.
(VI) above-mentioned target photosensitizer C1-1 is dissolved in DMF so as to the absorbance in 473nm is 0.1, with Phthalocyanine Zinc (singlet oxygen quantum yield ΦΔ=0.56) it is reference, be active oxygen using DPBF Trapping agent, complete the mensure of active oxygen quantum yield under conditions of the saturation of the air, result such as Fig. 2 institute Show.Illustrate that photosensitizer C1-1 creates reactive oxygen species under the conditions of 473nm laser excitation.
Embodiment 2
Repeat embodiment 1, its difference is,For cyclooctanone, catalyst is natrium carbonicum calcinatum, with(2,2- bipyridyl) replaces pyridine as reaction raw materials, and other conditions are constant.Produced Thing water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 34%.
Embodiment 3
Repeat embodiment 1, its difference is,For cycloheptanone, catalyst is Anhydrous potassium carbonate, with(2- benzyl pyridine) replaces pyridine as reaction raw materials, and other conditions are constant.Produced Thing water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 45%.
Embodiment 4
Repeat embodiment 1, its difference is,For Ketohexamethylene, catalyst is potassium hydroxide, with(dipyridyl ethane) replaces pyridine as reaction raw materials, and other conditions are constant. Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 24%.
Embodiment 5
Repeat embodiment 1, its difference is, with(7,8- benzoquinoline) replaces pyridine to make For reaction raw materials, other conditions are constant.Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, Yield 55%.
Embodiment 6
Repeat embodiment 1, its difference is, with(4,7- phenanthroline) replaces pyridine to make For reaction raw materials, other conditions are constant.Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, Yield 33%.
Embodiment 7
A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer, its synthetic method is as follows：
(I) preparation of midbody compound Q2-2：
With reference to the operation of (I) in embodiment 1, with mole 1：3 N, N- dihydroxy ethyl aniline and Vilsmeier reagent reacting, obtains intermediate product Q2-2 (yield 97%).
(II) preparation of midbody compound Q3-2：
With reference to the operation of (II) in embodiment 1, it is 1 with mole：1 Q2-2 and cyclobutanone react, and urge Agent is potassium hydroxide, obtains intermediate product Q3-2 (yield：39%).
(III) preparation of midbody compound Q5-2：
With reference to the operation of (III) in embodiment 1, with mole 1:1 Q3-2 and 4- (N, N- lignocaine) Benzaldehyde reacts, and catalyst is potassium hydroxide, obtains intermediate product Q5-2 (yield 62%).
(IV) preparation of target product C1-2：
With reference to the operation of (IV) in embodiment 1, it is 1 with mass ratio：10 Q5-2 and pyridine react, Obtain target photosensitizer C1-2 (yield：90%).HR-MS(ESI):[M]+:Calcd for [C36H40ClN4O]+579.2885；found 579.2889.
(IV) operation with reference to (V) in embodiment 1 is it was demonstrated that C1-2 dissolubility is more than 5mg/mL；And Have compared with strong absworption peak in 350～600nm wave-length coverage, see Fig. 3.
(V) with reference to the operation of embodiment 1 (VI), result has been also demonstrated that target photosensitizer C1-2 in 473nm Laser can produce reactive oxygen species under irradiating, and sees Fig. 4.
Embodiment 8
Repeat embodiment 7, its difference is,For Ketohexamethylene, catalyst is natrium carbonicum calcinatum, with(quinoline) replaces pyridine as reaction raw materials, and other conditions are constant.Obtain product water solublity sun Ion benzal cycloalkane ketone photosensitizer, yield 88%.
Embodiment 9
Repeat embodiment 7, its difference is,For cycloheptanone, catalyst is natrium carbonicum calcinatum, with(diphenyl -2- phridyl methane) replaces pyridine as reaction raw materials, and other conditions are constant. Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 77%.
Embodiment 10
Repeat embodiment 7, its difference is, with(2,2- diquinoline) replaces , as reaction raw materials, other conditions are constant for pyridine.Obtain product water-soluble cationic benzal cycloalkane ketone Photosensitizer, yield 47%.
