CN107200694A - Water-soluble anionic benzylidene naphthenone photosensitizer, preparation method and application thereof in photodynamic antimicrobial infection - Google Patents
Water-soluble anionic benzylidene naphthenone photosensitizer, preparation method and application thereof in photodynamic antimicrobial infection Download PDFInfo
- Publication number
- CN107200694A CN107200694A CN201610150006.6A CN201610150006A CN107200694A CN 107200694 A CN107200694 A CN 107200694A CN 201610150006 A CN201610150006 A CN 201610150006A CN 107200694 A CN107200694 A CN 107200694A
- Authority
- CN
- China
- Prior art keywords
- coo
- ethyl
- methyl
- butyl
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 208000015181 infectious disease Diseases 0.000 title claims abstract description 12
- 230000000845 anti-microbial effect Effects 0.000 title claims abstract description 9
- 239000003504 photosensitizing agent Substances 0.000 title abstract description 7
- -1 anionic benzylidene naphthene ketone Chemical class 0.000 claims abstract description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 66
- 241000700605 Viruses Species 0.000 claims abstract description 11
- 241000233866 Fungi Species 0.000 claims abstract description 6
- 244000005700 microbiome Species 0.000 claims abstract description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 118
- 230000001235 sensitizing effect Effects 0.000 claims description 107
- 239000000243 solution Substances 0.000 claims description 69
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 57
- 238000006243 chemical reaction Methods 0.000 claims description 54
- 241000894006 Bacteria Species 0.000 claims description 46
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 46
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical group [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 42
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 claims description 28
- 239000003054 catalyst Substances 0.000 claims description 25
- 239000000047 product Substances 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 23
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 23
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 23
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 21
- 238000003756 stirring Methods 0.000 claims description 21
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 19
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 17
- 238000001556 precipitation Methods 0.000 claims description 17
- 150000001768 cations Chemical group 0.000 claims description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 15
- 239000000741 silica gel Substances 0.000 claims description 15
- 229910002027 silica gel Inorganic materials 0.000 claims description 15
- 229960001866 silicon dioxide Drugs 0.000 claims description 15
- 241000191967 Staphylococcus aureus Species 0.000 claims description 14
- 241000723873 Tobacco mosaic virus Species 0.000 claims description 14
- 239000012670 alkaline solution Substances 0.000 claims description 14
- CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 14
- IIRFCWANHMSDCG-UHFFFAOYSA-N cyclooctanone Chemical compound O=C1CCCCCCC1 IIRFCWANHMSDCG-UHFFFAOYSA-N 0.000 claims description 13
- 239000012153 distilled water Substances 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 12
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims description 12
- 238000000967 suction filtration Methods 0.000 claims description 12
- 230000003197 catalytic effect Effects 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 claims description 10
- 241000222122 Candida albicans Species 0.000 claims description 9
- 241000588724 Escherichia coli Species 0.000 claims description 9
- 229940095731 candida albicans Drugs 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 150000003254 radicals Chemical class 0.000 claims description 9
- 239000013049 sediment Substances 0.000 claims description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 9
- 230000003115 biocidal effect Effects 0.000 claims description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 239000004599 antimicrobial Substances 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 7
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 6
- 241000192125 Firmicutes Species 0.000 claims description 6
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 229960003085 meticillin Drugs 0.000 claims description 6
- 241001515965 unidentified phage Species 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 4
- 235000011054 acetic acid Nutrition 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 235000011167 hydrochloric acid Nutrition 0.000 claims description 4
- 235000019260 propionic acid Nutrition 0.000 claims description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 241000228197 Aspergillus flavus Species 0.000 claims description 2
- 241000193738 Bacillus anthracis Species 0.000 claims description 2
- 241000588832 Bordetella pertussis Species 0.000 claims description 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 2
- 241001478240 Coccus Species 0.000 claims description 2
- 241000186227 Corynebacterium diphtheriae Species 0.000 claims description 2
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 claims description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 claims description 2
- 241000710799 Rubella virus Species 0.000 claims description 2
- 241000235342 Saccharomycetes Species 0.000 claims description 2
- 241000607764 Shigella dysenteriae Species 0.000 claims description 2
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims description 2
- 241000194017 Streptococcus Species 0.000 claims description 2
- 208000037386 Typhoid Diseases 0.000 claims description 2
- 241000700647 Variola virus Species 0.000 claims description 2
- 229940065181 bacillus anthracis Drugs 0.000 claims description 2
- 235000013405 beer Nutrition 0.000 claims description 2
- 238000005286 illumination Methods 0.000 claims description 2
- XXKNHBAFFJINCK-RVEJDSBJSA-N monascin Chemical compound C([C@@H]1[C@H](C(O[C@@]1(C)C1=O)=O)C(=O)CCCCC)C2=C1COC(\C=C\C)=C2 XXKNHBAFFJINCK-RVEJDSBJSA-N 0.000 claims description 2
- GFSMXLMQRWMHON-UHFFFAOYSA-N monascin Natural products CCCCCC(=O)C1C2C=C3C=C(OC=C3C(=O)C2(C)OC1=O)C=CC GFSMXLMQRWMHON-UHFFFAOYSA-N 0.000 claims description 2
- GIKQHOXMDCDAPT-UHFFFAOYSA-N monascusone B Natural products CC=CC1=CC2=C(CO1)C(=O)C3(C)OC(=O)C(C3C2)C(=O)C GIKQHOXMDCDAPT-UHFFFAOYSA-N 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 229940007046 shigella dysenteriae Drugs 0.000 claims description 2
- 201000008297 typhoid fever Diseases 0.000 claims description 2
- 241000712461 unidentified influenza virus Species 0.000 claims description 2
- 108010021119 Trichosanthin Proteins 0.000 claims 3
- 239000007789 gas Substances 0.000 claims 2
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 claims 2
- 241000193449 Clostridium tetani Species 0.000 claims 1
- 241000709721 Hepatovirus A Species 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010035664 Pneumonia Diseases 0.000 claims 1
- 208000006454 hepatitis Diseases 0.000 claims 1
- 231100000283 hepatitis Toxicity 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- JKQOBWVOAYFWKG-UHFFFAOYSA-N molybdenum trioxide Chemical compound O=[Mo](=O)=O JKQOBWVOAYFWKG-UHFFFAOYSA-N 0.000 claims 1
- 238000004088 simulation Methods 0.000 claims 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 claims 1
- 229910001948 sodium oxide Inorganic materials 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 8
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 abstract description 5
- 239000001301 oxygen Substances 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 2
- 238000009826 distribution Methods 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 150000001875 compounds Chemical class 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 239000013067 intermediate product Substances 0.000 description 12
- 238000004896 high resolution mass spectrometry Methods 0.000 description 11
- 230000002779 inactivation Effects 0.000 description 8
- 108091006146 Channels Proteins 0.000 description 7
- 238000002835 absorbance Methods 0.000 description 7
- 238000000862 absorption spectrum Methods 0.000 description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 6
- 150000001450 anions Chemical class 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 244000000010 microbial pathogen Species 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000003642 reactive oxygen metabolite Substances 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000002189 fluorescence spectrum Methods 0.000 description 4
- 235000013372 meat Nutrition 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 238000006862 quantum yield reaction Methods 0.000 description 4
- 235000014347 soups Nutrition 0.000 description 4
- 101710116435 Outer membrane protein Proteins 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- 230000009514 concussion Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 2
- 108010013381 Porins Proteins 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 2
- 229940011411 erythrosine Drugs 0.000 description 2
- 235000012732 erythrosine Nutrition 0.000 description 2
- 239000004174 erythrosine Substances 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 239000010985 leather Substances 0.000 description 2
- 229940107698 malachite green Drugs 0.000 description 2
- FDZZZRQASAIRJF-UHFFFAOYSA-M malachite green Chemical compound [Cl-].C1=CC(N(C)C)=CC=C1C(C=1C=CC=CC=1)=C1C=CC(=[N+](C)C)C=C1 FDZZZRQASAIRJF-UHFFFAOYSA-M 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229960000907 methylthioninium chloride Drugs 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- NZYCYASKVWSANA-UHFFFAOYSA-M new methylene blue Chemical compound [Cl-].CCNC1=C(C)C=C2N=C(C=C(C(NCC)=C3)C)C3=[S+]C2=C1 NZYCYASKVWSANA-UHFFFAOYSA-M 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 230000000886 photobiology Effects 0.000 description 2
- 238000002428 photodynamic therapy Methods 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000002132 β-lactam antibiotic Substances 0.000 description 2
- 229940124586 β-lactam antibiotics Drugs 0.000 description 2
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 1
- DNRTTXXWWAKULZ-UHFFFAOYSA-N 3-(4-formyl-n-methylanilino)propanenitrile Chemical class N#CCCN(C)C1=CC=C(C=O)C=C1 DNRTTXXWWAKULZ-UHFFFAOYSA-N 0.000 description 1
