CN111344060B - Method for oxidizing organic molecules - Google Patents
Method for oxidizing organic molecules Download PDFInfo
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- CN111344060B CN111344060B CN201880073497.6A CN201880073497A CN111344060B CN 111344060 B CN111344060 B CN 111344060B CN 201880073497 A CN201880073497 A CN 201880073497A CN 111344060 B CN111344060 B CN 111344060B
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- 238000000034 method Methods 0.000 title claims abstract description 59
- 230000001590 oxidative effect Effects 0.000 title claims abstract description 14
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 126
- 230000003647 oxidation Effects 0.000 claims abstract description 122
- 239000003054 catalyst Substances 0.000 claims abstract description 104
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 34
- 108010038807 Oligopeptides Proteins 0.000 claims abstract description 30
- 102000015636 Oligopeptides Human genes 0.000 claims abstract description 30
- 239000003446 ligand Substances 0.000 claims abstract description 29
- 239000007800 oxidant agent Substances 0.000 claims abstract description 28
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910001431 copper ion Inorganic materials 0.000 claims abstract description 14
- 230000003213 activating effect Effects 0.000 claims abstract description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 25
- 150000001413 amino acids Chemical class 0.000 claims description 14
- 239000000758 substrate Substances 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 9
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Chemical compound Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims description 6
- 239000011324 bead Substances 0.000 claims description 5
- 239000000017 hydrogel Substances 0.000 claims description 5
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 3
- 150000004965 peroxy acids Chemical class 0.000 claims description 3
- 150000001451 organic peroxides Chemical group 0.000 claims description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 abstract description 8
- 238000004061 bleaching Methods 0.000 abstract description 8
- 239000004471 Glycine Substances 0.000 abstract description 4
- -1 histidine amino acids Chemical class 0.000 abstract description 3
- 239000003619 algicide Substances 0.000 abstract description 2
- 238000005202 decontamination Methods 0.000 abstract description 2
- 230000003588 decontaminative effect Effects 0.000 abstract description 2
- 238000004065 wastewater treatment Methods 0.000 abstract description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 35
- 230000015556 catabolic process Effects 0.000 description 19
- 238000006731 degradation reaction Methods 0.000 description 19
- 239000000243 solution Substances 0.000 description 19
- 229930002875 chlorophyll Natural products 0.000 description 13
- 235000019804 chlorophyll Nutrition 0.000 description 13
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 102000003992 Peroxidases Human genes 0.000 description 9
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
- 108700020962 Peroxidase Proteins 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 239000012528 membrane Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000007995 HEPES buffer Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 239000010408 film Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 108040007629 peroxidase activity proteins Proteins 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000209140 Triticum Species 0.000 description 2
- 235000021307 Triticum Nutrition 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000010902 straw Substances 0.000 description 2
- VGVRPFIJEJYOFN-UHFFFAOYSA-N 2,3,4,6-tetrachlorophenol Chemical class OC1=C(Cl)C=C(Cl)C(Cl)=C1Cl VGVRPFIJEJYOFN-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000000987 azo dye Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 1
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- 150000004698 iron complex Chemical class 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
- B01J31/2243—At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
- B01J2231/70—Oxidation reactions, e.g. epoxidation, (di)hydroxylation, dehydrogenation and analogues
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
- B01J2531/0269—Complexes comprising ligands derived from the natural chiral pool or otherwise having a characteristic structure or geometry
- B01J2531/0275—Complexes comprising ligands derived from the natural chiral pool or otherwise having a characteristic structure or geometry derived from amino acids
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
- B01J2531/16—Copper
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- Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Catalysts (AREA)
Abstract
The present invention relates to a method of oxidizing an organic molecule, the method comprising adding an oxidizing agent and an oxidation catalyst for activating the oxidizing agent, wherein the oxidation catalyst comprises an oligopeptide ligand complexed with copper ions. In a preferred embodiment, the oligopeptide ligand comprises a tripeptide comprising glycine and histidine amino acids. The method of the present invention is applicable to a number of industrial applications, such as wastewater treatment, decontamination of contaminated sites, bleaching applications, and algaecide functions.
Description
Technical Field
The present invention relates to a method of oxidizing organic molecules and an oxidation catalyst.