Embodiment 11
Repeat embodiment 7, its difference is, pyridine is replaced as reaction raw materials using triethylamine, other conditions Constant.Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 87%.
Embodiment 12
A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer, its synthetic method is as follows：
(I) preparation of intermediate product Q5-3：
With reference to the operation of (III) in embodiment 1, it is 1 with mole：2 cyclobutanone and Q2-1 react, Catalyst is pyridine, obtains intermediate product Q5-3 (yield：85%).
(II) preparation of target product C1-3：
With reference to the operation of (IV) in embodiment 1, it is 1 with mass ratio：10 Q5-3 and pyridine react, Obtain target photosensitizer C1-3 (yield：50%).HR-MS(ESI):[M]+:Calcd for [C36H40ClN4O]+579.2885；found 579.2886.
(III) operation with reference to (V) in embodiment 1 is it was demonstrated that C1-3 dissolubility is more than 5mg/mL；And Have compared with strong absworption peak in 350～600nm wave-length coverage, see Fig. 5.
(IV) with reference to the operation of embodiment 1 (VI), result has been also demonstrated that target photosensitizer C1-3 in 473nm Laser can produce reactive oxygen species under irradiating, and sees Fig. 6.
Embodiment 13
Repeat embodiment 12, its difference is,For cycloheptanone, catalyst is Anhydrous potassium carbonate, with(2- pyridine radicals benzophenone) replaces pyridine as reaction raw materials, and other conditions are constant.? To product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 44%.
Embodiment 14
Repeat embodiment 12, its difference is,For cyclooctanone, catalyst is hexahydropyridine, with(acridine) replaces pyridine as reaction raw materials, and other conditions are constant.Obtain product water-soluble Property cation benzal cycloalkane ketone photosensitizer, yield 29%.
Embodiment 15
A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer, its synthetic method is as follows：
(I) preparation of midbody compound S2-1：
With reference to the operation of (I) in embodiment 1, with mole 1：2 commercially available chlorobenzene and vilsmeier Reagent reacting, obtains intermediate product S2-1 (yield 96%).
(II) preparation of midbody compound Q2-3：
With reference to the operation of (I) in embodiment 1, with mole 1：3 commercially available N, N- bis- (2- bromine Ethyl) aniline and vilsmeier reagent reacting, obtain intermediate product Q2-3 (yield 98%).
(III) preparation of midbody compound S3-1：
With reference to the operation of (II) in embodiment 1, it is 1 with mole：1 S2-1 and hexamethylene reactive ketone, urge Agent is sodium hydroxide, obtains intermediate product S3-1 (yield：50%).
(IV) preparation of midbody compound S4-1：
With reference to the operation of (III) in embodiment 1, with mole 1:1 S3-1 and Q2-3 reaction, catalysis Agent is sodium hydroxide, obtains intermediate product S4-1 (yield 88%).
(V) preparation of target product C2-1：
With reference to the operation of (IV) in embodiment 1, it is 1 with mass ratio：30 S4-1 with commercially available Triethylamine react, obtains target photosensitizer C2-1 (yield：50%).HR-MS(ESI):[M]+:Calcd for[C42H69Br2N4O]+803.3833；found 803.3847.
Embodiment 16
Repeat embodiment 15, its difference is,For Ketocyclopentane, catalyst is potassium hydroxide, with(2- benzyl pyridine) replaces triethylamine as reaction raw materials, and other conditions are constant.Obtain Product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 45%.
Embodiment 17
Repeat embodiment 15, its difference is, with(pyridine) replaces triethylamine as reaction raw materials, Other conditions are constant.Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 78%.
Embodiment 18
Repeat embodiment 15, its difference is, with(2,2- bipyridyl) replaces triethylamine As reaction raw materials, other conditions are constant.Obtain product water-soluble cationic benzal cycloalkane ketone photosensitive Agent, yield 38%.
Embodiment 19
Repeat embodiment 15, its difference is,For cycloheptanone, catalyst is natrium carbonicum calcinatum, with(quinoline) replaces triethylamine as reaction raw materials, and other conditions are constant.Obtain product water solublity Cation benzal cycloalkane ketone photosensitizer, yield 65%.