- SGTAWMQTFNSGLW-UHFFFAOYSA-N 3-(n-ethyl-4-formylanilino)propanenitrile Chemical group N#CCCN(CC)C1=CC=C(C=O)C=C1 SGTAWMQTFNSGLW-UHFFFAOYSA-N 0.000 description 1
- IICCLYANAQEHCI-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 IICCLYANAQEHCI-UHFFFAOYSA-N 0.000 description 1
- VEHBBQXEGOTTQX-UHFFFAOYSA-N 4-amino-2-ethylbenzaldehyde Chemical class CCC1=CC(N)=CC=C1C=O VEHBBQXEGOTTQX-UHFFFAOYSA-N 0.000 description 1
- FRXSZNDVFUDTIR-UHFFFAOYSA-N 6-methoxy-1,2,3,4-tetrahydroquinoline Chemical compound N1CCCC2=CC(OC)=CC=C21 FRXSZNDVFUDTIR-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 0 C**(C)(C)C(C=C1)=CC=CC1N Chemical compound C**(C)(C)C(C=C1)=CC=CC1N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 241001646716 Escherichia coli K-12 Species 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 244000168141 Geotrichum candidum Species 0.000 description 1
- 235000017388 Geotrichum candidum Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 1
- 108700028353 OmpC Proteins 0.000 description 1
- 108700006385 OmpF Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 206010041925 Staphylococcal infections Diseases 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- SURLGNKAQXKNSP-DBLYXWCISA-N chlorin Chemical compound C\1=C/2\N/C(=C\C3=N/C(=C\C=4NC(/C=C\5/C=CC/1=N/5)=CC=4)/C=C3)/CC\2 SURLGNKAQXKNSP-DBLYXWCISA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical class CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000002672 hepatitis B Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 244000144985 peep Species 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- 238000000013 phosphorescence detection Methods 0.000 description 1
- 230000000258 photobiological effect Effects 0.000 description 1
- 229940109328 photofrin Drugs 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940081623 rose bengal Drugs 0.000 description 1
- 229930187593 rose bengal Natural products 0.000 description 1
- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- YNHJECZULSZAQK-UHFFFAOYSA-N tetraphenylporphyrin Chemical compound C1=CC(C(=C2C=CC(N2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3N2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 YNHJECZULSZAQK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- 150000004992 toluidines Chemical class 0.000 description 1
- ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N verteporfin Chemical compound C=1C([C@@]2([C@H](C(=O)OC)C(=CC=C22)C(=O)OC)C)=NC2=CC(C(=C2C=C)C)=NC2=CC(C(=C2CCC(O)=O)C)=NC2=CC2=NC=1C(C)=C2CCC(=O)OC ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N 0.000 description 1
- 229960003895 verteporfin Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/18—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to carbon atoms of six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a water-soluble anionic benzylidene naphthene ketone photosensitizer, a preparation method thereof and application thereof in photodynamic antimicrobial infection. The photosensitizer has the advantages of simple molecular structure, easy synthesis, good solubility in water, proper lipid-water distribution ratio, strong absorption in the wavelength range of 350-600 nm, and capability of rapidly generating active oxygen substances under the irradiation of a light source in the waveband. Can be better applied to the infection of microorganisms such as photodynamic antibacterial, fungi or viruses.
Description
Technical field
The present invention relates to sensitising agent and its application.More particularly, to a kind of water soluble anion benzal cycloalkane ketone
Sensitising agent, preparation method and its application in light power anti-microbial infection.
Background technology
In recent years, with the aggravation of environmental pollution, the health of people is threatened by increasing pathogenic microorganism.Though
Right antibiotic has significant therapeutic effect to numerous cause pathogeny imcrobe infections, but because the unreasonable of a large amount of antibiotic uses, is permitted
Many pathogenic microorganisms under ambient pressure, drug resistance are generated to antibiotic, have been made a variation (also known as " super thin into multi-drug resistant bacteria
Bacterium ").The new antibiotic of exploitation although people just try one's best, it researches and develops the variation that speed lags far behind pathogenic microorganism
Speed.2015, U.S. government disclosed the national plan of action of 5 years by a definite date, and plan significantly cuts down that antibiotic is improper to be made
With accelerating to research and develop other therapies, with the threat for the bacterium antibiotic-resistant for tackling " urgent and serious ".
At present, photodynamic therapy anti-microbial infection (antimicrobial photodynamic therapy, aPDT)
The sterilization of blood product is clinically mainly used in, particularly the inactivation to virus.In addition, in the department of stomatology, orthopaedics and skin
In the intractable local infection such as section, aPDT also plays outstanding role, it is considered to be particularly suitable for treatment oral cavity bacterium and
The new method of fungal infection.(Chemical SocietyReviews,2002,31,128-136；Photochemical&
Photobiological Sciences,2004,3,412-418)。
Sensitising agent, as the key element of aPDT processes, is always researchers' focus of attention.It is clinical at present common
Multi-drug resistant bacteria is based on Gram-negative bacteria, due to its surface compact and negatively charged, usual only cation sensitising agent energy
Produce obvious aPDT effects to it, thus in electropositive cationic sensitising agent turn into current sensitising agent under physiological ph
Design, the main flow of synthesis and research；In contrast to this, because generally, neutral and anionic sensitising agent inactivates gram
The effect of negative bacterium can not show a candle to the effect that it inactivates gram-positive bacteria, therefore, in research in recent years, based on neutral and cloudy
The research of design, synthesis and the application of ionic sensitising agent is die-offed.
But also there is special example, studies have found that anion sensitising agent such as rose-red (rose bengal) inactivation leather is blue
The effect of family name's negative bacterium can be better than cation sensitising agent such as methylenum careuleum (methylene blue), malachite green (malachite
Green) etc.；And when resisting multi-drug resistant bacteria MRSA, the antibacterial effect of rose-red is even more far superior to existing a variety of photosensitive
Agent, such as cation sensitising agent：Crystal violet (crystal violet), new methylene blue (new methylene blue), toluidines
Blue (toluidine blue-O), methylenum careuleum (methylene blue)；Anion sensitising agent：Erythrosine (erythrosine),
Chlorin e 6 (NPe6).Illustrate in addition to light power produces reactive oxygen species inactivation of pathogenic microorganism, by between positive and negative charge
Electrostatic interaction upset and interrupt pathogenic microorganism membrane structure antibacterial mechanisms be not to realize efficient aPDT only
One means.
Yoshimura and Nikaido is in " Diffusion of beta-lactam antibiotics through the
porin channels of Escherichia coli K-12”Antimicrobial Agents and
Point out there is PFP to lead on the surface of Gram-negative bacteria in Chemotherapy, 1985, vol.27, pp84-92 article
Road (porin channels), the water soluble molecules that molecular weight is less than 600~700 dalton (Da) can be blue by leather by this passage
Family name's negative bacterium intake (almost all of beta-lactam antibiotic has this mechanism).Therefore, by this intake mechanism, it is cloudy from
Sub- sensitising agent is possible to realize and gram-positive bacteria and Gram-negative bacteria is effectively inactivated.Based on this, anionic
Sensitising agent is also once by extensive concern, but up to the present, except rose-red, blood porphyrin sensitising agent (such as HpD, photofrin
And verteporfin) etc. a few anionic sensitising agent, it is other to the significant anion of Gram-negative bacteria aPDT effects
The research of type sensitising agent is also rarely reported so far.
Benzal cycloalkane ketone structure is the raw material or functional group of many medicines and biological products synthesis, with good
Medicines structure basis, meanwhile, it has good photosensitive activity, by introducing the benzal prepared by water soluble anionic groups
Cycloalkane ketone sensitising agent can efficiently trigger the photopolymerization of water-soluble monomer, also with the antineoplastic function (Journal of light power
of Photochemistry and Photobiology A:Chemistry,2009,202,74-79；Journal of
Photochemistry and Photobiology A:Chemistry,2011,222,228-235).In the present invention, we
Attempt water soluble anionic benzal cycloalkane ketone sensitising agent first applied to grinding in terms of light power anti-microbial infection
Study carefully, achieve significant curative effect.
The content of the invention
First purpose of the present invention is to provide a class water soluble anion benzal cycloalkane ketone sensitising agent, such light
Quick agent molecule is simple in construction, synthesis easy, and solubility is good in water, with suitable fat moisture proportioning, and 350~
There is stronger absorption in 600nm wave-length coverages, reactive oxygen species can be quickly produced under light source irradiation.
Second object of the present invention is to provide a kind of preparation of water soluble anion benzal cycloalkane ketone sensitising agent
Method, this preparation method is simple, and product yield is high, purity is high.
Third object of the present invention is that provide a kind of water soluble anion benzal cycloalkane ketone sensitising agent moves in light
Resist the application in microorganism infection strenuously.
To reach above-mentioned first purpose, the present invention uses following technical proposals：
The present invention provides a kind of water soluble anion benzal cycloalkane ketone sensitising agent, with following structural formula C1, C2 or
C3：
Wherein：R1For methyl, ethyl, propyl group or isopropyl, it is preferable that R1For methyl or ethyl；
R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R2
For methyl, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3
For methyl, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone.
