CN110607552A - Method for preparing single crystal or amorphous substance by using aqueous solution - Google Patents
Method for preparing single crystal or amorphous substance by using aqueous solution Download PDFInfo
- Publication number
- CN110607552A CN110607552A CN201911039677.5A CN201911039677A CN110607552A CN 110607552 A CN110607552 A CN 110607552A CN 201911039677 A CN201911039677 A CN 201911039677A CN 110607552 A CN110607552 A CN 110607552A
- Authority
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- China
- Prior art keywords
- single crystal
- substance
- freezing
- pseudocrystalline
- ice
- Prior art date
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Links
- 239000013078 crystal Substances 0.000 title claims abstract description 226
- 239000000126 substance Substances 0.000 title claims abstract description 170
- 238000000034 method Methods 0.000 title claims abstract description 137
- 239000007864 aqueous solution Substances 0.000 title claims abstract description 72
- 238000007710 freezing Methods 0.000 claims abstract description 98
- 230000008014 freezing Effects 0.000 claims abstract description 98
- 230000008569 process Effects 0.000 claims abstract description 67
- 239000000463 material Substances 0.000 claims abstract description 50
- 239000000203 mixture Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 80
- 230000032683 aging Effects 0.000 claims description 40
- 239000000243 solution Substances 0.000 claims description 35
- 238000001816 cooling Methods 0.000 claims description 32
- 239000007787 solid Substances 0.000 claims description 28
- 239000007788 liquid Substances 0.000 claims description 25
- 238000010438 heat treatment Methods 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 12
- 239000012452 mother liquor Substances 0.000 claims description 11
- 238000005057 refrigeration Methods 0.000 claims description 10
- 230000000630 rising effect Effects 0.000 claims description 10
- 230000005540 biological transmission Effects 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 8
- 230000005070 ripening Effects 0.000 claims description 8
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 8
- 239000012498 ultrapure water Substances 0.000 claims description 8
- 230000003247 decreasing effect Effects 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 238000009792 diffusion process Methods 0.000 claims description 5
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 4
- 239000001569 carbon dioxide Substances 0.000 claims description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 4
- 235000011089 carbon dioxide Nutrition 0.000 claims description 4
- 230000006835 compression Effects 0.000 claims description 4
- 238000007906 compression Methods 0.000 claims description 4
- 239000001307 helium Substances 0.000 claims description 4
- 229910052734 helium Inorganic materials 0.000 claims description 4
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 4
- 239000004065 semiconductor Substances 0.000 claims description 4
- 238000000859 sublimation Methods 0.000 claims description 4
- 230000008022 sublimation Effects 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 238000005868 electrolysis reaction Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 238000010583 slow cooling Methods 0.000 claims description 3
- 239000008367 deionised water Substances 0.000 claims description 2
- 229910021641 deionized water Inorganic materials 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 239000002178 crystalline material Substances 0.000 claims 2
- 238000004090 dissolution Methods 0.000 claims 1
- 238000001179 sorption measurement Methods 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 230000002776 aggregation Effects 0.000 abstract description 19
- 238000004220 aggregation Methods 0.000 abstract description 19
- 238000002425 crystallisation Methods 0.000 abstract description 11
- 238000002360 preparation method Methods 0.000 abstract description 11
- 238000010899 nucleation Methods 0.000 abstract description 8
- 230000006911 nucleation Effects 0.000 abstract description 8
- 230000008025 crystallization Effects 0.000 abstract description 7
- 238000012258 culturing Methods 0.000 abstract description 4
- 230000007547 defect Effects 0.000 abstract description 2
- 238000001878 scanning electron micrograph Methods 0.000 description 27
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 16
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 15
- 229910052710 silicon Inorganic materials 0.000 description 15
- 239000010703 silicon Substances 0.000 description 15
- 239000002245 particle Substances 0.000 description 13
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 12
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 11
- 229910000365 copper sulfate Inorganic materials 0.000 description 8
- 230000001276 controlling effect Effects 0.000 description 7
- 230000033228 biological regulation Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 230000035800 maturation Effects 0.000 description 5
- 235000019371 penicillin G benzathine Nutrition 0.000 description 5
- 229940056360 penicillin g Drugs 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
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- 238000010586 diagram Methods 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 238000009776 industrial production Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000008247 solid mixture Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 238000002061 vacuum sublimation Methods 0.000 description 3
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- 229930191978 Gibberellin Natural products 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
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- IXORZMNAPKEEDV-UHFFFAOYSA-N gibberellic acid GA3 Natural products OC(=O)C1C2(C3)CC(=C)C3(O)CCC2C2(C=CC3O)C1C3(C)C(=O)O2 IXORZMNAPKEEDV-UHFFFAOYSA-N 0.000 description 2
- 239000003448 gibberellin Substances 0.000 description 2
- 229940089161 ginsenoside Drugs 0.000 description 2
- 229930182494 ginsenoside Natural products 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
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- 229910052751 metal Inorganic materials 0.000 description 2
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 2
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- 150000003839 salts Chemical class 0.000 description 2
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- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- FBFMBWCLBGQEBU-RXMALORBSA-N (2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5s,6r)-2-[[(3s,5r,6s,8r,9r,10r,12r,13r,14r,17s)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-[(2s)-6-methyl-2-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhept-5-en-2-yl]-2,3,5,6,7,9,11,12,13,15,16,17-dodecah Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FBFMBWCLBGQEBU-RXMALORBSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- FBFMBWCLBGQEBU-GYMUUCMZSA-N 20-gluco-ginsenoside-Rf Natural products O([C@](CC/C=C(\C)/C)(C)[C@@H]1[C@H]2[C@H](O)C[C@H]3[C@](C)([C@]2(C)CC1)C[C@H](O[C@@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@H]1C(C)(C)[C@@H](O)CC[C@]31C)[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 FBFMBWCLBGQEBU-GYMUUCMZSA-N 0.000 description 1
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- 108010087806 Carnosine Proteins 0.000 description 1
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- HYPFYJBWSTXDAS-UHFFFAOYSA-N Ginsenoside Rd Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C4CCC5C(C)(C)C(CCC5(C)C4CC(O)C23C)OC6OC(CO)C(O)C(O)C6OC7OC(CO)C(O)C(O)C7O)C HYPFYJBWSTXDAS-UHFFFAOYSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108010008488 Glycylglycine Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
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- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
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- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- FCPVYOBCFFNJFS-LQDWTQKMSA-M benzylpenicillin sodium Chemical compound [Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 FCPVYOBCFFNJFS-LQDWTQKMSA-M 0.000 description 1
- RTYJTGSCYUUYAL-YCAHSCEMSA-L carbenicillin disodium Chemical compound [Na+].[Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)C(C([O-])=O)C1=CC=CC=C1 RTYJTGSCYUUYAL-YCAHSCEMSA-L 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
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- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
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- 238000002003 electron diffraction Methods 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- NVVZQXQBYZPMLJ-UHFFFAOYSA-N formaldehyde;naphthalene-1-sulfonic acid Chemical compound O=C.C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 NVVZQXQBYZPMLJ-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- OCXSDHJRMYFTMA-KMFBOIRUSA-M nafcillin sodium monohydrate Chemical compound O.[Na+].C1=CC=CC2=C(C(=O)N[C@@H]3C(N4[C@H](C(C)(C)S[C@@H]43)C([O-])=O)=O)C(OCC)=CC=C21 OCXSDHJRMYFTMA-KMFBOIRUSA-M 0.000 description 1