Embodiment 20
Repeat embodiment 15, its difference is,For cyclobutanone, catalyst is natrium carbonicum calcinatum, with(2- pyridine radicals benzophenone) replaces triethylamine as reaction raw materials, and other conditions are constant. Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 67%.
Embodiment 21
A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer, its synthetic method is as follows：
(I) preparation of midbody compound Q2-4：
With reference to the operation of (I) in embodiment 1, with mole 1：2 commercially available N- (2- bromine second Base)-methylphenylamine and vilsmeier reagent reacting, obtain intermediate product Q2-4 (yield 98%).
(II) preparation of midbody compound S2-2：
With reference to the operation of (I) in embodiment 1, with mole 1：2 commercially available 2- (chloroethyl) Benzene and vilsmeier reagent reacting, obtain intermediate product S2-2 (yield 98%).
(III) preparation of midbody compound S3-2：
With reference to the operation of (II) in embodiment 1, it is 1 with mole：1 Q2-4 and hexamethylene reactive ketone, urge Agent is hexahydropyridine, obtains intermediate product S3-2 (yield：45%).
(IV) preparation of midbody compound S4-2：
With reference to the operation of (III) in embodiment 1, with mole 1:1 S2-2 and S3-2 reaction, catalysis Agent is hexahydropyridine, obtains intermediate product S4-2 (yield 60%).
(V) preparation of target product C2-2：
With reference to the operation of (IV) in embodiment 1, it is 1 with mass ratio：40 S4-2 with commercially available Triphenylamine reacts, and obtains target photosensitizer C2-2 (yield：50%).HR-MS(ESI):[M]+:Calcd for[C61H57BrN3O]+926.3680；found 926.3677.
Embodiment 22
Repeat embodiment 21, its difference is,For cyclobutanone, catalyst is potassium hydroxide, with(dipyridyl ethane) replaces triphenylamine as reaction raw materials, and other conditions are constant. Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 35%.
Embodiment 23
Repeat embodiment 21, its difference is,For Ketocyclopentane, catalyst is Anhydrous potassium carbonate, with(2,2- diquinoline) replaces triphenylamine as reaction raw materials, and other conditions are constant. Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 57%.
Embodiment 24
Repeat embodiment 21, its difference is,For cyclobutanone, catalyst is natrium carbonicum calcinatum, with(acridine) replaces triphenylamine as reaction raw materials, and other conditions are constant.Obtain product water Soluble cationic benzal cycloalkane ketone photosensitizer, yield 67%.
Embodiment 25
Repeat embodiment 21, its difference is,For cycloheptanone, catalyst is Anhydrous potassium carbonate, with(7,8- benzoquinoline) replaces triphenylamine as reaction raw materials, and other conditions are constant.Obtain Product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 77%.
Embodiment 26
Repeat embodiment 21, its difference is,For Ketocyclopentane, catalyst is potassium hydroxide, with(4,7- phenanthroline) replaces triphenylamine as reaction raw materials, and other conditions are constant.Obtain Product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 47%.
Embodiment 27
Repeat embodiment 21, its difference is,For cyclooctanone, catalyst is sodium hydroxide, with(diphenyl -2- phridyl methane) replaces triphenylamine as reaction raw materials, and other conditions are constant. Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 55%.
Embodiment 28
A kind of water-soluble cationic benzal cycloalkane ketone photosensitizer, its synthetic method is as follows：
(I) preparation of midbody compound S2-3：
With reference to the operation of (I) in embodiment 1, with mole 1：2 commercially available 2- iodoethyl Benzene and vilsmeier reagent reacting, obtain intermediate product S2-3 (yield 96%).
(II) preparation of midbody compound S3-3：
With reference to the operation of (II) in embodiment 1, it is 1 with mole：1 S2-3 and cycloheptyl reactive ketone, urge Agent is potassium carbonate, obtains intermediate product S3-3 (yield：40%).
(III) preparation of midbody compound T1-1：
With reference to the operation of (III) in embodiment 1, with mole 1:1 S3-3 and S2-1 reaction, catalysis Agent is potassium carbonate, obtains intermediate product T1-1 (yield 78%).