Background
Hydrogen peroxide is an environmentally friendly oxidizing agent because it releases only oxygen and water upon decomposition. However, when the temperature is lower than 50 ℃, the oxidation reaction involving hydrogen peroxide as the oxidizing agent is very slow. In order to accelerate the reaction, the oxidation reaction needs to be carried out at a higher temperature. To assist the oxidation process, peroxidases, a family of enzymes that catalyze the oxidation of organic molecules by using hydrogen peroxide as the oxidizing agent, are sometimes used. However, peroxidases are sensitive to temperature and pH, which limits their industrial application.
Thus, artificial peroxidases have been produced. These artificial peroxidases have similar or even higher activity than the natural peroxidases, but they are more stable and durable, making them suitable for industrial applications. An example of an artificial peroxidase is the tetra-amido macrocyclic iron complex (Fe-TAML). Fe-TAML has been used to catalyze the oxidation of azo dyes and chlorophenols at room temperature at a surprisingly high reaction rate. However, fe-TAML is synthesized for a long time and is very expensive. Moreover, fe-TAML is readily soluble in water, making recovery and reuse of Fe-TAML very difficult. Another problem is that since Fe-TAML is a synthetic molecule, the residual Fe-TAML remaining in the product is toxic and non-biodegradable.
Thus, there is a need for an improved method of oxidizing organic molecules and an improved oxidation catalyst.
Disclosure of Invention
The present invention aims to solve these problems and/or to provide an improved method of oxidizing organic molecules and an improved oxidation catalyst.
In general, the present invention relates to a green and cost effective method of oxidizing organic molecules. This is because the oxidation catalyst used in the method of the present invention activates hydrogen peroxide under various conditions and accelerates the oxidation reaction. In particular, oxidation reactions involving hydrogen peroxide as an oxidizing agent can be carried out at lower temperatures and over a wider pH range. Because hydrogen peroxide can be activated at lower temperatures, less energy will be used to heat the reaction mixture, and thus more environmentally friendly and cost effective. In addition, the oxidation catalyst is formed from oligopeptides. In this way, the catalyst will be non-toxic and generally biodegradable, so that the risk of the process of the invention is reduced.
According to a first aspect, the present invention provides a method of oxidising an organic molecule, the method comprising adding an oxidising agent and an oxidation catalyst for activating the oxidising agent, wherein the oxidation catalyst comprises an oligopeptide ligand complexed with copper ions.
The oxidizing agent may be any suitable oxidizing agent. For example, the oxidizing agent may be hydrogen peroxide (H 2 O 2 ) Organic peroxide, organic hydrogen peroxide, peroxyacid, ozone, hypochlorite, or combinations thereof.
According to a particular aspect, the oligopeptide ligand may be complexed with the copper ion via at least two peptide bonds. In particular, the oligopeptide ligand may comprise a tripeptide having the following general formula (I):
wherein R is 1 、R 2 And R is 3 May be the same or different amino acids.
According to a particular aspect, the oxidation catalyst may have the general formula (II):
wherein R is 1 、R 2 And R is 3 May be the same or different amino acids.
In particular, the method comprises the steps of,
R 1 may be H or histidine;
R 2 may be H; and
R 3 it may be either H or histidine which may be present,
and wherein R is 1 And R is 3 Not all of which are histidine.
More specifically: (i) R is R 1 、R 2 And R is 3 May be H such that the oxidation catalyst is Cu-GGG; (ii) R is R 1 May be histidine, and R 2 And R is 3 May be H such that the oxidation catalyst is Cu-HGG; or (iii) R 1 And R is 2 Each of which may be H, and R 3 May be histidine, such that the oxidation catalyst is Cu-GGH.
The oxidation catalyst may be: encapsulated in hydrogel beads; or immobilized on a solid substrate.
The process may be carried out under suitable conditions. For example, the oxidation may be performed at an appropriate temperature. According to a particular aspect, the temperature at which the process is carried out may be 20-100 ℃. The oxidation may be carried out at an appropriate pH. According to a particular aspect, the method may be carried out at a pH of 3-12.
According to a second aspect, the present invention also provides an oxidation catalyst comprising an oligopeptide ligand complexed with a copper ion, wherein the oligopeptide ligand is complexed with the copper ion via at least two peptide bonds.
The catalyst may comprise any suitable oligopeptide ligand. For example, the oligopeptide ligand may be as described above.