- 229960004387 nafcillin sodium monohydrate Drugs 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229910052755 nonmetal Chemical class 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
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- 230000002035 prolonged effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 1
- 229940043267 rhodamine b Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- UOJAEODBOCLNBU-UHFFFAOYSA-N vinaginsenoside R4 Natural products C1CC(C2(CC(O)C3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O UOJAEODBOCLNBU-UHFFFAOYSA-N 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C30—CRYSTAL GROWTH
- C30B—SINGLE-CRYSTAL GROWTH; UNIDIRECTIONAL SOLIDIFICATION OF EUTECTIC MATERIAL OR UNIDIRECTIONAL DEMIXING OF EUTECTOID MATERIAL; REFINING BY ZONE-MELTING OF MATERIAL; PRODUCTION OF A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; SINGLE CRYSTALS OR HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; AFTER-TREATMENT OF SINGLE CRYSTALS OR A HOMOGENEOUS POLYCRYSTALLINE MATERIAL WITH DEFINED STRUCTURE; APPARATUS THEREFOR
- C30B7/00—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions
- C30B7/08—Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions by cooling of the solution
Landscapes
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Crystallography & Structural Chemistry (AREA)
- Materials Engineering (AREA)
- Metallurgy (AREA)
- Organic Chemistry (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
Abstract
The invention relates to the field of single crystal preparation, in particular to a method for preparing a single crystal or an amorphous substance by using an aqueous solution, which is suitable for preparing and culturing any water-soluble molecular single crystal or amorphous substance. The method comprises the following steps: (a1) preparing an aqueous solution of a pseudo-crystalline substance; (a2) freezing and optionally curing the aqueous solution of the pseudocrystalline material of step (a1) to produce a single crystal or amorphous-ice mixture containing the pseudocrystalline material; optionally, (a3) separating the single crystal or amorphous-ice mixture of the pseudocrystalline material of step (a2) to obtain a single crystal or amorphous of the pseudocrystalline material. The method of the invention firstly proposes to induce the nucleation and crystallization of solute molecules by freezing aqueous solution to rapidly and effectively prepare solute molecule single crystals or amorphous substances aiming at the defects that the molecular nucleation and aggregation speed are difficult to control in the process of culturing single crystals or amorphous substances by the traditional method.
Description
The present application claims the priority of a prior application entitled "a method for preparing and growing single crystals using an aqueous solution" filed in 2018, 10 and 30.8 to the intellectual property office of china under patent application No. 2018112792527, which is incorporated herein by reference in its entirety.
Technical Field
The invention relates to the field of preparation of single crystals or amorphous substances, in particular to a method for preparing single crystals or amorphous substances by using an aqueous solution.
Technical Field
Single crystals play an important role in various modern scientific fields, such as structural analysis of organic molecules and proteins, optoelectronic devices, medicine, and aerospace. At present, the molecular crystallization method is widely studied, and a solvent slow volatilization method, a cooling method, a liquid phase diffusion method, a polymer induced crystallization and a gas phase diffusion method and the like are commonly used. However, the above methods generally have the problems of poor controllability of crystal nucleation and growth, difficulty in single crystal growth, easiness in generation of polycrystals, and the like. Some molecules cannot even be used to obtain single crystals by the above method, so how to efficiently prepare perfect single crystals remains a great challenge. In addition, certain amorphous materials play an important role in the scientific field.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a method for preparing a single crystal or an amorphous substance by using an aqueous solution.
A method of preparing a single crystal or amorphous substance using an aqueous solution, the method comprising the steps of:
(a1) preparing an aqueous solution of a pseudo-crystalline substance;
(a2) freezing the aqueous solution of the pseudocrystalline material of step (a 1);
optionally aging to obtain single crystal or amorphous substance-ice mixed system containing pseudocrystalline substance;
optionally, (a3) separating the single crystal or amorphous-ice mixture of the pseudocrystalline material of step (a2) to obtain a single crystal or amorphous of the pseudocrystalline material.
According to the invention, in step (a1)
The water includes but is not limited to ultrapure water, secondary water, deionized water.
The pseudocrystalline material includes, but is not limited to, inorganic and/or organic.
The pseudocrystalline material is insoluble, slightly soluble, soluble or readily soluble in water.
In the present invention, the step (a2) specifically includes the following steps:
and (c) cooling and freezing the aqueous solution of the pseudocrystalline substance in the step (a1) to obtain a solid mixture, and optionally performing aging treatment to prepare a mixed system of the single crystal or amorphous substance containing the pseudocrystalline substance and ice.
In the present invention, in the step (a2), the freezing is to convert the aqueous solution of the pseudocrystalline substance of the step (a1) from a liquid state to a solid state.
In the invention, the freezing method includes but is not limited to one or a combination of several temperature reduction freezing methods of compression refrigeration equipment, semiconductor refrigeration equipment, liquid nitrogen, liquid helium, liquid carbon dioxide, liquid oxygen, liquid ethane, dry ice, ice and the like.
In the invention, the freezing process includes but is not limited to one or a combination of several freezing processes of rapid cooling, slow cooling, stepwise cooling, first heating and then cooling, and the like.
In the present invention, the freezing includes, but is not limited to, complete freezing and incomplete freezing.
In the present invention, the aging maintains the aqueous solution of the pseudocrystalline material in a frozen state for a period of time.
In the present invention, the aging time refers to the time required for heating or cooling to the aging temperature after the freezing process is finished, and the time for maintaining at the aging temperature.
In one embodiment, the step (a2) of freezing the solution of the pseudocrystalline substance of step (a1) produces a mixed system of single crystals and ice containing the pseudocrystalline substance.
In one embodiment, the step (a2) includes a ripening step, that is, in the step (a2), the solution of the pseudocrystalline substance of the step (a1) is subjected to freezing and ripening to prepare a mixed system of ice and a single crystal or amorphous substance containing the pseudocrystalline substance.
In one embodiment, in the step (a2), the temperature is increased to a certain temperature at a temperature increasing or decreasing speed of 10 ℃/min or more during the curing process, and the curing time is less than 25min, so as to prepare a mixed system of the amorphous substance containing the pseudocrystalline substance and ice.
In yet another embodiment, the greater the difference between the temperature reached and the freezing temperature, the greater the particle size of the resulting amorphous material. The particle size of the amorphous material obtained can be controlled by adjusting the magnitude of this temperature difference.
In one embodiment, the step (a2) of aging is carried out by bringing the temperature to a certain temperature at a temperature rising or lowering rate of less than 10 ℃/min, and/or the aging time is at least 25min, to obtain a mixed system of single crystal and ice containing the pseudocrystalline substance.
Illustratively, during the aging process, the temperature is increased to a certain temperature at a temperature increasing or decreasing speed of less than 10 ℃/min, and the temperature is kept for a period of time, so as to prepare a mixed system of single crystals and ice containing the substances to be crystallized.
Illustratively, in the curing process, the temperature is increased to a certain temperature at any temperature rising or decreasing speed, and the curing is carried out for at least 25min, so as to prepare a mixed system of single crystals and ice containing the pseudo-crystalline substance.
Illustratively, in the curing process, the temperature is increased to a certain temperature at a temperature rising or decreasing speed of less than 10 ℃/min, and the curing is carried out for at least 25min, so as to prepare a mixed system of single crystals and ice containing the pseudo-crystalline substance.
In the present invention, in the step (a3), the separating physically and/or chemically separates the single crystal from the ice.
In the present invention, the physical means includes, but is not limited to, one or a combination of mechanical separation and sublimation (e.g. vacuum sublimation).
In the present invention, the chemical means includes but is not limited to one or a combination of several of chemical reaction and electrolysis.
In the present invention, the method further comprises the steps of:
(a4) collecting the single crystal or amorphous substance prepared in the step (a 3).
In the present invention, in step (a4), the collecting includes, but is not limited to, collecting by using one or more of optical microscope, scanning electron microscope, dual-beam electron microscope, and transmission electron microscope.
The present invention also provides a method of growing a single crystal, including the above-described method of preparing a single crystal.
In the present invention, the method for growing a single crystal further comprises the steps of:
(b1) transferring the single crystal of the pseudo-crystalline substance prepared above to a mother liquor of the pseudo-crystalline substance for culturing;
(b2) collecting the single crystal grown in the step (b 1).
In the step (b1), the transferring may be a step of transferring the mixed crystal-ice system containing the pseudo-crystalline substance of the step (a2) to a mother liquor of the pseudo-crystalline substance for single crystal cultivation; or directly transferring the ice-removed single crystal of the step (a3) into a mother liquor of a pseudo-crystalline substance for single crystal cultivation; or transferring the single crystal collected in the step (a4) to a mother liquor of a pseudo-crystalline substance to perform single crystal cultivation.
In the present invention, the transferring includes, but is not limited to, one or a combination of optical microscope transferring, scanning electron microscope transferring, dual-beam electron microscope transferring, and transmission electron microscope transferring.
In the present invention, in the step (b1), the single crystal is cultured by one or more methods selected from the group consisting of evaporation, cooling, and diffusion.
In the present invention, in step (b2), the collecting includes, but is not limited to, collecting by using one or more of optical microscope, scanning electron microscope, dual-beam electron microscope, and transmission electron microscope.
Advantageous effects
(1) Aiming at the defects that the molecule supply, aggregation and nucleation speed are difficult to control and the like in the process of preparing single crystals or amorphous substances by the traditional method, the invention provides a method for controlling the water solution freezing to induce the nucleation and crystallization of solute molecules for the first time. Crystallization of dissolved solute molecules is achieved in a water crystallization process, and single crystals or amorphous substances of solute molecules are rapidly and efficiently prepared by controlling freezing, and optionally curing, of an aqueous solution. Meanwhile, the method solves the problem of difficult molecular crystallization in the traditional single crystal preparation and culture process, can also solve the problem that some substances are difficult to form amorphous substances, particularly high-purity amorphous substances, and has universality.
(2) In the research process, the ice recrystallization method is adopted, the regulation and control range of the solution concentration is wider, and the preparation of single crystals or amorphous substances can be realized from very low concentration to supersaturated concentration. The acquisition of single crystals or amorphous substances under extremely low solution concentration is realized for the first time; the problems that the single crystal formation is not easy to control, polycrystal and/or twin crystal are easy to form and the like due to the over-quick aggregation of solute molecules under high concentration are solved; in addition, the invention also has the characteristic of obtaining the single crystal or amorphous substance of the substance to be crystallized in a short time (from a few minutes to a few hours).
(3) The freezing of the solution is a technical key point in the invention. The freezing process means that the aqueous solution is frozen in any manner, and the freezing time, freezing temperature gradient, freezing method, freezing process, and the like are not particularly limited. Experiments prove that the essence of preparing solute single crystals or amorphous substances by freezing aqueous solutions is that in the freezing process, water molecules form ice crystals, meanwhile, solute molecules are released and gathered at the interface of the ice crystals, and the release and gathering rates of the solute molecules are further regulated and controlled by controlling the water freezing process and the recrystallization of the ice crystals, so that the regulation and control on the nucleation and growth of the solute molecules are effectively realized, and the single crystals or amorphous substances of target molecules are obtained.
(4) The curing process of the present invention means that the frozen aqueous solution is maintained in a solid state for a certain period of time, and the temperature is not limited, but the temperature rise or decrease speed needs to be controlled. Experiments prove that the curing process optionally serves as a supplementary means of the freezing process, and can optimize the regulation and control of the recrystallization process of the ice crystal, so that the release rate of solute molecules in the ice crystal and the aggregation rate of the solute molecules to the interface of the ice crystal are regulated and controlled, and the growth of amorphous substances and the nucleation and growth of single crystals after the solution is frozen are further optimized. Moreover, the curing process does not limit the temperature too much, so that the frozen system can obtain single crystals or amorphous substances with the particle size ranging from nanometer to micrometer without continuously freezing but through the curing process, thereby being beneficial to realizing the optimized preparation of the single crystals or the amorphous substances with higher efficiency at more economic temperature, and being beneficial to reducing the energy consumption so as to greatly save the cost. Compared with the traditional method, the method realizes the optimized regulation and control of the recrystallization of the ice crystal by regulating and controlling the heating or cooling rate in the curing process, can further regulate and control the aggregation speed of solute molecules in the ice crystal to the interface of the ice crystal, further effectively obtains the single crystal or amorphous substance of the solute molecules, has the advantages of saving energy, improving efficiency and the like, and is more beneficial to large-scale industrial production.
(5) The preparation method of the single crystal or the amorphous substance and the further culture method provided by the invention have wide application range, are suitable for both the existing inorganic substance and organic substance, and can be used for realizing the acquisition of the single crystal or the amorphous substance of the substance which is difficult to crystallize by the traditional method. And the experimental method is simple and strong in operability. The method disclosed by the invention is not only suitable for basic research in a laboratory, but also meets the requirements of industrial production.
Drawings
FIG. 1 is a scanning electron micrograph of a copper sulfate single crystal prepared according to examples 1,2 and 3.
FIG. 2 is a scanning electron micrograph of a glutamic acid single crystal prepared according to examples 4,7,8 and 9.
FIG. 3 is a scanning electron micrograph of benzylpenicillin single crystals prepared in examples 5 and 6.
FIG. 4 is a scanning electron micrograph of a glycine single crystal prepared in example 10.
FIG. 5 is a scanning electron micrograph of the raffinose single crystal prepared in examples 11 and 12.
FIG. 6 is a SEM photograph of a glutathione single crystal prepared in example 13.
FIG. 7 is a scanning electron micrograph of an erythromycin single crystal prepared in example 14.
FIG. 8 is a SEM photograph of trehalose single crystals prepared in examples 15 and 16.
FIG. 9 is a scanning electron micrograph of a tartaric acid single crystal prepared according to examples 17 and 18.
FIG. 10 shows vitamin B prepared in example 193Scanning electron micrographs of single crystals.
FIG. 11 is a scanning electron micrograph of a single crystal of lysozyme prepared in example 20, the lysozyme being derived from chicken eggs.
FIG. 12 is a scanning electron micrograph of an alanine single crystal produced in example 21.
FIG. 13 is a scanning electron micrograph of a sodium chloride single crystal produced in example 22.
FIG. 14 is a scanning electron micrograph of chloramphenicol single crystals prepared in examples 23,24, and 25.
FIG. 15 is a scanning electron micrograph of a single crystal of penicillin G sodium salt prepared in examples 26 and 27.
FIG. 16 is a scanning electron micrograph of a monocrystals of carbenicillin disodium salt prepared in example 28.
FIG. 17 is a scanning electron micrograph of a single crystal of nafcillin sodium monohydrate prepared in example 29.
FIG. 18 shows ginsenoside Rh prepared in examples 30 and 312Scanning electron micrographs of single crystals.
FIG. 19 shows ginsenoside Rb prepared in examples 32 and 332Scanning electron micrographs of single crystals.
FIG. 20 is a SEM image of ginsenoside Rd single crystals prepared in examples 34 and 35.
FIG. 21 is gibberellin A prepared in example 361Scanning electron micrographs of single crystals.
FIG. 22 is gibberellin A prepared in example 375Scanning electron micrographs of single crystals.
FIG. 23 is a SEM of single crystal of AIE35 prepared in example 38 and shows the chemical structural formula.
FIG. 24 is a SEM photograph of a rhodamine B single crystal prepared in example 39.
FIG. 25 is a SEM photograph of L-carnosine single crystals prepared in examples 40,41 and 42.
FIG. 26 is a SEM photograph of a single crystal of diglycine prepared in example 43.
FIG. 27 is a scanning electron micrograph of an aminopeptidase single crystal produced in example 44.
FIG. 28 shows [ Cu (NH) prepared in examples 45 and 463)4]SO4Scanning electron micrographs of single crystals.
FIG. 29 shows K prepared in example 474[Fe(CN)6]Scanning electron micrographs of single crystals.
FIG. 30 is [ Co (NH) prepared in example 483)5Cl]Cl2Scanning electron micrographs of single crystals.
FIG. 31 is C prepared in example 496H9NaO7The single crystal of (1) and a chemical structural formula.
FIG. 32 is a SEM photograph of malic acid single crystal prepared in example 50.
FIG. 33 is a scanning electron micrograph of a sodium hydrogen phosphate single crystal produced in example 51.
FIG. 34 is a scanning electron micrograph of a sodium sulfite single crystal prepared in example 52.
FIG. 35 is a SEM photograph of single crystal of sodium benzoate prepared in example 53.
FIG. 36 is a scanning electron micrograph of a p-toluenesulfonic acid single crystal prepared according to example 54.
FIG. 37 is a schematic diagram of the principle of the present invention for forming a single crystal.
FIG. 38 is a diagram of the process of forming a single crystal of AIE35 of the present invention.
FIG. 39 is a diagram showing a process of forming a single crystal of p-toluenesulfonic acid according to the present invention.
Detailed Description
In the present invention, "optionally" means that the subsequent step is performed or not.
[ method for producing Single Crystal or amorphous Material ]
As previously stated, the present invention provides a method for preparing a single crystal or amorphous substance using an aqueous solution, the method comprising the steps of:
(a1) preparing an aqueous solution of a pseudo-crystalline substance;
(a2) freezing and optionally curing the aqueous solution of the pseudocrystalline material of step (a1) to produce a single crystal or amorphous-ice mixture containing the pseudocrystalline material; optionally, the step of (a) is carried out,
(a3) separating the single crystal or amorphous substance of the pseudo-crystalline substance from the single crystal or amorphous substance-ice mixture system containing the pseudo-crystalline substance of step (a 2).
[ method of producing Single Crystal ]
As described above, the present invention provides a method for producing a single crystal, the method comprising the steps of:
(a1) preparing an aqueous solution of a pseudo-crystalline substance;
(a2) freezing and optionally curing the aqueous solution of the pseudocrystalline material of step (a1) to produce a mixed system of single crystals and ice containing the pseudocrystalline material;
(a3) separating the mixed system of the single crystal of the pseudo-crystalline substance and ice of step (a2) to prepare a single crystal of the pseudo-crystalline substance;
wherein the temperature rising or reducing rate in the curing process is less than 10 ℃/min, and/or the curing time in the curing process is at least 25 min.
Illustratively, in the curing process, the temperature is increased or decreased at a speed of less than 10 ℃/min to a certain temperature, and the temperature is kept for a period of time, so that a mixed system of single crystals and ice containing the substances to be crystallized is obtained.
Illustratively, in the curing process, the temperature is raised to a certain temperature at any temperature raising or lowering speed, and the curing is carried out for at least 25min, so as to obtain the mixed system of the single crystal containing the pseudo-crystalline substance and the ice.
Illustratively, in the curing process, the temperature is increased to a certain temperature at a temperature rising or reducing speed of less than 10 ℃/min, and the curing is carried out for at least 25min, so as to obtain the mixed system of the single crystal containing the pseudocrystalline substance and the ice.
Illustratively, the certain temperature reached is, for example, 0 ℃ or less, further, for example-5 ℃ or less; specifically, it may be-10 ℃, -15 ℃, -18 ℃, -20 ℃, -24 ℃, -25 ℃, -30 ℃, -72 ℃, -80 ℃, -90 ℃, -100 ℃, or the liquid nitrogen temperature, or the like.
As described above, the temperature increase or decrease rate is less than 10 ℃/min, for example, less than 9 ℃/min, and further, for example, 5 ℃/min or less; depending on the different species to be crystallized. It is understood that the rate of 0 ℃/min means that the aging is maintained at the same temperature as the freezing temperature.
As mentioned above, the aging time is at least 25min, for example, 30min, 40min, 50min, 55min, 60min, 90min, 100min, 120min, 150min, 200min, 300min, 500min or more; depending on the different species to be crystallized.
[ Process for producing amorphous Material ]
As previously mentioned, the present invention provides a method for preparing an amorphous material, comprising the steps of:
(a1) preparing an aqueous solution of a pseudo-crystalline substance;
(a2) freezing and curing the aqueous solution of the pseudo-crystalline substance obtained in the step (a1) to prepare an amorphous and ice mixed system containing the pseudo-crystalline substance; optionally, the step of (a) is carried out,
(a3) isolating amorphous form of the pseudocrystalline material from the mixed system of step (a 2);
wherein the heating or cooling rate in the curing process is more than or equal to 10 ℃/min, and the curing time in the curing process is less than 25 min.
Illustratively, in the aging process of the step (a2), the temperature is increased to a certain temperature at a temperature increasing or decreasing speed of 10 ℃/min or more and aging is carried out for less than 25min, so as to obtain a mixed system of the amorphous substance containing the pseudo-crystalline substance and ice.
In one embodiment, the greater the difference between the temperature reached and the freezing temperature, the greater the particle size of the resulting amorphous material. The particle size of the amorphous material obtained can be controlled by adjusting the temperature. Illustratively, the certain temperature reached is, for example, 0 ℃ or less, further, for example-5 ℃ or less; specifically, it may be-5 ℃, -7 ℃, -8 ℃, -10 ℃, -12 ℃, -20 ℃, -45 ℃ or the like. Preferably, the temperature is increased from the liquid nitrogen temperature to the above temperature at a temperature increase rate of 10 ℃/min or more.
As described above, the temperature increase or decrease rate is 10 ℃/min or more, for example, 15 ℃/min or more, and may be, for example, 15 ℃/min, 16 ℃/min, 17 ℃/min, 18 ℃/min, 19 ℃/min, 20 ℃/min, 21 ℃/min, 22 ℃/min, 23 ℃/min, 24 ℃/min, 25 ℃/min, 26 ℃/min, 27 ℃/min, 28 ℃/min, 29 ℃/min, 30 ℃/min or more; the aging time is less than 25min, for example, less than 25min, less than or equal to 23min, less than or equal to 22min, less than or equal to 21min, less than or equal to 20min, less than or equal to 19min, less than or equal to 18min, less than or equal to 17min, or less than or equal to 16 min; depending on the different species to be crystallized.
[ detailed description of the above-mentioned method ]
According to an embodiment of the present invention, in step (a1), the preparation of the aqueous solution of the substance to be crystallized may be performed by a method known to those skilled in the art, such as a standard solution preparation method.
According to embodiments of the present invention, the pseudocrystalline material includes, but is not limited to, inorganic and/or organic. The pseudocrystalline material includes, but is not limited to, inorganic and organic materials. The inorganic substance is selected from metal salt or non-metal salt; the organic substance is an organic molecule soluble in water, and is selected from aromatic compounds, non-aromatic heterocyclic compounds, amino acids, saccharides, polypeptides, proteins, drugs, water-soluble metal-organic complexes, and the like. For example, the inorganic substance is selected from copper sulfate, sodium chloride, quaternary ammonium salt, etc.; the aromatic compound is selected from phenol, p-toluenesulfonic acid, naphthalene sulfonate formaldehyde condensate and the like, and the non-aromatic hybrid compound is selected from purine compounds; such as water-soluble bis-porphyrin metal complexes and the like.
According to an embodiment of the invention, the pseudocrystalline substance has a solubility in water; it will be understood by those skilled in the art that the solubility of the pseudocrystalline substance in water may be arbitrary, that is, the pseudocrystalline substance may be dissolved in water without particular limitation on the amount thereof dissolved in water; it will be appreciated that the solubility of the pseudocrystalline material in water may be, for example, readily soluble, sparingly soluble or poorly soluble.
According to an embodiment of the present invention, preferably, the amount of the pseudo-crystalline substance dissolved in water is 1 × 10 or more-7g/100g, for example, 0.001g/100g or more, such as 0.01g/100g or more, such as 0.1g/100g or more, such as 1g/100g or more, such as 10g/100g or more.
According to the embodiment of the present invention, the concentration of the aqueous solution of the pseudo-crystalline substance is not particularly limited, that is, the pseudo-crystalline substance can be dissolved in water; as known to those skilled in the art, the pseudocrystalline material may be a non-saturated solution or a saturated solution in water, or may be a supersaturated solution; of course, the concentration of the aqueous solution of the pseudocrystalline substance has a great influence on the aggregation rate of the pseudocrystalline substance, and when the concentration is lower, the aggregation speed of the pseudocrystalline substance is lower, and the time required for obtaining the single crystal or the amorphous substance is correspondingly increased; at higher concentrations, the rate of aggregation of the pseudocrystalline material is faster and the time required to obtain a single crystal or amorphous material is correspondingly reduced. Therefore, the preparation time of the single crystal or the amorphous substance is regulated and controlled by the concentration of the solution through reasonably selecting the concentration; of course, the time for preparing the single crystal or amorphous material is not only dependent on the concentration of the solution, but also closely related to the aging process (e.g., aging temperature, aging time).
According to an embodiment of the present invention, the concentration of the aqueous solution of the pseudocrystalline substance is 1X 10 or more-7g/100g, for example, 0.001g/100g or more, such as 0.01g/100g or more, such as 0.1g/100g or more, such as 1g/100g or more, such as 10g/100g or more. The upper limit of the concentration of the aqueous solution of the pseudocrystalline substance is not particularly limited, and it may be a supersaturated solution or a saturated solution of the pseudocrystalline substance in water.
Preferably, the concentration of the aqueous solution of the pseudocrystalline substance is 1X 10-7g/100g to 1g/100 g.
According to the present invention, the step (a2) specifically includes the steps of:
and (c) cooling and freezing the aqueous solution of the pseudocrystalline substance in the step (a1) to form a solid, and optionally performing aging treatment to prepare a mixed system of the single crystal or amorphous substance containing the pseudocrystalline substance and ice.
According to embodiments of the present invention, the inventors have surprisingly found that the aqueous solution provides the possibility that during freezing, water will freeze to a solid, and the pseudocrystalline material dissolved in the aqueous solution will achieve concentration aggregation at the ice interface, thereby forming a single crystal or amorphous material. In addition, the aqueous solution of the frozen pseudocrystalline substance, when further subjected to the freezing process and optionally further aging process, a certain amount of ice gradually becomes larger in grain size, the pseudocrystalline substance is gradually released from the disappearing solid solvent, and the pseudocrystalline substance is continuously aggregated at the interface of ice to form a single crystal or amorphous substance and continuously grow or the formed single crystal or amorphous substance is continuously grown, and finally a single crystal of the pseudocrystalline substance having a particle size of several tens nanometers to several hundreds nanometers can be obtained, as shown in fig. 36. In the case of a free molecular state, the condensed light-emitting material cannot be excited to emit light at any wavelength, but the molecule in the condensed state is excited to emit fluorescence; to demonstrate that ice crystals aggregate solute molecules at their interface during freezing, or optionally further maturation, we have selected aggregate luminescent materials (AIE35) to validate this process. During the experiment, when the AIE35 aqueous solution is frozen into solid by any method, ice forms independent polycrystalline systems, and AIE35 forms aggregates at the interface of any two contacted ice crystals, and then the aggregates crystallize, as shown in figure 37. As can be seen from a in FIG. 38, the fluorescence at the interface is enhanced, which indicates that the AIE35 molecules can be gathered at the interface and gradually transited from the amorphous substance to form AIE35 nano single crystal. And as can be seen from b in fig. 38, the aggregate formed at the interface underwent transition from the amorphous state to the single crystal, and the volume of the single crystal thereof gradually increased. Wherein, FIG. 38 shows the results of transmission electron microscopy and electron diffraction characterization.
In order to further prove the principle of single crystal formation, p-toluenesulfonic acid molecules are adopted, a transmission electron microscope is adopted to attenuate total reflection infrared at low temperature in situ, and the process that p-toluenesulfonic acid is aggregated in the freezing and curing processes of water, single crystals are formed, and the single crystals grow continuously is observed. The detection result shows that the freezing process forms p-toluenesulfonic acid single crystal which grows gradually during curing, and the characteristic peak of the p-toluenesulfonic acid is-1035 cm-1The generation and blue shift of (stretching vibration of sulfonate) also strongly demonstrates that the growing of single crystals formed by the accumulation of p-toluenesulfonic acid molecules with aging (see fig. 39).
According to an embodiment of the present invention, in step (a2), the freezing includes, but is not limited to, complete freezing, and incomplete freezing. As will be understood by those skilled in the art, the complete freezing refers to the complete freezing of the aqueous solution of the pseudocrystalline material of step (a1) to a solid; by incompletely frozen is meant that the aqueous solution of the substance to be crystallized of step (a1) is partially frozen to a solid state and partially remains in a liquid state.
According to an embodiment of the present invention, in step (a2), it is understood by those skilled in the art that the freezing may be performed by any one or more cooling methods to freeze an aqueous solution of the substance to be crystallized having any volume and shape into a solid by any one or more cooling processes. Namely, the freezing is to freeze the aqueous solution of the pseudocrystalline substance of step (a1) into a solid or a solid-liquid mixed state. Compared with the traditional evaporation method and cooling crystallization method, the freezing crystallization method has the advantages that the regulation and control range of the concentration of the aqueous solution of the pseudo-crystalline substance is wider, and the time for obtaining the pseudo-crystalline substance crystal is greatly shortened.
According to the embodiment of the present invention, the freezing time, the freezing temperature gradient, the freezing method, the freezing process, and the like are not particularly limited, and the aqueous solution of the pseudocrystalline substance having any volume and shape may be frozen into a solid or a solid-liquid mixed state. Of course, the concentration of the aqueous solution of the pseudomorphic material during the freezing process can be selected appropriately in order to control the diffusion rate of the water molecules and the molecules of the pseudomorphic material, thereby influencing the crystallization process. Illustratively, if the concentration of the aqueous solution of the substance to be crystallized is high, the freezing time selected at this time can be appropriately shortened, and the freezing temperature can be appropriately lowered; the purpose of this is to prevent the controlled formation of polycrystals of the pseudocrystalline material in the higher concentration solution; if the concentration of the aqueous solution of the substance to be crystallized is lower, the freezing time can be properly prolonged, and the freezing temperature can be properly increased; the purpose of such an operation is to achieve efficient aggregation of the molecules of the substance to be crystallized, thereby forming an amorphous substance or a single crystal.
According to an embodiment of the present invention, the freezing method is a method known to those skilled in the art, such as cooling and freezing operation using any refrigeration device or cooling and freezing using any low-temperature substance; illustratively, the freezing method includes but is not limited to one or a combination of several temperature-reducing freezing methods of compression refrigeration equipment, semiconductor refrigeration equipment, liquid nitrogen, liquid helium, liquid carbon dioxide, liquid oxygen, liquid ethane, dry ice, ice and the like.
According to an embodiment of the present invention, the freezing operation pressure is not limited, and may be freezing under normal pressure, or freezing under high pressure or low pressure.
According to an embodiment of the present invention, the freezing process is a manner known to those skilled in the art, such as freezing an aqueous solution of the substance to be crystallized from a liquid state to a solid state by any process, for example, the freezing process includes but is not limited to one or a combination of several freezing processes of rapid cooling, slow cooling, step cooling, first heating and then cooling, and the like.
According to the embodiment of the present invention, the volume and shape of the aqueous solution of the pseudocrystalline substance are not particularly limited; the volume and shape of the solid obtained by freezing the aqueous solution of the pseudocrystalline substance are not particularly limited as long as the solid can be frozen to obtain a solid or a solid-liquid mixture; as will be understood by those skilled in the art, the freezing can be either the bulk freezing of an aqueous solution of any volume of the pseudomorphic material, the freezing of a film formed from an aqueous solution of any volume of the pseudomorphic material, or the freezing of droplets formed from an aqueous solution of any volume of the pseudomorphic material.
According to embodiments of the present invention, the crystallization method may optionally be subjected to a ripening process, which may be used for the formation of a single crystal, the control of the rate of growth of the single crystal, and the control of the size of the single crystal of a system in which the single crystal is not formed during the freezing process; it can also be used to further optimize the control of the growth rate of the single crystal and the control of the size of the single crystal for systems in which the freezing process forms the single crystal. Because the curing process is not limited by temperature, the energy consumption caused by low temperature required in the freezing process can be reduced, the cost is reduced, and convenience is provided for industrial production.
According to an embodiment of the present invention, the aqueous solution of the pseudocrystalline substance frozen into a solid is subjected to a ripening treatment; the temperature, time and process of aging in the aging process are not particularly limited, but the aqueous solution of the pseudocrystalline substance frozen into solid in the aging process is ensured to be still in a solid state, namely the aqueous solution of the pseudocrystalline substance is still in a frozen state in the aging process; for example, by the same method as the freezing processCuring the solid, or curing the solid by other methods; the aim of the curing treatment is to realize the aggregation of the pseudo-crystalline substance and the regulation and control of the growth speed of the nano particles, and further prepare the single crystal or amorphous substance of the pseudo-crystalline substance. As will be appreciated by those skilled in the art, the maturation temperature should be below the temperature at which an aqueous solution of the frozen pseudocrystalline material will re-melt (i.e., T)Melting) Preferably, said maturation temperature is lower than TMeltingAbove 5 ℃, more preferably below TMeltingAbove 10 ℃.
According to an embodiment of the invention, the maturation process is a residence time of the aqueous solution of the substance to be crystallized in the frozen state. The frozen state may be completely frozen or not completely frozen, and may be selected according to the operation known to those skilled in the art.
According to the embodiment of the invention, the aging process, for example, by means of rapid heating (or cooling) or slow heating (or cooling), is exemplarily performed at a heating or cooling rate of 10 ℃/min or more, and the heating or cooling rate in this range can cause solute molecules to be rapidly released from the solid mixture and cause disordered aggregation, thereby providing security for the preparation of the amorphous substance through the limitation of the aging time.
Illustratively, the temperature rising or reducing rate of the curing process is less than 10 ℃/min, and the temperature rising or reducing rate in the range can make solute molecules slowly released from the solid mixture to generate ordered aggregation, so that single crystals can be prepared.
According to the embodiment of the invention, the ripening temperature (i.e. the temperature reached) is controlled by the size of ice particles and the aggregation speed of the pseudocrystalline substance, i.e. the larger the temperature difference between the ripening temperature and the freezing temperature is, the larger the size of ice particles is, the faster the aggregation speed of the pseudocrystalline substance is, the shorter the time required for forming single crystals or amorphous substances is, the larger the particle size of the single crystals or amorphous substances of the prepared pseudocrystalline substance is; the smaller the temperature difference between the curing temperature and the freezing temperature, the smaller the ice particle size, the slower the aggregation speed of the pseudocrystalline substance, the longer the time required for forming the single crystal or amorphous substance, and the smaller the particle size of the single crystal or amorphous substance of the prepared pseudocrystalline substance. That is, the larger the temperature difference between the ripening temperature and the freezing temperature, the larger the particle size of the single crystal or amorphous substance from which the pseudocrystalline substance is prepared.
According to the embodiments of the present invention, the aging time is not particularly limited, and may be performed by operations known to those skilled in the art, and as can be seen from the above description of the mechanism of the method of the present application, the aging process can be understood as the process of nucleation and growth or single crystal formation and growth of amorphous substance, and the appropriate extension of the aging time can obtain single crystal or amorphous substance with complete particle size and morphology, but it should be noted that, since the nature of adjusting the aging time is to adjust the aggregation concentration of the pseudocrystalline substance, the aging for too long time may result in too high aggregation concentration, which is not favorable for forming amorphous substance or single crystal. Illustratively, the curing time is more than 1 picosecond, preferably, the curing time is 1-1000 minutes, and further preferably, the curing time is 10-300 minutes.
Illustratively, the curing time is less than 25min, and the preparation of the amorphous substance can be realized by regulating and controlling the temperature rising or reducing rate of the curing process. When the aging time is 25min or more, the aggregation concentration of the pseudo-crystalline substance can be further controlled, and for example, a single crystal can be produced. However, the aging time cannot be too long, and the obtained single crystal may be further changed into a polycrystalline structure by the too long aging time.
According to the embodiment of the invention, the curing process can be any refrigeration device or any low temperature, so that the aqueous solution of the substance to be crystallized still keeps a frozen state; for example, a compression refrigeration device, a semiconductor refrigeration device, or a combination of one or more of liquid nitrogen, liquid helium, liquid carbon dioxide, liquid oxygen, liquid ethane, dry ice, and the like.
According to an embodiment of the present invention, in the step (a3), the ice may be physically and/or chemically separated. After freezing or optionally further maturation, a single crystal or amorphous material has been prepared, which is present at the ice interface and which needs to be separated by suitable means; or the ice may be removed.
According to the embodiment of the present invention, the physical means includes, but is not limited to, one or a combination of mechanical separation and sublimation (e.g., vacuum sublimation). The sublimation can be carried out, for example, by freeze-drying; the vacuum sublimation can be performed by freeze-drying under vacuum, for example.
According to the embodiment of the invention, the chemical mode includes but is not limited to one or a combination of several modes in chemical reaction and electrolysis.
According to the invention, the method further comprises the steps of:
(a4) collecting the single crystal or amorphous substance prepared in the step (a 3).
According to an embodiment of the present invention, in step (a4), the collecting includes, but is not limited to, collecting with one or more of an optical microscope, a scanning electron microscope, a dual-beam electron microscope, and a transmission electron microscope.
[ method of growing Single Crystal ]
As described above, the present invention also provides a method of growing a single crystal, including the above-described method of producing a single crystal.
According to an embodiment of the present invention, the method of growing a single crystal further comprises the steps of:
(b1) transferring the single crystal of the pseudo-crystalline substance prepared above to a mother liquor of the pseudo-crystalline substance for culturing;
(b2) collecting the single crystal of step (b 1).
According to an embodiment of the present invention, the transferring is any method known to those skilled in the art capable of removing single crystals, including but not limited to one or a combination of optical microscope removing, scanning electron microscope removing, dual beam electron microscope removing, and transmission electron microscope removing.
According to an embodiment of the present invention, the mother liquor is a mother liquor system adapted to the single crystal to be grown, as known to those skilled in the art.
The present invention will be described in further detail with reference to specific embodiments below, but it should not be construed that the scope of the present invention is limited to the specific examples below. Various substitutions and alterations of the following embodiments are also intended to be included within the scope of the present invention without departing from the spirit of the present invention.
The curing time in the following embodiments refers to the time required for heating or cooling to the curing temperature after the freezing process is finished, and the time for maintaining at the curing temperature; the holding time is the time at which the mixture is maintained at the aging temperature.
Example 1
Preparing a copper sulfate solution with the concentration of 500 mu M by using ultrapure water, taking 100ml of the solution by using a measuring cylinder, placing the solution into a beaker, slowly cooling the beaker in a refrigerator at the temperature of-24 ℃ until the solution is completely frozen, finally aging the beaker in a refrigerator at the temperature of-15 ℃ for 30min, and then freezing and drying the sample to completely sublimate solid ice to obtain the single crystal. And finally, selecting a single crystal with better quality from the beaker, transferring the single crystal to a saturated copper sulfate aqueous solution, and placing the single crystal in a constant-temperature and constant-humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow a copper sulfate crystal with larger volume, wherein the detection result is shown in the attached figure 1. As can be seen from fig. 1, the resulting crystal was a single crystal.
Example 2
Preparing a copper sulfate solution with the concentration of 10mM by using ultrapure water, taking 30 mu L of the solution by using an injector, spreading the solution on a silicon wafer, placing the silicon wafer in a refrigerator with the temperature of 24 ℃ below zero to slowly cool the silicon wafer until the silicon wafer is completely frozen, finally placing the silicon wafer in the refrigerator with the temperature of 18 ℃ below zero to age the silicon wafer for 40min, and then quenching the silicon wafer to remove ice to obtain a single crystal. And finally, selecting a single crystal with better quality from the silicon wafer, transferring the single crystal to a saturated copper sulfate aqueous solution, and placing the single crystal in a constant-temperature and constant-humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow copper sulfate crystals with larger volume.
Example 3
Preparing 6mM copper sulfate solution with ultrapure water, taking 15 μ L solution with a pipette, dripping the solution onto a silicon wafer at-90 deg.C, controlling the temperature of the silicon wafer by a cold-hot table, immediately heating to-25 deg.C at a rate of 15 deg.C/min, and maintaining at the temperature for 40 min. Then freeze-drying the sample, completely subliming the solid ice, selecting a single crystal with better quality from the silicon wafer, transferring the single crystal to a saturated copper sulfate aqueous solution, and placing the silicon wafer in a constant temperature and humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow copper sulfate crystals with larger volume.
Example 4
Preparing 50mM glutamic acid solution with ultrapure water, taking 100ml solution into a beaker by using a measuring cylinder, slowly cooling the beaker in a refrigerator at the temperature of-24 ℃ until the solution is completely frozen, finally aging the beaker in the refrigerator at the temperature of-20 ℃ for 15min, and then freeze-drying the sample to completely sublimate solid ice to obtain the single crystal. And finally, selecting a single crystal with better quality from a beaker, transferring the single crystal to a saturated glutamic acid aqueous solution, and placing the single crystal in a constant-temperature and constant-humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow a glutamic acid crystal with larger volume, wherein the detection result is shown in figure 2. As can be seen from fig. 2, the resulting crystal was a single crystal.
Example 5
Preparing benzyl penicillin solution with concentration of 1M by ultrapure water, taking 100ml of the solution by using a measuring cylinder, placing the solution into a beaker, slowly cooling the beaker in a refrigerator at the temperature of-24 ℃ until the solution is completely frozen, finally aging the beaker in a refrigerator at the temperature of-15 ℃ for 30min, and then freezing and drying the sample to completely sublimate solid ice to obtain the single crystal. Finally, selecting a single crystal with better quality from a beaker, transferring the single crystal to a saturated benzyl penicillin aqueous solution, and placing the single crystal in a constant temperature and humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow a benzyl penicillin crystal with larger volume, wherein the detection result is shown in the attached figure 3. As can be seen from fig. 3, the obtained crystal was a single crystal.
Example 6
Preparing 10mM benzyl penicillin solution with ultrapure water, taking 15 μ L solution with a pipette, dripping the solution onto a silicon wafer at-90 deg.C, controlling the temperature of the silicon wafer by a cold-hot table, immediately heating to-25 deg.C at a rate of 5 deg.C/min, and maintaining at the temperature for 60 min. And then freeze-drying the sample, completely subliming the solid ice, selecting a single crystal with better quality from a silicon wafer, transferring the single crystal into a saturated benzyl penicillin solution, and placing the single crystal in a constant-temperature and constant-humidity environment with the temperature of 25 ℃ and the relative humidity of 40% for a period of time to grow benzyl penicillin crystals with larger volume.
Examples 7 to 55
The procedure is as in example 1, with the following differences:
the embodiments of the present invention have been described above. However, the present invention is not limited to the above embodiment. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. A method of preparing a single crystal or amorphous substance using an aqueous solution, the method comprising the steps of:
(a1) preparing an aqueous solution of a pseudo-crystalline substance;
(a2) freezing the aqueous solution of the pseudocrystalline material of step (a 1);
optionally aging to obtain single crystal or amorphous substance-ice mixed system containing pseudocrystalline substance;
optionally, (a3) separating the single crystal or amorphous form of the pseudocrystalline material of step (a2) from the ice mixture to obtain a single crystal or amorphous form of the pseudocrystalline material.
2. Method according to claim 1, characterized in that it comprises the following steps:
(a1) preparing an aqueous solution of a pseudo-crystalline substance;
(a2) freezing, optionally aging, the aqueous solution of the pseudocrystalline material of step (a1) to produce a single crystal or amorphous mixture containing the pseudocrystalline material and ice,
optionally, (a3) separating the single crystal of the pseudocrystalline substance from the mixed system of the single crystal-frozen solution containing the pseudocrystalline substance of step (a 2);
wherein the temperature rising or reducing rate in the curing process is less than 10 ℃/min, and/or the curing time in the curing process is at least 25 min;
preferably, in the curing process, the temperature is raised or lowered to a certain temperature at a speed of less than 10 ℃/min, and is kept for a period of time, so that a mixed system of single crystals and ice containing the pseudo-crystalline substance is obtained;
preferably, in the curing process, the temperature reaches a certain temperature at any temperature rising or cooling speed, and curing is carried out for at least 25min, so as to obtain a mixed system of the single crystal containing the pseudo-crystalline substance and the ice;
preferably, in the curing process, the temperature is raised or lowered to a certain temperature at a speed of less than 10 ℃/min, and curing is carried out for at least 25min, so as to obtain the mixed system of the single crystal containing the pseudocrystalline substance and the ice.
3. The method according to claim 1, characterized in that it comprises the following steps:
(a1) preparing an aqueous solution of a pseudo-crystalline substance;
(a2) freezing and curing the aqueous solution of the pseudo-crystalline substance obtained in the step (a1) to prepare an amorphous-frozen solution mixed system containing the pseudo-crystalline substance; optionally, the step of (a) is carried out,
(a3) separating the amorphous form of the pseudo-crystalline material from the mixed amorphous and ice containing pseudo-crystalline material of step (a 2);
wherein the heating or cooling rate in the curing process is more than or equal to 10 ℃/min, and the curing time in the curing process is less than 25 min;
preferably, in the step (a2), in the curing process, the temperature is increased to a certain temperature at a temperature increasing or decreasing speed of more than or equal to 10 ℃/min, and the curing time is less than 25min, so as to obtain a mixed system of the single crystal containing the pseudocrystalline substance and the ice.
4. A method according to any of claims 1-3, wherein the water includes but is not limited to ultra pure water, secondary water, deionized water.
5. The method according to any one of claims 1 to 4, wherein in step (a1), the pseudocrystalline material includes, but is not limited to, inorganic and/or organic;
preferably, the pseudocrystalline material is sparingly soluble, soluble or readily soluble in water.
6. The method according to any one of claims 1 to 5, wherein in step (a2), the freezing is carried out by transforming the aqueous solution of the substance to be crystallized of step (a1) from a liquid state to a solid state by any freezing process using any freezing method;
preferably, the freezing method includes but is not limited to adopting one or a combination of several temperature reduction freezing methods of compression refrigeration equipment, semiconductor refrigeration equipment, liquid nitrogen, liquid helium, liquid carbon dioxide, liquid oxygen, liquid ethane, dry ice, ice and the like;
preferably, the freezing process includes but is not limited to one or a combination of several freezing processes of rapid cooling, slow cooling, step-by-step cooling, first heating and then cooling, and the like;
preferably, the freezing includes, but is not limited to, complete freezing, incomplete freezing.
7. A method according to any one of claims 1 to 6, wherein the ripening is such that an aqueous solution of the substance to be crystallised frozen to a solid is maintained in the solid state for a period of time.
8. The method according to any one of claims 1 to 7, wherein in step (a3), the separating is carried out by any means to separate the single crystal from the ice;
preferably, the arbitrary means includes, but is not limited to, physical means and/or chemical means;
preferably, the physical means includes but is not limited to one or a combination of mechanical separation, sublimation, dissolution and adsorption;
preferably, the chemical mode includes but is not limited to one or a combination of several modes in chemical reaction and electrolysis;
preferably, the method further comprises the steps of: (a4) collecting the single crystal prepared in the step (a 3);
preferably, in step (a4), the collecting includes, but is not limited to, collecting with one or more of optical microscope, scanning electron microscope, dual-beam electron microscope, and transmission electron microscope.
9. A method for growing a single crystal, comprising the method for producing a single crystal according to any one of claims 1 to 7;
preferably, the method further comprises the steps of:
(b1) transferring a single crystal of a pseudo-crystalline substance prepared by the method for preparing a single crystal according to any one of claims 1 to 8 into a mother liquor of the pseudo-crystalline substance for cultivation; optionally, the step of (a) is carried out,
(b2) collecting the single crystal grown in the step (b 1).
10. The method according to claim 9, wherein in the step (b1), the transferring is performed by transferring the mixed system of the single crystal containing the pseudo-crystalline substance and the ice of the step (a2) to a mother liquor of the pseudo-crystalline substance for single crystal cultivation; or directly transferring the ice-removed single crystal of the step (a3) into a mother liquor of a pseudo-crystalline substance for single crystal cultivation; or transferring the single crystal collected in the step (a4) into a mother liquor of a pseudo-crystalline substance to perform single crystal culture;
preferably, the transferring includes but is not limited to one or a combination of optical microscope transferring, scanning electron microscope transferring, double-beam electron microscope transferring and transmission electron microscope transferring;
preferably, in the step (b1), the single crystal is cultured by one or more of evaporation, cooling and diffusion; preferably, in step (b2), the collecting includes, but is not limited to, collecting by using one or more of optical microscope, scanning electron microscope, dual-beam electron microscope, and transmission electron microscope.
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