(IV) preparation of target product C3-1：
With reference to the operation of (IV) in embodiment 1, it is 1 with mass ratio：30 T1-1 with commercially available Triphenylphosphine reacts, and obtains target photosensitizer C3-1 (yield：50%).HR-MS(ESI):[M]+:Calcd for[C59H52IOP2]+965.2533；found 965.2539.
Embodiment 29
Repeat embodiment 28, its difference is,For Ketocyclopentane, catalyst is sodium hydroxide, with(7,8- benzoquinoline) replaces triphenylphosphine as reaction raw materials, and other conditions are constant.? To product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 56%.
Embodiment 30
Repeat embodiment 28, its difference is,For cyclobutanone, catalyst is sodium hydroxide, with(4,7- phenanthroline) replaces triphenylphosphine as reaction raw materials, and other conditions are constant.? To product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 44%.
Embodiment 31
Repeat embodiment 28, its difference is,For Ketohexamethylene, catalyst is sodium carbonate, with(diphenyl -2- phridyl methane) replaces triphenylphosphine as reaction raw materials, and other conditions are not Become.Obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer, yield 28%.
Embodiment 32
Repeat embodiment 28, its difference is, with(pyridine) replaces triphenylphosphine former as reaction Material, other conditions are constant, obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer.
Embodiment 33
Repeat embodiment 28, its difference is, with(bipyridyl) replaces triphenylphosphine conduct Reaction raw materials, other conditions are constant, obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer.
Embodiment 34
Repeat embodiment 28, its difference is, with(quinoline) replaces triphenylphosphine as anti- Answer raw material, other conditions are constant, obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer.
Embodiment 35
Repeat embodiment 28, its difference is, with(2- pyridine radicals benzophenone) replaces three , as reaction raw materials, other conditions are constant for Phenylphosphine, obtain product water-soluble cationic benzal cycloalkane Ketone photosensitizer.
Embodiment 36
Repeat embodiment 28, its difference is, with(acridine) replaces triphenylphosphine conduct Reaction raw materials, other conditions are constant, obtain product water-soluble cationic benzal cycloalkane ketone photosensitizer.
Embodiment 37
Repeat embodiment 28, its difference is, with(2- benzyl pyridine) replaces triphenyl , as reaction raw materials, other conditions are constant for phosphine, obtain product water-soluble cationic benzal cycloalkane ketone light Quick dose.
Embodiment 38
Repeat embodiment 28, its difference is, with(dipyridyl ethane) replaces , as reaction raw materials, other conditions are constant for triphenylphosphine, obtain product water-soluble cationic benzal cycloalkanes Hydrocarbon ketone photosensitizer.
Embodiment 39
Repeat embodiment 28, its difference is, with(2,2- diquinoline) replaces , as reaction raw materials, other conditions are constant for triphenylphosphine, obtain product water-soluble cationic benzal cycloalkanes Hydrocarbon ketone photosensitizer.
Embodiment 40
The photosensitizer being obtained in embodiment 2 is used for the experiment that light power inactivates staphylococcus aureuses
(I) antibacterial is recovered in broth bouillon, determine antibacterial by measuring the absorbance of 600nm Concentration.
(II) carry out minimal inhibitory concentration (minimum inhibitory using 96 aseptic orifice plates Concentration, MIC) mensure.See signal Fig. 7, four holes often adjacent in 96 orifice plates, for example Photosensitizer concentration added by C1, C2, D1 and D2 is identical.According to concentration shown in schematic diagram, every hole adds Enter the Broth solution of 100 microlitres of different photosensitizer concentrations.Wherein, negative control group is B+B group (100 10 microlitres of antibacterial is added in microlitre meat soup), positive controls are that (100 microlitres of meat soups add GM group 1% gentamycin), blank control group is Broth group (adding 10 microlitres of PBS in 100 microlitres of meat soups). Bacterial concentration in above-mentioned 96 orifice plates is about 5 × 105Every milliliter of CFU.
(III) utilize laser (the 30J cm of 532nm-2, 10min) irradiate above-mentioned 96 orifice plates after, put into Bacteriological incubator continues culture 18 hours.Then developed the color using 0.0675% "diazoresorcinol" sodium salt solution.
