CN109996801A - 光敏剂 - Google Patents
光敏剂 Download PDFInfo
- Publication number
- CN109996801A CN109996801A CN201780071239.XA CN201780071239A CN109996801A CN 109996801 A CN109996801 A CN 109996801A CN 201780071239 A CN201780071239 A CN 201780071239A CN 109996801 A CN109996801 A CN 109996801A
- Authority
- CN
- China
- Prior art keywords
- formula
- phthalocyanine
- pyridyl group
- znpcs
- pyridin
- 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
- 239000003504 photosensitizing agent Substances 0.000 title description 25
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 claims abstract description 82
- 238000000034 method Methods 0.000 claims abstract description 61
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- 125000001424 substituent group Chemical group 0.000 claims description 30
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- -1 Pyridine boronic acid ester Chemical class 0.000 claims description 21
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- JVZRCNQLWOELDU-UHFFFAOYSA-N 4-Phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 claims description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 12
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 12
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
- A01N25/10—Macromolecular compounds
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/088—Radiation using a photocatalyst or photosensitiser
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
- A61L2/23—Solid substances, e.g. granules, powders, blocks, tablets
- A61L2/232—Solid substances, e.g. granules, powders, blocks, tablets layered or coated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/06—Zinc compounds
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/06—Preparation from carboxylic acids or derivatives thereof, e.g. anhydrides, amides, mononitriles, phthalimide, o-cyanobenzamide
- C09B47/067—Preparation from carboxylic acids or derivatives thereof, e.g. anhydrides, amides, mononitriles, phthalimide, o-cyanobenzamide from phthalodinitriles naphthalenedinitriles, aromatic dinitriles prepared in situ, hydrogenated phthalodinitrile
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/08—Preparation from other phthalocyanine compounds, e.g. cobaltphthalocyanineamine complex
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B47/00—Porphines; Azaporphines
- C09B47/04—Phthalocyanines abbreviation: Pc
- C09B47/30—Metal-free phthalocyanines
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Agronomy & Crop Science (AREA)
- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Catalysts (AREA)
Abstract
本申请涉及酞菁、用于制备酞菁的方法和用酞菁涂覆或浸渍的物体。本申请还涉及用于提供反应性氧物类的方法和用于将材料消毒的方法,包括对材料提供反应性氧物类以通过氧化作用来消毒所述材料。
Description
本申请的领域
本申请涉及包含酞菁的光敏剂、用于制备它的方法和用所述酞菁涂覆或浸渍的物体。本申请还涉及用于提供反应性氧物类的方法、用于将材料消毒的方法和光动力学治疗的方法。
背景
医院感染或健康护理相关感染(HAI)是传染性疾病传播的主要来源。受污染的表面、空气和水在微生物的传播中起着重要作用。这些微生物倾向于形成生物膜,且对抗生素治疗具有抗性。此外,耐药菌的出现是另一种威胁。发现光动力学抗微生物化学治疗(PACT)可有效对抗耐药菌的传播和生物膜。该方法包括在光存在下使用光敏剂,以借助反应性氧物类(reactive oxygen specie,ROS) (例如单线态氧)诱导的氧化应激来灭活病原微生物。
概述
发现了包含酞菁的新型光敏剂,所述试剂显示高效的光敏化性质。
一个实施方式提供式I的酞菁,
式I:
其中M为金属离子或2个氢原子,
并且,其中取代基对R1和R2、R3和R4、R5和R6以及R7和R8独立于其它的取代基对,为
-氢,和
-另一个取代基在所有的取代基对中是相同的,并且选自
或
其中R9为C1-C18烷基。
一个实施方式提供用所述酞菁涂覆或浸渍的物体。
一个实施方式提供用于提供反应性氧物类的方法,所述方法包括:
-提供所述酞菁或所述物体,和
-用光照射所述酞菁或所述物体,
来获得反应性氧物类。
一个实施方式提供用于灭活微生物的方法,其包括用上述方法提供反应性氧物类以通过氧化作用来灭活所述微生物。
主要实施方式的特征在于独立权利要求。在从属权利要求中公开了各种实施方式。除非另有明确说明,否则权利要求中和说明书中所述的实施方式可相互自由组合。
本文所公开的材料和方法可用于对抗微生物,特别是病原体。通常,所述实施方式的酞菁提供同时对抗多种类型的病原体的功效,所述病原体包括病毒、真菌和细菌。还提供对抗未检出和不可培养的病原体,对抗生物膜、霉菌和多重耐药病原体,以及对抗医院获得性感染和“超级细菌”的功效。
所述材料和方法还提供对抗微生物的安全作用,例如预防细菌的抵抗性和控制超级细菌,以及减少环境污染。
由所述材料和方法提供的作用简单。只要暴露在光下1~2h即足以消毒。不需要热处理或化学处理,由于在地球上的许多地方根本不可能煮沸水,所以这是有利的。所述材料适合于大的表面,如布料、地毯、座椅、墙壁等。上述优点已在实验室中得到证实。
还发现,即使是普通的室内灯(例如消费者LED灯),也可用于获得利用本发明材料的效果。这作为廉价、经济和持久的光源是非常有益的,其特别有利于光动力学抗微生物化学治疗的广泛使用。
所述酞菁稳定且耐用。它们长时间保持它们的活性,且它们不会逐渐消失而是保留在目标中,例如在物体的表面上或浸渍在物体的材料中。
附图简述
图1显示使用大肠杆菌βBAV1C-T5-lux的筛选试验。
图2显示使用携带质粒pBAV1C-T5-lux的贝氏不动杆菌 ADP1的筛选试验。
图3显示照射的Pc4滤纸与对照样品的以CFU/ml计的微生物生长的比较。
图4显示式II的酞菁。
图5显示式III的酞菁。
图6显示式IV的酞菁。
图7显示式V的酞菁。
图8显示用酞菁Pc4和卟啉ZnPf染色的滤纸的灯特征和吸光率。
图9显示用ZnPf和Pc4染色的纸的PBS提取物的(a)吸收光谱和(b)发射光谱。ZnPf的激发波长为422nm,Pc4的激发波长为694nm。
图10显示初始和64小时后的ZnPf染色纸和Pc4染色纸相对于波长的吸光率(a%)。
图11显示在试验中用作参照的Pc4 (Zn(II)TMPyPc)和卟啉ZnPf (Zn(II)TMPyP)的结构。
详述
本申请公开了在其α-酞(phthalo)位置具有4个吡啶基取代基的酞菁染料和用于制备它们的方法。所述酞菁可作为游离碱或作为金属络合物(例如Zn络合物)存在,且所述吡啶基取代基可作为吡啶或其N-烷基化衍生物存在。
通常,所述具有4个吡啶基取代基的酞菁可用通式I表示:
式I
其中取代基对R1和R2、R3和R4、R5和R6以及R7和R8独立于其它的取代基对,为
-氢,和
-另一个取代基在所有的取代基对中是相同的,并且选自
或
其中R9为C1-C18烷基。
M可以是金属离子或2个氢原子。M可选自Zn、Mg、Al、Cu、Co、Mn、Fe、Pt、Pd、Si、P、Sn、Ru、Ag、Au、Ir、Ni、Cd、Hg、U、Li、Na、K、Be、B、Ti、V、Cr、Ga、Ge、As、Y、Mo、Rh、In、Sb、Ba、W、Os、Re、Tl、Pb和Bi。在一个具体的实例中M为Zn。
在分子中在标记为R1~R8的位置有4个R取代基,每个酞环1个,在酞菁和吡啶之间具有直接的C-C键。在一个实施方式中所述取代基为吡啶。在一个实施方式中所述取代基为N-烷基化吡啶。
R9可以是C1-C18烷基,例如甲基、乙基、丙基、丁基、戊基、己基、庚基、辛基、壬基、癸基、十一基或十二基。在一个实施方式中R9为C1-C12烷基。在一个实施方式中R9为C1-C10烷基。在一个实施方式中R9为C1-C8烷基。在一个实施方式中R9为C1-C6烷基。在一个实施方式中R9为C2-C12烷基。在一个实施方式中R9为C2-C10烷基。在一个实施方式中R9为C2-C8烷基。在一个实施方式中R9为C2-C6烷基。在一个实施方式中R9为C3-C12烷基。在一个实施方式中R9为C3-C10烷基。在一个实施方式中R9为C3-C8烷基。在一个实施方式中R9为C3-C6烷基。在一个实施方式中R9为C4-C12烷基。在一个实施方式中R9为C4-C10烷基。在一个实施方式中R9为C4-C8烷基。在一个实施方式中R9为C4-C6烷基。