Preferably, water soluble anion benzal cycloalkane ketone sensitising agent of the present invention has in 350~600nm wave-length coverages
Higher biological photodynamic activity.
To reach above-mentioned second purpose, the present invention uses following technical proposals：
The present invention provides a kind of system of the water soluble anion benzal cycloalkane ketone sensitising agent with aforementioned structural formula C1
Preparation Method, comprises the following steps：
1) in distilled water under the conditions of basic hydrolysis agent, by commercially available formula Q1 compounds
Hydrolysis, collects obtained formula Q2 intermediate products
Reaction equation is as follows：
Concretely comprise the following steps：It is 1 in molar ratio by commercially available formula Q1 compounds and basic hydrolysis agent：1~1：50
Ratio is added in reaction vessel；Distilled water is added into system to dissolve basic hydrolysis agent, is started after system is stirred
Heating, reaction mixture flows back 4~20 hours in 100 DEG C；Reaction terminates rear system natural cooling, and suction filtration removes insoluble matter, obtained
Filtrate；Acid solution is added dropwise until without Precipitation into filtrate under stirring condition；By sediment suction filtration and wash three times,
Precipitation is then neutralized to alkaline solution to disappear just, vacuum rotary steam solution, and be dried to obtain formula Q2 intermediate products；
Wherein, step 1) and step 1) specific steps in, basic hydrolysis agent be lithium hydroxide, sodium hydroxide or hydroxide
One or more in potassium；
Acid solution is the one or more in formic acid, acetic acid, propionic acid, hydrochloric acid or sulfuric acid；The concentration of the acid solution
For 0.01~3mol L-1；
Alkaline solution is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate, potassium carbonate
Or the one or more in saleratus；The concentration of the alkaline solution is 0.01~3molL-1；
2), will in ethanol-water solution under the conditions of base catalystWith commercially available formula Q3 compounds
Reaction, collects obtained formula Q4 intermediate products
Reaction equation is as follows：
Concretely comprise the following steps：WillWith commercially available formula Q3 compounds in molar ratio 1：1~10：1 ratio is added
Into reaction vessel, 10~500 times of ethanol-water solution is added into above-mentioned system, and (volumn concentration of wherein ethanol is
20%~80%), the base catalyst of catalytic amount is added, is reacted 2~48 hours under the conditions of -5~100 DEG C, solvent is removed,
Then the isolated formula Q4 intermediate products of silicagel column are used；
Wherein, above-mentioned steps 2) and step 2) specific steps in,
The base catalyst be lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate,
One or more in potassium carbonate, saleratus, pyridine or hexahydropyridine；
3) in methanol-water solution under the conditions of base catalyst, by step 2) gained Q4 and step 1) gained Q2 massages
You compare 1:1~1:2 ratio is reacted, and collects obtained structural formula C1 compounds；
Or,
, will in methanol-water solution under the conditions of base catalystWith step 1) gained Q2 in molar ratio 1:2~1:
10 ratio is reacted, and collects obtained structural formula C1 compounds；
Reaction equation is：
Concretely comprise the following steps：By step 2) obtained by Q4 and step 1) made from Q2 according to mol ratio 1:1~1：2 ratio adds
Enter reaction vessel, 10~500 times of methanol-water solutions are added into above-mentioned system, and (wherein the volumn concentration of methanol is 20%
~90%), the base catalyst of catalytic amount is added, is reacted 2~36 hours under the conditions of 20~120 DEG C, solvent is removed, then
Using the isolated structural formula C1 compounds of silicagel column；
Or,
WillWith step 1) made from Q2 according to mol ratio 1：2~1：10 ratio adds reaction vessel, to above-mentioned body
The methanol-water solution (wherein the volumn concentration of methanol is 20%~90%) of 10~500 times of addition in system, adds catalysis
The base catalyst of amount, reacts 2~48 hours under the conditions of 0~100 DEG C, solvent is removed, using the isolated target of silicagel column
Product C1-I compounds；
Wherein：Above-mentioned steps 3) and step 3) specific steps in,
The base catalyst be lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate,
One or more in potassium carbonate or saleratus；
Wherein：Above-mentioned steps 1) -3) in, R1For methyl, ethyl, propyl group or isopropyl, it is preferable that R1For methyl or ethyl；
R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R2
For methyl, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3
For methyl, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone.
The present invention provides a kind of system of the water soluble anion benzal cycloalkane ketone sensitising agent with aforementioned structural formula C2
Preparation Method, comprises the following steps：
1., will in ethanol-water solution under the conditions of base catalystWith commercially available formula Q3 compounds
Reaction, collects obtained formula Q4 intermediate products
Reaction equation is：
Concretely comprise the following steps：WillWith commercially available formula Q3 compounds in molar ratio 1：1~10：1 ratio is added
Into reaction vessel, 10~500 times of ethanol-water solution is added into above-mentioned system, and (volumn concentration of wherein ethanol is
20%~80%), the base catalyst of catalytic amount is added, is reacted 2~48 hours under the conditions of -5~100 DEG C, solvent is removed,
Then the isolated formula Q4 intermediate products of silicagel column are used；
Wherein, above-mentioned steps are 1. and in step specific steps 1.,
The base catalyst is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate sodium acid carbonate, carbon
One or more in sour potassium, saleratus, pyridine or hexahydropyridine；
2. in methanol-water solution under the conditions of base catalyst, by Q4 and commercially available 4- formylphenyls -3- aminopropans
Sour S1
Reaction, collects obtained formula S2 intermediate products
Reaction equation is：
Concretely comprise the following steps：By Q4 and commercially available S1 in molar ratio 1：1~1：2 ratio is added in reaction vessel,
The methanol-water solution (wherein the volumn concentration of methanol is 20%~90%) of 10~500 times of the addition into above-mentioned system, then
The base catalyst of catalytic amount is added, is reacted 2~36 hours under the conditions of 20~100 DEG C, solvent is removed, then using silicagel column
Isolated formula S2 intermediate products；
Wherein, above-mentioned steps are 2. and in step specific steps 2.,
The base catalyst be lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate,
One or more in potassium carbonate or saleratus；
3. under the conditions of acid solution, by step 2. gained S2 and propylene acid reaction, obtained structural formula C2 chemical combination is collected
Thing；
Reaction equation is：
Concretely comprise the following steps：By step 2. in obtained S2 according to mass ratio be 1：1~1：1000 ratio is dissolved in acid molten
In liquid, after stirring certain time, the acrylic acid that volume is 1~10 times of acid solution volume is added into above-mentioned system, by solution
Temperature rises to 60~100 DEG C, and is reacted 4~36 hours under the protection of inert gas, and reaction solution is cooled to suction filtration after room temperature, filter
Visible a large amount of Precipitations after being stirred 3~12 hours under appropriate distilled water, ice bath are added in liquid, sediment is neutralized with alkaline solution
Disappeared just to precipitating, then above-mentioned solution is added in ethanol in proper amount, separated out solid under ice bath, obtain target product structural formula
C2 compounds；
Wherein, above-mentioned steps are 3. and in step specific steps 3., and the acid solution is formic acid, acetic acid, propionic acid, hydrochloric acid
Or the one or more in sulfuric acid, the concentration of the acid solution is 0.01~3mol L-1；
The alkaline solution is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate, carbon
One or more in sour potassium or saleratus, the concentration of the alkaline solution is 0.01~3mol L-1；
Wherein, above-mentioned steps 1. -3. in, R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group
Or-CH2CH2-COO-X, it is preferable that R2For methyl, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3
For methyl, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone.
The present invention provides a kind of system of the water soluble anion benzal cycloalkane ketone sensitising agent with aforementioned structural formula C3
Preparation Method, comprises the following steps：
A), will in distilled water under the conditions of base catalystWith commercially available 4- formylphenyls -3- aminopropans
Sour S1
Reaction, collects obtained formula T1 intermediate products
Reaction equation is as follows：
Concretely comprise the following steps：WillWith commercially available S1 according to mol ratio 1：2~1：10 ratio adds reaction vessel,
Into above-mentioned system, the distilled water of 10~500 times of addition, adds the base catalyst of catalytic amount, anti-under the conditions of 0~100 DEG C
Answer 2~48 hours, solvent is removed, using the isolated intermediate product T1 of silicagel column；
Wherein, in above-mentioned steps a) and step a) specific steps,
The base catalyst be lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate,
One or more in potassium carbonate or saleratus；
B) under the conditions of acid solution, by T1 obtained by step a) and propylene acid reaction, collection obtains structural formula C3 compounds；
Reaction equation is：
Concretely comprise the following steps：According to mass ratio it is 1 by the T1 of gained in step a):1~1：1000 ratio is dissolved in acid molten
In liquid, after stirring, the acrylic acid that volume is 1~30 times of acid solution volume is added into above-mentioned system, solution temperature is risen to
60~100 DEG C, and reacted 4~48 hours under the protection of inert gas；Reaction solution is cooled in suction filtration after room temperature, filtrate and added
Visible a large amount of Precipitations after being stirred 3~12 hours under appropriate distilled water, ice bath, it is proper that sediment is neutralized to precipitation with alkaline solution
It is good to disappear, then above-mentioned solution is added in ethanol in proper amount, solid is separated out under ice bath, target product structural formula C3 chemical combination is obtained
Thing；
Wherein, in above-mentioned steps b) and step b) specific steps, the acid solution is formic acid, acetic acid, propionic acid, hydrochloric acid
Or the one or more in sulfuric acid, the concentration of the acid solution is 0.01~3mol L-1；
The alkaline solution is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate, carbon
One or more in sour potassium or saleratus, the concentration of the alkaline solution is 0.01~3mol L-1；
Wherein, above-mentioned steps a)-b) in, the X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone.