(IV) outline the photosensitizer concentration corresponding to concentration in the chromogenic reaction of 4 hours, 96 orifice plates For minimum inhibitory concentration.See Fig. 8.
Embodiment 41
With reference to the operation in embodiment 40, the photosensitizer being obtained is used for the inactivation of light power big in embodiment 2 The experiment of enterobacteria, is shown in Fig. 9.
Embodiment 42
The photosensitizer being obtained in embodiment 2 is used for the experiment that light power inactivates Candida albicanss.
(I) take appropriate bacterium solution to be inoculated in Sabouraud dextrose broth bouillon, cultivate 48～72 hours.
(II) take the photosensitizer adding variable concentrations in the fungi solution of suitable concentration, make the final of photosensitizer Concentration is 25 micromoles, 50 micromoles and 100 micromoles.After picked-up 1 hour, using 532nm's Laser carries out illumination (30J cm to above-mentioned mixed liquor-2,10min).And cultivate 24 hours in dark place.
(III) using coating bacterium plate method, observe the colony count under variable concentrations, the antibacterial measuring photosensitizer is lived Property.See Figure 10.
Embodiment 43
The photosensitizer being obtained in embodiment 8 is used for the experiment that light power inactivates staphylococcus aureuses, sees Figure 11.
Embodiment 44
The photosensitizer being obtained in embodiment 8 is used for the experiment of light power colibacillus deactivating, sees Figure 12.
Embodiment 45
The photosensitizer being obtained in embodiment 8 is used for the experiment that light power inactivates Candida albicanss, sees Figure 13.
Embodiment 46
The photosensitizer being obtained in embodiment 13 is used for the experiment that observation of cell absorbs such photosensitizer.
(I) by cell with 105In every hole implantation culture vessel with glass bottom (35 millimeters of diameter), after 24 hours Change the culture fluid containing 10 micromole's photosensitizer into, continue culture 4 hours；
(II) 100 nanomole fluorescent probes are added to continue culture 20 minutes in culture fluid, clear with PBS Wash away except free probe；
(III) add 1 milliliter of PBS solution, observe photosensitizer in cell with confocal microscope Positioning figure.See Figure 14.
Embodiment 47
The photosensitizer being obtained in embodiment 15 is used for the determination experiment of fat moisture proportioning
A certain amount of photosensitizer is dissolved in 2mL PBS, is subsequently adding 2mL n-octyl alcohol, will mix molten Liquid shakes 3min, then is placed in ultrasound wave vibration 5min, then under 5000 turns per minute of speed from The heart 5 minutes, makes two-phase laminated flow.The abosrption spectrogram of the photosensitizer during mensure is biphase, by Lambert-beer Law is calculated concentration in biphase for the photosensitizer, and fat moisture proportioning (Log PC) is photosensitizer and exists Concentration proportion in biphase.It is shown in Table 1.
Embodiment 48
The photosensitizer being obtained in embodiment 21 is used for the determination experiment of fat moisture proportioning, is shown in Table 1.
Embodiment 49
The photosensitizer being obtained in embodiment 28 is used for the determination experiment of fat moisture proportioning, is shown in Table 1.
Embodiment 50
The photosensitizer being obtained in embodiment 31 is used for light power inactivation tobacco mosaic virus (TMV).
To in 96 orifice plates 100 μ L variable concentrations (0.125,0.25,0.5,1.0,2.0,4.0,8.0, 16.0th, 32.0 and 64.0 μM) photosensitizing agent solution in add appropriate tobacco mosaic virus (TMV) and ensure virus Final concentration of 2x1011Pfu/mL, concussion and cultivate 30 minutes in the dark, are that 550nm is left with wavelength Right Oriel 91192 solar simulator (5mW/cm2, 50min) irradiate after, by 96 orifice plates Mixed solution is transferred in the agar disks containing culture medium, calculates tobacco mosaic virus (TMV) with colony counting method Survival rate.Wherein, the bacteria suspension of the same concentration without photosensitizer is used as matched group.
Table 1
Photosensitizer title Log PC
C2-1 -2.66
C2-2 5.72
C3-1 4.58
Obviously, the above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and It is not the restriction to embodiments of the present invention, for those of ordinary skill in the field, Can also make other changes in different forms on the basis of described above, here cannot be to all Embodiment be exhaustive, every belong to the obvious change that technical scheme is extended out Change or change the row still in protection scope of the present invention.

Claims (11)

1. a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer it is characterised in that include have as The compound of lower formula C1, C2 or C3 structure：
Wherein：
R2, R3And R4Identical or different, R2、R3And R4Selected from methyl, ethyl, propyl group, isopropyl, Normal-butyl, isobutyl group, the tert-butyl group or-(CH2)n-R1X；Preferably, R2, R3And R4Selected from methyl, second Base or-(CH2)n-R1X；
R5And R6Identical or different, R5And R6Selected from N or P；Preferably, R5And R6For N；
X is anion Cl-、Br-Or I-；
N=1,2,3 or 4；Preferably, n is 1 or 2；
N1 and n2=0,1,2,3 or 4；Preferably, n1 and n2 is 0,1 or 2；
R1For quaternary ammonium salt cationic；Preferably, R1It is selected from
A is selected from N or P；Preferably, A is N；
A1, A2And A3Identical or different, A1、A2And A3Selected from methyl, ethyl, propyl group, isopropyl, Normal-butyl, isobutyl group, the tert-butyl group or phenyl；Preferably, A1, A2And A3Selected from methyl, ethyl or benzene Base；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
2. the system of a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 1 Preparation Method is it is characterised in that the described compound with formula C1 structure includes following synthesis step：
1) after phosphorus pentachloride being reacted with dimethylformamide, then with formula Q1 compound
Reaction, collects and obtains formula Q2 intermediate product
2) under the conditions of the base catalyst of ethanol-dichloromethane solution, willIn gained formula Q2 Between product reaction, collect obtain formula Q3 intermediate product
3) under the conditions of the base catalyst of ethanol-dichloromethane solution, by gained formula Q3 intermediate product With formula Q4 compound
Reaction；
Or, under the conditions of the base catalyst of ethanol-dichloromethane solution, willWith gained formula Q2 Compound reacts；
Collect the formula Q5 intermediate product obtaining
4) under the conditions of solvent is for dimethylformamide (DMF), by gained formula Q5 intermediate product with Tertiary amine or nitrogen heterocyclic reaction, collect the compound obtaining formula C1 structure；
Wherein：
N3 and n4 is identical or different, n3, n4=1,2,3 or 4；Preferably, n3, n4 are 1 or 2；
N5 and n6 is identical or different, n5, n6=1,2,3 or 4；Preferably, n5 and n6 be 1 or 2；
B1And B2Identical or different, B1And B2Selected from-H ,-OH ,-Cl ,-Br or-I；
B3Selected from N or P；Preferably, B3For N；
B4、B5Selected from-H ,-Cl ,-Br or-I；B4、B5Identical or different, but at least one be selected from-Cl, - Br or-I；
B6Selected from N or P；Preferably, B6For N；
B7And B8Selected from-H ,-Cl ,-Br or-I；B7And B8Identical or different, but at least one choosing From-Cl ,-Br or-I；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
3. the system of a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 1 Preparation Method is it is characterised in that the described compound with formula C2 structure includes following synthesis step：
1) after phosphorus pentachloride being reacted with dimethylformamide, then with formula S1 compound
Reaction, collects and obtains formula S2 intermediate product
2) under the conditions of the base catalyst of ethanol-dichloromethane solution, willIn gained formula S2 Between product reaction, collect obtain formula S3 intermediate product
3) under the conditions of the base catalyst of ethanol-dichloromethane solution, by gained formula S3 intermediate product With formula Q2 compound
Reaction；
Or, under the conditions of the base catalyst of ethanol-dichloromethane solution, by gained formula S2 chemical combination Thing and formula Q3 compound
Reaction, collects the formula S4 intermediate product obtaining
4) under the conditions of solvent is for dimethylformamide (DMF), by gained formula S4 intermediate product with Tertiary amine or nitrogen heterocyclic reaction, collect the compound obtaining formula C2 structure；
Wherein：
N1=0,1,2,3 or 4；Preferably, n1 is 0,1 or 2；