According to a particular aspect, the oxidation catalyst may have the general formula (II):
wherein R is 1 、R 2 And R is 3 May be the same or different amino acids.
In particular, the method comprises the steps of,
R 1 may be H or histidine;
R 2 may be H; and
R 3 may be H or a groupAn amino acid is used as the amino acid,
and wherein R is 1 And R is 3 Not all of which are histidine.
More specifically: (i) R is R 1 、R 2 And R is 3 May be H such that the oxidation catalyst is Cu-GGG; (ii) R is R 1 May be histidine, and R 2 And R is 3 May be H such that the oxidation catalyst is Cu-HGG; or (iii) R 1 And R is 2 Each of which may be H, and R 3 May be histidine, such that the oxidation catalyst is Cu-GGH.
The oxidation catalyst may be: encapsulated in hydrogel beads; or immobilized on a solid substrate.
Drawings
In order that the invention may be fully understood and readily put into practical effect, there shall now be described by way of non-limitative example only exemplary embodiments, the description being with reference to the accompanying illustrative drawings.
In the drawings:
FIG. 1 shows trypan blue in quilt H 2 O 2 And time-course degradation upon oxidation of the oxidation catalyst according to one embodiment of the invention;
FIG. 2 shows H in the absence and presence of different oxidation catalysts according to embodiments of the invention 2 O 2 Comparison of oxidation efficiency;
FIG. 3 shows a change H 2 O 2 Influence of concentration on trypan blue degradation;
FIG. 4 illustrates the effect of varying the oxidation catalyst concentration according to one embodiment of the invention;
FIG. 5 shows pH versus H in the presence of an oxidation catalyst, according to one embodiment of the invention 2 O 2 Degrading the effect of trypan blue; and
FIG. 6 shows the use of H in the presence and absence of an oxidation catalyst according to one embodiment of the invention 2 O 2 Bleaching chlorophyll.
Detailed Description
As noted above, there is a need for an improved method of oxidizing organic molecules, and for an improved oxidation catalyst.
The process of the invention enables oxidation of organic molecules to be carried out over a wider range of conditions and without being too energy-intensive. For example, oxidation can be performed at lower temperatures and over a wider pH range. This is a result of the use of an oxidation catalyst in the oxidation process. The oxidation catalyst comprises an oligopeptide ligand complexed with copper ions. The oxidation catalyst of the invention also has high stability, easy preparation and high catalytic activity.
In particular, different amino acids and peptides can be used to customize the oligopeptide ligand. Since peptides are natural molecules, they can be obtained from natural sources, they are generally non-toxic and biodegradable. This makes the oxidation catalyst environmentally friendly and easy to produce.
According to a first aspect, the present invention provides a method of oxidising an organic molecule, the method comprising adding an oxidising agent and an oxidation catalyst for activating the oxidising agent, wherein the oxidation catalyst comprises an oligopeptide ligand complexed with copper ions.
The organic molecule may be any suitable organic molecule that needs to be oxidized. For example, the organic molecules may be phenolic compounds, chlorophyll, bacterial cells and spores and/or organic molecules found in waste water, dyes, and the like.
The oxidizing agent may be any suitable oxidizing agent. For example, the oxidizing agent may be, but is not limited to: hydrogen peroxide (H) 2 O 2 ) The method comprises the steps of carrying out a first treatment on the surface of the Organic peroxides such as, but not limited to, benzoyl peroxide; organic hydrogen peroxide; a peroxyacid; ozone; hypochlorite; or a combination thereof.
The oxidation catalyst added in the process of the present invention may be any suitable oxidation catalyst. In particular, the oxidation catalyst may be a peroxidase mimic enzyme. Even more particularly, the oxidation catalyst may be an artificial cuprase in which the oligopeptide ligand may be complexed with at least one copper ion. According to a particular aspect, the oligopeptide ligand may be complexed with copper ions through at least two peptide bonds.
The oligopeptide ligand may be any suitable oligopeptide. For example, the oligopeptide ligand may comprise different amino acids. In particular, the oligopeptide ligand may comprise a tripeptide. According to a particular aspect, the oligopeptide ligand may comprise a tripeptide having the following general formula (I):
wherein R is 1 、R 2 And R is 3 May be the same or different amino acids.
In particular, by substituting different amino acids in the tripeptide, different copper-tripeptide composite oxidation catalysts may be formed.
According to a particular aspect of the present invention,
R 1 may be H or histidine;
R 2 may be H; and
R 3 it may be either H or histidine which may be present,
and wherein R is 1 And R is 3 Not all of which are histidine.
Specifically: (i) R is R 1 、R 2 And R is 3 May be H such that the oligopeptide ligand is triglycine (GGG); (ii) R is R 1 May be histidine, and R 2 And R is 3 May be H, such that the oligopeptide ligand is HGG; or (iii) R 1 And R is 2 Each of which may be H, and R 3 May be histidine, such that the oligopeptide ligand is GGH, wherein G represents glycine and H represents histidine.
According to a particular aspect, the oxidation catalyst may have the general formula (II):
wherein R is 1 、R 2 And R is 3 May be the same or different amino acids.
Specifically, R 1 、R 2 And R is 3 May be as described above. More specifically: (i) R is R 1 、R 2 And R is 3 May be H such that the oxidation catalyst is Cu-GGG; (ii) R is R 1 May be histidine, and R 2 And R is 3 May be H such that the oxidation catalyst is Cu-HGG; or (iii) R 1 And R is 2 Each of which may be H, and R 3 May be histidine, such that the oxidation catalyst is Cu-GGH, wherein G represents glycine and H represents histidine.
The oxidation catalyst may be in any suitable form. For example, the oxidation catalyst may be unencapsulated, encapsulated, or immobilized on a solid substrate. According to a particular aspect, the oxidation catalyst may be encapsulated. The oxidation catalyst may be encapsulated in any suitable manner. For example, the oxidation catalyst may be encapsulated in hydrogel beads, films, membranes, or fibers. According to another particular aspect, the oxidation catalyst may be immobilized on a solid substrate. Examples of solid substrates include, but are not limited to, films, membranes, fibers. When the oxidation catalyst is encapsulated or immobilized, the oxidation catalyst may be more easily recovered after use in the process. In this way, the oxidation catalyst can be reused in a subsequent oxidation process.
The process of the present invention may be carried out under suitable conditions. These conditions may include the temperature at which oxidation is performed. For example, the process may be carried out at a temperature of 20-100 ℃. In particular, the process may be carried out at a temperature of 30-90 ℃, 40-80 ℃, 50-70 ℃, 55-60 ℃. More particularly, the process may be carried out at a temperature of 60℃or less, preferably about 50 ℃. It will be apparent to those skilled in the art that by adding an oxidation catalyst to the process of the present invention, the temperature at which oxidation can occur in the presence of an oxidizing agent such as hydrogen peroxide is lower. For example, when the oxidant is H 2 O 2 When in the absence of the oxidation catalyst of the invention H 2 O 2 Usually activated only at temperatures of > 90 ℃. However, in the presence of the oxidation catalyst of the present invention, H may be 2 O 2 The temperature of activation was reduced to about 50 ℃.
These conditions may include the pH at which the oxidation is performed. When the oxidant is H 2 O 2 When in the absence of the oxidation catalyst of the invention H 2 O 2 Typically activated only in a specific and narrow pH range. For example, when oxidation is carried out by a Fenton reaction catalyzed by Fe (II), the oxidation is carried out at a pH of 2.6 to 3.4. When oxidation is performed by using tetra-amido macrocyclic iron complexes (Fe-TAML) as oxidation catalysts, oxidation occurs at neutral pH or alkaline conditions. In contrast, the process of the invention can be carried out at a pH of 3 to 12. In particular, the pH may be 7-12, 8-11, 9-10. More particularly, the pH may be 11. It will be apparent to those skilled in the art that by adding an oxidation catalyst to the process of the present invention, the pH range over which oxidation can occur in the presence of an oxidizing agent such as hydrogen peroxide is wider.
The method of the present invention is applicable to a number of industrial applications, such as wastewater treatment, decontamination of contaminated sites, bleaching applications including fabric bleaching, food bleaching and pharmaceutical bleaching, and algaecide functions.
The invention also provides an oxidation catalyst. According to a second aspect, there is provided an oxidation catalyst comprising an oligopeptide ligand complexed with copper ions, wherein the oligopeptide ligand is complexed with copper ions through at least two peptide bonds.
The catalyst may comprise any suitable oligopeptide ligand. For example, the oligopeptide ligand may be as described above.
According to a particular aspect, the oxidation catalyst may have the general formula (II):
wherein R is 1 、R 2 And R is 3 May be the same or different amino acids.
Specifically, R 1 、R 2 And R is 3 May be as described above in the first aspect of the invention. More specifically: (i) R is R 1 、R 2 And R is 3 May be H such that the oxidation catalyst is Cu-GGG; (ii) R is R 1 May be histidine, and R 2 And R is 3 May be H such that the oxidation catalyst is Cu-HGG; or (iii) R 1 And R is 2 Each of which may be H, and R 3 May be histidine, such that the oxidation catalyst is Cu-GGH, wherein G represents glycine and H represents histidine.
The oxidation catalyst may be in any suitable form. For example, the oxidation catalyst may be unencapsulated, encapsulated, or immobilized on a solid substrate. According to a particular aspect, the oxidation catalyst may be encapsulated. The oxidation catalyst may be encapsulated in any suitable manner. For example, the oxidation catalyst may be encapsulated in hydrogel beads, films, membranes, or fibers. According to another particular aspect, the oxidation catalyst may be immobilized on a solid substrate. Examples of solid substrates include, but are not limited to, films, membranes, or fibers. When the oxidation catalyst is encapsulated or immobilized, the oxidation catalyst may be more easily recovered after use in the process. In this way, the oxidation catalyst can be reused in a subsequent oxidation process.
The oxidation catalyst of the present invention may be prepared by any suitable method. For example, the overall reaction that can produce an oxidation catalyst is as follows:
having now generally described the invention, the same will be more readily understood through reference to the following embodiments, which are provided by way of example and are not intended to be limiting.
Examples
Material
Copper acetate monohydrate (copper acetate monohydrate), NH purchased from Sigma-Aldrich (Singapore) 2 -glycine-COOH (GGG) and sodium hydroxide. Trypan blue solution purchased from Fisher (Singapore)0.4%). From 1 st (4- (2-hydroxyethyl) -1-piperazineethanesulfonic acid) (HEPES) buffer (1M, pH 7.5) purchased from BASE (Singapore). NH (NH) 2 Histadyl-glycine-COOH (HGG) and NH 2 -glycine-histidine-COOH (GGH) was custom synthesized from BACHEM (switzerland) with a minimum purity of 98%. Wheat straw was purchased from a local market. All materials were used as received without further purification.
Preparation of copper-tripeptide oxidation catalysts
Tripeptide solutions (100 mM) were prepared by dissolving tripeptide powder in HEPES buffer (10 mM, pH 8.0). Buffers (10 mM, pH 8.0) were prepared by diluting HEPES buffer stock (1M, pH 7.5) with deionized water. The pH was adjusted to 8.0 using sodium hydroxide (1M solution). Three types of tripeptide solutions (GGG, HGG, and GGH) were prepared. Copper acetate solution (100 mM) was prepared by dissolving copper acetate monohydrate in deionized water. The copper acetate solution was centrifuged at 10,000rpm for 3 minutes to remove all insoluble particles. Then, copper-tripeptide artificial enzymes (cuprases, cuzymes) were prepared by mixing a tripeptide solution (100 mm,100 μl) with copper acetate (100 mm,100 μl) and HEPES buffer (10 mm, ph8.0, 800 μl). Oxidation catalysts Cuz-1, cuz-2 and Cuz-3 were prepared using GGG, HGG and GGH, respectively. The solution was vortexed prior to use.
Oxidation catalyst for degrading trypan blue and chlorophyll
In the presence of an oxidation catalyst (50 ppm) in 4mL of a mixture containing 200. Mu.M trypan blue and 0.5% H 2 O 2 The degradation of trypan blue is carried out in the aqueous solution of (a). Degradation of trypan blue was carried out at 50℃for 30 minutes with stirring at 300 rpm. The absorbance of the solution at 595nm was measured. Percent (%) degradation of trypan blue is defined as:
wherein A is 0 And A i The absorbance values of the reaction mixture at 0 minutes and at different time intervals, respectively.
Preparation by milling 250g wheat straw in 500mL deionized waterChlorophyll solution. The solution was filtered through a 0.45 μm membrane before use. The final concentration of chlorophyll in the solution was 50mg/mL. Chlorophyll was bleached using Cuz-1 as the oxidizing agent. Briefly, 4mL chlorophyll solution was combined with Cuz-1 (50 ppm), H 2 O 2 (0.5%) and NaOH (2 g/L). The mixture was stirred at 300rpm for 60 minutes.
Results and discussion
(i) Degradation of trypan blue
Trypan blue is selected as a substrate, H 2 O 2 As an oxidant, cuz-1 was used as an oxidation catalyst. The oxidation catalyst was added at 0 min and the solution was stirred by a magnetic stirrer at 50 ℃ for 30 min.
The absorbance of the solution at 595nm was also measured to estimate the percent degradation of trypan blue. As shown in FIG. 1, the color of the trypan blue solution became lighter within 5 minutes, indicating that trypan blue was H-substituted in the presence of Cuz-1 2 O 2 And (5) oxidizing. After 30 minutes, the solution became colorless. Based on the absorbance value at 595nm, about 98% of trypan blue was degraded within 30 minutes. In contrast, when Cuz-1 was not added, the trypan blue solution remained blue after 30 minutes. This indicates that trypan blue cannot be H alone 2 O 2 And (5) oxidizing. In this case Cuz-1 plays an important role in the degradation of trypan blue. Cuz-1 shows peroxidase-like activity and is capable of activating H 2 O 2 To degrade trypan blue.
(ii) Specificity of the Oxidation catalyst
To understand the effect of different oligopeptide ligands on the catalytic activity of the oxidation catalysts, three different oxidation catalysts (Cuz-1, cuz-2 and Cuz-3) prepared were used as catalysts to degrade trypan blue at 50 ℃ and H was used 2 O 2 As an oxidizing agent. Cuz-1 and Cuz-2 are both effective in catalyzing the oxidation of trypan blue. In contrast, when Cuz-3 was used, only partial degradation of trypan blue resulted after 30 minutes. By using absorbance values at 595nm, the percent degradation of trypan blue in the presence of Cuz-1, cuz-2 and Cuz-3 was determined to be 98%, 83% and 42%, respectively (fig. 2). These results indicate that when in tripeptidesWhen the amino acid at the COOH terminal is histidine, the oxidation catalyst activates H 2 O 2 The aspect is less effective. This is probably because the GGH ligand forms a very stable tetradentate structure with copper ions (tetradentate structure). Thus, there is no available activated H at the copper ion 2 O 2 Is not included in the pattern. Cuz-1 was used in the subsequent experiments since Cuz-1 showed the highest activity against degradation of trypan blue.
(iii)H 2 O 2 Influence of concentration
To get knowledge of H 2 O 2 Effect of concentration on trypan blue degradation, different amounts of H were added to the reaction mixture containing 50ppm Cuz-1 as oxidation catalyst 2 O 2 (0-0.5%). The temperature of the reaction mixture was 50 ℃. FIG. 3 shows that in the absence of H 2 O 2 In the case of (2), trypan blue is not degraded. The results clearly show H 2 O 2 Importance in the reaction. By combining H 2 O 2 Increasing from 0.05% to 0.2%, the degradation of trypan blue increases proportionally. When H is 2 O 2 At a concentration of 0.2%, all trypan blue degraded in 20-25 minutes. Higher H 2 O 2 Concentrations (up to 0.4%) do result in faster reaction rates during trypan blue degradation. In these cases, the reaction rate is limited by the trypan blue concentration, and not by H 2 O 2 Is limited by the number of (a). Thus, in subsequent experiments, H 2 O 2 Is fixed at 0.2%.
(iv) Influence of the concentration of the oxidation catalyst
The concentration of the oxidation catalyst Cuz-1 in the reaction mixture at 50℃varies from 0 to 100 ppm. The effect of oxidation catalyst concentration on trypan blue degradation is shown in figure 4. As expected, H alone in the absence of Cuz-1 2 O 2 Cannot lead to degradation of trypan blue within 30 minutes. However, at a concentration of Cuz-1 of 5ppm, the reaction rate was significantly increased. After 30 minutes of reaction, about 70% of the trypan blue was degraded. As the concentration of Cuz-1 was further increased to 50ppm, the reaction rate was further increased. After 20-25 minutes, almost all trypanosomesBlue is degraded. However, when the concentration of Cuz-1 was further increased to 100ppm, no increase in the reaction rate was observed. Therefore, the optimum concentration of Cuz-1 was set to 50ppm.
(v) Influence of pH
The use of 0.2% H was tested under different pH conditions 2 O 2 And 50ppm Cuz-1 on 0.1% trypan blue degradation at 90℃to understand the effect of pH on oxidation catalyst performance. The pH was controlled with HCl or NaOH. As shown in fig. 5, cuz-1 is capable of operating over a wide pH range of 3-11. In all cases, trypan blue degraded within 30 minutes.
(vi) Degradation of chlorophyll
Degradation of chlorophyll (50 mg/mL) using oxidation catalysts was tested. Chlorophyll (a chloropigment) can be purified by H in the presence of peroxidase and phenol (an oxidation system common in plants) 2 O 2 Bleaching. In this experiment Cuz-1 was used instead of peroxidase as oxidation catalyst. The experiment was performed in a water-based system without phenol. Aqueous chlorophyll (50 mg/mL) was combined with 50ppm Cuz-1 and 0.5% H 2 O 2 The reaction was carried out at 50℃for 60 minutes. As shown in FIG. 6, chlorophyll could not be bleached after 60 minutes without Cuz-1. In contrast, in the presence of Cuz-1, the chlorophyll solution became colorless rapidly within 30 minutes, indicating that chlorophyll can be Cuz-1 and H 2 O 2 Effectively bleaching.
While the foregoing specification has described exemplary embodiments, those skilled in the art will appreciate that many changes can be made without departing from the invention.
Claims (16)
1. A method of oxidizing an organic molecule, the method comprising adding an oxidizing agent and an oxidation catalyst for activating the oxidizing agent, wherein the oxidation catalyst comprises an oligopeptide ligand complexed with copper ions through at least two peptide bonds, wherein the oligopeptide ligand comprises a tripeptide having the general formula (I):
(I),
wherein R is 1 、R 2 And R is 3 Each of which is the same or different amino acid;
and wherein the process is carried out at a pH of 9-12.
2. The method of claim 1, wherein the oxidizing agent is hydrogen peroxide (H 2 O 2 ) A peroxyacid, ozone, hypochlorite, or a combination thereof.
3. The process of claim 1, wherein the oxidation catalyst has the general formula (II):
(II),
wherein R is 1 、R 2 And R is 3 Each of which is the same or different amino acids.
4. The method according to claim 1, wherein:
R 1 is H or histidine;
R 2 is H; and
R 3 is H or histidine, and is H or histidine,
and wherein R is 1 And R is 3 Not all of which are histidine.
5. The method of claim 4, wherein R 1 、R 2 And R is 3 Is H such that the oxidation catalyst is Cu-GGG.
6. The method of claim 4, wherein R 1 Is histidine, and R 2 And R is 3 Is H such that the oxidation catalyst is Cu-HGG.
7. According to claim 4The method, wherein R 1 And R is 2 Each of which is H, and R 3 Is histidine, such that the oxidation catalyst is Cu-GGH.
8. A method according to claim 3, wherein:
R 1 is H or histidine;
R 2 is H; and
R 3 is H or histidine;
and wherein R is 1 And R is 3 Not all of which are histidine.
9. The method of claim 8, wherein R 1 、R 2 And R is 3 Is H such that the oxidation catalyst is Cu-GGG.
10. The method of claim 8, wherein R 1 Is histidine, and R 2 And R is 3 Is H such that the oxidation catalyst is Cu-HGG.
11. The method of claim 8, wherein R 1 And R is 2 Is H, and R 3 Is histidine, such that the oxidation catalyst is Cu-GGH.
12. The method of claim 1, wherein the oxidation catalyst is: encapsulated in hydrogel beads; or immobilized on a solid substrate.
13. The process of claim 1, wherein the process is carried out at a temperature of 20-100 ℃.
14. The method of claim 1, wherein the method is performed at a pH of 10 "11.
15. The method of claim 1, wherein the oxidizing agent is an organic peroxide.
16. The method of claim 1, wherein the oxidizing agent is organic hydrogen peroxide.
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4100202A (en) * | 1977-02-18 | 1978-07-11 | Ici Americas Inc. | Oxidative coupling of alkylphenols or 1-naphthols catalyzed by cupric complexes |
DE4118626A1 (en) * | 1991-06-06 | 1992-12-10 | Inventa Ag | Oxidn. of organic substances in waste water - by reaction with hydrogen peroxide in presence of insol. cupric cpd. and air |
US6153576A (en) * | 1996-02-16 | 2000-11-28 | Henkel Kommanditgesellschaft Auf Aktien | Transition-metal complexes used as activators for peroxy compounds |
WO2005117997A1 (en) * | 2004-06-01 | 2005-12-15 | The Ohio State University | Ligands having metal binding ability and targeting properties |
WO2011137190A1 (en) * | 2010-04-27 | 2011-11-03 | Carnegie Mellon University | Carbon supported tetraamido macrocyclic ligand catalytic activators and methods for making the same |
CN105597826A (en) * | 2015-12-28 | 2016-05-25 | 中国纺织科学研究院江南分院 | Low-temperature hydrogen peroxide catalyst as well as preparation method and application thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030017941A1 (en) * | 1997-03-07 | 2003-01-23 | The Procter & Gamble Company | Catalysts and methods for catalytic oxidation |
JP5534128B2 (en) * | 2007-10-31 | 2014-06-25 | 公益財団法人北九州産業学術推進機構 | Artificial peroxidase and method of using the same |
US8722881B2 (en) * | 2009-10-13 | 2014-05-13 | Board Of Trustees Of The University Of Arkansas | Method of synthesis of tetradentate amide macrocycle ligand and its metal-complex |
US20150352540A1 (en) * | 2014-06-03 | 2015-12-10 | Board Of Trustees Of Michigan State University | Multi-ligand metal complexes and methods of using same to perform oxidative catalytic pretreatment of lignocellulosic biomass |
-
2018
- 2018-10-24 SG SG11202003281VA patent/SG11202003281VA/en unknown
- 2018-10-24 CN CN201880073497.6A patent/CN111344060B/en active Active
- 2018-10-24 WO PCT/SG2018/050532 patent/WO2019083453A1/en active Application Filing
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4100202A (en) * | 1977-02-18 | 1978-07-11 | Ici Americas Inc. | Oxidative coupling of alkylphenols or 1-naphthols catalyzed by cupric complexes |
DE4118626A1 (en) * | 1991-06-06 | 1992-12-10 | Inventa Ag | Oxidn. of organic substances in waste water - by reaction with hydrogen peroxide in presence of insol. cupric cpd. and air |
US6153576A (en) * | 1996-02-16 | 2000-11-28 | Henkel Kommanditgesellschaft Auf Aktien | Transition-metal complexes used as activators for peroxy compounds |
WO2005117997A1 (en) * | 2004-06-01 | 2005-12-15 | The Ohio State University | Ligands having metal binding ability and targeting properties |
WO2011137190A1 (en) * | 2010-04-27 | 2011-11-03 | Carnegie Mellon University | Carbon supported tetraamido macrocyclic ligand catalytic activators and methods for making the same |
CN105597826A (en) * | 2015-12-28 | 2016-05-25 | 中国纺织科学研究院江南分院 | Low-temperature hydrogen peroxide catalyst as well as preparation method and application thereof |
Non-Patent Citations (4)
Title |
---|
Complexation of Copper Ions with Histidine-Containing Tripeptides Immobilized on Solid Surfaces;Xinyan Bi et al.;Langmuir;第23卷(第22期);第11067-11073页 * |
Copper(II)-coordinated organic nanotube: A novel heterogeneous catalyst for various oxidation reactions;Tanmay Chattopadhyay et al.;Catalysis Communications;第12卷;第9-13页 * |
EPR and O2•- scavenger activity: Cu(II)-peptide complexes as superoxide dismutase models;Rebecca Pogni et al.;Journal of Inorganic Biochemistry;第73卷;第157-165页 * |
Oxidation of linoleic acid by copper(Ⅱ) complexes: effects of ligand;Jun-ichi Ueda et al.;《Journal of Inorganic Biochemistry》;19991231;第76卷;摘要,第56页2.2.Cu(Ⅱ)络合物反应溶液的制备、2.3.反应条件 * |
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