In the application in the preparation method of water soluble anion benzal cycloalkane ketone sensitising agent, above-mentioned formula Q1 chemical combination
Thing, formula Q3 compounds, S1 etc. are commercially available, unless otherwise specified, are commercially available gained.
To reach above-mentioned 3rd purpose, the present invention uses following technical proposals：
Application of the water soluble anion benzal cycloalkane ketone sensitising agent of the present invention in light power anti-microbial infection.
Preferably, the microorganism refers to bacterium, fungi or virus.
Further, the bacterium is gram-positive bacteria or Gram-negative bacteria；The gram-positive bacteria is selected from gold
Staphylococcus aureus, methicillin-resistant staphylococcus aureus, streptococcus, Diplococcus pneumopniae, bacillus anthracis, corynebacterium diphtheriae or broken
Cold bacillus；The Gram-negative bacteria is selected from Escherichia coli, shigella dysenteriae, typhoid bacillus, proteus or Bordetella pertussis.
Further, the fungi is selected from the female bacterium of mould, saccharomycete, beer, monascin, Candida, Candida albicans
Bacterium, aspergillus flavus, geotrichum candidum or antibiotic bacteria.
Further, the virus is selected from bacteriophage, tobacco mosaic virus (TMV), avian influenza virus, variola virus, HIV, A type
Hepatitis B virus hepatitis viruse, rubella virus or MERS viruses.
Preferably, the OPK irradiation light is laser, LED light or simulated solar irradiation.
Further, simulated solar irradiation is obtained by the solar simulators of Oriel 91192, commercially available, is such as purchased from U.S.'s reason
Ripple company, model Oriel 91192.
Further, the wavelength of the irradiation light is 350~600nm；The light application time of the irradiation light is 30 seconds~1 small
When, intensity of illumination is 5~1000mW/cm2。
Preferably, the minimum inhibitory concentration of the water soluble anion benzal cycloalkane ketone sensitising agent is 0.001~100
μM。
Preferably, the PFP for water soluble anion benzal cycloalkane ketone sensitising agent being activated into Gram-negative bacteria leads to
Road, inactivates Gram-negative bacteria.
The present invention provides a kind of water soluble anion sensitising agent by activating the PFP passage of Gram-negative bacteria, realizes
The new approaches that Gram-negative bacteria is effectively inactivated.
Further, described water soluble anion sensitising agent effectively inactivate Gram-negative bacteria new approaches refer to it is water-soluble
Property anion sensitising agent effectively activate PFP passage, intake of the Gram-negative bacteria to sensitising agent is improved, so that maximum journey
The light power inactivation Gram-negative bacteria of degree.
Further, the PFP passage refers to the protein that a class is present on Gram-negative bacteria outer membrane.This
Proteinoid act as the molecular filter of hydroaropic substance, play a part of on outer membrane " molecular sieve ".These albumen are generated
The passage for filling water can allow hydroaropic substance enter periplasmic space in.The diffusion paths of cell channels albumen generation can allow greatly
The solute of the small exclusion limit of size passes through, and other then have specific binding site in duct, can only allow a kind of molten
Matter passes through.PFP passage is a kind of main protein on bacterial outer membrane, it is highly preferred that PFP passage is logical for outer membrane protein
Road OmpF, outer membrane protein passage OmpC and outer membrane protein passage PhoE.
Beneficial effects of the present invention are as follows：
1. water soluble anion benzal cycloalkane ketone sensitising agent in the present invention is simple in construction, molecular weight is small, with true
Fixed chemical constitution, it is easy to prepare, purify and further modify, meets the basic demand of clinical application.
2. the characteristics of water soluble anion benzal cycloalkane ketone sensitising agent in the present invention has fat water parents, its fat water
Distribution ratio disclosure satisfy that the use requirement of clinical optical dynamic therapy.
3. the synthetic method of the water soluble anion benzal cycloalkane ketone sensitising agent in the present invention has simple to operate, production
The characteristics of product yield is high, purity is high, can high-volume synthesize.
4. the water soluble anion benzal cycloalkane ketone sensitising agent in the present invention has in 350~600nm wave-length coverages
Higher biological photodynamic activity, has good application prospect as photo-dynamical medicine inactivation of pathogenic microorganism aspect.
5. the water soluble anion benzal cycloalkane ketone sensitising agent in the present invention can realize bacterium, fungi and virus
Effective light inactivation.
6. the water soluble anion benzal cycloalkane ketone sensitising agent in the present invention can activate the hole of Gram-negative bacteria
Protein channel, realizes and effective light of Gram-negative bacteria is inactivated.
Brief description of the drawings
The embodiment to the present invention is described in further detail below in conjunction with the accompanying drawings.
Fig. 1 shows photosensitizer concentration schematic diagram in light power inactivation Staphylococcus aureus bacillus, 96 orifice plates of Escherichia coli.
Fig. 2 shows experimental result of the obtained sensitising agent applied to light power colibacillus deactivating in embodiment 1.
Fig. 3 shows obtained uv-visible absorption spectra and fluorescent emission of the sensitising agent in chloroform in embodiment 3
Spectrum.
Fig. 4 shows that obtained sensitising agent is applied to the experimental result that light power inactivates staphylococcus aureus in embodiment 4.
Fig. 5 shows that obtained sensitising agent is applied to the experimental result before and after light power inactivation Candida albicans in embodiment 6.
Fig. 6 shows obtained uv-visible absorption spectra and fluorescent emission of the sensitising agent in chloroform in embodiment 7
Spectrum.
Fig. 7 shows that obtained sensitising agent is applied to the experiment knot that observation protein channel influence sensitising agent is absorbed in embodiment 11
Really.
Embodiment
In order to illustrate more clearly of the present invention, the present invention is done further with reference to preferred embodiments and drawings
It is bright.Similar part is indicated with identical reference in accompanying drawing.It will be appreciated by those skilled in the art that institute is specific below
The content of description is illustrative and be not restrictive, and should not be limited the scope of the invention with this.
Embodiment 1
Water-soluble benzal cycloalkane ketone sensitising agent C1-1 preparation：
(I) sodium hydroxide (0.14mol, 5.60g) and commercially available N- ethyls-N- cyanogen are added in 500mL there-necked flasks
Ethyl -4- aminobenzaldehydes (0.04mmol, 8.08g), 120mL distilled water is added into above-mentioned system.Start after stirring
Temperature reaction mixed liquor, flows back 4 hours in 100 DEG C.Reaction terminates rear system natural cooling, and suction filtration removes insoluble matter.Under stirring
Watery hydrochloric acid (0.5mol L are added dropwise into filtrate-1) until without Precipitation.By sediment suction filtration and wash three times, then use
0.1mol L-1Sodium hydroxide solution be neutralized to precipitation just disappear.Vacuum rotary steam solution, is dried to obtain product Q2-1, yield
For 96%,
(II) 8.85 grams of (0.05mol) commercially available N, N- lignocaines are added into 100 milliliters of three-necked flasks
Benzaldehyde, 3.52 grams of (0.05mol) cyclobutanones, adding 50 milliliters of ethanol-water solutions, (volumn concentration of wherein ethanol is
80%), stirring makes it disposably add 0.05 gram of sodium hydroxide after being uniformly dissolved, and ice bath reacts 10 hours, and reaction solution is through revolving
Remove solvent and obtain crude product, obtain orange solids Q4-1 with chromatographic column separating-purifying, yield 50%,
(III) 2.29 grams of (0.01mol) Q4-1,2.43 grams (0.01mol) are added into 100 milliliters of three-necked flasks
Q2-1, adds 30 ml methanols-aqueous solution (wherein the volumn concentration of methanol is 70%), it is latter that stirring is uniformly dissolved it
Secondary property adds 0.03 gram of sodium hydroxide, stirs 12 hours at room temperature, and removing solvent through revolving obtains crude product, uses chromatogram post separation
Purification obtains target product C1-1, yield 80%.HR-MS(ESI):[M]+:Calcd for[C27H33N2O3+2H+]+
435.2497；Found 435.2339,
Water-soluble benzal cycloalkane ketone sensitising agent C1-1 is used for light power colibacillus deactivating：
(IV) commercially available Escherichia coli are recovered in broth bouillon, determined by determining 600nm absorbance
The concentration of bacterium.Then, minimum inhibitory concentration (minimum inhibitory are carried out using 96 sterile orifice plates
Concentration, MIC) measure, see accompanying drawing 1.Added by every four adjacent holes in 96 orifice plates, such as C1, C2, D1 and D2
Photosensitizer concentration is identical.According to concentration shown in schematic diagram, the meat soup that 100 microlitres of different photosensitizer concentrations are added per hole is molten
Liquid.Wherein, negative control group is B+B groups (Escherichia coli that 10 microlitres are added in 100 microlitres of meat soups), and positive controls are GM groups
(100 microlitres of meat soups add 1% gentamicin), blank control group is that Broth groups (add 10 microlitres in 100 microlitres of meat soups
PBS).Bacterial concentration in above-mentioned 96 orifice plate is about 5 × 105Every milliliter of CFU.Utilize 532nm laser (50mW/cm2,10min)
Irradiate after above-mentioned 96 orifice plate, be put into bacteriological incubator and continue to cultivate 18 hours.Then it is molten using 0.0675% resazurin sodium salt
Liquid is developed the color.By the chromogenic reaction of 4 hours, liquid color was not changed into photosensitive corresponding to pink colour from blueness in 96 orifice plates
Agent concentration is minimum inhibitory concentration, and minimum inhibitory concentration is 1.0 μm, sees accompanying drawing 2.
