CN115557926A - Squarylium cyanine compound and preparation method and application thereof - Google Patents
Squarylium cyanine compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN115557926A CN115557926A CN202211171304.5A CN202211171304A CN115557926A CN 115557926 A CN115557926 A CN 115557926A CN 202211171304 A CN202211171304 A CN 202211171304A CN 115557926 A CN115557926 A CN 115557926A
- Authority
- CN
- China
- Prior art keywords
- formula
- compound
- tetrahydrobenzo
- squarylium
- reaction
- 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
- -1 cyanine compound Chemical class 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 39
- 238000000034 method Methods 0.000 claims abstract description 11
- ANRHNWWPFJCPAZ-UHFFFAOYSA-M thionine Chemical compound [Cl-].C1=CC(N)=CC2=[S+]C3=CC(N)=CC=C3N=C21 ANRHNWWPFJCPAZ-UHFFFAOYSA-M 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 47
- OIHZGFWAMWHYPA-UHFFFAOYSA-N xanthylium Chemical class C1=CC=CC2=CC3=CC=CC=C3[O+]=C21 OIHZGFWAMWHYPA-UHFFFAOYSA-N 0.000 claims description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 26
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 23
- 239000007810 chemical reaction solvent Substances 0.000 claims description 17
- PWEBUXCTKOWPCW-UHFFFAOYSA-N squaric acid Chemical compound OC1=C(O)C(=O)C1=O PWEBUXCTKOWPCW-UHFFFAOYSA-N 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 125000000542 sulfonic acid group Chemical group 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000005036 alkoxyphenyl group Chemical class 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 229910052711 selenium Chemical group 0.000 claims description 2
- 239000011669 selenium Chemical group 0.000 claims description 2
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims 5
- 238000004519 manufacturing process Methods 0.000 claims 3
- IHXWECHPYNPJRR-UHFFFAOYSA-N 3-hydroxycyclobut-2-en-1-one Chemical class OC1=CC(=O)C1 IHXWECHPYNPJRR-UHFFFAOYSA-N 0.000 claims 1
- 238000007626 photothermal therapy Methods 0.000 abstract description 6
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- 239000000463 material Substances 0.000 abstract description 4
- 238000011282 treatment Methods 0.000 abstract description 4
- 206010028980 Neoplasm Diseases 0.000 abstract description 3
- 238000000862 absorption spectrum Methods 0.000 abstract description 3
- 239000012620 biological material Substances 0.000 abstract description 2
- 238000000295 emission spectrum Methods 0.000 abstract description 2
- 230000003287 optical effect Effects 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 230000015572 biosynthetic process Effects 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 17
- 239000000243 solution Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 9
- OITQDWKMIPXGFL-UHFFFAOYSA-N 1-hydroxy-2-naphthaldehyde Chemical compound C1=CC=C2C(O)=C(C=O)C=CC2=C1 OITQDWKMIPXGFL-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 150000003384 small molecules Chemical class 0.000 description 5
- DQXKOHDUMJLXKH-PHEQNACWSA-N (e)-n-[2-[2-[[(e)-oct-2-enoyl]amino]ethyldisulfanyl]ethyl]oct-2-enamide Chemical compound CCCCC\C=C\C(=O)NCCSSCCNC(=O)\C=C\CCCCC DQXKOHDUMJLXKH-PHEQNACWSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- BXBJZYXQHHPVGO-UHFFFAOYSA-N 4-hydroxycyclohexan-1-one Chemical compound OC1CCC(=O)CC1 BXBJZYXQHHPVGO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000012295 chemical reaction liquid Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 239000012221 photothermal agent Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- SLJYPZJZQIHNGU-UHFFFAOYSA-N 4-(4-hydroxyphenyl)cyclohexan-1-one Chemical compound C1=CC(O)=CC=C1C1CCC(=O)CC1 SLJYPZJZQIHNGU-UHFFFAOYSA-N 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 230000001678 irradiating effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000002103 nanocoating Substances 0.000 description 2
- 238000011056 performance test Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- KOUVJIHCNBZHNG-UHFFFAOYSA-N 4-bromo-1-hydroxynaphthalene-2-carbaldehyde Chemical compound C1=CC=C2C(O)=C(C=O)C=C(Br)C2=C1 KOUVJIHCNBZHNG-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- RBSLJAJQOVYTRQ-UHFFFAOYSA-N croconic acid Chemical compound OC1=C(O)C(=O)C(=O)C1=O RBSLJAJQOVYTRQ-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 238000007709 nanocrystallization Methods 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- FYNROBRQIVCIQF-UHFFFAOYSA-N pyrrolo[3,2-b]pyrrole-5,6-dione Chemical compound C1=CN=C2C(=O)C(=O)N=C21 FYNROBRQIVCIQF-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000001931 thermography Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
-
- 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
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1003—Carbocyclic compounds
- C09K2211/1007—Non-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
- C09K2211/1018—Heterocyclic compounds
- C09K2211/1025—Heterocyclic compounds characterised by ligands
- C09K2211/1088—Heterocyclic compounds characterised by ligands containing oxygen as the only heteroatom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of biological materials, and particularly relates to a near-infrared efficient photo-thermal squarylium cyanine dye, and a preparation method and application thereof. The absorption spectrum and the emission spectrum of the squarylium cyanine compound with the structure shown in the formula (I) are positioned in the near-infrared second optical window region, the squarylium cyanine compound shows strong absorption and weak emission, has higher photothermal conversion efficiency and photothermal stability, and can be used as a candidate material of a photothermal sensitizer for photothermal therapy of tumors. The method for preparing the squarylium cyanine compound with the structure shown in the formula (I) has the advantages of short synthetic route, mild reaction conditions, no need of complex purification treatment, high product yield and good purity.