本文所述的“取代基对”指每1个酞环中的2个可能的吡啶基取代基,其中2个中仅1个存在。式I中的取代基R1~R8可以是吡啶或其N-烷基化衍生物,但应为下述方式:取代基对R1和R2、取代基对R3和R4、取代基对R5和R6以及取代基对R7和R8中,取代基只有一个是吡啶或其烷基化衍生物,而另一个是氢,即实际上不是取代基。所述实施方式的酞菁的制备方法得到异构体的混合物,其中吡啶基取代基可在式I的分子中4个位置各自的酞环的任一异构位置上,并且吡啶基取代基在所有取代基对中是相同的。将这些分子的代表性实例显示在下面和图4~7中,其中取代基呈现在4个酞环各自的相同异构位置(例如对应于R1、R3、R5和R7)。
在一个实施方式中所述酞菁为式II的四[α-吡啶基]酞菁(Pc1):
式II。
该分子的系统命名为1(4),8(11),15(18),22(25)-四(吡啶-4-基)-29H,31H-酞菁。括号中的数字代表取代基的备选位置。
在一个实施方式中所述酞菁为式III的四[α-吡啶基]锌酞菁(Pc2):
式III。
该分子的系统命名为[1(4),8(11),15(18),22(25)-四(吡啶-4-基)-29H,31H-酞菁(2-)-κ4N29,N30,N31,N32]锌。括号中的数字代表取代基的备选位置。
在一个实施方式中所述酞菁为式IV的四[甲基α-吡啶基碘鎓盐]酞菁(Pc3):
式IV。
所述酞菁也可以另一种盐的形式提供。也可以提供其它的抗衡离子代替碘鎓,例如氯离子、甲苯磺酸根、溴、硫酸根、六氟磷酸根等。
该分子的系统命名为4,4',4'',4'''-(29H,31H-酞菁-1(4),8(11),15(18),22(25)-四基)四(1-甲基吡啶鎓)四碘化物。括号中的数字代表取代基的备选位置。
在一个实施方式中所述酞菁为式V的四[甲基α-吡啶基碘鎓盐]锌酞菁(Pc4):
式V。
该分子的系统命名为{4,4',4'',4'''-(29H,31H-酞菁-1(4),8(11),15(18),22(25)-四基-κ4N29,N30,N31,N32)四[1-甲基吡啶鎓 (2-)]}锌(4+)四碘化物。括号中的数字代表取代基的备选位置。
所述实施方式的酞菁具有高效的光催化性质,特别是光敏剂性质,可应用于多种不同的应用。
所述实施方式的酞菁可用于将材料消毒,即通过释放反应性氧物类来杀死微生物。例如,它可用于覆盖或浸渍固体基质,并且在用光照射时,酞菁染料灭活与表面近距离的细菌。“灭活”指细菌的菌落形成单位的量减少。
本公开提供固体材料,其表面通过用上述酞菁染料覆盖固体基质而在光、特别是可见光下自消毒或自杀菌。用酞菁浸渍的材料可在整个材料中表现出消毒或杀菌性质。本公开还提供用于制备这样的材料的方法。
特别是Pc4的抗微生物活性与目前公布的微生物光动力学灭活的最佳结果相当或更优。
本文所述的α-吡啶基-取代的酞菁Pc1~Pc4在细菌的光动力学灭活中表现出高效率。特别是Pc4作为用于纸材料的染料也表现出高稳定性,并且一旦浸渍到纸中,就不会释放回溶液中。回退释放是用于制备抗微生物表面的许多其它的物质的问题。
所述实施方式的酞菁例如作为染料分子可用于涂料、墙壁、金属表面、瓷砖或其它的产品、构造或内表面和外表面。所述酞菁Pc1~Pc4可用于过滤材料,用于气体(例如通风系统中的空气)或液体(例如饮用水、医院污水、工业废水或市政废水或私人废水)的消毒。
一个实施方式提供用所述实施方式的酞菁涂覆或浸渍的物体。所述物体可称作可杀菌或可消毒的物体。
在一个实施方式中所述物体选自:包含纤维材料的物体,例如纸、过滤器、纺织品或织物;多孔材料;墙壁;玻璃表面;金属,例如金属表面;塑料,例如塑料表面;和陶瓷材料,例如陶瓷表面,或多孔陶瓷材料,例如瓷砖。通常,纺织品也可称作织物或布料。织物可以是织造的或非织造的。在布料的情况下,织物通常是织造的。更具体而言,纺织品指由交织纤维制成的任何材料。织物指通过编织、针织、铺展、钩编或粘合制成的任何材料,其可用于生产更进一步的商品(服装等)。过滤器可含有纤维材料,例如纸或纺织品。过滤器可以是安排空气或液体流过过滤器的空气过滤器或液体过滤器。如本公开所使用的纤维材料可包含天然纤维或合成纤维,或它们的组合。天然纤维的实例包含来自植物、动物和矿物来源的纤维,例如纤维素纤维。合成纤维的实例包含尼龙、丙烯酸纤维(acrylic)、聚酯、人造丝、玻璃和金属纤维。
如本文所使用的塑料指可延展并且可模塑成固体物体的合成或半合成的有机化合物。塑料通常是高分子量的有机聚合物,例如热塑性或热固性的聚合物,但它们也可含有其它的物质。塑料的实例包含聚酯、聚对苯二甲酸乙二醇酯、聚乙烯、高密度聚乙烯、聚氯乙烯、聚偏二氯乙烯、低密度聚乙烯、聚丙烯、聚苯乙烯、高抗冲聚苯乙烯、聚酰胺、丙烯腈丁二烯苯乙烯、聚乙烯/丙烯腈丁二烯苯乙烯、聚碳酸酯、聚碳酸酯/丙烯腈丁二烯苯乙烯、聚氨酯、马来酰亚胺/双马来酰亚胺、三聚氰胺甲醛、可塑性淀粉材料(Plastarch Material)、酚醛树脂、聚环氧化物、聚醚醚酮、聚醚酰亚胺、聚酰亚胺、聚乳酸、聚甲基丙烯酸甲酯、聚四氟乙烯(特氟隆)、脲甲醛、呋喃、硅酮和聚砜。
珠、颗粒、微粒等球形或球状的物体也可用所述实施方式的酞菁涂覆、浸渍或缀合。这样的珠的实例包含玻璃珠、塑料珠、陶瓷珠。所述珠、颗粒、微粒等球形或球状的物体可以是多孔的。