Embodiment 2
Water-soluble benzal cycloalkane ketone sensitising agent C1-2 preparation：
The preparation method of be the same as Example 1, its difference is, cyclobutanone in step (II) is changed into cyclopentanone, remaining condition
It is constant, prepare target product C1-2, yield 85%, HR-MS (ESI):[M]+:Calcd for[C28H35N2O3+2H+]+
449.2653；Found 449.2660,
Water-soluble benzal cycloalkane ketone sensitising agent C1-2 is used for light power and inactivates staphylococcus aureus：
Application process (IV) in be the same as Example 1, difference is, Escherichia coli are changed into commercially available golden yellow grape
Coccus, remaining condition is constant, and income effect is close with embodiment 1.
Embodiment 3
Water-soluble benzal cycloalkane ketone sensitising agent C1-3 preparation：
The preparation method of be the same as Example 1, its difference is, cyclobutanone in step (II) is changed into cyclohexanone, remaining condition
It is constant, prepare target product C1-3, yield 63%, HR-MS (ESI):[M]+:Calcd for[C29H37N2O3+2H+]+
463.2810；The uv-visible absorption spectra and fluorescence emission spectrum of found 463.2885, C1-3 in chloroform are shown in attached
Fig. 3, illustrates that sensitising agent C1-3 has stronger absorption in 350~600nm wave-length coverages, has and can quickly produce under light source irradiation
The ability of reactive oxygen species；From the point of view of uv-visible absorption spectra and fluorescence emission spectrum, sensitising agent C1-3 is on this condition
Exist with either as singular molecular entities, the reactive oxygen species without aggregation, therefore prediction generation will not be quenched because of aggregation problem.
Water-soluble benzal cycloalkane ketone sensitising agent C1-3 is used for light power and inactivates methicillin-resistant staphylococcus aureus：
Application process (IV) in be the same as Example 1, difference is, Escherichia coli are changed into commercially available methicillin-resistant
Staphylococcus aureus, remaining condition is constant, and income effect is close with embodiment 1.
Embodiment 4
Water-soluble benzal cycloalkane ketone sensitising agent C1-4 preparation：
The preparation method of be the same as Example 1, its difference is that, by step (I), sodium hydroxide changes hydrogen-oxygen agent, hydrogen-oxygen into
Change sodium solution and change potassium hydroxide solution into, remaining condition is constant, prepares target product C1-4, yield 78%.HR-MS
(ESI):[M]+:Calcd for[C27H33N2O3+2H+]+435.2340；found 435.2369.
Water-soluble benzal cycloalkane ketone sensitising agent C1-4 is used for light power and inactivates staphylococcus aureus：
Application process (IV) in be the same as Example 1, difference is, changes Escherichia coli into staphylococcus aureus, will swash
Light is changed to 515nm LED light (20mW/cm2, 20min), and after LED light 96 orifice plates of irradiation, with 0.0675% resazurin sodium salt
Solution is developed the color, and remaining condition is constant, and it is 2.0 μm to determine minimum inhibitory concentration, sees accompanying drawing 4.
Embodiment 5
Water-soluble benzal cycloalkane ketone sensitising agent C1-5 preparation：
The preparation method of be the same as Example 4, its difference is, cyclobutanone in step (II) is changed into cyclooctanone, remaining condition
It is constant, prepare target product C1-5, yield 55%, HR-MS (ESI):[M]+:Calcd for[C31H41N2O3+2H+]+
491.3123；found 491.3321.
Water-soluble benzal cycloalkane ketone sensitising agent C1-5 is used for light power and inactivates methicillin-resistant staphylococcus aureus：
Be the same as Example 4, difference is, staphylococcus aureus is changed into methicillin-resistant staphylococcus aureus, other
Condition is constant, and income effect is close with embodiment 4.
Embodiment 6
Water-soluble benzal cycloalkane ketone sensitising agent C2-1 preparation：
(I) 8.85 grams of (0.05mol) commercially available N, N- diethylanilines are added into 100 milliliters of three-necked flasks
Formaldehyde, 3.52 grams of (0.05mol) cyclobutanones, adding 40 milliliters of ethanol-water solutions, (volumn concentration of wherein ethanol is
80%), stirring makes it disposably add 0.05 gram of sodium hydroxide after being uniformly dissolved, and ice bath reacts 10 hours, and reaction solution is through revolving
Remove solvent and obtain crude product, orange solids Q4-1, yield 50% are obtained with chromatographic column separating-purifying.
(II) with reference to the operation of (III) in embodiment 1,2.29 grams are added into 100 milliliters of three-necked flasks
(0.01mol) Q4-1 and commercially available 4- formylphenyls -3- alanine S1 mass are 1.93 grams (0.01mol), and solvent is
Methanol-water solution (wherein the volumn concentration of methanol is 60%), stirring makes its disposable 0.10 gram of addition after being uniformly dissolved
Lithium hydroxide, reacts 12 hours under the conditions of 50 DEG C, and removing solvent through revolving obtains crude product, is obtained with chromatographic column separating-purifying
Target product obtains S2-1, yield 85%,
(III) S2-1 (2.0mmol, 0.82g) is dissolved in 7mL dilution heat of sulfuric acid (1mol L-1), after stirring 20 minutes
Add 50mL acrylic acid.Solution is warming up to 85 DEG C, in N2The lower reaction of protection 10 hours, reaction solution is cooled to suction filtration after room temperature, filter
Liquid is added in 300mL distilled water, visible a large amount of Precipitations after ice bath is stirred 3 hours.Sediment 0.1mol L-1Hydrogen-oxygen
Change lithium solution and be neutralized to precipitation disappearance just, obtained aqueous solution is added in 400mL ethanol, and ice bath separates out solid after stirring 3 hours
Body, and drying is washed, obtain target product C2-1, yield 39%.HR-MS(ESI):[M]+:Calcd for[C28H30N2O5+3H+]+477.2166；found 477.2188.
Water-soluble benzal cycloalkane ketone sensitising agent C2-1 is used for light power and inactivates Candida albicans：
Take 1 microlitre of Candida albicans bacterium solution to be inoculated into Sabouraud dextrose broth bouillon, cultivate 48~72 hours.Take 1
×105The sensitising agent of various concentrations is added in every milliliter of Candida albicans solution of CFU, the ultimate density of sensitising agent micro- is rubbed for 25
That, 50 micromoles and 100 micromoles.After intake 1 hour, 532nm (40mW/cm are utilized2, 10min) laser.It is flat using coating
Colony count under plate method, observation various concentrations, determines the antifungal activity of sensitising agent, sees accompanying drawing 5, as can be seen from the figure add
Enter sensitising agent to carry out after light power antibacterial, the clump count of Candida albicans is significantly reduced, and illustrates that the antibacterial activity of sensitising agent is good.
Embodiment 7
Water-soluble benzal cycloalkane ketone sensitising agent C2-2 preparation：
The preparation method in embodiment 6 is repeated, difference is, the cyclobutanone in step (I) is changed into cycloheptanone, remaining
Part is constant, prepares target product C2-2, yield 29%, HR-MS (ESI):[M]+:Calcd for[C31H36N2O5+3H+]+
519.2635；The uv-visible absorption spectra and fluorescence emission spectrum of found 519.2677, gained C2-2 in chloroform
See accompanying drawing 6, illustrate that sensitising agent C2-2 has stronger absorption in 350~600nm wave-length coverages, having under light source irradiation can be quick
Produce the ability of reactive oxygen species；From the point of view of uv-visible absorption spectra and fluorescence emission spectrum, sensitising agent C2-2 is at this
Exist under part with either as singular molecular entities, the reactive oxygen species without aggregation, therefore prediction generation will not be quenched because of aggregation problem
Go out.