N3 and n4 is identical or different, n3, n4=1,2,3 or 4；Preferably, n3, n4 are 1 or 2；
D1Selected from-H ,-OH ,-Cl ,-Br or-I；
D2Selected from-H ,-Cl ,-Br or-I；
B3Selected from N or P；Preferably, B3For N；
B4、B5Selected from-H ,-Cl ,-Br or-I；B4、B5Identical or different, but at least one be selected from-Cl, - Br or-I；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
4. the system of a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 1 Preparation Method is it is characterised in that the described compound with formula C3 structure includes following synthesis step：
1) by formula S3 compound
With formula S5 compound
React under the conditions of the base catalyst of ethanol-dichloromethane solution；
Or, by formula S2
With formulaReact under the conditions of the base catalyst of ethanol-dichloromethane solution；
Collection obtains formula T1 intermediate product
2) under the conditions of solvent is for dimethylformamide (DMF), by gained formula T1 intermediate product with Tertiary amine or nitrogen heterocyclic reaction, collect the compound obtaining formula C3 structure；
Wherein：
N1=0,1,2,3 or 4；Preferably, n1 is 0,1 or 2；
N2=0,1,2,3 or 4；Preferably, n2 is 0,1 or 2；
D2Selected from-H ,-Cl ,-Br or-I；
D3Selected from-H ,-Cl ,-Br or-I；D3And D2Identical or different, but at least one be selected from-Cl, - Br or-I；
Selected from cyclobutanone, Ketocyclopentane, Ketohexamethylene, cycloheptanone or cyclooctanone.
5. the conjunction of a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 2 One-tenth method is it is characterised in that have the synthesis step 2 of the compound of formula C1 structure), 3) described in Base catalyst is Lithium hydrate, sodium hydroxide, potassium hydroxide, natrium carbonicum calcinatum, Anhydrous potassium carbonate, pyrrole The combination of one or more of pyridine or hexahydropyridine.
6. the conjunction of a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 3 One-tenth method is it is characterised in that have the synthesis step 2 of the compound of formula C2 structure), 3) described in Base catalyst is Lithium hydrate, sodium hydroxide, potassium hydroxide, natrium carbonicum calcinatum, Anhydrous potassium carbonate, pyrrole The combination of one or more of pyridine or hexahydropyridine.
7. the conjunction of a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 4 One-tenth method is it is characterised in that have the synthesis step 1 of the compound of formula C3 structure) described in alkalescence Catalyst be Lithium hydrate, sodium hydroxide, potassium hydroxide, natrium carbonicum calcinatum, Anhydrous potassium carbonate, pyridine or The combination of one or more of hexahydropyridine.
8. a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer application according to claim 1 In light power inactivation of bacterial, funguses and virus.
9. a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 8 should With it is characterised in that described antibacterial includes the gram positive bacteria according to Gram’s staining classification and gram Negative bacterium；Described gram positive bacteria includes staphylococcus aureuses, streptococcus, Diplococcus pneumoniae, anthrax Bacillus, diphtheria corynebacterium or clostridium tetani；Described gram negative bacteria include escherichia coli, dysentery bacterium, Bacillus typhi, Bacillus proteuss or bordetella pertussis.
10. a kind of water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 8 should With it is characterised in that described funguses include mycete, yeast, Candida albicans, medicated beer mother bacterium, Monas cuspurpureus Went Mycin, candida mycoderma, Aspergillus flavus, geotrichum candidum or antibiotic bacteria.
A kind of 11. water-soluble cationic benzal cycloalkane ketone photosensitizer according to claim 8 should With it is characterised in that described virus includes bacterial viruses according to host types classification, plant viruses, dynamic Thing virus；Described bacterial viruses include phage；Described plant viruses include tobacco mosaic virus (TMV)；Described dynamic Thing virus includes HIV, smallpox virus, hepatitis A virus, hepatitis B viruss or rubella viruses.
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CN114634495A (en) * 2022-04-18 2022-06-17 内蒙古大学 Water-soluble photosensitizer with broad-spectrum antibacterial activity and preparation method and application thereof
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