一组物体包含可用作光敏剂(例如在PDT中)的稳定剂和递送载体的纳米粒,所述纳米粒包含纳米团簇、纳米粉末、纳米晶体和纳米棒。纳米粒是特征尺寸小于100nm的颗粒,通常是尺寸(例如平均外径或至少一个维度)为1~100纳米(例如5~80纳米)的颗粒。纳米粒的实例包含:金纳米粒,二氧化硅纳米粒,聚合物纳米粒,例如合成有机聚合物,例如丙烯酸酯;磁性纳米粒,例如氧化铁纳米粒;半导体纳米粒,例如金属氧化物半导体纳米粒,例如二氧化钛和氧化锌纳米粒,其是催化产生反应性氧物类的半导体纳米晶体;量子点,其是半导体纳米晶体,例如硒化镉;和其他纳米粒。例如,闪烁纳米粒吸收可比UV或可见光更深地穿透人体组织的电离辐射(例如X射线或γ射线)。在吸收后,闪烁纳米粒被激发并辐射可见光,这将激活组织中的光敏剂。闪烁纳米粒的实例包含氟化镧纳米粒,优选掺杂有铽离子。同样,上转换(upconverting)纳米粒寻求通过一种机制克服穿透组织的光的限制,其中所述上转换纳米粒被近红外光激发,然后纳米粒在光谱的可见区发射光以激活组织中的光敏剂。上转换纳米粒的实例包含共掺杂有镱和铒离子的氟化钇钠纳米粒。纳米粒可用于例如治疗应用,例如癌症治疗。
先前公开的物体可包含在用于本文所述应用的产品中。所述产品的具体实例包含自消毒布、用于卫生用途的自消毒织物(床上用品等)、自消毒保护面罩和用于水的自消毒过滤器。这些产品的活性适中,并且价格适中。大规模应用的实例包含用于空调系统的消毒过滤器、用于开放式蓄水池和游泳池的自洁表面、用于医院废水和其它的生物危害性废水的消毒系统。
活性适中并且价格较低的产品包含:用于幼儿园、公共场所、医院或家庭的自消毒地毯和座椅,用于飞机、客车、火车、汽车中的座椅套和其它的表面的自消毒织物,用于蓄水池、游泳池、淋浴器、卫生间的自消毒瓷砖,自消毒一次性面罩,用于墙壁的自消毒油漆,用于医院废水的自消毒过滤器,和用于饮用水的便携式消毒设备。
高活性并且高价格的产品的实例包含用于鼻和皮肤感染、伤口、溃疡的抗微生物治疗药物,和牙科治疗药物。
一个实施方式提供包含所述实施方式的酞菁的药物组合物。所述药物组合物还可包含药学上可接受的载体、赋形剂、填充剂、任何其它的试剂或它们的组合。所述组合物可以是含水的,或者可以干燥形式提供。这样的药物组合物,其也可称为医药组合物,可以凝胶、悬浮液、乳液、液体等形式提供,其可以施用到皮肤、牙齿或其它的组织上,还可在癌症治疗中施用到组织中。所述药物组合物可包含如本文所述的任何形式的酞菁,例如与纳米粒或其它的物体偶联。
高活性并且低价格的产品的实例包含用于时疫地区的大型陆地/水域的粉末和消毒处理。
可通过使用包含所述实施方式的酞菁的涂料、油漆或浸渍组合物来涂覆或浸渍所述物体,即通过涂漆,例如通过刷涂、喷雾、蘸涂、施胶或以其它的方式涂覆涂料、油漆或浸渍组合物来涂覆或浸渍所述物体。所述浸渍组合物可以是例如溶液、悬浮液、分散液或乳液,例如含水的溶液、悬浮液、分散液或乳液。
一个实施方式提供包含所述实施方式的酞菁的涂料,优选在物体上。可使用本领域已知的方法,例如通过使用纤维材料或颗粒材料作为载体来制备所述涂料。所述载体可以是例如纤维质材料,例如纳米原纤维纤维素,其可以例如粉末形式提供。例如,可将填充剂与酞菁染料混合,然后与油混合。用于涂覆物体的方法包括:形成涂料组合物,所述组合物包含所述实施方式的酞菁以及一种以上的载体和任选的其它成分;和将所述涂料组合物施加到待涂覆的物体上。用于浸渍物体的方法包括:形成浸渍组合物,所述组合物包含所述实施方式的酞菁以及一种以上的载体和任选的其它成分;和用所述浸渍组合物浸渍待浸渍的物体。
在一个实例中,如Decraene等人在Curr Microbiol 2008 57: 269中所公开的,如下制备由含有甲苯胺蓝(TBO,Sigma)和玫瑰红(RB,Sigma)的乙酸纤维素(Sigma, Poole,UK)组成的光活化抗微生物涂料。将TBO和RB加入乙酸纤维素的丙酮(50mg/ml)溶液中,使得每种光敏剂的最终浓度为25μm。一旦完全溶解,将3.5ml的乙酸纤维素/光敏剂溶液倒入小的(直径=50mm)玻璃DUROPLAN®皮氏培养皿(Sigma)中,让丙酮蒸发48h。以类似的方法制备由不含光敏剂的乙酸纤维素组成的对照涂料。
在另一个实例中,如下制备涂料(Decraene等人 Appl. Environ. Microbiol.2006, 72, 4436-4439)。将乙酸纤维素(Sigma)溶解在丙酮中(50mg/ml),加入光敏剂在丙酮中的储备溶液(100g/ml),使得每种光敏剂的最终浓度为25M。将每种混合物的等分试样(450l)转移到平底玻璃容器(直径,18mm)中,让丙酮蒸发过夜。使用Starrett (Athol,Mass.)测微计测定涂料的厚度。使用UNICAM UV 500 UV/可见分光光度计(ThermoSpectronic)在250~800nm范围内测定涂料的吸收光谱。在包含光源的三个主发射峰的500nm和675nm之间应该发生强吸收。
一个实施方式提供包含所述实施方式的酞菁的油漆,优选在物体上。可使用本领域已知的方法,例如通过使用标准油漆或涂料组合物作为载体(例如透明的油漆或涂料组合物)来制备所述油漆。
在一个实例中,如下制备油漆(Preuss等人, Journal of Photochemistry &Photobiology, B: Biology 2016 160 79-85)。使用市售的标准硅酮面漆(StoColorLotusan (Art. No. 03206-064))检查构建生物膜的微生物的光动力学失活的概念。对于试验,使用没有添加罐内防腐剂的实验室制剂以排除这些物质的影响。通过用Vollrath实验室混合设备EXF在1500U/min下温和搅拌1min来并入TMPyP,以得到均匀分布以及1.950mPa·s (20℃)的动态粘度。作为阳性对照,使用相同配制的油漆,其在湿油漆中含有一定浓度的干膜杀生物剂的活性物质:600ppm去草净(Cas No. 886-50-0),1200ppm异丙隆(Cas No. 34123-59- 6)和1200ppm IPBC (Cas No. 55406-53-6)。
一个实施方式提供用于提供反应性氧物类的方法,所述方法包括:
-提供所述实施方式的酞菁或先前所述的物体,和
-用光照射所述酞菁或所述物体,
来获得反应性氧物类。