Water-soluble benzal cycloalkane ketone sensitising agent C2-2 is used for light power and inactivates Candida albicans：
Application process in embodiment 6 is repeated, difference is, by 532nm (40mW/cm2, 10min) laser change 515nm into
LED light (20mW/cm2, 20min), remaining condition is constant, and the antifungal activity performance of gained sensitising agent is close with embodiment 6.
Embodiment 8
Repeat embodiment 6, difference is, changes Candida albicans into mould, and remaining condition is constant, gained sensitising agent it is anti-
Mold activity performance is close with embodiment 6.
Embodiment 9
Water-soluble benzal cycloalkane ketone sensitising agent C2-3 preparation：
(1) step of embodiment 6 (I) is repeated, difference is, by 0.05molN, N- lignocaines benzaldehyde and 0.05mol rings
Butanone changes mol ratio 1 into:20 by method in above-described embodiment 1 prepare Q2-1 and cyclohexanone, and remaining condition is constant, prepare
Obtain intermediate product Q4-2 (yields：32%),
(2) with reference to the method for (III) in embodiment 1,3.23 grams are added into 100 milliliters of three-necked flasks
(0.01mol) Q4-1 and commercially available 4- formylphenyls -3- alanine S1 mass are 1.93 grams (0.01mol), add 50
Ml methanol-the aqueous solution (wherein the volumn concentration of methanol is 20%), stirring makes its disposable addition after being uniformly dissolved
0.05 gram of potassium hydroxide, reacts 24 hours under the conditions of 35 DEG C, and removing solvent through revolving obtains crude product, is carried with chromatogram post separation
The pure target product that obtains obtains C2-3, yield 66%.HR-MS(ESI):[M]+:Calcd for[C31H33N2O7+4H+]+
549.2304；Found 549.2311,
Water-soluble benzal cycloalkane ketone sensitising agent C2-3 is used for light power and inactivates tobacco mosaic virus (TMV)：
100 μ L various concentrations (0.125,0.25,0.5,1.0,2.0,4.0,8.0,16.0,32.0 and into 96 orifice plates
64.0 μM) photosensitizing agent solution in add appropriate tobacco mosaic virus (TMV) and ensure virus final concentration of 2x1011Pfu/mL,
Solar simulator (the 5mW/cm of Oriel 91192 that concussion and cultivate 30 minutes in dark are 550nm or so with wavelength2,
After 50min) irradiating, the mixed solution in 96 orifice plates is transferred in the agar disks containing culture medium, calculated with colony counting method
The survival rate of tobacco mosaic virus (TMV).Wherein, the bacteria suspension of the same concentration without sensitising agent is used as control group.As a result show, not
Same concentration (0.125,0.25,0.5,1.0,2.0,4.0,8.0,16.0,32.0 and 64.0 μM) under, relative to control group, tobacco
The survival rate of mosaic virus is respectively 100%, 96%, 93%, 89%, 80%, 70%, 55%, 34%, 11% and 0.1%.Say
Bright sensitising agent C2-3 can effectively inactivate tobacco mosaic virus (TMV).
Embodiment 10
Water-soluble benzal cycloalkane ketone sensitising agent C2-4 preparation：
The preparation method of embodiment 9 is repeated, difference is, makes the cyclobutanone of step (1) into cycloheptanone, remaining condition is not
Become, prepare target product C2-4, yield 45%, HR-MS (ESI):[M]+:Calcd for[C32H35N2O7+4H+]+
563.2461；found 563.2489.
Water-soluble benzal cycloalkane ketone sensitising agent C2-4 is used for light power and inactivates bacteriophage：
Repeat embodiment 9 application, difference is, makes tobacco mosaic virus (TMV) into bacteriophage, by the concentration in every hole from
2x1011Pfu/mL is changed to 2x105CFU mL-1.As a result show, various concentrations (0.125,0.25,0.5,1.0,2.0,4.0,
8.0th, 16.0,32.0 and 64.0 μM) under, relative to control group, the survival rate of bacteriophage is respectively 100%, 96%, 90%,
89%, 86%, 77%, 60%, 45%, 23% and 11%.Illustrate that sensitising agent C2-4 can effectively inactivate bacteriophage.
Embodiment 11
Water-soluble benzal cycloalkane ketone sensitising agent C3-1 preparation：
(1) with reference to the operation of (III) in embodiment 1, by cyclopentanone (0.42 gram, 5mmol) and commercially available 4- formyls
Phenyl -3- alanines S1 (3.86 grams, 20mmol) is according to mol ratio 1：4 ratio adds reaction vessel, adds 45 milliliters of first
Alcohol-water solution (wherein the volumn concentration of methanol is 30%), stirring makes its well mixed base catalyst that adds be 0.03
Gram potassium hydroxide, reacts 2 hours under the conditions of 70 DEG C, solvent is removed, using the isolated intermediate product T1-1 of silicagel column, yield
42%.
(2) with reference to the operation of (III) in embodiment 6, T1-1 (2.0mmol, 1.02g) is dissolved in 10mL dilution heat of sulfuric acid
In (2mol L-1), stirring adds 60mL acrylic acid after 40 minutes.Solution is warming up to 95 DEG C, in N2The lower reaction of protection 24 hours, instead
Liquid is answered to be cooled to suction filtration after room temperature, filtrate is added in 200mL distilled water, visible a large amount of Precipitations after ice bath is stirred 6 hours.
Sediment 0.5mol L-1Sodium hydroxide solution be neutralized to precipitation and disappear just, obtained aqueous solution is added to 300mL ethanol
In, ice bath separates out solid after stirring 6 hours, and washs drying, obtains target product C3-1, yield 80%.HR-MS(ESI):
[M]+:Calcd for[C31H30N2O9+5H+]+579.1973；Found 579.1973,
Water-soluble benzal cycloalkane ketone sensitising agent C2-4 is used for the activation of peep hole protein channel：
It is 10 to take concentration8CFU mL-1Escherichia coli solution 5mL, and add appropriate above-mentioned sensitising agent and regulation thereto
Its concentration is 10 μM, in the dark concussion intake 1 hour；The bacterium solution of the same concentration of control group is first 0.1% with mass concentration
Trypsase handles after 30 minutes (memebrane protein of destruction Escherichia coli, so as to upset the function of protein channel) in the dark, to
Wherein add appropriate above-mentioned sensitising agent and adjust its concentration for 10 μM, in the dark concussion intake 1 hour.Bacterium solution is centrifuged and obtained
Thalline and after being rinsed with PBS, cracks bacterium using 10% lauryl sodium sulfate (SDS), observes it by fluorescence intensity and take the photograph
The difference of taken amount, determines whether protein channel is activated, and sees accompanying drawing 7, it is seen that when the protein channel of control group is broken
After bad, bacterium substantially reduces to the intake of sensitising agent, illustrates that sensitising agent C2-4 can enter bacterium by activating PFP passage
Cell.
Embodiment 12
Embodiment 11 is repeated, difference is, makes cyclopentanone into cyclobutanone, and remaining condition is constant, prepare target production
Thing C3-2, yield 77%, HR-MS (ESI):[M]+:Calcd for[C30H28N2O9+5H+]+565.1817；found
565.1834。
Embodiment 13
Obtained sensitising agent in embodiment 1~12 is used for the determination experiment of solubility：
To determine the maxima solubility of sensitising agent, 10,50,100,500,1000 and 3000 μ g/mL sensitising agent is first configured
And its uv-visible absorption spectra is determined, obtain the standard curve that concentration is mapped to absorption maximum peak position absorbance.Determine light
The absorbance of quick dose of PBS saturated solution, and it is most to find its corresponding concentration on the standard curve of concentration-absorbance
Big solubility.When absorbance exceedes range, suitable multiple can be diluted with PBS, determine its absorbance and extrapolate maximum suction
Luminosity, is shown in Table 1.
Embodiment 14：
Obtained sensitising agent in embodiment 1~12 is used for the determination experiment that fat moisture is matched：
10 micromolar sensitising agents are dissolved in 2mL PBS, 2mL n-octyl alcohols is then added, mixed solution is shaked into 3min,
It is placed in again in ultrasonic wave and vibrates 5min, is then centrifuged 5 minutes under 5000 turns per minute of speed, make two-phase laminated flow.Determine two
The abosrption spectrogram of sensitising agent in phase, is calculated by Lambert-beer laws and obtains concentration of the sensitising agent in two-phase, fat
Moisture proportioning (Log PC) is concentration proportion of the sensitising agent in two-phase, is shown in Table 1.
Embodiment 15：
Obtained sensitising agent in embodiment 1~12 is used for the determination experiment of singlet oxygen quantum yield
Singlet oxygen quantum yield is tested using phosphorescence detection method, and reference is (single for the chloroform soln of tetraphenylporphyrin
0.5) line state oxygen quantum yield is.At room temperature, singlet oxygen phosphorescent emissions are near 1270nm, in this spectral region, no
It can be influenceed by exciting light.473nm diode lasers are used for light source, (NIR-512L-1.7T1 is surveyed near infrared spectrometer
Measure scope 900-1684nm) it is detecting system, using relative measurement, testing sample or reference are dissolved in chloroform, made
It is consistent in 473nm absorbances.Prepare liquid is placed in cuvette, detects that the singlet oxygen of generation exists under laser irradiation
Solution keeps being stirred vigorously fully contacting with air in phosphorescence emission intensity at 1270nm, test process.Singlet oxygen quantum
The data of yield are shown in Table 1.