Description
Technical Field
The invention belongs to the field of biological materials, and particularly relates to a squarylium cyanine compound, and a preparation method and application thereof.
Background
Photothermal therapy (PTT) is an emerging noninvasive and remotely controlled treatment modality that can ablate tumors using localized heat generated by external Near Infrared (NIR) light energy absorbed and converted by photothermal agents (PTA). To date, inorganic and organic photothermal agents based on noble metal materials, up-conversion nanoparticles (UCNPs), transition metal chalcogenides, oxide nanoparticles, carbon nanotubes, semiconducting polymer nanoparticles, and organic small molecule dyes, etc. have been developed for photothermal therapy. Among many materials, organic small molecule dyes have great application potential in the field of photothermal therapy due to advantages of designability, minimal biotoxicity, in vivo biocompatibility, biodegradability and the like. However, the currently reported organic small-molecule near-infrared photothermal sensitizers based on cyanine, diketopyrrolopyrrole, croconic acid, porphyrin and the like all face the problems of low photothermal conversion efficiency, poor stability and the like, and need to be subjected to polymer or nanocrystallization treatment in the application process, because the two-region near-infrared dye molecules generally have the characteristics of long conjugation length, relatively large molecules, poor solubility in water and poor light stability, many two-region near-infrared dyes need to be prepared into a nano material or coated by other materials.
Therefore, it is very necessary to develop an organic small molecule near infrared thermal sensitizer which has good performance and can be directly used without performing a nano-coating process to solve the above problems.
Disclosure of Invention
In view of this, the technical problem to be solved by the present invention is to provide a squarylium compound with a novel structure, which has the defects of low photo-thermal conversion efficiency and poor stability of the existing organic small-molecule near-infrared photo-sensitizer, and has higher photo-thermal conversion efficiency and photo-thermal stability.
The invention also aims to provide a method for preparing the squarylium compound.
The purpose of the invention is realized by the following technical scheme:
the invention provides a squarylium cyanine compound with a structure shown as a formula (I):
wherein X is selected from oxygen, sulfur or selenium; r is 1 、R 3 Each independently selected from hydrogen, bromine or hydroxy; r is 2 、R 4 Each independently selected from hydrogen, hydroxy, saturated or unsaturated alkoxy, substituted or unsubstituted phenyl.
Alternatively, the substituted phenyl is hydroxyphenyl, propargyloxyphenyl or a sulfonate-substituted alkoxyphenyl.
Alternatively, the unsaturated alkoxy group is propargyloxy.
Optionally, the substituted alkoxy is C1-C5 alkoxy substituted by sulfonic acid group.
Optionally, the squarylium cyanine compound is selected from any one of the following structural formulas:
the invention also provides a method for preparing the squaraine compound, which comprises the following steps: s1, under the catalytic action of concentrated sulfuric acid, reacting a 1-hydroxy-2-naphthaldehyde compound shown in a formula (II) with a compound shown in a formula (III) to obtain a tetrahydrobenzo [ c ] xanthylium salt shown in a formula (IV);
s2, reacting tetrahydrobenzo [ c ] xanthylium salt shown in a formula (IV) with 3, 4-dihydroxy-3-cyclobutene-1, 2-diketone to obtain the tetrahydrobenzo [ c ] xanthylium salt;
the synthetic route is as follows:
alternatively, the molar ratio of the 1-hydroxy-2-naphthaldehyde compound shown in the formula (II) to the compound shown in the formula (III) is 1.1-1.2.
Optionally, the mass ratio of the concentrated sulfuric acid to the compound represented by formula (III) is 6 to 8.
Optionally, the reaction temperature of step S1 is 90 ℃, and the reaction time is 3-4 h.
Alternatively, the molar ratio of the tetrahydrobenzo [ c ] xanthylium salt represented by formula (IV) to the 3, 4-dihydroxy-3-cyclobutene-1, 2-dione is 2.2 to 2.4:1.
alternatively, when R in formula (IV) 1 ≠R 3 Or R 2 ≠R 4 Then two of said tetrahydrobenzo [ c]The molar ratio of xanthylium salt is 1.
Firstly, one tetrahydrobenzo [ c ] xanthylium salt reacts with the 3, 4-dihydroxy-3-cyclobutene-1, 2-diketone for 4 to 5 hours, and then another tetrahydrobenzo [ c ] xanthylium salt is added for continuous reaction for 4 to 5 hours.
Alternatively, the mass ratio of the reaction solvent in step S2 to the tetrahydrobenzo [ c ] xanthylium salt represented by formula (IV) is 20 to 25.
Optionally, the reaction solvent is isopropanol, and the reaction temperature is not lower than the boiling point of the reaction solvent.
The invention also provides the application of the squaraine compound or the squaraine compound prepared by the method for preparing the squaraine compound as a near-infrared photothermal sensitizer.
Compared with the prior art, the technical scheme of the invention has the following advantages:
the squarylium cyanine compound with the structure shown in the formula (I) shows strong absorption and weak emission in the absorption and emission spectrum of the near-infrared second optical window region, and oxygen atom parts in the middle of molecules can form hydrogen bonds with water molecules, so that the excitation state of the molecules is disturbed slightly, and efficient energy exchange is caused between the compound molecules and the water molecules, therefore, the squarylium cyanine compound has high photo-thermal conversion efficiency and photo-thermal stability, and can be used as a candidate material of a photo-thermal sensitizer for the photo-thermal therapy of tumors.
The squarylium cyanine compound with the structure shown in the formula (I) is an inner salt, has hydrophile and lipophile, can exist in a single molecule in a certain concentration range, and part of compound molecules are subjected to hydrophilicity improvement, such as hydrophilic sulfonic acid group connection, so that the molecules are dissolved in water, the dispersion degree of the compound molecules is increased, and the squarylium cyanine compound in the single molecule state has good light stability and higher photo-thermal conversion efficiency, so that the squarylium cyanine compound can be used without being subjected to polymer or nano coating treatment before being used, and the convenience and safety in use are greatly improved.
The method for preparing the squarylium cyanine compound with the structure shown in the formula (I) has the advantages of short synthetic route, mild reaction conditions, no need of complex purification treatment, high product yield and good purity.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is a graph of the ultraviolet absorption versus fluorescence emission of Compound I-1, prepared in example 1 of the present invention;
FIG. 2 is a graph of the light exposure temperature rise of Compound I-1 prepared in example 1 of the present invention;
FIG. 3 is a graph showing the photothermal stabilizing effect of compound I-1 prepared in example 1 of the present invention;
FIG. 4 is a mouse photothermographic image of Compound I-3 prepared in example 3 of the present invention.
Detailed Description
The following examples are provided to better understand the present invention, not to limit the best mode, and not to limit the content and protection scope of the present invention, and any product that is the same or similar to the present invention and is obtained by combining the present invention with other features of the prior art and the present invention falls within the protection scope of the present invention.
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.
Example 1
Compound I-1 was synthesized according to the following synthetic route:
(1) Synthesis of 9-hydroxy-8, 9,10, 11-tetrahydrobenzo [ c ] xanthylium salt represented by the formula (IV-1)
1.72g of 1-hydroxy-2-naphthaldehyde represented by the formula (II-1) and 1.37g of 4-hydroxycyclohexanone represented by the formula (III-1) (molar ratio of aldehyde to ketone: 1.2) were charged into a round-bottomed flask, and then 12g of concentrated sulfuric acid was added, and the mixture was heated to 90 ℃ and stirred to react for 4 hours. After the reaction is stopped, the reaction solution is poured into ice brine, is kept stand for a period of time and is filtered under reduced pressure to obtain 3.1g (MS (m/z): C) 17 H 15 O 2 + ]= 251.11) yield 90% purity 90%.
(2) Synthesis of Compound I-1
Into a round-bottomed flask were added 1.1g of squaric acid and 9-hydroxy-8, 9,10, 11-tetrahydrobenzo [ c ] represented by the formula (IV-1)]7.7g of xanthylium salt, 25g of isopropyl alcohol was added as a reaction solvent, and the mixture was heated to reflux for 8 hours. After cooling to room temperature, filtration gave 3.7g (MS (m/z): C) 38 H 26 O 6 +H]= 579.18), yield 65% and purity 95%. 1 H NMR(400MHz,CDCl 3 )δppm:8.15(d,J＝8.0Hz,2H),7.91(d,J＝8.0Hz,2H),7.8(d,J＝8.0Hz,2H),7.85(d,J＝8.4Hz,2H),7.72(s,2H),7.60(t,J＝6.0Hz,2H),8.15(t,J＝8.0Hz,2H),7.51(t,J＝6.0Hz,2H),3.37(d,J＝4.0Hz,2H),3.19(s,2H),2.78(t,J＝8.0Hz,2H),1.90-1.88(m,4H),1.39(s,2H),1.22(s,2H)。
Example 2
Compound I-2 was synthesized according to the following synthetic route:
(1) Synthesis of 9- (4-hydroxyphenyl) -8,9,10, 11-tetrahydrobenzo [ c ] xanthylium salt represented by the formula (IV-2)
1.72g of 1-hydroxy-2-naphthaldehyde and 2.1g of 4- (4-hydroxyphenyl) cyclohexanone are added into a round-bottom flask, then 12g of concentrated sulfuric acid is added, and the temperature is raised to 90 ℃ to be stirred and reacted for 4 hours. After the reaction is stopped, the reaction solution is poured into ice brine, stands for a period of time and is filtered to obtain 4g (MS (m/z): C) 23 H 19 O 2 + ]= 327.14), yield 95%, purity over 90%.
(2) Synthesis of Compound I-2
A round bottom flask was charged with squaric acid 1.1g and 9- (4-hydroxyphenyl) -8,9,10, 11-tetrahydrobenzo [ c ]]8.8g of xanthylium salt, 25g of isopropyl alcohol was added as a reaction solvent, and the mixture was heated to reflux for 8 hours. After cooling to room temperature, filtration gave 4.2g (MS (m/z): C) 50 H 34 O 6 +H]= 731.33), yield 58% and purity 95%. 1 H NMR(400MHz,CDCl 3 )δppm:8.58(t,J＝8.0Hz,2H),8.22-8.13(m,2H),8.08-7.99(m,2H),7.93(d,J＝8.0Hz,1H),7.86(d,J＝8.0Hz,2H),7.67(t,J＝7.4Hz,2H),7.60-7.58(m,2H),7.41-7.38(m,2H),7.07(d,J＝8.0Hz,4H),6.79(d,J＝8.0Hz,4H),3.95(d,J＝4.4Hz,2H),3.80-3.74(m,1H),2.85-2.78(m,2H),2.38-2.28(m,2H),2.19(s,1H)。
Example 3
Compound I-3 was synthesized according to the following synthetic route:
(1) Synthesis of 4- (2-alkynyloxy) -cyclohexanone represented by the formula (III-3)
Adding 1.1g of 4-hydroxycyclohexanone and 2.2g of 3-bromopropyne into a round-bottom flask, adding 20g of acetonitrile serving as a reaction solvent, refluxing for reaction for 12 hours, concentrating the reaction solution, and separating by column chromatography to obtain 1.05g of white solid (MS (m/z): [ C ]: C) 9 H 12 O 2 +H]= 153.08), yield 70%, purity 98%.
(2) Synthesis of Tetrahydrobenzo [ c ] xanthylium salt represented by the formula (IV-3)
1.72g of 1-hydroxy-2-naphthaldehyde and 1.8g of 4- (2-alkynyl oxy) -cyclohexanone are added into a round-bottom flask for synthesis, 11g of concentrated sulfuric acid is added, and the temperature is raised to 90 ℃ and the reaction is stirred for 4 hours. After the reaction is stopped, the reaction liquid is poured into ice brine, and after standing for a period of time, the reaction liquid is filtered to obtain a brown yellow product (MS (m/z): C 20 H 17 O 2 + ]= 289.12) 3.6g, yield 95%, purity 90%. 1 H NMR(400MHz,CDCl 3 )δppm:8.56(t,J＝8.0Hz,2H),8.24-8.15(m,2H),8.02-7.92(m,2H),7.90(d,J＝8.0Hz,1H),7.85(d,J＝8.0Hz,2H),7.63(t,J＝7.4Hz,2H),7.60-7.58(m,2H),7.41-7.38(m,2H),7.04(d,J＝8.0Hz,4H),6.75(d,J＝8.0Hz,4H),3.95(d,J＝4.4Hz,2H),3.80-3.74(m,1H),2.85-2.78(m,2H),2.38-2.28(m,2H),2.19(s,1H),2.5(d,J＝6Hz,2H),3.5(s,4H)。
(3) Synthesis of Compound I-3
A round bottom flask was charged with squaric acid 1.1g and tetrahydrobenzo [ c ]]8g of xanthylium salt, 25g of isopropyl alcohol as a reaction solvent, and heating to reflux reaction for 8 hours. Cooling to room temperature, and vacuum-filtering to obtain a beige product (MS (m/z): C) 44 H 30 O 6 +H]= 655.20) yield 47% purity 95%.
Example 4
Compound I-4 was synthesized according to the following synthetic route:
(1) Synthesis of potassium 3- [4- (4-carbonyl-cyclohexyl) -oxy ] -propane-1-sulfonate represented by the formula (III-4)
A round bottom flask was charged with 1.1g of 4-hydroxycyclohexanone and 1, 4-butanesultone2g, adding KOH 0.6g and acetone 15g as reaction solvent, reacting at room temperature for 24 hours, filtering and recrystallizing with ethanol 5g to obtain white solid 2g (MS (m/z): C 9 H 15 O 5 S - +2H]= 237.06), yield 88% and purity 98%.
(2) Synthesis of Tetrahydrobenzo [ c ] xanthylium salt represented by the formula (IV-4)
1.72g of 1-hydroxy-2-naphthaldehyde and 3- [4- (4-carbonyl-cyclohexyl) -oxy ] are placed in a round-bottomed flask]2.6g of-propane-1-sulfonate, then 12g of concentrated sulfuric acid is added, the temperature is raised to 90 ℃, and the reaction is stirred for 4 hours. After the reaction is stopped, the reaction solution is poured into ice brine, is kept stand for a period of time and is filtered to obtain 3.3g (MS (m/z): C 20 H 20 O 5 S+H]= 373.10), yield 91%, purity 95%. 1 H NMR(400MHz,CDCl 3 )δppm:8.58(t,J＝8.0Hz,2H),8.22-8.13(m,2H),8.08-7.99(m,2H),7.93(d,J＝8.0Hz,1H),7.86(d,J＝8.0Hz,2H),7.67(t,J＝7.4Hz,2H),7.60-7.58(m,2H),7.41-7.38(m,2H),7.07(d,J＝8.0Hz,4H),6.79(d,J＝8.0Hz,4H),3.95(d,J＝4.4Hz,2H),3.80-3.74(m,1H),3.36-3.33(m,2H),3.05-2.96(m,8H),2.85-2.78(m,2H),2.38-2.28(m,2H),2.19(s,1H),1.86-1.77(m,8H).。
(4) Synthesis of Compound I-4
A round bottom flask was charged with squaric acid 1.1g and tetrahydrobenzo [ c ]]Adding isopropanol 25g as reaction solvent into xanthylium salt 7g, heating to reflux reaction for 8 hr, cooling to room temperature, and filtering to obtain grey brown product 3.4g (MS (m/z): C 44 H 36 O 12 S 22 - +H]= 821.17), yield 42% and purity 95%.
Example 5
Compound I-5 was synthesized according to the following synthetic route:
(1) Synthesis of 4-bromo-1-hydroxy-2-naphthaldehyde represented by the formula (II-5)
1.72g of 1-hydroxy-2-naphthaldehyde and 3.1g of liquid bromine were added in a round-bottomed flask, and 20g of chloroform was added for reactionThe solvent was stirred at room temperature for 24 hours, filtered and recrystallized from 5g of chloroform to give 1.5g (MS (m/z): C 11 H 7 O 2 Br+H]= 250.83), yield was 62%, purity was 92%.
(2) Synthesis of 5-bromo-8, 9,10, 11-tetrahydrobenzo [ c ] xanthylium salt represented by the formula (IV-5)
1.25g of 4-bromine-1-hydroxy-2-naphthaldehyde and 0.72g of cyclohexanone are added into a round-bottom flask, then 10g of concentrated sulfuric acid is added, and the temperature is raised to 90 ℃ to be stirred and reacted for 4 hours. After the reaction is stopped, the reaction solution is poured into ice brine, and after standing for a period of time, the reaction solution is filtered to obtain 3.7g (MS (m/z): C) 17 H 14 O 2 Br + ]= 313.17), yield 93%, purity 95%. 1 H NMR(400MHz,CDCl 3 )δppm:8.58(t,J＝8.0Hz,2H),8.22-8.13(m,2H),8.08-7.99(m,1H),7.93(d,J＝8.0Hz,1H),7.86(d,J＝8.0Hz,2H),7.67(t,J＝7.4Hz,2H),7.60-7.58(m,2H),7.41-7.38(m,2H),7.07(d,J＝8.0Hz,4H),6.79(d,J＝8.0Hz,4H),3.95(d,J＝4.4Hz,2H),3.80-3.74(m,1H),2.85-2.78(m,2H),2.38-2.28(m,2H),2.19(s,1H)。
(3) Synthesis of Compound I-5
A round-bottomed flask was charged with 1.1g of squaric acid and 5-bromo-8, 9,10, 11-tetrahydrobenzo [ c ] represented by the formula (IV-5)]4.4g of xanthylium salt, 25g of isopropyl alcohol as a reaction solvent, heating to reflux reaction for 4 hours, and adding 9-hydroxy-8, 9,10, 11-tetrahydrobenzo [ c ] represented by the formula (IV-1)]The xanthylium salt 3.7g is continuously refluxed for 4 hours, cooled to room temperature and filtered to obtain 1.9g of gray brown product (MS (m/z): C 38 H 25 O 5 Br+H]= 641.23), yield 31%, purity 95%.
Example 6
Compound I-6 was synthesized according to the following synthetic route:
a round-bottom flask was charged with 1.1g of squaric acid and tetrahydrobenzo [ c ] of the formula (IV-1)]4.0g of xanthylium salt, 25g of isopropanol as a reaction solvent, and heating to reflux for 4 hoursThen adding 9-hydroxy-8, 9,10, 11-tetrahydrobenzo [ c ] of the formula (IV-3)]The xanthylium salt 3.8g is continuously refluxed for 4 hours, cooled to room temperature and filtered to obtain 1.3g of a grayish brown product (MS (m/z): C 41 H 28 O 6 +H]= 617.23) yield 23% purity 96%. 1 H NMR(400MHz,CDCl 3 )δppm:8.56(t,J＝8.0Hz,2H),8.24-8.15(m,2H),8.02-7.92(m,2H),7.90(d,J＝8.0Hz,1H),7.85(d,J＝8.0Hz,2H),7.63(t,J＝7.4Hz,2H),7.60-7.58(m,2H),7.41-7.38(m,2H),7.04(d,J＝8.0Hz,4H),6.75(d,J＝8.0Hz,4H),3.95(d,J＝4.4Hz,2H),3.80-3.74(m,1H),2.85-2.78(m,2H),2.38-2.28(m,2H),2.19(s,1H),2.5(d,J＝6Hz,1H),3.5(s,2H)。
Example 7
Compound I-7 was synthesized according to the following synthetic route:
a round-bottomed flask was charged with 1.1g of squaric acid and a sulfoacid-containing tetrahydrobenzo [ c ] compound of the formula (IV-1)]4g of xanthylium salt, 25g of isopropyl alcohol as a reaction solvent, heating to reflux reaction for 4 hours, and adding 9-hydroxy-8, 9,10, 11-tetrahydrobenzo [ c ] represented by the formula (IV-4)]The xanthylium salt 3.8g is continuously refluxed for 4 hours, cooled to room temperature and filtered to obtain 1.9g of a grayish brown product (MS (m/z): C 41 H 31 O 9 S -] = 759.21), yield 27% and purity 94%. 1 H NMR(400MHz,CDCl 3 )δppm:8.58(t,J＝8.0Hz,2H),8.22-8.13(m,2H),8.08-7.99(m,2H),7.93(d,J＝8.0Hz,1H),7.86(d,J＝8.0Hz,2H),7.67(t,J＝7.4Hz,2H),7.60-7.58(m,2H),7.41-7.38(m,2H),7.07(d,J＝8.0Hz,4H),6.79(d,J＝8.0Hz,4H),3.95(d,J＝4.4Hz,2H),3.80-3.74(m,1H),3.36-3.33(m,2H),2.85-2.78(m,2H),2.38-2.28(m,2H),2.19(s,1H),1.86-1.77(m,8H)。
Example 8
Compound I-8 was synthesized according to the following synthetic route:
(1) Synthesis of 3- [4- (4-carbonyl-cyclohexyl) -phenoxy ] -propane-1-sulfonate represented by the formula (III-8)
Adding 1.9g of 4- (4-hydroxyphenyl) cyclohexanone and 1.2g of 1, 4-butyl sultone into a round-bottom flask, adding 0.6g of KOH and 25g of anhydrous acetone serving as reaction solvents, reacting at room temperature for 24 hours, adding hydrochloric acid for neutralization, performing suction filtration, and recrystallizing by using 10g of ethanol to obtain a white solid (MS (m/z): [ C) 15 H 19 O 5 S - +2H]= 313.10), yield 88% and purity 95%.
(2) Synthesis of Tetrahydrobenzo [ c ] xanthylium salt represented by the formula (IV-8)
A round-bottomed flask was charged with 2.1g of 1-hydroxy-2-naphthaldehyde and 3- [4- (4-carbonyl-cyclohexyl) -phenoxy ] benzene]3.5g of (E) -propane-1-sulfonic acid, 10g of concentrated sulfuric acid is added, the temperature is raised to 90 ℃, and the reaction is stirred for 4 hours. After the reaction is stopped, the reaction liquid is poured into ice brine, stands for a period of time and is filtered by suction to obtain a brown yellow product (MS (m/z): C 26 H 24 O 5 S+H]= 449.13), yield 91%, purity 93%.
(3) Synthesis of Compound I-8
A round bottom flask was charged with squaric acid 1.2g and tetrahydrobenzo [ c ]]9g of xanthylium salt was added to 30g of isopropyl alcohol as a reaction solvent, and the mixture was heated to reflux reaction for 8 hours. Cooling to room temperature, and vacuum filtering to obtain a dark brown product (MS (m/z): (C) 56 H 54 O 12 S 2 2- +H]= 973.23), yield 42% and purity 91%. 1 H NMR(400MHz,CDCl3)δppm:8.58(t,J＝8.0Hz,2H),8.22-8.13(m,2H),8.08-7.99(m,2H),7.93(d,J＝8.0Hz,1H),7.86(d,J＝8.0Hz,2H),7.67(t,J＝7.4Hz,2H),7.60-7.58(m,2H),7.41-7.38(m,2H),7.07(d,J＝8.0Hz,4H),6.79(d,J＝8.0Hz,4H),3.95(d,J＝4.4Hz,2H),3.80-3.74(m,1H),3.36-3.33(m,2H),3.05-2.96(m,8H),2.85-2.78(m,2H),2.38-2.28(m,2H),2.19(s,1H),1.86-1.77(m,8H).ESI-HRMS m/z calcd for[C58H48O12S22-],1000.2598；found,1000.6835.
Experimental example 1 spectral analysis
The ultraviolet absorption signal and the fluorescence emission signal of the near-infrared second window region of the compound I-1 prepared in the embodiment 1 of the invention are tested, and the specific test steps are as follows:
compound I-1 was dissolved in dimethyl sulfoxide to give a solution at a concentration of 1mM, which was then diluted to 5. Mu.M with methylene chloride, and the solution was tested for ultraviolet absorption and fluorescence emission spectra, respectively. As a result, as shown in FIG. 1, the maximum absorption and emission wavelengths of Compound I-1 were at 899nm and 1067nm, respectively.
Experimental example 2 photothermal Property test
The photothermal performance tests of the compounds I-1 to I-8 prepared in the embodiment of the invention are respectively carried out, wherein the photothermal performance test of the compound I-1 prepared in the embodiment 1 specifically comprises the following steps: compound I-1 prepared in example 1 was dissolved in dimethyl sulfoxide to give a 1mM solution, which was then made into a 100. Mu.M agar solution, and cooled to give a gel of Compound I-1. The result of irradiating the gel sample with 915nm laser is shown in fig. 2, and the temperature of the sample is rapidly increased, which shows that the squarylium compound provided by the invention has high photothermal conversion efficiency, through calculation, the photothermal conversion efficiency of the compound I-1 prepared in example 1 is 55%, and the result of irradiating the gel sample with 915nm laser for multiple times is shown in fig. 3, and the temperature rise effect of the sample does not obviously change after 5 times of irradiation, which shows that the compound I-1 prepared in example 1 of the invention has stable photothermal performance.
The compounds I-2 to I-8 prepared in example 2-8 were tested and calculated using the same photothermal property test method as that for the compound I-1 prepared in example 1, and the photothermal conversion efficiencies of the compounds I-2 to I-8 were calculated to be 63%,52%,67%,59%,57%,62% and 74%, respectively.
Experimental example 3 mouse thermal imaging experiment
Compound I-3 prepared in example 3 of the present invention was dissolved in dimethyl sulfoxide to obtain a 5mM solution, 40. Mu.L of the solution was injected into the abdominal cavity of a mouse, and the mouse was continuously irradiated with 915nm laser for 3min, as shown in FIG. 4, the body temperature of the mouse was significantly increased.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. This need not be, nor should it be exhaustive of all embodiments. And obvious variations or modifications derived therefrom are intended to be within the scope of the invention.
Claims (10)
1. A squarylium cyanine compound with a structure shown as a formula (I):
wherein X is selected from oxygen, sulfur or selenium; r is 1 、R 3 Each independently selected from hydrogen, bromine or hydroxy; r is 2 、R 4 Each independently selected from hydrogen, hydroxy, saturated or unsaturated alkoxy, substituted or unsubstituted phenyl.
2. The squaraine compound of claim 1, wherein the substituted phenyl group is a hydroxyphenyl, propargyloxyphenyl, or a sulfonate-substituted alkoxyphenyl group; and/or the presence of a gas in the gas,
the unsaturated alkoxy group is propargyloxy; and/or the presence of a gas in the atmosphere,
the substituted alkoxy is C1-C5 alkoxy substituted by sulfonic acid group.
3. The squarylium compound according to claim 1 or 2, characterized by being selected from any one of the following structural formulae:
4. a process for preparing squarylium compounds according to any one of claims 1 to 3, comprising the steps of:
s1, under the catalytic action of concentrated sulfuric acid, reacting a 1-hydroxy-2-naphthaldehyde compound shown in a formula (II) with a compound shown in a formula (III) to obtain a tetrahydrobenzo [ c ] xanthylium salt shown in a formula (IV);
s2, reacting tetrahydrobenzo [ c ] xanthylium salt shown in a formula (IV) with 3, 4-dihydroxy-3-cyclobutene-1, 2-diketone to obtain the tetrahydrobenzo [ c ] xanthylium salt;
the synthetic route is as follows:
5. the method for preparing squaraines according to claim 4, wherein the molar ratio of the 1-hydroxy-2-naphthaldehyde compound represented by the formula (II) to the compound represented by the formula (III) is 1.1 to 1.2.
6. The method for preparing squaraine compounds according to claim 4 or 5, wherein the mass ratio of the concentrated sulfuric acid to the compound represented by formula (III) is 6 to 8; and/or the presence of a gas in the atmosphere,
the reaction temperature of the step S1 is 90 ℃, and the reaction time is 3-4 h.
7. The method for preparing squarylium compounds according to claim 4, wherein the molar ratio of tetrahydrobenzo [ c ] xanthylium salt represented by formula (IV) to 3, 4-dihydroxy-3-cyclobutene-1, 2-dione is 2.2 to 2.4:1.
8. the method for preparing squarylium cyanine according to claim 7A process according to (IV) wherein R is 1 ≠R 3 Or R 2 ≠R 4 When two of said tetrahydrobenz [ c ]]The molar ratio of the xanthylium salt is 1;
firstly, one tetrahydrobenzo [ c ] xanthylium salt and the 3, 4-dihydroxy-3-cyclobutene-1, 2-diketone react for 4 to 5 hours, and then another tetrahydrobenzo [ c ] xanthylium salt is added for continuous reaction for 4 to 5 hours.
9. The method for producing a squarylium compound according to claim 4, 7 or 8, wherein the mass ratio of the reaction solvent to the tetrahydrobenzo [ c ] xanthylium salt represented by formula (IV) in step S2 is 20 to 25; and/or the presence of a gas in the atmosphere,
the reaction solvent is isopropanol, and the reaction temperature is not lower than the boiling point of the reaction solvent.
10. Use of the squarylium compound of any one of claims 1 to 3 or the squarylium compound produced by the method for producing a squarylium compound of any one of claims 4 to 9 as a near-infrared photothermographic sensitizer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211171304.5A CN115557926B (en) | 2022-09-23 | 2022-09-23 | Squaraine compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211171304.5A CN115557926B (en) | 2022-09-23 | 2022-09-23 | Squaraine compound and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115557926A true CN115557926A (en) | 2023-01-03 |
| CN115557926B CN115557926B (en) | 2024-02-06 |
Family
ID=84742141
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211171304.5A Active CN115557926B (en) | 2022-09-23 | 2022-09-23 | Squaraine compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115557926B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105585872A (en) * | 2016-03-09 | 2016-05-18 | 清华大学 | Asymmetric near-infrared cyanine dye and preparing method and application thereof |
| CN109053531A (en) * | 2018-08-14 | 2018-12-21 | 清华大学 | A kind of asymmetric side's acid cyanines material and its preparation method and application |
| CN114656493A (en) * | 2022-03-15 | 2022-06-24 | 华南理工大学 | Dye pyrrolopyrrole cyanine compound with aggregation-induced emission and near-infrared emission and preparation method thereof |
-
2022
- 2022-09-23 CN CN202211171304.5A patent/CN115557926B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105585872A (en) * | 2016-03-09 | 2016-05-18 | 清华大学 | Asymmetric near-infrared cyanine dye and preparing method and application thereof |
| CN109053531A (en) * | 2018-08-14 | 2018-12-21 | 清华大学 | A kind of asymmetric side's acid cyanines material and its preparation method and application |
| CN114656493A (en) * | 2022-03-15 | 2022-06-24 | 华南理工大学 | Dye pyrrolopyrrole cyanine compound with aggregation-induced emission and near-infrared emission and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115557926B (en) | 2024-02-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113462187B (en) | Heptamethine indocyanine dye and preparation method and application thereof | |
| CN111689950B (en) | Organic diheterocyclic near-infrared fluorescent probe based on diphenylamino and preparation method and application thereof | |
| CN111718365B (en) | Trimeric indenyl conjugated tri-BODIPY near-infrared fluorescent dye and preparation method thereof | |
| CN108102408A (en) | A kind of preparation and application of the nir dye based on azepine fluorine borine | |
| CN110283586B (en) | Near-infrared fluorescent dye and preparation method thereof | |
| CN105985363B (en) | The synthesis and its application of a kind of fluorine boron fluorochrome | |
| CN112358493B (en) | Micromolecular photothermal reagent based on boron-fluorine complex and preparation method and application thereof | |
| CN115557926B (en) | Squaraine compound and preparation method and application thereof | |
| CN111039853B (en) | Iron complex for photoacoustic imaging and photothermal therapy and preparation method and application thereof | |
| CN108558834B (en) | Pyridazinyl three-color fluorescence emission organic luminescent material and application thereof | |
| EP3553054B1 (en) | Fluorescent coumarin compounds and method of synthesis thereof | |
| CN113372339B (en) | Photodynamic/photothermal bifunctional compound NS-STPA and application thereof | |
| CN111961072B (en) | Lysosome-targeted infrared two-window emission fluorescent dye and preparation method and application thereof | |
| CN113072574B (en) | Fluoroborazine 29897 | |
| CN114539306A (en) | Novel process for synthesizing cresol trozole trisiloxane | |
| CN115466187A (en) | 1 '-hydroxy-2' -anthracene chalcone derivative and preparation method and application thereof | |
| CN115627082A (en) | D-A-pi-A type benzothiadiazole functional dye and preparation method and application thereof | |
| CN111778016B (en) | Near infrared fluorescent probe and preparation method and application thereof | |
| CN104803984B (en) | A kind of 2,6 2（2‑（1 phenyl）Benzimidazole）The preparation method of pyridine | |
| CN111849196B (en) | Near-infrared two-region dye and synthetic method thereof | |
| CN112898328A (en) | Coupled double-BODIPY fluorescent dye and preparation method thereof | |
| CN113501836A (en) | Star BODIPY near-infrared fluorescent dye and preparation method thereof | |
| CN115710269B (en) | Multicolor perylene imide fluorescent dye and synthetic method and application thereof | |
| CN115850993B (en) | Chiral amphiphilic near-infrared aza-BODIPY dye and preparation method thereof | |
| CN116143682B (en) | Near infrared two-region contrast agent based on xanthene skeleton, 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 |