通常,用于提供反应性氧物类的方法可以是治疗性的方法或非治疗性的方法。通常,用于将材料消毒的杀菌的方法被认为是非治疗性的。治疗性的方法在人体或动物体上实施。在一个实施方案中,用于提供反应性氧物类的方法是非治疗性的方法。
反应性氧物类是含有氧的化学反应性化学物类。反应性氧物类的实例包含例如过氧化物(例如过氧化氢H2O2)、超氧阴离子(O2 -)、超氧自由基(O2·)、羟基自由基(OH·)和单线态氧(1O2)。
光包含可见光,但也包含UV范围和IR范围的一部分,例如具有350~850nm范围内(例如400~800nm范围内)的波长λ的光。所述实施方式的酞菁分子的一个最适波长在600~750nm范围内,一个最适波长在约450nm。光可以是自然光(阳光),或者可来源于一个以上的人造光源(例如灯、LED、激光等)。在一个实例中,所述方法包括提供光源,使其排列为照射所述实施方式的酞菁或先前所述的物体。
在闪烁纳米粒、上转换纳米粒或其它的类似材料的情况下,由于照射将被转换成具有会激活光敏剂的波长的光,所以辐射或红外光也可用于照射。
在用光照射所述实施方式的酞菁或先前所述的物体时,光子被酞菁即敏化剂吸收。吸收的光子将敏化剂激发到一种以上的富含能量的状态。激发的敏化剂经历内部反应,导致基质的化学变化。这可以两种类型的反应发生,即I型和II型光反应,产生反应性氧物类等。
I型光反应的特征在于依赖于靶标-基质浓度。在缺氧环境中,光敏剂的光诱导激发可将电子提升到更高的能态。此时可发生多种反应。例如,该激发的光敏剂可通过电子交换直接与有机基质反应,填充被激发的电子腾出的空穴,产生氧化的基质和还原的光敏剂。鸟嘌呤是最易氧化的碱基,是推测的靶标,导致形成各种氧代-鸟嘌呤络合物并最终导致分解细胞DNA。还原的光敏剂可与氧反应生成超氧阴离子(O2 -),其然后可形成高反应性的羟基自由基(OH·)。激发的光敏剂也可与超氧自由基(O2·)反应生成超氧阴离子(O2 -),其然后可产生高反应性的羟基自由基(OH·)。
依赖于氧浓度的II型机制也包括用光激发光敏剂,但在这种机制中将能量转移到分子氧的基态,产生激发的单线态氧(1O2),其继续破坏细胞功能。由于氧具有独特的三重基态和低位激发态,所以光敏剂和氧通过三重态相互作用。在氧中三重态至单线态所需的能量为22kcal mol-1,其对应于1274nm波长的能量(红外光)。产生单线态氧所需的能量相对较低。
一个实施方式提供用于灭活微生物的方法,其包括用上述方法提供反应性氧物类,以通过氧化作用来灭活微生物。微生物可包含在含有所述实施方式的酞菁的物体中,或者包含在与物体接触或紧密接近(例如0~5mm)的材料中。例如,所述方法可用于灭活在用所述实施方式的酞菁处理的物体的表面上或内部的微生物,或者灭活在通过所述物体(例如过滤器)的表面或内部的空气或液体(例如含水的液体)中的微生物。
一个实施方式提供用于将材料消毒的方法,其包括用上述方法向所述材料提供反应性氧物类,以通过氧化作用来消毒所述材料。一个实施方式提供用于消毒靶标的方法,其包括用上述方法向所述靶标提供反应性氧物类,以通过氧化作用来消毒所述材料。所述靶标或所述材料可以指表面、空气、液体(例如水、含水的液体或其它的液体)或产品(例如本文所述的产品),其可与反应性氧接触,或者其可以是用于进一步消毒其它的靶标、材料或物质。消毒指在靶标或材料中提供消毒或杀菌效果的作用,例如灭活微生物。代替术语“消毒”,也可使用术语“杀菌”。反应性氧物类可被认为是消毒剂或杀菌剂。
一个实施方式提供所述实施方式的酞菁用于提供反应性氧物类的用途。一个实施方式提供所述实施方式的酞菁用于灭活微生物或将材料或靶标(例如本文所述的材料或靶标)消毒或灭菌的用途。
所述实施方式的试剂可用于利用光动力学灭活(光灭活)或光动力学抗微生物化学治疗PACT的原理的方法中。它采用所述实施方式的光敏剂,其在光照射时产生单线态氧1O2的高反应性物类,这继而通过氧化作用破坏被处理的细胞。该光毒效应在抗微生物处理中具有重要的优点。首先,单线态氧的寿命长到足以扩散数微米(在液体中)或甚至数毫米(在空气中),因此允许在过滤器上、甚至在生物膜上进行抗微生物处理,而光敏剂与病原体细胞之间没有直接接触。它还使得可在过滤器和绷带中使用PACT材料。其次,光灭活是通用的方法,允许同时处理不同种的微生物,对多重耐药(MDR)微生物也有效。第三,与抗微生物药物相比,光毒作用是一般的氧化过程,而不诱导耐药性。
所述实施方式的酞菁可用作光动力学治疗(PDT) (例如用于治疗癌症)中的光敏剂。这样的癌症的一个实例为黑色素瘤,也称为皮肤癌,其进一步分为3种类型的癌症:基底细胞、鳞状细胞和黑色素瘤。基底细胞癌和鳞状细胞癌是最常见的皮肤癌类型,但它们比黑色素瘤致命性更低,并且更容易治疗。
PDT可用于治疗许多其它的健康相关病症。例如,PDT可用于治疗免疫效应(新抗生素)、炎症和细菌感染。PDT通过光治疗后开始的效应的组合激活并且抑制免疫系统。在癌症治疗中,有疗效的性质来自受照射的癌细胞的死亡。单线态氧对质膜和细胞器的膜的损害可引发其它的具有深远影响的事件。PDT还可用于治疗牙科感染、鼻感染、伤口、溃疡等。
另一种PDT诱导的效应是炎症。在PDT后观察到的血管破坏类似于组织损伤或细菌感染后的炎症反应。该过程的典型之处是释放广泛的强效介质,包括血管活性物质、凝血级联组分、蛋白酶、过氧化物酶、自由基、白细胞、化学引诱剂、细胞因子、生长因子和其它的免疫调节剂。
在光动力学治疗中,通常可使用特定的光源(例如配备有光纤的医疗激光系统或其它的光源)。可将光纤插入受试者内,且可将光导向靶标,例如导向肿瘤。
一个实施方式提供含有所述实施方式的酞菁或本文所述的物体的医疗装置,例如过滤器。一个实施方式提供含有所述实施方式的酞菁的医疗材料,例如消毒物质如糊、凝胶、乳液、悬浮液、液体、过滤器、条带等。医疗应用的一个特定领域是牙科应用和牙科学。
一个实施方式提供所述实施方案的酞菁,其用于用作治疗剂。一个实施方式提供所述实施方案的酞菁,其用于用作光动力学治疗中的光敏剂,通常用于治疗本文所公开的疾病或障碍。一个实例提供用于治疗疾病或障碍的方法,所述方法包括:提供所述实施方式的酞菁作为光动力学治疗中的光敏剂,和实施用于治疗所述疾病或障碍的光动力学治疗。所述疾病的实例包含癌症,例如黑色素瘤,食管癌,非小细胞肺癌,癌前期病变,脑、皮肤、前列腺、宫颈和腹膜腔的癌症。所述实施方式的酞菁可作为如本文所述的药物组合物提供,例如与颗粒(例如纳米粒)偶联和/或与一种以上的其它的药剂(例如抗癌剂)组合。
一个实施方式提供3-(吡啶-4-基)苯-1,2-二甲腈。这是中间体化合物,其可用于合成所述实施方式的酞菁。3-(吡啶-4-基)苯-1,2-二甲腈用式VI表示:
式VI。
一个实施方式提供用于制备3-(吡啶-4-基)苯-1,2-二甲腈的方法,所述方法包括:
-以溶液的形式(例如溶解在水和甲苯中)提供吡啶硼酸酯、邻苯二甲腈三氟甲磺酸酯、钯催化剂和K3PO4的混合物,并且加热并搅拌,例如在90~100℃范围内的温度下(例如在约90℃下)进行1~3h (例如2h),和
-从所述溶液回收所述3-(吡啶-4-基)苯-1,2-二甲腈。
一个实施方式提供用于制备式II的酞菁的方法,
式II:
所述方法包括:
-优选在90~100℃范围内的温度下(例如在约90℃下)在氩气氛下,提供溶解在溶剂中的锂,
-将所述混合物冷却至室温,
-优选在氩气氛下,加入3-(吡啶-4-基)苯-1,2-二甲腈,
-在加热下反应,例如在90~100℃范围的温度下(例如在约90℃下),优选在混合中,和
-回收式II的酞菁。
在一个实施方式中所述方法包括:
-提供获得的式II的酞菁和Zn(OAc)2·2H2O在溶剂中的混合物,和
-回收获得的式III的四[α-吡啶基]锌酞菁,
式III。
在一个实施方式中所述方法包括:
-提供获得的酞菁和甲基碘在溶剂中的混合物,
-在加热下使所述混合物反应,例如在40~60℃范围内的温度下(例如在约45℃下)进行6~24h (例如约18h),
-冷却所述混合物,和
-回收获得的式IV的四[甲基α-吡啶基碘鎓盐]酞菁,
式IV。
一个实施方式提供用于制备式III的四[α-吡啶基]锌酞菁的方法,
式III,
所述方法包括:
-提供3-(吡啶-4-基)苯-1,2-二甲腈,
-在回流下在二甲基氨基乙醇中加热所述3-(吡啶-4-基)苯-1,2-二甲腈和乙酸锌,例如在120~150℃范围内的温度下(例如在约140℃下)进行6~24h (例如约12h),
-冷却所述混合物,和
-回收获得的式III的四[α-吡啶基]锌酞菁。
在一个实施方式中所述方法包括:
-提供获得的四[α-吡啶基]锌酞菁和甲基碘在溶剂中的混合物,
-在加热下混合,例如在40~60℃范围内的温度下(例如在约45℃下)进行6~24h (例如约18h),
-冷却所述混合物,和
-回收获得的式V的四[甲基α-吡啶基碘鎓盐]锌酞菁,
式V。
实施例
实施例1. 酞菁Pc1~Pc4的合成
1) 3-(吡啶-4-基)苯-1,2-二甲腈
将溶解在7.5ml的水和甲苯(7.5ml)中的吡啶硼酸酯(120mg,0.628mmol)、邻苯二甲腈三氟甲磺酸酯(173.5mg,0.628mmol)、PdCl2(dppf).DCM (25.64mg,0.0314mmol)、K3PO4(399.89mg,1.884mmol)的混合物在90℃下加热2h。将产物用CHCl3提取,用盐水洗涤,用无水Na2SO4干燥,在减压下蒸发,得到105mg的粗产物。通过使用CHCl3/己烷混合物(75mg,60%)的再沉淀来分离纯产物。产物3-(吡啶-4-基)苯-1,2-二甲腈也可被称作吡啶邻苯二甲腈或3-吡啶基邻苯二甲腈。
2) 四[α-吡啶基]酞菁Pc1
在90℃下在氩气氛下将锂的新鲜切片(57mg,8.212mmol)溶解在正丁醇(5.7ml)中。将反应混合物冷却至室温,在氩气氛下向上述溶液中加入吡啶邻苯二甲腈(80mg,0.3898mmol)。将温度升高至90℃,搅拌18h。将产物用CHCl3提取,用水洗涤数次直至水层的pH为中性。在减压下蒸发有机层,得到粗残留物。将残留物用ACN洗涤,然后通过柱色谱法(中性氧化铝,CHCl3中的1% EtOH)纯化,得到酞菁游离碱(40mg,50%)。MS (ESI-TOF): [M+H]+对C52H30N12 +计算值823.2795;实测值823.2832。
3) 四[α-吡啶基]锌酞菁Pc2
将吡啶酞菁的游离碱(12mg,0.0146mmol)溶解在CHCl3 (1.5ml)中,向其中加入120µlH2O中的 Zn(OAc)2·2H2O (12mg,0.0547mmol)。将产物用CHCl3 (20ml)提取,用水洗涤(25ml×3),用无水Na2SO4干燥,在减压下蒸发,得到粗残留物。将产物用柱色谱法(中性氧化铝,CHCl3中的10% EtOH)纯化,然后用乙醚和ACN洗涤,得到纯化合物(11mg,85%)。MS (ESI-TOF): [M+H]+ 对C52H28N12Zn+计算值885.1929;实测值885.1970。
4) 四[甲基α-吡啶基碘鎓盐]酞菁Pc3
将吡啶酞菁的游离碱(15mg,0.0182mmol)溶解在DMF(3ml)中,向其中加入甲基碘(1ml,0.0161mmol)。将反应混合物在45℃下搅拌18h。将反应混合物在冰浴中冷却,通过向其中加入二甲醚(15ml)来沉淀产物。将过滤的固体用乙醚洗涤数次,然后用丙酮洗涤数次,得到纯产物(14.8mg,58.32%)。MS (ESI-TOF): [M]4+ 对C56H42N12 4+计算值220.5914;实测值220.5888; [M+I] 3+对C56H42IN12 3+计算值336.4233;实测值336.4203。
5) 四[α-吡啶基]锌酞菁Pc2 (直接法)
在140℃下将吡啶邻苯二甲腈(77mg,0.3752mmol)和乙酸锌Zn(OAc)2 (84.67mg,0.4615mmol)在二甲基氨基乙醇(DMAE,810µl)中的混合物在回流下加热12h。将反应混合物冷却至室温,通过加入MeOH/H2O (9:1)的混合物来沉淀产物。将固体过滤,用甲醇洗涤,得到纯产物(80mg,96%)。MS (ESI-TOF): [M+H]+对C52H28N12Zn+计算值885.1929;实测值885.1904。
6) 四[甲基α-吡啶基碘鎓盐]锌酞菁Pc4
将吡啶酞菁(20mg,0.0225mmol)溶解在DMF (3ml)中,向其中加入甲基碘(1ml,0.0161mmol)。将反应混合物在45℃下搅拌18h。将反应混合物在冰浴中冷却,通过向其中加入乙醚(15ml)来沉淀产物。将过滤的固体用乙醚洗涤数次,然后用丙酮/H2O (1:1)的混合物洗涤数次,得到纯产物(15mg,45.71%)。MS (ESI-TOF): [M+I]3+ 对C56H40IN12Zn3+计算值357.0612;实测值357.0623。
实施例2. 抗微生物试验
筛选试验
通过用携带质粒pBAV1C-T5-lux(所述质粒是pBAV1K-T5-lux质粒(Addgene #55800)的氯霉素抗性衍生物)的生物发光细菌菌株大肠杆菌(Escherichia coli,XL1-Blue,Stratagene, USA)和贝氏不动杆菌 ADP1 (Acinetobacter baylyi ADP1,DSM 24193)进行抗微生物试验,来筛选染料(Pc1、Pc2、Pc3、Pc4)的效力。将滤纸(12.25cm2)浸泡在各染料溶液(200μl的溶剂中0.9mg的染料)中,使染料溶液在滤纸上干燥。在干燥后,从每个滤纸上切下3个圆盘(直径为0.5cm),以每排对应每种染料的方式粘贴在LA琼脂(15g/l琼脂,10g/l胰蛋白胨,5g/l酵母提取物,5g/l NaCl)凝胶平板上。在琼脂平板上放置中心有方孔的高度为0.3cm的圆形挡板(screen)。以使得包含所有4种染料的一列将位于挡板的暗区域下,而剩余的两列将位于方孔内的方式切割方孔。将两个滤光片[KG3带通滤光片(315~750nm透射)和ЖC-17黄色滤光片(透射>485nm)]放置在方孔上以除去红外辐射和UV辐射。将整个装置放置在太阳模拟器(Luzchem,加拿大)内,将照射的强度调节至18mWcm-2。通过切割相同尺寸的未染色滤纸并置于LA琼脂平板的暗区域和照射区域下,制备检查染料的效果的对照样品。在微生物沉积在滤纸盘上前记录(Xenogen IVIS 100)由装置产生的发光。将微生物溶液(5μl)移液到这些滤纸盘和对照样品上,来确定滤纸对微生物生长的影响,通过将微生物溶液移液在琼脂平板的暗区域上而确立。测定在照射1h之前和之后的琼脂板的发光,从所述组中筛选出产生更少发光的有效染料。图1显示用大肠杆菌βBAV1C-T5-lux的筛选结果,图2显示用携带质粒pBAV1C-T5-lux的贝氏不动杆菌 ADP1的筛选结果。
菌落形成单位(CFU)法
通过使用微生物大肠杆菌MG1655 (耶鲁的E. coli Genetic Resources)和贝氏不动杆菌(A. baylyi ADP1,ATCC 33305)的CFU方法证实染料的抗微生物效力。将最有效的染料(Pc4)和未染色(染料对照)滤纸的滤纸盘(原始的和重复的)置于微孔板的孔中,将微生物溶液(25μl)移液到其上。将微孔板在太阳模拟器中照射1h。使用KG3带通滤光片(315~750nm透射)和ЖC-17黄色滤光片(透射>485nm)的组合截断UV-IR辐射。类似地,通过在染色样品和未染色样品上沉积微生物培养基,通过在室温下用铝箔覆盖微孔板1h,来制备光对照样品。在照射或培育1h后,用LB培养基(10g/l胰蛋白胨,5g/l酵母提取物,5g/l NaCl) (975μl)提取微生物,并从每种提取物制备连续稀释液。然后将稀释液接种在LA琼脂平板上,在30℃下培育过夜。计数在琼脂平板上生长的菌落数,由此计算每毫升的CFU。在由照射的滤纸制备的平板上没有观察到微生物生长(对于大肠杆菌和贝氏不动杆菌),而在由对照滤纸制备的平板上观察到大肠杆菌和贝氏不动杆菌的生长分别为109和108CFU/ml。该实验清楚地证明了在光照射下用染料Pc4处理的滤纸的抗微生物作用,如表1和图3中汇总。
表1. 用Pc4的光动力学灭活细菌后的CFU计数结果
实施例3. 在弱室内光下的抗微生物活性
本文证明染料Pc4可被消费者级LED灯(OSRAM LED Star PAR16 80 36°GU10,功耗为6.9W)成功激活。测定在实验前从灯发射的光的光谱。发现灯发射的波长在594nm处最大(图8)。另外,还在不同距离处测定灯的功率密度。发现距离检测器,在28cm距离处的强度为4mW/cm2,在20cm处的强度为8mW/cm2,在14cm处的强度为15mW/cm2,在9cm距离处的强度为35mW/cm2。为了比较活性,使用最著名的PACT光敏剂之一,Zn(II)四[甲基吡啶鎓碘化物]卟啉ZnPf (Zn(II)TMPyP),作为参照(结构如图11所示)。如上所述,将Pc4和ZnPf都沉积在滤纸上。使用积分球(IS)检测器,由染色纸的反射率和透射率测定结果,计算酞菁Pc4和卟啉ZnPf纸的吸光率。吸光率特征与溶液中的吸光率测定结果非常相似。对于卟啉和酞菁,对应于最大吸收的波长分别为430nm和696nm。但是,由于两种染料在两种不同波长下吸收,所以每种染料的光剂量是不同的(图8b)。在使用LED光的相同条件下,卟啉的光剂量是酞菁(4.4J/cm2)的1.2倍(5.2J/cm2)。如上所述对大肠杆菌和贝氏不动杆菌实施利用从LED灯进行照射的抗微生物灭活实验。Pc4和ZnPf均在照射1h后显示完全灭活微生物。
实施例4. 浸出试验
用pH7.2的PBS缓冲液试验染料Pc4对抗的稳定性。测定与染料纸一起培育的PBS缓冲液的吸光率和发射以检查浸出(图9a和b)。在室温下将28mg的每种染色纸在玻璃小瓶中的4ml的PBS缓冲液中浸泡1小时。在1h后测定来自每个小瓶的PBS缓冲液的吸光率和发射,以检查染料从纸的浸出。含有ZnPf的PBS溶液在422nm显示出强吸收峰,这证实了卟啉浸出至溶液中。在422nm激发的含有卟啉纸的PBS溶液的发射测定结果显示在培育1h后从600nm出现强发射峰。但是,即使在室温下培育20h后,Pc4纸的PBS提取物也未显示与染料对应的任何峰。但是,在694nm激发时,它产生强度可忽略不计的非常微弱的发射峰。这表明即使不与纤维素载体化学键合,染料Pc4也具有格外高的抗浸出稳定性。图10显示初始和在35mW/cm2下恒定照射64h后的卟啉染色纸和Pc4染色纸相对于波长的吸光率(a%)。
Claims (13)
1.式I的酞菁,
式I:
其中M为金属离子或2个氢原子,
并且,其中取代基对R1和R2、R3和R4、R5和R6以及R7和R8独立于其它的取代基对,为
-氢,和
-另一个取代基在所有的取代基对中是相同的,并且选自
或
其中R9为C1-C18烷基。
2.根据权利要求1所述的酞菁,其选自以下化合物:
-式II的四[α-吡啶基]酞菁:
式II,
-式III的四[α-吡啶基]锌酞菁:
式III,
-式IV的四[甲基α-吡啶基碘鎓盐]酞菁:
式IV,和
-式V的四[甲基α-吡啶基碘鎓盐]锌酞菁:
式V。
3.用前述权利要求中任一项所述的酞菁涂覆或浸渍的物体,优选其中所述物体选自:包含纤维材料的物体,例如纸、过滤器、纺织品或织物;多孔材料;珠、颗粒、微粒、纳米粒;墙壁;玻璃表面;金属表面;塑料表面;和陶瓷表面。
4.用于提供反应性氧物类的方法,所述方法包括:
-提供根据权利要求1~2中任一项所述的酞菁或根据权利要求3所述的物体,和
-用光照射所述酞菁或所述物体,
来获得反应性氧物类。
5.用于灭活微生物的方法,其包括用根据权利要求4所述的方法提供反应性氧物类以通过氧化作用来灭活所述微生物。
6.3-(吡啶-4-基)苯-1,2-二甲腈。
7.用于制备3-(吡啶-4-基)苯-1,2-二甲腈的方法,所述方法包括:
-以溶液的形式提供吡啶硼酸酯、邻苯二甲腈三氟甲磺酸酯、钯催化剂和K3PO4的混合物,加热并搅拌,例如在90~100°C范围内的温度下进行约1~3h,和
-从所述溶液回收所述3-(吡啶-4-基)苯-1,2-二甲腈。
8.用于制备式II的四[α-吡啶基]酞菁的方法,
式II:
所述方法包括:
-提供溶解在溶剂中的锂,优选在90~100℃范围内的温度下在氩气氛下,
-将所述混合物冷却至室温,
-加入3-(吡啶-4-基)苯-1,2-二甲腈,优选在氩气氛下,
-在加热下反应,例如在约90~100℃的温度下,优选在混合中,和
-回收获得的式II的四[α-吡啶基]酞菁。
9.根据权利要求8所述的方法,其包括:
-提供获得的式II的酞菁和Zn(OAc)2·2H2O在溶剂中的混合物,和
-回收获得的式III的四[α-吡啶基]锌酞菁,
式III。
10.根据权利要求9所述的方法,其包括:
-提供获得的式III的四[α-吡啶基]锌酞菁和甲基碘在溶剂中的混合物,
-在加热下混合,例如在40~60℃范围内的温度下进行约6~24h,
-冷却所述混合物,和
-回收获得的式V的四[甲基α-吡啶基碘鎓盐]锌酞菁
式V。
11.根据权利要求8所述的方法,其包括:
-提供获得的酞菁和甲基碘在溶剂中的混合物,
-在加热下使所述混合物反应,例如在40~60℃范围内的温度下进行约6~24h,
-冷却所述混合物,和
-回收获得的式IV的四[甲基α-吡啶基碘鎓盐]酞菁
式IV。
12.用于制备式III的四[α-吡啶基]锌酞菁的方法,
式III
所述方法包括:
-提供3-(吡啶-4-基)苯-1,2-二甲腈,
-在回流下加热在二甲基氨基乙醇中的所述3-(吡啶-4-基)苯-1,2-二甲腈和乙酸锌,例如在120~150℃范围内的温度下进行约6~24h,
-冷却所述混合物,和
-回收获得的式III的四[α-吡啶基]锌酞菁。
13.根据权利要求12所述的方法,其包括:
-提供获得的四[α-吡啶基]锌酞菁和甲基碘在溶剂中的混合物,
-在加热下混合,例如在40~60℃范围内的温度下进行约6~24h,
-冷却所述混合物,和
-回收获得的式V的四[甲基α-吡啶基碘鎓盐]锌酞菁,
式V。
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CN115286638A (zh) * | 2022-08-08 | 2022-11-04 | 王佳玉 | 一种基于共轭酞菁框架的单原子Ag抗菌材料及其制备方法 |
CN115286638B (zh) * | 2022-08-08 | 2024-03-08 | 王佳玉 | 一种基于共轭酞菁框架的单原子Ag抗菌材料及其制备方法 |
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US20190337958A1 (en) | 2019-11-07 |
RU2019115122A3 (zh) | 2021-02-19 |
US10875871B2 (en) | 2020-12-29 |
EP3541818A4 (en) | 2020-07-29 |
RU2019115122A (ru) | 2020-12-17 |
WO2018091774A1 (en) | 2018-05-24 |
FI127163B (en) | 2017-12-29 |
FI20165867A (fi) | 2017-12-29 |
EP3541818A1 (en) | 2019-09-25 |
CN109996801B (zh) | 2022-03-22 |
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