Embodiment 16：
(I) operation of step (I) in embodiment 1 is repeated, difference is N- ethyl-N-cyanoethyl -4- aminobenzaldehydes
Change commercially available N- methyl-N- cyanoethyl -4- aminobenzaldehydes into, other conditions are constant, obtain product Q2-2, yield is
80%,
By Q2-2 (2.29 made from Q4-2 (3.23 grams, 0.01mol) made from step (I) in embodiment 9 and step (I)
Gram, 0.01mol) according to mol ratio 1:1 ratio adds reaction vessel, and 40 grams of methanol-water solution is added into above-mentioned system
(methanol percent by volume is 35%), adds 0.06 gram of lithium hydroxide, is reacted 4 hours under the conditions of 50 DEG C, remove solvent, so
The isolated target product C1-6 of silicagel column, yield 89% are used afterwards.
Embodiment 17：
By Q2-1 made from (I) (2.43 grams, 0.01mol) the step of cyclobutanone (0.35 gram, 0.005mol) and embodiment 1
According to mol ratio 1：2 ratio adds reaction vessel, and 30 grams of methanol-water solution (methanol volume basis are added into above-mentioned system
Than 20%), to add 0.03 gram of sodium hydroxide, reacting 12 hours at ambient temperature, solvent is removed, using silica gel post separation
Obtain target product C1-7, yield 98%.
Maxima solubility, fat moisture proportioning and the singlet oxygen quantum yield of the different sensitising agents of table 1
Obviously, the above embodiment of the present invention is only intended to clearly illustrate example of the present invention, and is not pair
The restriction of embodiments of the present invention, for those of ordinary skill in the field, may be used also on the basis of the above description
To make other changes in different forms, all embodiments can not be exhaustive here, it is every to belong to this hair
Row of the obvious changes or variations that bright technical scheme is extended out still in protection scope of the present invention.
Claims (10)
1. water soluble anion benzal cycloalkane ketone sensitising agent, it is characterised in that with following structural formula C1, C2 or C3：
Wherein：R1For methyl, ethyl, propyl group or isopropyl, it is preferable that R1For methyl or ethyl；
R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R2For first
Base, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3For first
Base, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone.
2. a kind of preparation method of water soluble anion benzal cycloalkane ketone sensitising agent as claimed in claim 1, its feature
It is, structural formula is the preparation method of C1 sensitising agent, is comprised the following steps：
1) Q2 is synthesized, reaction equation is as follows：
Wherein：R1For methyl, ethyl, propyl group or isopropyl, it is preferable that R1For methyl or ethyl；
X is cation Li+、Na+Or K+；
Comprise the following steps that：
It is 1 in molar ratio by compound Q 1 and basic hydrolysis agent：1~1：50 ratio is added in reaction vessel；Into system
Appropriate distilled water is added to dissolve basic hydrolysis agent, is started to warm up after system is stirred, reaction mixture is returned in 100 DEG C
Stream 4~20 hours；Reaction terminates rear system natural cooling, and suction filtration is removed to be added dropwise under insoluble matter, stirring condition into filtrate
Acid solution by sediment suction filtration and is washed three times until without Precipitation, and precipitation is then neutralized to alkaline solution and is disappeared just
Lose, vacuum rotary steam solution, and be dried to obtain Q2；
2) Q4 is synthesized, reaction equation is as follows：
Wherein：R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that
R2For methyl, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3For first
Base, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
The X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone；
Comprise the following steps that：
WillWith compound Q 3 in molar ratio 1：1~10：1 ratio is added in reaction vessel, is added into above-mentioned system
10~500 times of ethanol-water solution, adds the base catalyst of catalytic amount, 2~48 is reacted under the conditions of -5~100 DEG C small
When, solvent is removed, then using the isolated Q4 of silicagel column；
3) C1 is synthesized, reaction equation is as follows：
Wherein：R1For methyl, ethyl, propyl group or isopropyl, it is preferable that R1For methyl or ethyl；
R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R2For first
Base, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3For first
Base, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone；
Concretely comprise the following steps：
By step 2) made from Q4 and step 1) made from Q2 according to mol ratio 1：1~1：2 ratio adds reaction vessel, upwards
The methanol-water solution of 10~500 times of addition in system is stated, the base catalyst of catalytic amount is added, under the conditions of 20~120 DEG C
Reaction 2~36 hours, removes solvent, then using the isolated target product C1 of silicagel column；
Or, willWith step 1) made from Q2 according to mol ratio 1：2~1：10 ratio adds reaction vessel, to above-mentioned system
10~500 times of methanol-water solutions of middle addition, add the base catalyst of catalytic amount, and 2~48 are reacted under the conditions of 0~100 DEG C
Hour, solvent is removed, using the isolated target product C1-I of silicagel column.
3. a kind of preparation method of water soluble anion benzal cycloalkane ketone sensitising agent as claimed in claim 1, its feature
It is, structural formula is the preparation method of C2 sensitising agent, is comprised the following steps：
1. Q4 is synthesized, reaction equation is as follows：
Wherein：R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that
R2For methyl, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3For first
Base, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
The X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone；
Comprise the following steps that：
WillWith compound Q 3 in molar ratio 1：1~10：1 ratio is added in reaction vessel, is added into above-mentioned system
10~500 times of ethanol-water solution, adds the base catalyst of catalytic amount, 2~48 is reacted under the conditions of -5~100 DEG C small
When, solvent is removed, then using the isolated Q4 of silicagel column；
2. S2 is synthesized, reaction equation is as follows：
Wherein：R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that
R2For methyl, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3For first
Base, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
The X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone；
Comprise the following steps that：
By step 1. gained Q4 and S1 in molar ratio 1：1~1：2 ratio is added in reaction vessel, is added into above-mentioned system
10~500 times of methanol-water solution, adds the base catalyst of catalytic amount, 2~36 is reacted under the conditions of 20~100 DEG C small
When, solvent is removed, then using the isolated S2 of silicagel column；
3. C2 is synthesized, reaction equation is as follows：
Wherein：R2For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that
R2For methyl, ethyl or-CH2CH2-COO-X；
R3For methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group or-CH2CH2-COO-X, it is preferable that R3For first
Base, ethyl or-CH2CH2-COO-X；
R2And R3Can be identical or different substituted radical, but R2And R3Can not be-CH simultaneously2CH2-COO-X；
The X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone；
Comprise the following steps that：
By step 2. in obtained S2 according to mass ratio be 1:1~1：1000 ratio is dissolved in acid solution, after stirring, upwards
The acrylic acid for adding that volume is 1~10 times of acid solution volume in system is stated, solution temperature rises to 60~100 DEG C, and in inertia
Reacted 4~36 hours under the protection of gas；Reaction solution, which is cooled in suction filtration after room temperature, filtrate, adds appropriate distilled water, under ice bath
Visible a large amount of Precipitations after stirring 3~12 hours, sediment is neutralized to precipitation with dilute alkaline solution and disappeared just, then will be molten
Liquid is added in ethanol, and solid is separated out under ice bath, obtains target product C2.
4. a kind of preparation method of water soluble anion benzal cycloalkane ketone sensitising agent as claimed in claim 1, its feature
It is, structural formula is the preparation method of C3 sensitising agent, is comprised the following steps：
A) T1 is synthesized, reaction equation is as follows：
Wherein：X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone；
Concretely comprise the following steps：
WillWith S1 according to mol ratio 1：2~1：10 ratio adds reaction vessel, and 10~500 times are added into above-mentioned system
Distilled water, add the base catalyst of catalytic amount, under the conditions of 0~100 DEG C react 2~48 hours, remove solvent, use
The isolated T1 of silicagel column；
B) C3 is synthesized, reaction equation is as follows：
Wherein：X is cation Li+、Na+Or K+；
For cyclobutanone, cyclopentanone, cyclohexanone, cycloheptanone or cyclooctanone；
Comprise the following steps that：
According to mass ratio it is 1 by obtained T1 in step a):1~1：1000 ratio is dissolved in acid solution, after stirring, upwards
The acrylic acid for adding that volume is 1~30 times of acid solution volume in system is stated, solution temperature rises to 60~100 DEG C, and in inertia
Reacted 4~48 hours under the protection of gas；Reaction solution, which is cooled in suction filtration after room temperature, filtrate, adds appropriate distilled water, under ice bath
Visible a large amount of Precipitations after stirring 3~12 hours, sediment is neutralized to precipitation with alkaline solution and disappeared just, then solution is added
Enter into ethanol in proper amount, separate out solid under ice bath, obtain C3.
