JP5590654B2 - Heterocycle-substituted aromatic compound, molecular detection agent, molecular detection method, and molecular capture method - Google Patents
Heterocycle-substituted aromatic compound, molecular detection agent, molecular detection method, and molecular capture method Download PDFInfo
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- JP5590654B2 JP5590654B2 JP2010031792A JP2010031792A JP5590654B2 JP 5590654 B2 JP5590654 B2 JP 5590654B2 JP 2010031792 A JP2010031792 A JP 2010031792A JP 2010031792 A JP2010031792 A JP 2010031792A JP 5590654 B2 JP5590654 B2 JP 5590654B2
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- 238000001514 detection method Methods 0.000 title claims description 49
- 238000000034 method Methods 0.000 title claims description 45
- 150000001491 aromatic compounds Chemical class 0.000 title claims description 26
- 239000007788 liquid Substances 0.000 claims description 79
- 239000002775 capsule Substances 0.000 claims description 68
- 229910021645 metal ion Inorganic materials 0.000 claims description 50
- 239000003795 chemical substances by application Substances 0.000 claims description 26
- 230000015572 biosynthetic process Effects 0.000 claims description 18
- 238000001926 trapping method Methods 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 82
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 43
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Chemical compound [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 24
- -1 tetrafluoroborate ion Chemical class 0.000 description 23
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 150000001450 anions Chemical class 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000005755 formation reaction Methods 0.000 description 11
- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 229910020366 ClO 4 Inorganic materials 0.000 description 9
- 239000010949 copper Substances 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000002798 polar solvent Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 230000035945 sensitivity Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 150000002500 ions Chemical class 0.000 description 7
- 150000003839 salts Chemical class 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 125000001309 chloro group Chemical group Cl* 0.000 description 6
- 229910000365 copper sulfate Inorganic materials 0.000 description 6
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 125000005843 halogen group Chemical group 0.000 description 5
- 239000012454 non-polar solvent Substances 0.000 description 5
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 5
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 150000004698 iron complex Chemical class 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000000542 sulfonic acid group Chemical group 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 3
- 239000002689 soil Substances 0.000 description 3
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- XTEGARKTQYYJKE-UHFFFAOYSA-M Chlorate Chemical compound [O-]Cl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-M bromate Inorganic materials [O-]Br(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-M 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 150000004696 coordination complex Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 235000013336 milk Nutrition 0.000 description 2
- 239000008267 milk Substances 0.000 description 2
- 210000004080 milk Anatomy 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- POILWHVDKZOXJZ-ARJAWSKDSA-M (z)-4-oxopent-2-en-2-olate Chemical compound C\C([O-])=C\C(C)=O POILWHVDKZOXJZ-ARJAWSKDSA-M 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- BPRYUXCVCCNUFE-UHFFFAOYSA-N 2,4,6-trimethylphenol Chemical compound CC1=CC(C)=C(O)C(C)=C1 BPRYUXCVCCNUFE-UHFFFAOYSA-N 0.000 description 1
- SVAMWRLVURFKRX-UHFFFAOYSA-N 3,5-bis(bromomethyl)-2,4,6-trimethylphenol Chemical compound CC1=C(O)C(C)=C(CBr)C(C)=C1CBr SVAMWRLVURFKRX-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N Azide Chemical compound [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- ROKACKSEMAYTTL-UHFFFAOYSA-N CC(C1=C(C)C(CBr)=C(C)C(CBr)=C1C)O Chemical compound CC(C1=C(C)C(CBr)=C(C)C(CBr)=C1C)O ROKACKSEMAYTTL-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical group [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000018997 Growth Hormone Human genes 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 208000036626 Mental retardation Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000002521 alkyl halide group Chemical group 0.000 description 1
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- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910001431 copper ion Inorganic materials 0.000 description 1
- RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 description 1
- NHELIHXBJRANPL-UHFFFAOYSA-L copper;diperchlorate;hexahydrate Chemical compound O.O.O.O.O.O.[Cu+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O NHELIHXBJRANPL-UHFFFAOYSA-L 0.000 description 1
- 238000012926 crystallographic analysis Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- IYWCBYFJFZCCGV-UHFFFAOYSA-N formamide;hydrate Chemical compound O.NC=O IYWCBYFJFZCCGV-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 239000010842 industrial wastewater Substances 0.000 description 1
- 239000008235 industrial water Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229910052976 metal sulfide Inorganic materials 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
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- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
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- 125000002098 pyridazinyl group Chemical group 0.000 description 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
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Description
本発明は、複素環置換芳香族化合物、分子検出剤、分子検出方法、及び分子捕捉方法に関する。 The present invention relates to a heterocyclic-substituted aromatic compound, a molecular detection agent, a molecular detection method, and a molecular capture method.
従来より、液体試料中の分子サイズ１ｎｍ以下の分子を除去する技術や検出する技術に関し、種々の検討が行われている。
例えば、分子サイズ１ｎｍ以下の分子のうち過塩素酸イオンは、甲状腺のヨウ素の取り込みを阻害し、その結果成長ホルモンの生成が妨げられる作用がある。そのため、過塩素酸イオンを乳幼児が摂取しすぎると、成長阻害や運動障害、あるいは精神遅滞などの悪影響を及ぼすことが懸念されている。また、近年、土壌・水中において過塩素酸塩の混入が増加しつつあることが知られている。
過塩素酸イオン（ＣｌＯ４ −）は、水に対して高い溶解度を示し、また金属イオンと相互作用が極めて低い。このため、液体試料中の過塩素酸イオンを検出する方法として、従来は、イオンクロマトグラフィー等の機器分析を利用する方法や、まず液体試料に可溶な鉄錯体を添加して過塩素酸イオンを対イオンとして含む鉄錯体を生成させ、次に、生じた鉄錯体をニトロベンゼンで抽出し、抽出された鉄錯体の吸光度を測定するという煩雑な方法等が用いられてきた。従って、液体試料中の過塩素酸イオンを直接的に検出できる検出剤の開発が望まれている。
Conventionally, various studies have been made on techniques for removing and detecting molecules having a molecular size of 1 nm or less in a liquid sample.
For example, perchlorate ions among molecules having a molecular size of 1 nm or less inhibit the thyroid iodine uptake, and as a result, have the effect of preventing growth hormone production. For this reason, there are concerns that adverse effects such as growth inhibition, movement disorders, and mental retardation will occur when infants take too much perchlorate ions. In recent years, it is known that perchlorate contamination is increasing in soil and water.
Perchlorate ion (ClO 4 − ) exhibits high solubility in water and has extremely low interaction with metal ions. For this reason, as a method for detecting perchlorate ions in a liquid sample, conventionally, a method using instrumental analysis such as ion chromatography or a method in which a soluble iron complex is first added to a liquid sample and perchlorate ions are added. A complex method has been used, in which an iron complex containing as a counter ion is generated, the resulting iron complex is extracted with nitrobenzene, and the absorbance of the extracted iron complex is measured. Accordingly, it is desired to develop a detection agent that can directly detect perchlorate ions in a liquid sample.
液体試料中の過塩素酸イオンを除去する方法としては、液体試料を濃縮する必要がある従来の方法（例えば、特許文献１参照）や、樹脂を用いて除去する従来の方法（例えば、特許文献２及び非特許文献１参照）に代えて、特定の複素環置換芳香族化合物を用い、液体試料中の過塩素酸イオンを捕捉カプセル型分子に取り込んで沈殿させる方法が知られている（例えば、特許文献３参照）。
種々のイオンを取り込むようにカプセルを形成し得る化合物としては、例えば非特許文献２に記載された化合物も知られているが、上記特許文献３に記載の複素環置換芳香族化合物は、特定のイオンを選択的に取り込んで捕捉カプセル型分子を形成できる点で、非特許文献２に記載された化合物とは異なる。
As a method for removing perchlorate ions in a liquid sample, a conventional method in which the liquid sample needs to be concentrated (for example, see Patent Document 1) or a conventional method for removing using a resin (for example, Patent Document 1). 2 and Non-Patent Document 1), instead of using a specific heterocyclic-substituted aromatic compound, a method is known in which perchlorate ions in a liquid sample are taken into a capture capsule type molecule and precipitated (for example, (See Patent Document 3).
As a compound capable of forming a capsule so as to take in various ions, for example, a compound described in Non-Patent Document 2 is also known, but the heterocyclic-substituted aromatic compound described in Patent Document 3 is a specific compound. It is different from the compound described in Non-Patent Document 2 in that ions can be selectively taken in to form a capture capsule type molecule.
また、分子サイズ１ｎｍ以下の分子のうち、テトラフルオロホウ酸イオン（ＢＦ４ −）は、半導体製造工程やめっき工程等の廃液に含まれるイオンである。
テトラフルオロホウ酸イオンを含む廃液の処理方法、即ち、廃液中からテトラフルオロホウ酸イオンを除去する除去方法は、テトラフルオロホウ酸イオンをフッ素とホウ素とに分解し、得られたフッ素とホウ素とを個別に処理する方法が主流となっている（例えば、特許文献４及び５参照）。
テトラフルオロホウ酸イオンを分解せず直接的に沈殿させる化合物としても、上記特許文献３と同様の複素環置換芳香族化合物が有効であることが報告されている（例えば、特許文献６参照）。
Further, among the molecules having a molecular size of 1 nm or less, tetrafluoroborate ion (BF 4 − ) is an ion contained in a waste liquid such as a semiconductor manufacturing process or a plating process.
The treatment method of the waste liquid containing tetrafluoroborate ions, that is, the removal method of removing the tetrafluoroborate ions from the waste liquid, decomposes the tetrafluoroborate ions into fluorine and boron, and obtains the obtained fluorine and boron. The method of processing each of them has become the mainstream (see, for example, Patent Documents 4 and 5).
It has been reported that a heterocyclic-substituted aromatic compound similar to Patent Document 3 is effective as a compound that directly precipitates tetrafluoroborate ions without decomposing (see, for example, Patent Document 6).
しかしながら、液体試料中の分子サイズ１ｎｍ以下の分子を検出する方法としては、より短時間に、より感度良く検出する方法の開発が望まれている。
従って、本発明の目的は、液体試料中の分子サイズ１ｎｍ以下の標的分子を、短時間に感度良く検出できる複素環置換芳香族化合物、分子検出剤、分子検出方法、及び分子捕捉方法を提供することである。
However, as a method for detecting a molecule having a molecular size of 1 nm or less in a liquid sample, it is desired to develop a method for detecting with higher sensitivity in a shorter time.
Therefore, an object of the present invention is to provide a heterocyclic-substituted aromatic compound, a molecular detection agent, a molecular detection method, and a molecular capture method that can detect a target molecule having a molecular size of 1 nm or less in a liquid sample in a short time with high sensitivity. That is.
前記課題を解決するための手段は以下のとおりである。
＜１＞ 下記式（ａ）、下記式（ｃ）、下記式（ｅ）、又は下記式（ｇ）で表される複素環置換芳香族化合物。
Means for solving the above-mentioned problems are as follows.
<1> A heterocyclic substituted aromatic compound represented by the following formula (a), the following formula (c), the following formula (e), or the following formula (g) .
＜２＞ 前記式（ａ）又は前記式（ｃ）で表される＜１＞記載の複素環置換芳香族化合物。 <2> The heterocyclic substituted aromatic compound according to <1> , which is represented by the formula (a) or the formula (c) .
＜３＞ 前記式（ａ）で表される＜１＞記載の複素環置換芳香族化合物。 <3> the formula (a) <1> Symbol mounting heterocyclic-substituted aromatic compound.
＜４＞ ＜１＞〜＜３＞のいずれか１項に記載の複素環置換芳香族化合物を含み、液体試料中の分子サイズ１ｎｍ以下の標的分子を検出する分子検出剤。 <4> A molecular detection agent for detecting a target molecule having a molecular size of 1 nm or less in a liquid sample, comprising the heterocyclic-substituted aromatic compound according to any one of <1> to <3> .
＜５＞ 液体試料中の分子サイズ１ｎｍ以下の標的分子を検出する方法であって、
＜１＞〜＜３＞のいずれか１項に記載の複素環置換芳香族化合物と、平面四配位又は正八面体配位可能な金属イオンと、前記液体試料と、を接触させて、前記標的分子を捕捉した捕捉カプセル型分子を形成させ、該捕捉カプセル型分子の形成に伴う液体試料の色の変化により前記標的分子を検出する分子検出方法。
<5> A method for detecting a target molecule having a molecular size of 1 nm or less in a liquid sample,
<1>-<3> The heterocyclic substituted aromatic compound according to any one of the above, a metal ion capable of planar tetracoordination or regular octahedral coordination, and the liquid sample are brought into contact with each other, and the target A molecular detection method in which a capture capsule type molecule capturing a molecule is formed, and the target molecule is detected by a change in color of a liquid sample accompanying the formation of the capture capsule type molecule.
＜６＞ 液体試料中の分子サイズ１ｎｍ以下の標的分子を捕捉する方法であって、
＜１＞〜＜３＞のいずれか１項に記載の複素環置換芳香族化合物と、平面四配位又は正八面体配位可能な金属イオンと、前記液体試料と、を接触させて、前記標的分子を捕捉した捕捉カプセル型分子を形成させることを含む分子捕捉方法。
<6> A method for capturing a target molecule having a molecular size of 1 nm or less in a liquid sample,
<1>-<3> The heterocyclic substituted aromatic compound according to any one of the above, a metal ion capable of planar tetracoordination or regular octahedral coordination, and the liquid sample are brought into contact with each other, and the target A molecular trapping method comprising forming a trapping capsule molecule trapping a molecule.
本発明によれば、液体試料中の分子サイズ１ｎｍ以下の標的分子を、短時間に感度良く検出できる複素環置換芳香族化合物、分子検出剤、分子検出方法、及び分子捕捉方法を提供することができる。 According to the present invention, it is possible to provide a heterocyclic-substituted aromatic compound, a molecular detection agent, a molecular detection method, and a molecular capture method that can detect a target molecule having a molecular size of 1 nm or less in a liquid sample in a short time with high sensitivity. it can.
＜複素環置換芳香族化合物＞
本発明の複素環置換芳香族化合物は、下記一般式（Ｉ）で表される複素環置換芳香族化合物のうち、後述する、式（ａ）、式（ｃ）、式（ｅ）、又は式（ｇ）で表される複素環置換芳香族化合物である。
<Heterocyclic substituted aromatic compound>
Heterocyclic-substituted aromatic compound of the present invention, among the heterocyclic-substituted aromatic compound represented by the following formula (I), described below, formula (a), Formula (c), Formula (e), or Formula It is a heterocyclic substituted aromatic compound represented by (g).
［式中、Ｒ２、Ｒ３、及びＲ４のうち１つは、Ｒｘに対してメタ位又はパラ位にあるＲｙであり、Ｒｘ及びＲｙは互いに独立して下記の複素環置換基を表し、 Wherein, R 2, R 3, and one of R 4 is in the meta or para to R x R y, R x and R y heterocycle below each independently Represents a substituent,
Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５からＲｙを除いた残りは、それぞれ独立に、水酸基、メチロール基（−ＣＨ２ＯＨ基）、水素原子、アセチル基、ハロゲン原子、炭素数１〜３０の置換若しくは未置換の脂肪族基、又はスルホン酸基を表す。Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５からＲｙを除いた残りのうち、少なくとも１つは水酸基又はメチロール基（−ＣＨ２ＯＨ基）である。
前記複素環置換基のうち、Ｒ６及びＲ７はそれぞれ独立に、水素原子又はメチル基を表し、Ａは、窒素原子を少なくとも１つ含む５員又は６員の複素環基を表す。
The rest of R 1 , R 2 , R 3 , R 4 and R 5 except R y is each independently a hydroxyl group, a methylol group (—CH 2 OH group), a hydrogen atom, an acetyl group, a halogen atom, or a carbon number. 1-30 substituted or unsubstituted aliphatic groups or sulfonic acid groups are represented. At least one of R 1 , R 2 , R 3 , R 4 and the remainder obtained by removing R y from R 5 is a hydroxyl group or a methylol group (—CH 2 OH group).
Among the heterocyclic substituents, R 6 and R 7 each independently represent a hydrogen atom or a methyl group, and A represents a 5-membered or 6-membered heterocyclic group containing at least one nitrogen atom.
一般式（Ｉ）で表される複素環置換芳香族化合物（以下、「一般式（Ｉ）で表される化合物」ともいう）は、液体試料中で、平面四配位又は正八面体配位可能な金属イオンと、分子サイズ１ｎｍ以下の標的分子、に接触すると、複数集まって前記金属イオンとともに、前記標的分子を取り込んでカプセル型分子を形成する（自己集積化反応）。
本発明においては「分子サイズ１ｎｍ以下の標的分子」を、単に「標的分子」ともいう。
また、本発明においては前記標的分子を取り込んだカプセル型分子を、「捕捉カプセル型分子」という。捕捉カプセル型分子の構造の一例については、後述する実施例２（図１）で詳細に説明する。
上記接触により捕捉カプセル型分子が形成される理由は、前記標的分子のサイズが、前記一般式（Ｉ）で表される化合物と前記金属イオンとで形成されるカプセル骨格の内部空間（捕捉空間）のサイズよりも小さく、かつ、前記標的分子が前記内部空間から離脱しにくいため、と考えられる。
Heterocyclic-substituted aromatic compound represented by a general formula (I) (hereinafter, also referred to as "the general formula (compound represented by I)") is a liquid sample, the planar four-coordinate or octahedral coordination When contact is made with a possible metal ion and a target molecule having a molecular size of 1 nm or less, a plurality of them gather together with the metal ion to form a capsule molecule (self-assembly reaction).
In the present invention, “target molecule having a molecular size of 1 nm or less” is also simply referred to as “target molecule”.
In the present invention, the capsule molecule incorporating the target molecule is referred to as a “capture capsule molecule”. An example of the structure of the capture capsule type molecule will be described in detail in Example 2 (FIG. 1) described later.
The reason why a capture capsule type molecule is formed by the contact is that the size of the target molecule is the internal space (capture space) of the capsule skeleton formed by the compound represented by the general formula (I) and the metal ion. This is considered to be because the target molecule is less likely to be detached from the internal space.
一般式（Ｉ）で表される化合物は、分子中に水酸基（メチロール基中の水酸基を含む）を少なくとも１つ有しているため、極性溶媒（例えば水）に対する溶解性が高い。更に、前記一般式（Ｉ）で表される化合物は骨格中に芳香環を有するため、非極性溶媒に対する溶解性も高い。
従って、前記一般式（Ｉ）で表される化合物は、溶媒として極性溶媒及び非極性溶媒の少なくとも一方を含む液体試料中に容易に溶解されるとともに、短時間で捕捉カプセル型分子を形成できる。更に、形成された捕捉カプセル型分子自体も水酸基を有し、かつ、骨格中に芳香環を有するため、溶媒として極性溶媒及び非極性溶媒の少なくとも一方を含む液体試料への溶解性が高い。このため、捕捉カプセル型分子の形成に伴い、液体試料が該捕捉カプセル型分子に由来する色（例えば紫色）に着色する。
従って、一般式（Ｉ）で表される化合物と、平面四配位又は正八面体配位可能な金属イオンと、標的分子を含む液体試料と、を接触させて、該標的分子を捕捉した捕捉カプセル型分子を形成させ、該捕捉カプセル型分子の形成に伴う液体試料の色の変化を確認することにより、液体試料中の標的分子を、短時間に感度良く検出できる。
One general formula (I) compound represented by the because the hydroxyl group (including a hydroxyl group in the methylol groups) at least one has in the molecule, has high solubility in polar solvents (e.g., water). Furthermore, since the compound represented by the general formula (I) has an aromatic ring in the skeleton, it has high solubility in a nonpolar solvent.
Therefore, the compound represented by the general formula (I) can be easily dissolved in a liquid sample containing at least one of a polar solvent and a nonpolar solvent as a solvent, and can form a capture capsule type molecule in a short time. Furthermore, since the formed capture capsule type molecule itself has a hydroxyl group and an aromatic ring in the skeleton, it has high solubility in a liquid sample containing at least one of a polar solvent and a nonpolar solvent as a solvent. For this reason, with the formation of the capture capsule type molecule, the liquid sample is colored in a color derived from the capture capsule type molecule (for example, purple).
Therefore, the capture capsule that captures the target molecule by contacting the compound represented by the general formula (I), the metal ion capable of planar tetracoordinate or octahedral coordination, and the liquid sample containing the target molecule The target molecule in the liquid sample can be detected with high sensitivity in a short time by forming the type molecule and confirming the change in the color of the liquid sample accompanying the formation of the capture capsule type molecule.
従って、一般式（１）で表される化合物による標的分子の検出では、長時間（例えば１時間以上）を必要とせず、標的分子の濃度が高い液体試料（例えば２０ｍＭ以上）を用いる必要もない。
一般式（１）で表される化合物による標的分子の検出では、検出に要する時間は、例えば１０分以内とすることができ、更には５分以内とすることもでき、更には１分以内とすることもでき、更には５秒以内とすることもできる。
一般式（１）で表される化合物による標的分子の検出では、液体試料中における標的分子の濃度は、例えば１０ｍＭ以内とすることができ、更には５ｍＭ以内とすることもでき、更には１ｍＭ以内とすることもでき、更には０．５ｍＭ以内とすることもできる。
Therefore, the detection of the target molecule by the compound represented by the general formula (1) does not require a long time (for example, 1 hour or more), and it is not necessary to use a liquid sample (for example, 20 mM or more) having a high concentration of the target molecule. .
In the detection of the target molecule by the compound represented by the general formula (1), the time required for detection can be, for example, within 10 minutes, further within 5 minutes, and within 1 minute. It can also be within 5 seconds.
In the detection of the target molecule by the compound represented by the general formula (1), the concentration of the target molecule in the liquid sample can be, for example, within 10 mM, further within 5 mM, and further within 1 mM. It can also be within 0.5 mM.
前記平面四配位又は正八面体配位可能な金属イオンとして、具体的には、Ｃｕ２＋、Ｎｉ２＋、Ｃｏ２＋、Ｆｅ２＋、及びＭｎ２＋が挙げられる。 Specific examples of the metal ions capable of planar tetracoordinate or regular octahedral coordination include Cu 2+ , Ni 2+ , Co 2+ , Fe 2+ , and Mn 2+ .
前記標的分子において、分子サイズ１ｎｍ以下とは、分子の最大径が１ｎｍ以下であることを指す。
ここで、分子の最大径は、ファンデルワールス半径を考慮して作製した構造モデルを基に、その分子を構成する末端の原子間距離の最長距離の平均から求められた値を指す。
また、前記標的分子は、陰イオン及び中性分子のいずれであってもよいが、陰イオンが好ましい。
In the target molecule, the molecular size of 1 nm or less means that the maximum diameter of the molecule is 1 nm or less.
Here, the maximum diameter of a molecule refers to a value obtained from the average of the longest distances between the atoms at the ends constituting the molecule based on a structural model prepared in consideration of the van der Waals radius.
The target molecule may be either an anion or a neutral molecule, but is preferably an anion.
本発明における標的分子の具体例を以下に示す。
陰イオンである標的分子としては、例えば、ＸＯａ −で表されるオキソ酸イオン、硝酸イオン（ＮＯ３ −）、テトラフルオロホウ酸イオン（ＢＦ４ −）、ヘキサフルオロリン酸イオン（ＰＦ６ −）、リン酸イオン（ＰＯ４ ３−）、トリフルオロメタンスルホン酸イオン（ＣＦ３ＳＯ３ −）、アジ化物イオン（Ｎ３ −）、等が挙げられる。
前記ＸＯａ −におけるＸは、塩素原子、臭素原子、ヨウ素原子等のハロゲン原子を表し、中でも、塩素原子又は臭素原子が好ましい。前記ＸＯａ −におけるａは、１〜４の整数を表し、中でも３〜４の整数が好ましい。
具体的には、前記ＸＯａ −で表されるオキソ酸イオンとしては、過塩素酸イオン（ＣｌＯ４ −）、塩素酸イオン（ＣｌＯ３ −）、又は臭素酸イオン（ＢｒＯ３ −）が好ましく、過塩素酸イオン（ＣｌＯ４ −）が特に好ましい。
陰イオンである標的分子としては、上記のうち、過塩素酸イオン（ＣｌＯ４ −）、塩素酸イオン（ＣｌＯ３ −）、臭素酸イオン（ＢｒＯ３ −）、硝酸イオン（ＮＯ３ −）、テトラフルオロホウ酸イオン（ＢＦ４ −）、ヘキサフルオロリン酸イオン（ＰＦ６ −）、リン酸イオン（ＰＯ４ ３−）、トリフルオロメタンスルホン酸イオン（ＣＦ３ＳＯ３ −）が好ましい。
また、中性分子である標的分子としては、例えば、ベンゼン、トルエン、キシレン、シクロヘキサン、シクロヘキセン、が挙げられる。
Specific examples of the target molecule in the present invention are shown below.
Examples of the target molecule that is an anion include an oxo acid ion represented by XO a − , a nitrate ion (NO 3 − ), a tetrafluoroborate ion (BF 4 − ), and a hexafluorophosphate ion (PF 6 − ), Phosphate ion (PO 4 3− ), trifluoromethanesulfonate ion (CF 3 SO 3 − ), azide ion (N 3 − ), and the like.
The XO a - for X, a chlorine atom, a bromine atom, a halogen atom such as iodine atom, among them, a chlorine atom or a bromine atom. A in XO a − represents an integer of 1 to 4, and an integer of 3 to 4 is particularly preferable.
Specifically, the oxoacid ion represented by XO a − is preferably a perchlorate ion (ClO 4 − ), a chlorate ion (ClO 3 − ), or a bromate ion (BrO 3 − ). Perchlorate ion (ClO 4 − ) is particularly preferred.
Among the target molecules which are anions, among the above, perchlorate ion (ClO 4 − ), chlorate ion (ClO 3 − ), bromate ion (BrO 3 − ), nitrate ion (NO 3 − ), tetra Fluoroborate ions (BF 4 − ), hexafluorophosphate ions (PF 6 − ), phosphate ions (PO 4 3− ), and trifluoromethanesulfonate ions (CF 3 SO 3 − ) are preferable.
Examples of the target molecule that is a neutral molecule include benzene, toluene, xylene, cyclohexane, and cyclohexene.
また、本発明における「液体試料」は、溶媒として極性溶媒及び非極性溶媒の少なくとも一方を含む試料であれば特に限定はない。
「液体試料」としては、金属イオン及び一般式（Ｉ）で表される化合物の溶解性が高く、捕捉カプセル型分子をより形成し易い観点からは、溶媒として極性溶媒を含む液体試料が好ましく、溶媒中における極性溶媒の比率が３０質量％以上である液体試料がより好ましく、溶媒中における極性溶媒の比率が５０質量％以上である液体試料が更に好ましく、溶媒中における極性溶媒の比率が８０質量％以上である液体試料が更に好ましい。
ここで、極性溶媒としては、水、メタノール、エタノール、１−プロパノール、２−プロパノール、１−ブタノール、酢酸、ギ酸、等の極性プロトン性溶媒；テトラヒドロフラン、アセトン、アセトニトリル、ジメチルホルムアミド、ジメチルスルホキシド、等の極性非プロトン性溶媒；が挙げられる。また、非極性溶媒としては、ベンゼン、ヘキサン、トルエン、ジエチルエーテル、クロロホルム、酢酸エチル、塩化メチレン等が挙げられる。
本発明における「液体試料」の具体例としては、例えば、上水、下水、各種廃水（工業廃水等）、液状の中間生成物、工業用水、飲料水、各種水溶液、コロイド溶液（牛乳等）、食品や土壌等を含む懸濁液、等が含まれる。
Further, the “liquid sample” in the present invention is not particularly limited as long as it is a sample containing at least one of a polar solvent and a nonpolar solvent as a solvent.
As the “liquid sample”, a liquid sample containing a polar solvent as a solvent is preferable from the viewpoint of high solubility of the compound represented by the metal ion and the general formula (I) and easier formation of the capture capsule type molecule. A liquid sample in which the ratio of the polar solvent in the solvent is 30% by mass or more is more preferable, a liquid sample in which the ratio of the polar solvent in the solvent is 50% by mass or more is further preferable, and the ratio of the polar solvent in the solvent is 80% by mass. A liquid sample that is at least% is more preferred.
Here, as a polar solvent, polar protic solvents such as water, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, acetic acid, formic acid, etc .; tetrahydrofuran, acetone, acetonitrile, dimethylformamide, dimethyl sulfoxide, etc. A polar aprotic solvent. Examples of the nonpolar solvent include benzene, hexane, toluene, diethyl ether, chloroform, ethyl acetate, methylene chloride and the like.
Specific examples of the “liquid sample” in the present invention include, for example, clean water, sewage, various wastewater (industrial wastewater, etc.), liquid intermediate products, industrial water, drinking water, various aqueous solutions, colloidal solutions (milk, etc.), Suspensions containing food and soil are included.
前記一般式（Ｉ）において、ＲｙとＲｘは同一の複素環置換基であることが、生成する捕捉カプセル型分子の異性体の数を制限でき、生成物の同定を行いやすい観点から好ましい。
Ｒｘ及びＲｙにおいて、Ｒ６及びＲ７は、芳香族環の他の置換基と立体障害を起こすことなく、捕捉カプセル型分子を形成しうる観点から、共に水素原子であることが好ましい。
In the general formula (I), it is preferable that R y and R x are the same heterocyclic substituent from the viewpoint of being able to limit the number of isomers of the captured capsule-type molecule to be formed and easily identifying the product. .
In R x and R y , R 6 and R 7 are preferably both hydrogen atoms from the viewpoint of forming a trapped capsule molecule without causing steric hindrance with other substituents of the aromatic ring.
また、前記一般式（Ｉ）において、ＲｙがＲｘに対してメタ位にあること、即ち、Ｒ２又はＲ４がＲｙであることが、合成容易性の観点から好ましい。
また、前記一般式（Ｉ）において、ＲｙがＲｘに対してパラ位にあること、即ち、Ｒ３がＲｙであることは、標的分子が離脱しない、隙間の無い捕捉空間を形成させる観点からは、好ましい。
Further, the above formula (I), the R y is in the meta position with respect to R x, i.e., it is preferable from the viewpoint of ease of synthesis R 2 or R 4 is R y.
In the general formula (I), when R y is in the para position relative to R x , that is, R 3 is R y , the target molecule does not leave and forms a capture space without a gap. From the viewpoint, it is preferable.
また、前記一般式（Ｉ）において、Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５からＲｙを除いた残りは、それぞれ独立に、水酸基、メチロール基、水素原子、アセチル基、ハロゲン原子（好ましくはフッ素原子、塩素原子、臭素原子、ヨウ素原子、より好ましくはフッ素原子、塩素原子、臭素原子、更に好ましくは塩素原子又は臭素原子、特に好ましくは塩素原子）、炭素数１〜３０の置換若しくは未置換の脂肪族基、又はスルホン酸基を表す。ここで、Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５からＲｙを除いた残りのうち、少なくとも１つは水酸基又はメチロール基である。
Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５からＲｙを除いた残りとして、より好ましい形態は、水酸基が隣合う形態以外の形態である。ここで、「水酸基が隣合う形態」とは、Ｒ１及びＲ２が同時に水酸基となる形態、Ｒ２及びＲ３が同時に水酸基となる形態、Ｒ３及びＲ４が同時に水酸基となる形態、Ｒ４及びＲ５が同時に水酸基となる形態、Ｒ１、Ｒ２及びＲ３が同時に水酸基となる形態、又は、Ｒ３、Ｒ４及びＲ５が同時に水酸基となる形態を指す。
Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５からＲｙを除いた残りが、水酸基が隣合う形態以外の形態であれば、脱水環化をより抑制でき、捕捉カプセル型分子の形成性をより向上させることができる。
In the general formula (I), the remainders of R 1 , R 2 , R 3 , R 4 and R 5 except R y are each independently a hydroxyl group, a methylol group, a hydrogen atom, an acetyl group, a halogen atom. (Preferably fluorine atom, chlorine atom, bromine atom, iodine atom, more preferably fluorine atom, chlorine atom, bromine atom, more preferably chlorine atom or bromine atom, particularly preferably chlorine atom), substitution having 1 to 30 carbon atoms Alternatively, it represents an unsubstituted aliphatic group or a sulfonic acid group. Here, at least one of R 1 , R 2 , R 3 , R 4 and the rest of R 5 excluding R y is a hydroxyl group or a methylol group.
As the remainder obtained by removing R y from R 1 , R 2 , R 3 , R 4 and R 5 , a more preferable form is a form other than the form in which the hydroxyl groups are adjacent to each other. Here, “a form in which hydroxyl groups are adjacent” means a form in which R 1 and R 2 are simultaneously hydroxyl groups, a form in which R 2 and R 3 are simultaneously hydroxyl groups, a form in which R 3 and R 4 are simultaneously hydroxyl groups, R A form in which 4 and R 5 simultaneously become a hydroxyl group, a form in which R 1 , R 2 and R 3 simultaneously become a hydroxyl group, or a form in which R 3 , R 4 and R 5 simultaneously become a hydroxyl group.
If the rest of R 1 , R 2 , R 3 , R 4 and R 5 except R y is in a form other than the form in which the hydroxyl groups are adjacent to each other, dehydration cyclization can be further suppressed, and the formation of the trapping capsule type molecule Can be further improved.
Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５からＲｙを除いた残りのうち、水酸基（メチロール基中の水酸基を含む）の総数は１〜３であることが好ましく、合成容易性の観点からは１又は２であることがより好ましい。 Of the rest of R 1 , R 2 , R 3 , R 4, and R 5 except R y , the total number of hydroxyl groups (including the hydroxyl group in the methylol group) is preferably 1 to 3, which facilitates synthesis. From the viewpoint, it is more preferably 1 or 2.
また、Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５から、Ｒｙ、水酸基、及びメチロール基を除いた残りは、いずれも、炭素数１〜３０の置換若しくは未置換の炭化水素基であることが、カプセル骨格内からの標的分子の離脱を防ぐ観点から好ましい。
また、Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５から、Ｒｙ、水酸基、及びメチロール基を除いた残りにおいて、隣り合う基が互いに結合して脂肪族環を形成してもよい。
In addition, the rest of R 1 , R 2 , R 3 , R 4 and R 5 excluding R y , hydroxyl group and methylol group are all substituted or unsubstituted hydrocarbon groups having 1 to 30 carbon atoms. It is preferable from the viewpoint of preventing detachment of the target molecule from the capsule skeleton.
Further, in the remainder excluding R y , hydroxyl group and methylol group from R 1 , R 2 , R 3 , R 4 and R 5 , adjacent groups may be bonded to each other to form an aliphatic ring.
Ｒ１、Ｒ２、Ｒ３、Ｒ４及びＲ５で表される炭化水素基の炭素数としては、合成容易性の観点や、一般式（Ｉ）で表される化合物同士が立体的に障害となることなくカプセルを形成し、またカプセル骨格内からの標的分子の離脱を防ぐ観点から、１〜１０が好ましく、１〜２がより好ましい。
この炭化水素基に置換可能な置換基としては、ハロゲン原子、スルホン酸基、ニトロ基、ヒドロキシル基、ハロゲン化アルキル基を挙げることができるが、合成容易性、安定性、及び水に対する不溶性の観点から、フッ素原子、又はパーフルオロアルキル基が好ましい。
As the number of carbon atoms of the hydrocarbon group represented by R 1 , R 2 , R 3 , R 4 and R 5 , the compound represented by the general formula (I) is sterically hindered from the viewpoint of ease of synthesis. From the viewpoints of forming a capsule without becoming and preventing the target molecule from leaving the capsule skeleton, 1 to 10 is preferable, and 1 to 2 is more preferable.
Examples of the substituent that can be substituted on the hydrocarbon group include a halogen atom, a sulfonic acid group, a nitro group, a hydroxyl group, and an alkyl halide group. From the viewpoint of ease of synthesis, stability, and insolubility in water. Therefore, a fluorine atom or a perfluoroalkyl group is preferable.
Ｒｘ及びＲｙにおいて、Ａで表される複素環基は、炭素数１〜６のアルキル基やスルホン酸基等の置換基で置換されていてもよい。また、前記複素環基中には、窒素原子の他に、酸素原子や硫黄原子が含まれていてもよい。
Ａで表される複素環基としては、前記金属イオンに配位可能な複素環基が挙げられる。このような複素環基としては、ピロール−１−イル基以外のピロリル基、２Ｈ−ピロール−１−イル基以外の２Ｈ−ピロリル基、イミダゾリル基、ピラゾリル基、イソチアゾール−１−イル基以外のイソチアゾリル基、イソオキサゾール−１−イル基以外のイソオキサゾリル基、ピロリジン−１−イル基以外のピロリジニル基、イミダゾリジニル基、ピラゾリジニル基、ピリジン−１−イル基以外のピリジル基、ピラジル基、ピリミジニル基、ピリダジニル基、ピペリジン−１−イル基以外のピペリジニル基、ピペラジニル基、モルホリン−４−イル基以外のモルホリニル基、下記構造式で表される基が好ましい。
In R x and R y , the heterocyclic group represented by A may be substituted with a substituent such as an alkyl group having 1 to 6 carbon atoms or a sulfonic acid group. The heterocyclic group may contain an oxygen atom or a sulfur atom in addition to the nitrogen atom.
Examples of the heterocyclic group represented by A include a heterocyclic group capable of coordinating with the metal ion. Examples of such heterocyclic groups include pyrrolyl groups other than pyrrol-1-yl groups, 2H-pyrrolyl groups other than 2H-pyrrol-1-yl groups, imidazolyl groups, pyrazolyl groups, and isothiazol-1-yl groups. Isothiazolyl group, isoxazolyl group other than isoxazol-1-yl group, pyrrolidinyl group other than pyrrolidin-1-yl group, imidazolidinyl group, pyrazolidinyl group, pyridyl group other than pyridin-1-yl group, pyrazyl group, pyrimidinyl group, pyridazinyl Groups, piperidinyl groups other than piperidin-1-yl groups, piperazinyl groups, morpholinyl groups other than morpholin-4-yl groups, and groups represented by the following structural formulas are preferred.
前記の中でも、合成容易性と金属イオンに対する配位性との観点からは、ピロール−１−イル基以外のピロリル基、イミダゾリル基、ピリジン−１−イル基以外のピリジル基、下記構造式で表される基がより好ましい。 Among these, from the viewpoint of ease of synthesis and coordination with metal ions, a pyrrolyl group other than a pyrrol-1-yl group, an imidazolyl group, a pyridyl group other than a pyridin-1-yl group, and the following structural formula More preferred are the groups
前記の中でもイミダゾリル基が特に好ましい。 Of these, an imidazolyl group is particularly preferred.
前記一般式（Ｉ）で表される化合物の合成方法としては、国際公開第２００８／０２９８０４号パンフレットに記載されている方法に準じた方法や、C.-H. Zhou, R.-G. Xie, and H.-M. Zhao, Organic. Preparations and Procedures Int., 1996, 28(3), 345 に記載されている方法に準じた方法を用いることができる。
合成方法について、具体的には、１〜３個の水酸基で置換された芳香族化合物と、１，３，５−トリオキサンと、ハロゲン化水素と、酸性条件下で反応させて、一旦ハロゲン置換された芳香族化合物を合成しておき、その後、一般式（Ｉ）中のＡに相当する化合物とを反応させて、ハロゲン原子をＡで置換する方法、等が挙げられる。
As a synthesis method of the compound represented by the general formula (I), a method according to the method described in International Publication No. 2008/029804 pamphlet, C.-H. Zhou, R.-G. Xie , and H.-M. Zhao, Organic. Preparations and Procedures Int., 1996, 28 (3), 345 can be used.
Regarding the synthesis method, specifically, an aromatic compound substituted with 1 to 3 hydroxyl groups, 1,3,5-trioxane, and a hydrogen halide are reacted under acidic conditions to be once halogen-substituted. And a method in which a halogen atom is substituted with A by reacting with a compound corresponding to A in formula (I).
以下、一般式（Ｉ）で表される化合物の例示化合物を示す。
なお、本発明の複素環置換芳香族化合物は、下記式（ａ）、下記式（ｃ）、下記式（ｅ）、又は下記式（ｇ）で表される化合物である。
下記式（ｂ）、下記式（ｄ）、下記式（ｆ）、下記式（ｈ）、下記式（ｉ）、又は下記式（ｊ）で表される化合物は、参考化合物である。
Hereinafter, exemplary compounds of the compound represented by formula (I) are shown.
The heterocyclic-substituted aromatic compound of the present invention is a compound represented by the following formula (a), the following formula (c), the following formula (e), or the following formula (g).
The compound represented by the following formula (b), the following formula (d), the following formula (f), the following formula (h), the following formula (i), or the following formula (j) is a reference compound.
＜分子検出剤＞
本発明の分子検出剤は、前記一般式（Ｉ）で表される化合物を含む。
本発明の分子検出剤の形態としては、前記一般式（Ｉ）で表される化合物単体の形態が挙げられる。この場合、一般式（Ｉ）で表される化合物が粉末状又は錠剤状等の固体であることが好ましい。
また、本発明の分子検出剤の別の形態としては、前記固体と他の成分との混合物の形態であってもよい。
また、本発明の分子検出剤の別の形態としては、前記固体又は混合物が溶剤中に溶解または分散された形態であってもよい。
<Molecular detector>
The molecular detection agent of this invention contains the compound represented by the said general formula (I).
As a form of the molecule | numerator detection agent of this invention, the form of the compound single-piece | unit represented with the said general formula (I) is mentioned. In this case, the compound represented by the general formula (I) is preferably a solid such as powder or tablet.
Moreover, as another form of the molecule | numerator detection agent of this invention, the form of the mixture of the said solid and another component may be sufficient.
As another form of the molecular detection agent of the present invention, the solid or mixture may be dissolved or dispersed in a solvent.
前述のとおり、一般式（Ｉ）で表される化合物が、液体試料中で、標的分子と、平面四配位又は正八面体配位可能な金属イオン（例えば、Ｃｕ２＋、Ｎｉ２＋、Ｃｏ２＋、Ｆｅ２＋、Ｍｎ２＋）と、に接触すると、捕捉カプセル型分子が形成される。そして、捕捉カプセル型分子の形成に伴い、液体試料は、捕捉カプセル型分子に由来する色（例えば紫色）に着色される。
従って、分子検出剤としての一般式（Ｉ）で表される化合物を、前記金属イオンとともに液体試料中に添加することにより、液体試料中の標的分子の捕捉及び検出を行うことができる。
また、分子検出剤としての一般式（Ｉ）で表される化合物と、前記金属イオンと、を予め容器に入れておき、そこに液体試料を添加することによっても液体試料中の標的分子の捕捉及び検出を行うことができる。
As described above, the compound represented by the general formula (I) can be converted into a tetragonal or octahedrally coordinated metal ion (for example, Cu 2+ , Ni 2+ , Co 2+ , (Fe 2+ , Mn 2+ ), a trapped capsule molecule is formed. As the capture capsule type molecule is formed, the liquid sample is colored in a color (for example, purple) derived from the capture capsule type molecule.
Therefore, the target molecule in the liquid sample can be captured and detected by adding the compound represented by the general formula (I) as a molecular detection agent to the liquid sample together with the metal ions.
In addition, the target molecule in the liquid sample can also be captured by preliminarily placing the compound represented by the general formula (I) as a molecular detection agent and the metal ion in a container and adding the liquid sample to the container. And detection can be performed.
また、本発明の分子検出剤は、前記一般式（Ｉ）で表される化合物と前記金属イオンとを含む形態であってもよい。
この形態の分子検出剤と、液体試料と、を接触させることによっても、捕捉カプセル型分子を形成させることができ、標的分子の捕捉及び検出を行うことができる。
Further, the molecular detection agent of the present invention may be in a form containing the compound represented by the general formula (I) and the metal ion.
By bringing the molecular detection agent of this form into contact with the liquid sample, a capture capsule type molecule can be formed, and the target molecule can be captured and detected.
本発明の分子検出剤が、前記一般式（Ｉ）で表される化合物と前記金属イオンとを含む形態としては特に限定はないが、以下の２形態が好適である。
第１の形態は、本発明の分子検出剤が、前記一般式（Ｉ）で表される化合物と、前記金属イオンを含む金属塩と、を含む混合物である形態である。
第２の形態は、本発明の分子検出剤が、前記一般式（Ｉ）で表される化合物と前記金属イオンとを含む配位化合物を含有する形態である。
Although there is no limitation in particular as a form in which the molecular detection agent of this invention contains the compound represented with the said general formula (I), and the said metal ion, the following two forms are suitable.
The first form is a form in which the molecular detection agent of the present invention is a mixture containing the compound represented by the general formula (I) and a metal salt containing the metal ion.
In the second form, the molecular detection agent of the present invention contains a coordination compound containing the compound represented by the general formula (I) and the metal ion.
〜 金属塩 〜
第１の形態は、本発明の分子検出剤が、前記一般式（Ｉ）で表される化合物と、前記金属イオンを含む金属塩と、を含む混合物である形態である。
前記金属塩としては、前記金属イオンと、標的分子以外の特定の陰イオンと、からなる金属塩が挙げられる。
標的分子以外の特定の陰イオンとしては、例えば、ＯＨ−、ＳＯ４ ２−、ＣＯ３ ２−、ＣＨ３ＣＯＯ−、Ｃ２Ｏ４ ２−、ＨＣＯＯ−、Ｃｌ−、Ｂｒ−、Ｆ−、アセチルアセトナト（Ｃ５Ｈ７Ｏ２ −）、ＳｉＦ６ ２−、ＮＯ２ −等が挙げられる。
前記金属塩としては、ＣｕＳＯ４、Ｃｕ（ＯＨ）２、又はＣｕＣＯ３が好ましい。
~ Metal salt ~
The first form is a form in which the molecular detection agent of the present invention is a mixture containing the compound represented by the general formula (I) and a metal salt containing the metal ion.
Examples of the metal salt include a metal salt composed of the metal ion and a specific anion other than the target molecule.
Specific anions other than the target molecule include, for example, OH − , SO 4 2− , CO 3 2− , CH 3 COO − , C 2 O 4 2− , HCOO − , Cl − , Br − , F − , acetylacetonate (C 5 H 7 O 2 - ), SiF 6 2-, NO 2 - and the like.
As the metal salt, CuSO 4 , Cu (OH) 2 , or CuCO 3 is preferable.
〜配位化合物〜
第２の形態は、本発明の分子検出剤が、前記一般式（Ｉ）で表される化合物と前記金属イオンとを含む配位化合物を含有する形態である。
前記配位化合物を液体試料中で標的分子に接触させると、該配位化合物を構成する前記一般式（Ｉ）で表される化合物及び前記金属イオンが、標的分子を取り込んだ捕捉カプセル型分子に再構成される。
このため、単独で存在する一般式（Ｉ）で表される化合物を用いる場合と同様に、標的分子を捕捉し、検出することができる。
また、前記配位化合物を用いる方法では、液体試料中に金属イオンを直接溶解させる必要がないため、金属イオンによって着色されていない無色透明の液体試料を、捕捉カプセル型分子に由来する色に着色させることができる。このため、より感度の高い検出が可能となる。
~ Coordination compounds ~
In the second form, the molecular detection agent of the present invention contains a coordination compound containing the compound represented by the general formula (I) and the metal ion.
When the coordination compound is brought into contact with a target molecule in a liquid sample, the compound represented by the general formula (I) and the metal ion constituting the coordination compound are converted into a capture capsule type molecule incorporating the target molecule. Reconfigured.
For this reason, the target molecule can be captured and detected as in the case of using the compound represented by the general formula (I) which exists alone.
Further, in the method using the coordination compound, since it is not necessary to directly dissolve the metal ions in the liquid sample, a colorless and transparent liquid sample that is not colored by the metal ions is colored in a color derived from the capture capsule type molecule. Can be made. For this reason, detection with higher sensitivity is possible.
前記配位化合物の具体的な構造としては、該配位化合物に含まれる複数の金属イオンのそれぞれに対し、前記一般式（Ｉ）で表される化合物が複数配位した高分子錯体の構造が挙げられる。
このような高分子錯体の構造としては、国際公開第２００８／０２９８０４号パンフレットの段落００６２〜段落００６９、段落０１０６〜段落０１２２に記載されている構造と同様の構造が挙げられる。
前記高分子錯体の構造として、具体的には、各金属イオンに対し前記一般式（Ｉ）で表される化合物が４分子ずつ配位し、この単位が無限鎖状に広がった二次元シート型構造などがある。該二次元シート型構造においては、各一般式（Ｉ）で表される化合物は、二つの金属イオン間に配置され、一方の複素環中の窒素原子の部分で一方の金属イオンに配位し、他方の複素環中の窒素原子の部分で他方の金属イオンに配位している。
前記配位化合物には、前記特定の陰イオンや水分子が含まれることがあるが、これらの水分子や陰イオンは、前記金属イオンに配位していてもよいし、前記金属イオンに配位していなくてもよい。
As a specific structure of the coordination compound, there is a structure of a polymer complex in which a plurality of compounds represented by the general formula (I) are coordinated with each of a plurality of metal ions contained in the coordination compound. Can be mentioned.
Examples of the structure of such a polymer complex include structures similar to those described in paragraphs 0062 to 0069 and paragraphs 0106 to 0122 of WO 2008/029804.
As the structure of the polymer complex, specifically, a two-dimensional sheet type in which four molecules of the compound represented by the general formula (I) are coordinated to each metal ion, and this unit extends in an infinite chain. There are structures. In the two-dimensional sheet type structure, the compound represented by each general formula (I) is arranged between two metal ions, and is coordinated to one metal ion at a nitrogen atom portion in one heterocyclic ring. And is coordinated to the other metal ion at the nitrogen atom in the other heterocycle.
The coordination compound may contain the specific anion or water molecule. The water molecule or anion may be coordinated to the metal ion or coordinated to the metal ion. It doesn't have to be ranked.
また、前記配位化合物の構造が前記陰イオンを含む前記二次元シート型構造である場合、該二次元シート型構造中の陰イオンは、（１）別の二次元シート型構造中の金属イオンと配位結合するか、（２）別の二次元シート型構造中の金属イオンに配位した水分子と水素結合していてもよい。前記（１）及び（２）の場合には、前記配位化合物の構造は二次元シート型構造が複数重なった三次元構造となる。
また、三次元構造の別の例としては、金属イオンに水分子が配位した二次元シート型構造同士が、陰イオン（例えば、硫酸イオン）を介して相互に重なった構造も挙げられる。この構造では、二次元シート型構造中の水分子と、別の二次元シート型構造中の水分子と、が陰イオンを介して相互作用している。
Moreover, when the structure of the coordination compound is the two-dimensional sheet type structure containing the anion, the anion in the two-dimensional sheet type structure is (1) a metal ion in another two-dimensional sheet type structure. Or (2) hydrogen bonds to water molecules coordinated to metal ions in another two-dimensional sheet type structure. In the cases (1) and (2), the structure of the coordination compound is a three-dimensional structure in which a plurality of two-dimensional sheet-type structures are stacked.
Another example of the three-dimensional structure is a structure in which two-dimensional sheet-type structures in which water molecules are coordinated to metal ions overlap each other via an anion (for example, sulfate ion). In this structure, water molecules in the two-dimensional sheet type structure interact with water molecules in another two-dimensional sheet type structure via anions.
前記配位化合物の合成方法としては、前記金属イオン（Ａ成分）と、前記一般式（Ｉ）で表される化合物（Ｂ成分）とを、モル比〔Ａ成分／Ｂ成分〕が１／２となる割合で反応させる方法が挙げられる。 As a method for synthesizing the coordination compound, the metal ion (component A) and the compound represented by the general formula (I) (component B) have a molar ratio [component A / component B] of 1/2. The method of making it react in the ratio which becomes.
前記Ａ成分と前記Ｂ成分とを反応させる方法としては、前記Ａ成分と前記標的分子以外の特定の陰イオン（具体例は前述のとおりである）とからなる金属塩を、溶剤（例えば、水、ジメチルホルムアミド、メタノール、エタノール、プロパノール、アセトニトリル、アセトン、等）中に溶解させて溶液Ａとし、前記Ｂ成分を別の溶剤（例えば、ジメチルホルムアミド、メタノール、エタノール、プロパノール、アセトニトリル、アセトン、等）中に溶解させて溶液Ｂとし、溶液Ａと溶液Ｂとを混合して反応させる方法が挙げられる。 As a method of reacting the A component and the B component, a metal salt composed of the A component and a specific anion other than the target molecule (specific examples are as described above), a solvent (for example, water , Dimethylformamide, methanol, ethanol, propanol, acetonitrile, acetone, etc.) to obtain a solution A, and the B component is another solvent (for example, dimethylformamide, methanol, ethanol, propanol, acetonitrile, acetone, etc.) There is a method in which the solution B is dissolved in the solution B, and the solution A and the solution B are mixed and reacted.
また、前記Ａ成分と前記Ｂ成分とを同一の溶剤中に溶解させて反応させてもよく、この場合の溶剤としては、メタノール、ジメチルホルムアミド、又はエタノール等の単一溶媒を使用してもよいし、水／アセトニトリル、水／ジメチルホルムアミド、水／メタノール、水／エタノール、メタノール／ジメチルホルムアミド、エタノール／ジメチルホルムアミド等の混合溶剤を使用してもよい。 Further, the component A and the component B may be dissolved and reacted in the same solvent. In this case, a single solvent such as methanol, dimethylformamide, or ethanol may be used as the solvent. In addition, a mixed solvent such as water / acetonitrile, water / dimethylformamide, water / methanol, water / ethanol, methanol / dimethylformamide, ethanol / dimethylformamide or the like may be used.
以上で説明した配位化合物を分子検出剤として用いる形態には特に限定はなく、例えば、粉末状、錠剤状、又はシート状等の固体である配位化合物を用いる形態が挙げられる。また、前記固体と他の成分との混合物を用いる形態であってもよい。また、前記固体又は混合物が溶剤中に溶解または分散された液体を用いる形態であってもよい。 The form in which the coordination compound described above is used as a molecular detection agent is not particularly limited, and examples thereof include a form using a coordination compound that is a solid such as powder, tablet, or sheet. Moreover, the form using the mixture of the said solid and another component may be sufficient. Moreover, the form using the liquid which the said solid or mixture melt | dissolved or disperse | distributed in the solvent may be sufficient.
＜分子捕捉方法、分子検出方法＞
本発明の分子捕捉方法は、液体試料中の標的分子を捕捉する方法であって、前記一般式（Ｉ）で表される化合物と、平面四配位又は正八面体配位可能な金属イオンと、前記液体試料と、を接触させて、前記標的分子を捕捉した捕捉カプセル型分子を形成させることを含む方法である。
また、本発明の分子検出方法は、液体試料中の標的分子を検出する方法であって、前記一般式（Ｉ）で表される化合物と、平面四配位又は正八面体配位可能な金属イオンと、前記液体試料と、を接触させて、前記標的分子を捕捉した捕捉カプセル型分子を形成させ、該捕捉カプセル型分子の形成に伴う液体試料の色の変化により前記標的分子を検出する方法である。
<Molecular capture method, molecular detection method>
The molecular capturing method of the present invention is a method for capturing a target molecule in a liquid sample, which is a compound represented by the general formula (I), a metal ion capable of planar tetracoordination or regular octahedral coordination, Contacting the liquid sample to form a capture capsule type molecule capturing the target molecule.
The molecular detection method of the present invention is a method for detecting a target molecule in a liquid sample, and a compound represented by the general formula (I) and a metal ion capable of planar tetracoordinate or octahedral coordination. And a liquid sample to form a capture capsule type molecule that captures the target molecule, and the target molecule is detected by a change in the color of the liquid sample accompanying the formation of the capture capsule type molecule. is there.
本捕捉方法及び本検出方法では、液体試料中で、前記一般式（Ｉ）で表される化合物と、前記金属イオンと、標的分子と、が接触して捕捉カプセル型分子が形成される。
捕捉カプセル型分子は、標的分子１分子を内包して捕捉するほか、前記捕捉カプセル型分子の外側（２個の金属イオン）にも、配位結合により標的分子を捕捉することができる。従って、捕捉カプセル型分子１分子は、標的分子を３分子捕捉することが可能である。さらに、捕捉カプセル型分子１分子は、標的分子３分子に加え、別の捕捉カプセル型分子との間に、標的分子をさらに１分子捕捉することが確認されている。即ち、捕捉カプセル型分子１分子は、標的分子を最大４分子まで捕捉できることがわかっている（例えば、図１参照）。
以上の形態は、例えば単結晶構造解析及び可視・紫外分光スペクトル等により確認することができる。
In the capture method and the detection method, the compound represented by the general formula (I), the metal ion, and the target molecule are brought into contact with each other in a liquid sample to form a capture capsule molecule.
In addition to encapsulating and capturing one target molecule, the capture capsule type molecule can also capture the target molecule by coordination bond outside the capture capsule type molecule (two metal ions). Therefore, one capture capsule molecule can capture three target molecules. Furthermore, it has been confirmed that one capture capsule type molecule captures one more target molecule with another capture capsule type molecule in addition to three target molecules. That is, it is known that one capture capsule molecule can capture up to four target molecules (see, for example, FIG. 1).
The above forms can be confirmed by, for example, single crystal structure analysis and visible / ultraviolet spectrum.
また、既述のとおり、捕捉カプセル型分子の形成に伴い、液体試料が該捕捉カプセル型分子に由来する色（例えば紫色）に着色するため、本検出方法では、液体試料中の標的分子を、短時間に感度良く検出できる。
液体試料の色の変化は、目視により簡易的に確認することができる。但し、分光スペクトル測定等により確認してもよい。
Further, as described above, the liquid sample is colored in a color derived from the capture capsule type molecule (for example, purple) with the formation of the capture capsule type molecule. Therefore, in this detection method, the target molecule in the liquid sample is Sensitivity can be detected in a short time.
The change in the color of the liquid sample can be easily confirmed visually. However, it may be confirmed by spectroscopic measurement or the like.
液体試料中で、一般式（Ｉ）で表される化合物と、前記金属イオンと、前記標的分子と、を接触させる方法については、特に限定はない。
例えば、一般式（Ｉ）で表される化合物単体である分子検出剤を、前記金属イオンとともに液体試料中に添加することにより、液体試料中の標的分子の捕捉及び検出を行うことができる。
また、一般式（Ｉ）で表される化合物単体である分子検出剤と、前記金属イオンと、を予め容器に入れておき、そこに液体試料を添加することにより、液体試料中の標的分子の捕捉及び検出を行うことができる。
また、一般式（Ｉ）で表される化合物と前記金属イオンとを含む分子検出剤を、液体試料中に添加することにより、液体試料中の標的分子の捕捉及び検出を行うことができる。
また、一般式（Ｉ）で表される化合物と前記金属イオンとを含む分子検出剤を予め容器に入れておき、そこに液体試料を添加することによっても液体試料中の標的分子の捕捉及び検出を行うことができる。
There is no particular limitation on the method for bringing the compound represented by the general formula (I), the metal ion, and the target molecule into contact in a liquid sample.
For example, a target molecule in a liquid sample can be captured and detected by adding a molecular detection agent, which is a single compound represented by the general formula (I), to the liquid sample together with the metal ions.
In addition, a molecular detection agent that is a single compound represented by the general formula (I) and the metal ion are placed in a container in advance, and a liquid sample is added thereto, whereby the target molecule in the liquid sample Capture and detection can be performed.
Moreover, the target molecule | numerator in a liquid sample can be capture | acquired and detected by adding the molecule | numerator detection agent containing the compound represented with general formula (I), and the said metal ion in a liquid sample.
In addition, a molecular detection agent containing the compound represented by the general formula (I) and the metal ion is put in a container in advance, and the target molecule in the liquid sample is captured and detected by adding the liquid sample to the container. It can be performed.
本捕捉方法及び本検出方法では、前記一般式（Ｉ）で表される化合物と金属イオンと標的分子との接触頻度を高め、捕捉カプセル型分子形成反応の反応性を向上させる観点からは、液体試料を加熱してもよい。
加熱の温度としては、前記一般式（Ｉ）で表される化合物の種類、分子検出剤の種類、標的分子の種類などによっても異なるが、０〜１００℃が好ましく、２０〜７０℃がより好ましい。
In the capture method and the detection method, from the viewpoint of increasing the contact frequency between the compound represented by the general formula (I), the metal ion, and the target molecule, and improving the reactivity of the capture capsule type molecule formation reaction, The sample may be heated.
The heating temperature varies depending on the type of compound represented by the general formula (I), the type of molecular detection agent, the type of target molecule, etc., but is preferably 0 to 100 ° C., more preferably 20 to 70 ° C. .
本捕捉方法及び本検出方法では、液体試料中における前記一般式（Ｉ）で表される化合物と金属イオンと標的分子との接触後、液体試料を撹拌してもよく、撹拌せずにそのまま放置してもよいが、接触頻度を高め、捕捉カプセル型分子形成反応の反応性を向上させる観点からは、撹拌することが好ましい。
撹拌には、攪拌器、容器の振とう、超音波の照射、マイクロウェーブの照射、加熱による対流、などの手段を用いることができる。中でも、超音波の照射が好ましい。
In this capture method and this detection method, the liquid sample may be stirred after contacting the compound represented by the general formula (I), the metal ion, and the target molecule in the liquid sample, or left as it is without stirring. However, from the viewpoint of increasing the contact frequency and improving the reactivity of the capture capsule type molecule formation reaction, stirring is preferable.
For stirring, means such as a stirrer, shaking of a container, ultrasonic irradiation, microwave irradiation, convection by heating, and the like can be used. Among these, ultrasonic irradiation is preferable.
本捕捉方法及び本検出方法では、液体試料中の捕捉カプセル型分子を前記一般式（Ｉ）で表される化合物に再生し、回収することができる。
ここで、前記捕捉カプセル型分子は、一般的な金属錯体と同様の構成を有するため、一般的な金属錯体と同様の方法により分解し、再度前記一般式（Ｉ）で表される化合物を生じる。
再生の方法としては、例えば、以下の方法を用いることができる。
即ち、捕捉カプセル型分子をアセトニトリル、あるいはメタノール等の有機溶媒に抽出し、その溶液に硫化水素などを金属沈殿剤として接触させて、金属硫化物を沈殿させる。該金属沈殿剤としては、硫化水素以外に、金属を水酸化物塩や炭酸塩として沈殿させることができる、アルカリ試薬や炭酸カリウムなどを用いることができる。次に、溶液中に残った前記一般式（Ｉ）で表される化合物を濃縮乾固して集め、アセトニトリル、あるいはメタノールなどの有機溶媒から再結晶させ、前記一般式（Ｉ）で表される化合物を再生させることが可能である。
また、前記一般式（Ｉ）で表される化合物を再生する方法として、上記の金属沈殿剤を接触させる方法以外に、硝酸や塩酸などの酸を接触させる方法を用いることもできる。即ち、捕捉カプセル型分子が抽出された溶液に前記酸を添加することにより、前記金属イオンと前記一般式（Ｉ）で表される化合物との間の配位結合を切断し、捕捉カプセル型分子を分解することができる。捕捉カプセル型分子分解後の前記溶液を濃縮乾固後、水を添加して前記一般式（Ｉ）で表される化合物を沈殿として取り出し、続いて、アセトニトリルやメタノールなどの有機溶媒から前記一般式（Ｉ）で表される化合物を再結晶させて再生させることが可能である。
In the capture method and the detection method, the capture capsule type molecule in the liquid sample can be regenerated and recovered into the compound represented by the general formula (I).
Here, since the capture capsule type molecule has the same configuration as that of a general metal complex, it is decomposed by the same method as that of a general metal complex, and again yields a compound represented by the general formula (I). .
As a reproduction method, for example, the following method can be used.
That is, the trapped capsule type molecule is extracted into an organic solvent such as acetonitrile or methanol, and hydrogen sulfide or the like is contacted with the solution as a metal precipitant to precipitate the metal sulfide. As the metal precipitating agent, in addition to hydrogen sulfide, an alkali reagent, potassium carbonate, or the like that can precipitate a metal as a hydroxide salt or carbonate can be used. Next, the compound represented by the general formula (I) remaining in the solution is collected by concentration to dryness, recrystallized from an organic solvent such as acetonitrile or methanol, and represented by the general formula (I). It is possible to regenerate the compound.
Moreover, as a method for regenerating the compound represented by the general formula (I), a method of contacting an acid such as nitric acid or hydrochloric acid can be used in addition to the method of contacting the metal precipitant. That is, by adding the acid to the solution from which the capture capsule type molecule is extracted, the coordination bond between the metal ion and the compound represented by the general formula (I) is cleaved, and the capture capsule type molecule is obtained. Can be disassembled. The solution after trapping capsule-type molecular decomposition is concentrated to dryness, water is added to remove the compound represented by the general formula (I) as a precipitate, and then the general formula is removed from an organic solvent such as acetonitrile or methanol. The compound represented by (I) can be recrystallized and regenerated.
本発明の分子検出方法では、上述のように液体試料中の標的分子を直接的に短時間に感度良く検出できるため、廃液、飲料、又は牛乳等の液体だけでなく、液体試料中で前記一般式（Ｉ）で表される化合物及び前記金属イオンと共に撹拌することにより、食品、土壌等に含まれる標的分子を容易に検出することができる In the molecular detection method of the present invention, since the target molecule in the liquid sample can be detected with high sensitivity directly in a short time as described above, not only the liquid such as waste liquid, beverage, or milk, but also the general By stirring together with the compound represented by formula (I) and the metal ions, target molecules contained in food, soil, etc. can be easily detected.
以下、本発明の実施例について説明するが、本発明はこれらの実施例に限定されるものではない。以下の実施例において、溶液の調製、または測定に用いた水はすべてイオン交換水を用いた。 Examples of the present invention will be described below, but the present invention is not limited to these examples. In the following examples, ion-exchanged water was used for all the water used for preparing or measuring the solution.
〔実施例１〕
＜例示化合物（ａ）（３，５−ビス（イミダゾール−１−イル−メチル）−２，４，６−テトラメチルフェノール；ｂｉｔｐｈ）の合成＞
下記反応スキーム１に従って例示化合物（ａ）（ｂｉｔｐｈ）の合成を行った。
[Example 1]
<Synthesis of Exemplary Compound (a) (3,5-bis (imidazol-1-yl-methyl) -2,4,6-tetramethylphenol; bitph)>
According to the following reaction scheme 1, exemplary compound (a) (bitph) was synthesized.
反応スキーム１の詳細を以下に説明する。
まず、２，４，６−トリメチルフェノール（上記化合物１）（１３．６ｇ，０．１０ｍｏｌ）と、１，３，５−トリオキサン（９．００ｇ，０．１０ｍｏｌ）と、を３０％ＨＢｒ／ＣＨ３ＣＯＯＨ溶液（１４１ｍｌ）の中に入れ、８０℃で２時間還流した。その後、室温で冷やし、７００ｍｌの氷水に注ぎ、出てきた生成物を濾過して集め、真空乾燥した（生成物の収量：３１．４３ｇ）。
生成物は、３，５−ビス（ブロモメチル）−２，４，６−トリメチルフェノール（上記化合物２）と、３，５−ビス（ブロモメチル）−２，４，６−トリメチルフェニルエタノエート（上記化合物３）と、の混合物であった。
Details of Reaction Scheme 1 are described below.
First, 2,4,6-trimethylphenol (the above compound 1) (13.6 g, 0.10 mol) and 1,3,5-trioxane (9.00 g, 0.10 mol) were mixed with 30% HBr / CH. It was placed in 3 COOH solution (141 ml) and refluxed at 80 ° C. for 2 hours. Thereafter, the mixture was cooled at room temperature, poured into 700 ml of ice water, and the resulting product was collected by filtration and dried under vacuum (product yield: 31.43 g).
The products are 3,5-bis (bromomethyl) -2,4,6-trimethylphenol (compound 2) and 3,5-bis (bromomethyl) -2,4,6-trimethylphenylethanolate (compound 3).
上記で得られた化合物２と化合物３との混合物（２．０６ｇ）と、イミダゾール（４．２９ｇ，０．０６３ｍｏｌ）と、をメタノール（５１ｍｌ）中で、６５℃で１６時間還流した。その後、炭酸ナトリウム（６．３０ｇ，０．０５９ｍｏｌ）を加え、さらに２時間還流を続けた。氷冷した後濾過し、瀘液を濃縮した。濃縮したものをジクロロメタンと水で分液し、ジクロロメタン層を抽出した。そこに硫酸マグネシウムを入れて残った水を除去した後、硫酸マグネシウムを濾過して除き、ジクロロメタンを濃縮した。濃縮したものをヘキサンに滴下したところ、白色の固体（ｂｉｔｐｈの粗生成物）が析出した。
この白色固体（ｂｉｔｐｈの粗生成物）をメタノールに溶かし水を加えて再結晶して、ｂｉｔｐｈを得た（収量：０．６００ｇ）。ｂｉｔｐｈの化合物１からの収率は２９％であった。
得られたｂｉｔｐｈの構造は、元素分析及びＮＭＲにより同定した。測定結果は以下のとおりである。
The mixture (2.06 g) of Compound 2 and Compound 3 obtained above and imidazole (4.29 g, 0.063 mol) were refluxed in methanol (51 ml) at 65 ° C. for 16 hours. Thereafter, sodium carbonate (6.30 g, 0.059 mol) was added, and the reflux was further continued for 2 hours. After cooling with ice, the mixture was filtered and the filtrate was concentrated. The concentrated product was partitioned between dichloromethane and water, and the dichloromethane layer was extracted. Magnesium sulfate was added thereto to remove the remaining water, and then magnesium sulfate was removed by filtration, and dichloromethane was concentrated. When the concentrated product was added dropwise to hexane, a white solid (bitph crude product) was precipitated.
This white solid (bitph crude product) was dissolved in methanol, water was added and recrystallized to obtain bitph (yield: 0.600 g). The yield of bitph from compound 1 was 29%.
The structure of the obtained bitph was identified by elemental analysis and NMR. The measurement results are as follows.
〜元素分析結果（％）〜
Calcd for C17H20N4O : C, 68.89; H, 6.80; N, 18.90.
Found: C, 68.89; H, 7.01; N, 18.65.
〜ＮＭＲ結果〜
1H NMR (CDCl3)δ7.22 (s, 2H), 7.03 (s, 2H), 6.79 (s, 2H), 5.17 (s, 4H), 2.25(s, 6H), 2.18 (3H)
~ Elemental analysis results (%) ~
Calcd for C 17 H 20 N 4 O: C, 68.89; H, 6.80; N, 18.90.
Found: C, 68.89; H, 7.01; N, 18.65.
-NMR results-
1 H NMR (CDCl 3 ) δ7.22 (s, 2H), 7.03 (s, 2H), 6.79 (s, 2H), 5.17 (s, 4H), 2.25 (s, 6H), 2.18 (3H)
以上、一般式（Ｉ）で表される化合物の合成例として例示化合物（ａ）の合成例を説明したが、その他の一般式（Ｉ）で表される化合物についても、出発物質や反応させる物質を適宜変更すること等により、上記と同様の方法により合成できる。 As mentioned above, the synthesis example of exemplary compound (a) was demonstrated as a synthesis example of the compound represented by general formula (I), However, About the compound represented by other general formula (I), it is a starting material and the substance made to react Can be synthesized by the same method as described above by appropriately changing.
〔実施例２〕
＜過塩素酸を取り込んだ捕捉カプセル型分子の形成＞
過塩素酸銅六水和物を溶かした水溶液（３ｍＭ）と、ｂｉｔｐｈを溶かしたアセトニトリル溶液（６ｍＭ）と、を混合し、約１週間静置したところ、紫色の結晶が得られた。この結晶を何回か再結晶したところ、きれいな紫色のブロック状の結晶（以下、「紫色結晶」ともいう）が析出した（収率７４％）。
以下、得られた紫色結晶について、元素分析及び結晶解析を行った結果を示す。
[Example 2]
<Formation of trapped capsule molecules incorporating perchloric acid>
When an aqueous solution (3 mM) in which copper perchlorate hexahydrate was dissolved and an acetonitrile solution (6 mM) in which bitph was dissolved were mixed and allowed to stand for about 1 week, purple crystals were obtained. When this crystal was recrystallized several times, clean purple block crystals (hereinafter also referred to as “purple crystals”) were precipitated (yield 74%).
Hereinafter, the results of elemental analysis and crystal analysis of the obtained purple crystals are shown.
〜元素分析結果（％）〜
Calcd for C68H100Cl4Cu2N16O30 : C, 43.20; H, 5.33; N, 11.85.
Found: C, 43.57; H, 5.12; N, 11.83
〜単結晶Ｘ線構造解析結果〜
a = 13.502(5) Å, b = 14.020(7) Å, c = 13.940(7) Å, α = 87.83(3)°, β = 66.237(19)°, γ = 66.89(2)°, V = 2198.4(18) Å3, Space Group : P-1(#2), Z = 1, R(I>2.00σ(I)) = 0.1362, Rw = 0.1952
~ Elemental analysis results (%) ~
Calcd for C 68 H 100 Cl 4 Cu 2 N 16 O 30 : C, 43.20; H, 5.33; N, 11.85.
Found: C, 43.57; H, 5.12; N, 11.83
-Single crystal X-ray structural analysis results-
a = 13.502 (5) Å, b = 14.020 (7) Å, c = 13.940 (7) α, α = 87.83 (3) °, β = 66.237 (19) °, γ = 66.89 (2) °, V = 2198.4 (18) Å 3 , Space Group: P-1 (# 2), Z = 1, R (I> 2.00σ (I)) = 0.1362, Rw = 0.1952
上記元素分析結果及び単結晶Ｘ線構造解析結果より、前記紫色結晶は、以下の反応によって得られた捕捉カプセル型分子の１０水和物であることがわかった。 From the above-mentioned elemental analysis results and single crystal X-ray structure analysis results, it was found that the purple crystals are decacapsulated capsule hydrate molecules obtained by the following reaction.
上記元素分析結果及び結晶解析結果より明らかとなった捕捉カプセル型分子の構造を、図１に示す。
図１に示すように、捕捉カプセル型分子の構造は、Ｃｕ２＋イオン２個及びｂｉｔｐｈ４分子により形成されたカプセル骨格が、過塩素酸イオン１分子を内包する構造である。更に、このカプセル骨格に含まれる２個のＣｕ２＋イオンには、カプセル骨格の外側に過塩素酸イオンが１分子ずつ配位している。更に、当該カプセル骨格と別のカプセル骨格との間に、過塩素酸イオン１分子が捕捉されている。
以上のようにして捕捉カプセル型分子１分子は、過塩素酸イオンを合計４分子捕捉している。
FIG. 1 shows the structure of the trapping capsule molecule that has been clarified from the results of the elemental analysis and the crystallographic analysis.
As shown in FIG. 1, the structure of the capture capsule type molecule is a structure in which a capsule skeleton formed by two Cu 2+ ions and a bitph4 molecule includes one molecule of perchlorate ion. Furthermore, perchlorate ions are coordinated one molecule at a time to the two Cu 2+ ions contained in the capsule skeleton. Furthermore, one molecule of perchlorate ion is trapped between the capsule skeleton and another capsule skeleton.
As described above, one molecule of the capture capsule type molecule captures a total of four perchlorate ions.
〔実施例３〕
＜過塩素酸イオンの捕捉に伴う液体試料の分光特性の変化＞
硫酸銅とｂｉｔｐｈとを含む水溶液（モル比〔Ｃｕ２＋：ｂｉｔｐｈ〕＝２：４）に、過塩素酸ナトリウム水溶液を滴下していき、過塩素酸イオン（ＣｌＯ４ −）のモル比率を上げていったときの可視紫外吸収スペクトルの変化を測定した。
ここで、可視紫外吸収スペクトルは、日本分光（株）製のV570 UV-Vis.NIR supectrometerにて測定した。
測定結果を図２に示す。
Example 3
<Changes in spectroscopic characteristics of liquid samples due to perchlorate ion capture>
A sodium perchlorate aqueous solution was dropped into an aqueous solution containing copper sulfate and bitph (molar ratio [Cu 2+ : bitph] = 2: 4) to increase the molar ratio of perchlorate ions (ClO 4 − ). The change in the visible ultraviolet absorption spectrum was measured.
Here, the visible ultraviolet absorption spectrum was measured with a V570 UV-Vis.NIR supectrometer manufactured by JASCO Corporation.
The measurement results are shown in FIG.
図２に示すように、過塩素酸ナトリウム水溶液滴下前は６５０ｎｍ付近に吸収がみられた（波形ａ）。このとき溶液の色は青緑色であった。
過塩素酸イオン（ＣｌＯ４ −）のモル比率を増加させるに従い、６５０ｎｍ付近に吸収が小さくなっていった。更に、過塩素酸イオン（ＣｌＯ４ −）のモル比率を増加させると、６５０ｎｍ付近に吸収は更に小さくなり、代わりに５６０ｎｍ付近に新たな吸収が現れ、溶液の色が次第に紫色に変化していった。
モル比〔Ｃｕ２＋：ｂｉｔｐｈ：ＣｌＯ４ −〕が２：４：１となった以降はスペクトルの変化がとまった（波形ｂ）。このとき溶液の色は紫色であった。
新たに現れた５６０ｎｍの吸収は、捕捉カプセル型分子の吸収と一致したことから、過塩素酸を取り込んだ捕捉カプセル型分子が形成されたことが確認された。
また、捕捉カプセル型分子の形成に伴い、溶液の色が紫色に変化することが確認された。
As shown in FIG. 2, absorption was observed at around 650 nm before the sodium perchlorate aqueous solution was dropped (waveform a). At this time, the color of the solution was blue-green.
As the molar ratio of perchlorate ion (ClO 4 − ) was increased, the absorption became smaller near 650 nm. Furthermore, when the molar ratio of perchlorate ion (ClO 4 − ) is increased, the absorption is further reduced around 650 nm, and a new absorption appears around 560 nm, and the color of the solution gradually changes to purple. It was.
After the molar ratio [Cu 2+ : bitph: ClO 4 − ] became 2: 4: 1, the change in the spectrum stopped (waveform b). At this time, the color of the solution was purple.
The newly appearing absorption at 560 nm coincided with the absorption of the trapping capsule type molecule, so it was confirmed that the trapping capsule type molecule incorporating perchloric acid was formed.
It was also confirmed that the color of the solution changed to purple with the formation of the trapping capsule type molecule.
〔実施例４〕
＜呈色を利用した過塩素酸イオンの検出＞
（試料１の調製）
１．５ｍｇ（６×１０−６ｍｏｌ）の硫酸銅と、３．６ｍｇ（１．２×１０−５ｍｏｌ）のｂｉｔｐｈと、をサンプル瓶にそれぞれ量りとり、そこに、純水３ｍｌを滴下して試料１（ブランク）とした。
純水の滴下から１分後の試料１の色を目視で観察した。結果を表１及び図３に示す。
Example 4
<Detection of perchlorate ion using coloration>
(Preparation of sample 1)
1.5 mg (6 × 10 −6 mol) of copper sulfate and 3.6 mg (1.2 × 10 −5 mol) of bitph are weighed into sample bottles, respectively, and 3 ml of pure water is added dropwise thereto. Sample 1 (blank).
The color of Sample 1 after 1 minute from the dropping of pure water was visually observed. The results are shown in Table 1 and FIG.
（試料２〜試料５の調製）
試料１の調製において、純水３ｍｌを、下記表１に示す過塩素酸ナトリウム（ＮａＣｌＯ４）濃度の過塩素酸ナトリウム水溶液３ｍｌに変更したこと以外は試料１の調製と同様にして、試料２〜試料５をそれぞれ調製した。
過塩素酸ナトリウム水溶液の滴下から１分後の試料２〜試料５の色を目視で観察した。結果を表１及び図３に示す。
(Preparation of sample 2 to sample 5)
Sample 2 was prepared in the same manner as Sample 1 except that 3 ml of pure water was changed to 3 ml of a sodium perchlorate aqueous solution having a sodium perchlorate (NaClO 4 ) concentration shown in Table 1 below. Sample 5 was prepared respectively.
The color of Sample 2 to Sample 5 after 1 minute from the dropping of the sodium perchlorate aqueous solution was visually observed. The results are shown in Table 1 and FIG.
図３は、試料１〜試料５の写真であり、左から順に、試料１、試料２、試料３、試料４、試料５である。 FIG. 3 is a photograph of Sample 1 to Sample 5, which are Sample 1, Sample 2, Sample 3, Sample 4, and Sample 5 in order from the left.
表１及び図３に示すように、ブランク（純水）である試料１、ＮａＣｌＯ４濃度が０．５ｍＭである試料２では、試料の色は薄い青緑色であった。
これに対し、ＮａＣｌＯ４濃度が１．０ｍＭ以上である試料３〜試料５では、試料の色は、濁りがかった薄い紫色であった。
以上の結果より、ｂｉｔｐｈは、液体試料中の過塩素酸イオンを検出できることがわかった。
As shown in Table 1 and FIG. 3, in sample 1 which is blank (pure water) and sample 2 in which the NaClO 4 concentration is 0.5 mM, the color of the sample was light blue-green.
In contrast, in Samples 3 to 5 in which the NaClO 4 concentration was 1.0 mM or more, the color of the sample was cloudy and light purple.
From the above results, it was found that bitph can detect perchlorate ions in a liquid sample.
以上のように、モル比〔Ｃｕ２＋：ｂｉｔｐｈ：ＣｌＯ４ −〕が２：４：１である試料３、及び、試料３よりも過塩素酸イオンのモル比率が高い試料４及び試料５において、試料の色が、濁りがかった薄い紫色に変化した。この結果は、銅原子２個とｂｉｔｐｈ４分子とで形成されるカプセル骨格に過塩素酸イオン１分子が内包されて捕捉カプセル型分子が形成され、その結果、試料の色が、銅イオンに由来する薄い青緑色から捕捉カプセル型分子に由来する濁りがかった薄い紫色に変化したことを示している。
ここで、粉末固体として使用した硫酸銅及びｂｉｔｐｈの量を調整することで、過塩素酸イオン濃度の検出下限を変更することもできる。例えば、上記において硫酸銅及びｂｉｔｐｈの量をいずれも１／２とした場合には、過塩素酸イオン濃度０．５ｍＭの試料中における過塩素酸イオンを検出することが可能となる。
また、未知の過塩素酸イオン濃度の溶液に対し、硫酸銅及びｂｉｔｐｈの量を変化させながら添加していき、溶液の色が変化したときの硫酸銅及びｂｉｔｐｈの量から、過塩素酸イオン濃度を定量することもできる。
As described above, in sample 3 in which the molar ratio [Cu 2+ : bitph: ClO 4 − ] is 2: 4: 1, and in samples 4 and 5 in which the molar ratio of perchlorate ions is higher than that of sample 3, The color of the sample changed to turbid and light purple. This result shows that a capsule skeleton formed by two copper atoms and 4 bitph molecules encapsulates one molecule of perchlorate ion to form a trapped capsule type molecule. As a result, the color of the sample is derived from the copper ion. It shows that the light blue-green color changed to a turbid light purple color derived from the trapping capsule type molecule.
Here, the detection lower limit of the perchlorate ion concentration can be changed by adjusting the amounts of copper sulfate and bitph used as the powder solid. For example, when both the amount of copper sulfate and bitph is halved in the above, it is possible to detect perchlorate ions in a sample having a perchlorate ion concentration of 0.5 mM.
In addition, to the solution of unknown perchlorate ion concentration, adding while changing the amount of copper sulfate and bitph, from the amount of copper sulfate and bitph when the color of the solution changed, the concentration of perchlorate ion Can also be quantified.
以上、ｂｉｔｐｈを用い試料の発色により過塩素酸イオンを検出する実施例について説明したが、ｂｉｔｐｈは硝酸イオンに対しても同様の発色を示した。更に、テトラフルオロホウ酸イオン（ＢＦ４ −）、ヘキサフルオロリン酸イオン（ＰＦ６ −）、トリフルオロメタンスルホン酸イオン（ＣＦ３ＳＯ３ −）等、分子サイズ１ｎｍ以下の分子について、同様の発色を示した。
また、上記実施例では、一般式（Ｉ）で表される化合物の一例としてｂｉｔｐｈを用いたが、ｂｉｔｐｈ以外の一般式（Ｉ）で表される化合物を用いた場合にも、液体試料中の分子サイズ１ｎｍ以下の分子を、直接的に短時間に感度良く検出できる。
The example in which perchlorate ion is detected by color development of a sample using bitph has been described above, but bitph showed similar color development to nitrate ion. Furthermore, similar color development is achieved for molecules having a molecular size of 1 nm or less, such as tetrafluoroborate ion (BF 4 − ), hexafluorophosphate ion (PF 6 − ), trifluoromethanesulfonate ion (CF 3 SO 3 − ), and the like. Indicated.
In the above examples, bitph was used as an example of the compound represented by the general formula (I). However, when a compound represented by the general formula (I) other than bitph is used, Molecules with a molecular size of 1 nm or less can be directly detected with high sensitivity in a short time.
Claims (6)
請求項１〜請求項３のいずれか１項に記載の複素環置換芳香族化合物と、平面四配位又は正八面体配位可能な金属イオンと、前記液体試料と、を接触させて、前記標的分子を捕捉した捕捉カプセル型分子を形成させ、該捕捉カプセル型分子の形成に伴う液体試料の色の変化により前記標的分子を検出する分子検出方法。 A method for detecting a target molecule having a molecular size of 1 nm or less in a liquid sample,
The heterocycle-substituted aromatic compound according to any one of claims 1 to 3, a metal ion capable of planar tetracoordination or regular octahedral coordination, and the liquid sample are brought into contact with each other, and the target A molecular detection method in which a capture capsule type molecule capturing a molecule is formed, and the target molecule is detected by a change in color of a liquid sample accompanying the formation of the capture capsule type molecule.
請求項１〜請求項３のいずれか１項に記載の複素環置換芳香族化合物と、平面四配位又は正八面体配位可能な金属イオンと、前記液体試料と、を接触させて、前記標的分子を捕捉した捕捉カプセル型分子を形成させることを含む分子捕捉方法。 A method for capturing a target molecule having a molecular size of 1 nm or less in a liquid sample,
The heterocycle-substituted aromatic compound according to any one of claims 1 to 3, a metal ion capable of planar tetracoordination or regular octahedral coordination, and the liquid sample are brought into contact with each other, and the target A molecular trapping method comprising forming a trapping capsule molecule trapping a molecule.
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