5. the method according to claim any one of 2-4, it is characterised in that the basic hydrolysis agent is lithium hydroxide, hydrogen
One or more in sodium oxide molybdena or potassium hydroxide；
Acid solution is the one or more in formic acid, acetic acid, propionic acid, hydrochloric acid or sulfuric acid, and the concentration of the acid solution is
0.01~3mol L-1；
Alkaline solution is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate, potassium carbonate or carbon
One or more in potassium hydrogen phthalate, the concentration of the alkaline solution is 0.01~3mol L-1；
Base catalyst is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium bicarbonate, sodium carbonate, sodium acid carbonate, potassium carbonate, carbon
One or more in potassium hydrogen phthalate, pyridine or hexahydropyridine.
6. water soluble anion benzal cycloalkane ketone sensitising agent as claimed in claim 1 is in light power anti-microbial infection
Application, it is characterised in that the microorganism be bacterium, fungi or virus.
7. application according to claim 6, it is characterised in that the OPK irradiation light is laser, LED light or simulation
Sunshine；The wavelength of the irradiation light is 350~600nm；The light application time of the irradiation light is 30 seconds~1 hour, and illumination is strong
Spend for 5~1000mW/cm2。
8. application according to claim 6, it is characterised in that the water soluble anion benzal cycloalkane ketone sensitising agent
Minimum inhibitory concentration be 0.001~100 μM.
9. application according to claim 6, it is characterised in that the bacterium is gram-positive bacteria or Gram-negative
Bacterium；It is double that the gram-positive bacteria is selected from staphylococcus aureus, methicillin-resistant staphylococcus aureus, streptococcus, pneumonia
Coccus, bacillus anthracis, corynebacterium diphtheriae or clostridium tetani；The Gram-negative bacteria is selected from Escherichia coli, shigella dysenteriae, typhoid fever
Bacillus, proteus or Bordetella pertussis；
The fungi is selected from the female bacterium of mould, saccharomycete, beer, monascin, Candida, Candida albicans, aspergillus flavus, Bai Di
Mould or antibiotic bacteria；
The virus is selected from bacteriophage, tobacco mosaic virus (TMV), avian influenza virus, variola virus, HIV, hepatitis A virus, B-mode
Hepatitis viruse, rubella virus or MERS viruses.
10. application according to claim 9, it is characterised in that by water soluble anion benzal cycloalkane ketone sensitising agent
The PFP passage of Gram-negative bacteria is activated, Gram-negative bacteria is inactivated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610150006.6A CN107200694B (en) | 2016-03-16 | 2016-03-16 | Water-soluble anionic benzylidene naphthenone photosensitizer, preparation method and application thereof in photodynamic antimicrobial infection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610150006.6A CN107200694B (en) | 2016-03-16 | 2016-03-16 | Water-soluble anionic benzylidene naphthenone photosensitizer, preparation method and application thereof in photodynamic antimicrobial infection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107200694A true CN107200694A (en) | 2017-09-26 |
| CN107200694B CN107200694B (en) | 2019-08-16 |
Family
ID=59903779
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610150006.6A Active CN107200694B (en) | 2016-03-16 | 2016-03-16 | Water-soluble anionic benzylidene naphthenone photosensitizer, preparation method and application thereof in photodynamic antimicrobial infection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107200694B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63226642A (en) * | 1986-10-14 | 1988-09-21 | Canon Inc | Optical recording medium |
| JP2002080822A (en) * | 2000-07-04 | 2002-03-22 | Hayashibara Biochem Lab Inc | Photofunctional material |
| CN1635029A (en) * | 2003-12-26 | 2005-07-06 | 中国科学院理化技术研究所 | Coumarin dye connected by naphthenone and its synthesis and use |
| CN1634909A (en) * | 2003-12-26 | 2005-07-06 | 中国科学院理化技术研究所 | 3-or 4-carbonyl substituted coumarin connected by naphthenone and its synthesis and use |
| CN102249939A (en) * | 2010-05-19 | 2011-11-23 | 中国科学院理化技术研究所 | Lipid-water amphiphilic benzylidene cyclopentanone dye, preparation method thereof and application thereof in photodynamic therapy |
-
2016
- 2016-03-16 CN CN201610150006.6A patent/CN107200694B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63226642A (en) * | 1986-10-14 | 1988-09-21 | Canon Inc | Optical recording medium |
| JP2002080822A (en) * | 2000-07-04 | 2002-03-22 | Hayashibara Biochem Lab Inc | Photofunctional material |
| CN1635029A (en) * | 2003-12-26 | 2005-07-06 | 中国科学院理化技术研究所 | Coumarin dye connected by naphthenone and its synthesis and use |
| CN1634909A (en) * | 2003-12-26 | 2005-07-06 | 中国科学院理化技术研究所 | 3-or 4-carbonyl substituted coumarin connected by naphthenone and its synthesis and use |
| CN102249939A (en) * | 2010-05-19 | 2011-11-23 | 中国科学院理化技术研究所 | Lipid-water amphiphilic benzylidene cyclopentanone dye, preparation method thereof and application thereof in photodynamic therapy |
Non-Patent Citations (6)
| Title |
|---|
| ALEKSANDR OVSIANIKOV等: "Laser Photofabrication of Cell-Containing Hydrogel Constructs", 《LANGMUIR》 * |
| WEI YANG等: "Carboxylate modified benzylidene cyclopentanone dyes for one- and two-photon excited photodynamic therapy", 《JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A: CHEMISTRY》 * |
| XIAOJUNWAN等: "Water-soluble benzylidene cyclopentanone dye for two-photon photopolymerization", 《JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A:CHEMISTRY》 * |
| YANYAN FANGA等: "Water-soluble benzylidene cyclopentanone photosensitizers for two-photon excited photodynamic therapy", 《PROC. OF SPIE》 * |
| ZHIQUAN LI等: "Initiation efficiency and cytotoxicity of novel watersoluble soluble microfabrication of hydrogels", 《RSC ADVANCES》 * |
| 万晓君: "双固化型全息用光致聚合物材料的研制&水溶性双光子聚合光敏染料的研究", 《中国优秀硕士学位论文全文数据库 工程科技第I》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107200694B (en) | 2019-08-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107011511B (en) | A kind of protoporphyrin fluorescent carbon point and preparation method and application | |
| CN115433367B (en) | Porphyrin COF material, preparation method and application | |
| CN114671813A (en) | Photosensitizer with activities of fluorescence imaging and photodynamic killing of gram-positive bacteria and preparation method and application thereof | |
| CN115403576A (en) | Antibacterial photosensitizer, preparation method thereof and application thereof in preparation of photodynamic antibacterial drugs | |
| CN106947089B (en) | Super molecular compound and preparation method thereof and the method for distinguishing microorganism | |
| CN106467487B (en) | Water-soluble cationic benzal naphthene ketone photosensitizer and preparation method and application thereof in photodynamic sterilization | |
| CN110407864A (en) | Solubilized BODIPY photosensitizer, preparation method and the application in preparation treatment body surface disease medicament | |
| CN111943868B (en) | Diethylamine-containing azine hydrazine compound and preparation method and application thereof | |
| Matlou et al. | Photophysico-chemical properties and photoinactivation of Staphylococcus Aureus using zinc phthalocyanines linked silver nanoparticles conjugates | |
| Wagner et al. | Chalcogenoxanthylium photosensitizers for the photodynamic purging of blood-borne viral and bacterial pathogens | |
| CN106035351B (en) | It is a kind of load photosensitizer polymer micelle preparation method and the micella planktonic bacteria, bacterial biofilm kill in application | |
| CN107200694B (en) | Water-soluble anionic benzylidene naphthenone photosensitizer, preparation method and application thereof in photodynamic antimicrobial infection | |
| CN107286197B (en) | A kind of complex of iridium and its preparation method and application with phosphorescence ion-pair structure | |
| CN108467475A (en) | A kind of cyclic polymer and its preparation method and application | |
| CN115385826B (en) | Aggregation-induced emission type photosensitizer with active oxygen and photo-thermal generation capability and preparation method and application thereof | |
| CN113980011B (en) | Active oxygen generating agent and application thereof in preparation of photodynamic bactericide | |
| CN102249939B (en) | Lipid-water amphiphilic benzylidene cyclopentanone dye, preparation method thereof and application thereof in photodynamic therapy | |
| CN115385825A (en) | Aggregation-induced emission characteristic photosensitizer with active oxygen generation capacity and preparation method and application thereof | |
| CN114377021B (en) | Preparation and application of photo-responsive nitric oxide delivery/photo-thermal synergistic material | |
| CN116655524B (en) | Tetraphenyl ethylene compound and preparation method and application thereof | |
| CN114702952A (en) | Adjustable near-infrared photosensitizer based on pillared aromatic hydrocarbon macrocycle with aggregation-induced emission and preparation method and application thereof | |
| CN115381830B (en) | Use of water-soluble anionic-pi-aryl azo compounds | |
| CN114634499B (en) | Aggregation-induced emission material, and preparation method and application thereof | |
| CN114031635B (en) | Difluoroborocurcumin derivative and preparation method and application thereof | |
| CN116987027B (en) | Aggregation-induced emission photosensitizer and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |