A method and device for removing oxalic acid and iron oxalate complex from a molten solution

Abstract

The present invention discloses a method for removing oxalic acid and ferric oxalate complexes from a molten liquid. The method comprises the following steps: S1, subjecting a solution containing a target metabolic small molecule, oxalic acid, and ferric oxalate complexes to UV irradiation at a low temperature not higher than 77K, and then placing the solution in a dDNP spectrometer for polarization and melting to obtain a molten liquid; S2, rapidly adding a sodium hydroxide solution to the molten liquid to adjust the pH of the solution to alkaline, causing precipitation to begin; S3, after the precipitation is complete, rapidly filtering and removing the precipitate to obtain a filtrate; S4, rapidly adding a hydrochloric acid solution to the filtrate to adjust the pH of the filtrate to neutral, causing precipitation to begin; S5, after the precipitation is complete, rapidly filtering and removing the precipitate to obtain a polarized clear liquid from which oxalic acid and ferric oxalate complexes are removed, and injecting the polarized clear liquid into a magnet to be detected in the dDNP spectrometer. The present invention introduces excess sodium hydroxide and a pressurized filtration impurity removal device to successfully remove oxalic acid and oxalate complexed iron from the molten liquid.

Description

Technical Field

[0001] The present invention belongs to the field of nuclear magnetic resonance technology, and in particular relates to a method and a device for removing oxalic acid and iron oxalate complexes from a molten solution. Background Art

[0002] Dissolution Dynamic Nuclear Polarization (dDNP) technology can improve the sensitivity of nuclear magnetic resonance detection and plays a vital role in the current nuclear magnetic resonance field. In the process of dDNP implementation, photosensitive free radical technology is an important method to produce the free radical polarizer required in dDNP.

[0003] The Chinese invention patent "Application of Oxalic Acid and Iron Complexes in Melt Dynamic Nuclear Polarization" (Patent No. ZL202411085775.3) discloses oxalic acid as a photosensitive free radical polarizer for melt dynamic nuclear polarization. Its UV spectrum range is between 200-280 nm. Conventional available UV light sources can only excite oxalic acid to produce a very weak photosensitivity reaction, and the concentration of generated free radicals is very low. In experiments, it was found that when the photocatalyst iron oxalate complex was added to the oxalic acid solution, its photosensitive free radical production could be greatly increased, which could provide a suitable concentration of unpaired free radical electrons for dDNP, and is expected to achieve more efficient and faster electron-nuclear polarization transfer.

[0004] However, during subsequent free radical removal, even if the generated photosensitive free radicals are quenched with increasing temperature, the presence of ferric oxalate and oxalic acid in the polarization solution will still affect the use of the hyperpolarized molecular solution. The iron ions in the oxalate-complexed iron, as paramagnetic ions, will accelerate the relaxation process and affect the observation of polarized molecular results. At the same time, excessive oxalic acid content can cause damage to organisms, thus affecting the application of hyperpolarized molecules in metabolic tracing. Therefore, during the transfer of the dDNP solution to the magnet to be tested, the solution needs to be quality controlled to remove oxalic acid and ferric oxalate from the solution. Summary of the Invention

[0005] Based on the above-mentioned prior art, the present invention provides a method and device for removing oxalic acid and iron oxalate complexes from a molten solution. The present invention introduces excess sodium hydroxide and a pressurized filtration impurity removal device to successfully remove oxalic acid and iron oxalate complexes from the molten solution.

[0006] The technical solution adopted to achieve the above-mentioned purpose of the present invention is:

[0007] A method for removing oxalic acid and ferric oxalate complexes from a molten solution comprises the following steps:

[0008] S1. treating a solution containing a target metabolic small molecule, oxalic acid, and an iron oxalate complex with UV light at a low temperature of less than 77 K, and then placing the solution in a dDNP spectrometer for polarization and melting to obtain a melt solution;

[0009] S2. Rapidly add sodium hydroxide solution to the melt to adjust the pH of the melt to alkaline, and precipitation begins to appear;

[0010] S3. After the precipitation is complete, the precipitate is removed by rapid filtration to obtain a filtrate;

[0011] S4. Rapidly add hydrochloric acid solution to the filtrate to adjust the pH of the filtrate to neutral, and precipitation begins to appear;

[0012] S5. After the precipitation is complete, the precipitate is quickly filtered to remove it, and a polarized clear solution is obtained from which oxalic acid and the iron oxalate complex are removed. The polarized clear solution is injected into the magnet to be detected in the dDNP spectrometer.

[0013] Furthermore, the target metabolic small molecule is selected from [1- 13 C]-pyruvic acid, 13 C-urea and 15 At least one of N-glycine.

[0014] Furthermore, in step S2, the pH of the melt is adjusted to pH ≥ 9.

[0015] Furthermore, the concentration of the sodium hydroxide solution is 1 M~4 M.

[0016] Furthermore, the concentration of the hydrochloric acid solution is 0.05M~0.15M.

[0017] A device for removing oxalic acid and iron oxalate complexes from a molten solution, comprising a first-stage removal mechanism, a second-stage removal mechanism, and a conveying mechanism for conveying polarized clear liquid to a magnet to be detected by a dDNP spectrometer.

[0018] The first-stage removal mechanism includes a first injection pump, an alkali solution injection pipeline and a first filter. The downstream end of the melt injection pipeline is connected to the liquid cavity of the first injection pump, the outlet of the first injection pump is connected to the inlet of the first filter, the downstream end of the alkali solution injection pipeline is connected to the liquid cavity of the first injection pump, and a first pH meter for detecting the pH of the liquid in the liquid cavity of the first injection pump is installed on the liquid cavity of the first injection pump;

[0019] The second-stage removal mechanism includes a second syringe pump, a filtrate injection pipeline, an acid injection pipeline, and a second filter, the first filter outlet is connected to the upstream end of the filtrate injection pipeline, the downstream ends of the filtrate injection pipeline and the acid injection pipeline are respectively connected to the liquid cavity of the second syringe pump, the liquid cavity of the second syringe pump is equipped with a second pH meter for detecting the pH of the liquid in the liquid cavity of the second syringe pump, and the second syringe pump outlet is connected to the second filter inlet;

[0020] The conveying mechanism comprises a buffer container for containing the polarized clear liquid and a conveying pipeline. The second filter outlet is connected to the buffer container, and the upstream end of the conveying pipeline is connected to the buffer container.

[0021] The melt injection pipeline includes a melt injection pipe and a first one-way valve, the first one-way valve is installed on the melt injection pipe, and the downstream end of the melt injection pipe is connected to the liquid cavity of the first injection pump. The alkali solution injection pipeline includes an alkali solution bottle, an alkali solution injection pipe, a second one-way valve and a first liquid pump, the upstream end of the alkali solution injection pipe is connected to the alkali solution bottle, and the downstream end of the alkali solution injection pipe is connected to the liquid cavity of the first injection pump. The second one-way valve and the first liquid pump are respectively installed on the alkali solution injection pipe.

[0022] The filtrate injection pipeline includes a filtrate injection pipe and a third one-way valve. The upstream end of the filtrate injection pipe is connected to the outlet of the first filter, and the downstream end of the filtrate injection pipe is connected to the liquid cavity of the second injection pump. The third one-way valve is installed on the filtrate injection pipe. The acid injection pipeline includes an acid bottle, an acid injection pipe, a fourth one-way valve and a second liquid pump. The upstream end of the acid injection pipe is connected to the acid bottle, and the downstream end of the acid injection pipe is connected to the liquid cavity of the second injection pump. The fourth one-way valve and the second liquid pump are respectively installed on the acid injection pipe.

[0023] The delivery pipeline includes a delivery pipe and a third liquid pump. The upstream end of the delivery pipe is connected to the buffer container, and the third liquid pump is installed on the delivery pipe.

[0024] Compared with the prior art, the advantages and beneficial effects of the present invention are:

[0025] 1. The present invention adds excess sodium hydroxide as a chemical treatment method, utilizing the reaction of oxalic acid and sodium hydroxide to form sodium oxalate precipitate and the property that iron oxalate is insoluble in water under alkaline conditions, thereby simultaneously removing oxalic acid and oxalate-complexed iron in the melt.

[0026] 2. The present invention introduces a pressurized filtration impurity removal device, which can quickly remove the precipitated impurities produced through the filter, and quickly inject the hyperpolarized molecular solution after removing oxalic acid and ferric oxalate into the NMR magnet for metabolic tracing or detection. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1Schematic diagram of the structure of a device for removing oxalic acid and iron oxalate complex from a melt.

[0028] Among them, 1-first injection pump, 2-melt injection pipe, 3-first one-way valve, 4-alkali solution bottle, 5-alkali solution injection pipe, 6-second one-way valve, 7-first liquid pump, 8-first pH meter, 9-first filter, 10-second injection pump, 11-second pH meter, 12-filtrate injection pipe, 13-third one-way valve, 14-acid bottle, 15-acid injection pipe, 16-fourth one-way valve, 17-second liquid pump, 18-second filter, 19-buffer container, 20-delivery pipe, 21-third liquid pump.

[0029] Figure 2 The relaxation time comparison chart of the supernatant obtained by filtering different simulated solutions adjusted to different pH values.

[0030] Figure 3 This is the HPLC spectrum of the clear solution obtained after filtering when a 2 M oxalic acid solution was adjusted to neutral. DETAILED DESCRIPTION

[0031] In order to facilitate those skilled in the art to understand and implement the present invention, the present invention is further described in detail below in conjunction with embodiments. It should be understood that the embodiments described herein are only used to illustrate and explain the present invention and are not used to limit the present invention.

[0032] The device for removing oxalic acid and ferric oxalate complex from a molten solution of the present invention is described in detail below with reference to the accompanying drawings.

[0033] Example 1

[0034] The structure of the device for removing oxalic acid and iron oxalate complex from a molten solution provided in this embodiment is as follows: Figure 1 As shown, it includes a first-stage removal mechanism, a second-stage removal mechanism and a transport mechanism for transporting the polarized clear liquid to the magnet to be detected in the dDNP spectrometer.

[0035] The melt injection pipeline is an existing one for conveying the melt. The melt injection pipeline comprises a melt injection pipe 2 and a first one-way valve 3 , wherein the first one-way valve 3 is mounted on the melt injection pipe 2 .

[0036] The first-stage removal mechanism includes a first syringe pump 1, an alkali solution injection pipeline, and a first filter. The downstream end of the melt injection pipeline 2 is connected to the liquid chamber of the first syringe pump 1. The alkali solution injection pipeline includes an alkali solution bottle 4, an alkali solution injection pipe 5, a second one-way valve 6, and a first liquid pump 7. The upstream end of the alkali solution injection pipe 5 is connected to the alkali solution bottle 4, and the downstream end of the alkali solution injection pipe 5 is connected to the liquid chamber of the first syringe pump 1. The second one-way valve 6 and the first liquid pump 7 are respectively installed on the alkali solution injection pipe 5. A first pH meter 8 is installed in the liquid chamber of the first syringe pump 1 to detect the pH of the liquid in the liquid chamber of the first syringe pump 1.

[0037] The outlet of the first syringe pump 1 is connected to the inlet of the first filter 9 (diameter: 13 mm, pore size: 0.22 μm, material: polyethersulfone, Jinteng). The piston of the first syringe pump 1 is quickly pushed to quickly push the mixed liquid with precipitate in the liquid cavity of the first syringe pump 1 into the first filter 9 for filtration.

[0038] The second-stage removal mechanism includes a second syringe pump 10, a filtrate injection line, an acid injection line, and a second filter 18. The filtrate injection line includes a filtrate injection line 12 and a third one-way valve 13. The upstream end of the filtrate injection line 12 is connected to the outlet of the first filter 10, and the downstream end of the filtrate injection line 12 is connected to the liquid chamber of the second syringe pump 10. The third one-way valve 13 is mounted on the filtrate injection line 12. The acid injection line includes an acid bottle 14, an acid injection line 15, a fourth one-way valve 16, and a second liquid pump 17. The upstream end of the acid injection line 15 is connected to the acid bottle 14, and the downstream end of the acid injection line 15 is connected to the liquid chamber of the second syringe pump 10. The fourth one-way valve 16 and the second liquid pump 17 are respectively mounted on the acid injection line 15. A second pH meter 11 is mounted in the liquid chamber of the second syringe pump 10 for detecting the pH of the liquid in the liquid chamber of the second syringe pump 10.

[0039] The outlet of the second syringe pump 10 is connected to the inlet of the second filter 18. The piston of the second syringe pump 10 is quickly pushed to quickly push the mixed liquid with precipitation in the liquid cavity of the second syringe pump 10 into the second filter 18 for filtration.

[0040] The delivery mechanism includes a buffer container 19 (such as a buffer bottle) for holding the polarized clear solution and a delivery pipeline. The outlet of the second filter 18 is connected to the buffer container 19, and the hyperpolarized molecular solution, after removal of oxalic acid and ferric oxalate, enters the buffer container 19. The delivery pipeline includes a delivery pipe 20 and a third liquid pump 21. The upstream end of the delivery pipe 20 is connected to the buffer container 19. The third liquid pump 21 is installed on the delivery pipe 20 and rapidly pumps the polarized clear solution to the magnet to be detected in the dDNP spectrometer.

[0041] The method for removing oxalic acid and ferric oxalate complex from a molten solution of the present invention will be described in detail below in conjunction with the above-mentioned device.

[0042] Example 2

[0043] 1. Pour 2 M sodium hydroxide solution into the alkali solution bottle 4 and 0.1 M hydrochloric acid solution into the acid solution bottle 14.

[0044] 2. 150 μL containing 2 M oxalic acid, 15 mM ferric oxalate and [1- 13 The sample solution of [C]-pyruvic acid was irradiated with UV light at 77 K and then placed in a dDNP spectrometer for polarization and melting to obtain a molten solution.

[0045] 3. Open the first one-way valve 3, allowing the melt to flow through the melt injection tube 2 into the liquid chamber of the first syringe pump 1. After the melt is injected, close the first one-way valve 3. Then, open the second one-way valve 6 and the first liquid pump 7. Rapidly inject the sodium hydroxide solution from the lye bottle 4 into the liquid chamber of the first syringe pump 1, mixing with the melt in the liquid chamber of the first syringe pump 1. Sodium oxalate and ferric oxalate precipitate begin to form in the liquid chamber of the first syringe pump 1. Adjust the pH of the melt to 9 using the first pH meter 8. Then, close the second one-way valve 6 and the first liquid pump 7.

[0046] 4. After the precipitation is complete, open the third one-way valve 13 and simultaneously quickly push the piston of the first syringe pump 1 to quickly push the mixed liquid in the first syringe 1 into the first filter 9. The mixed liquid is quickly filtered through the first filter 9 to quickly remove the sodium oxalate and ferric oxalate precipitates. The filtrate is injected into the liquid chamber of the second syringe pump 10 through the filtrate injection tube 12.

[0047] 5. After the filtrate is injected, close third one-way valve 13. Open fourth one-way valve 16 and second liquid pump 17. Rapidly inject the hydrochloric acid solution from acid bottle 14 into the liquid chamber of second syringe pump 10. It mixes with the filtrate in the liquid chamber of second syringe pump 10, causing precipitation to begin in the liquid chamber of second syringe pump 10. Adjust the pH of the filtrate to 7 using second pH meter 11. Then close fourth one-way valve 16 and second liquid pump 17.

[0048] 6. After the precipitation is complete, quickly push the piston of the second syringe pump 10 to quickly push the mixed liquid in the liquid chamber of the second syringe pump 10 into the second filter 18. The second filter 18 quickly filters the mixed liquid to quickly remove the precipitate. The resulting polarized clear liquid enters the buffer container 19.

[0049] 7. After the polarized clear liquid has completely entered the buffer container 19, the third liquid pump 21 is turned on to pump the polarized clear liquid in the buffer container 19 into the magnet to be detected of the dDNP spectrometer.

[0050] Experiment 1: Changes in relaxation time of oxalic acid, ferric oxalate, and oxalic acid-ferric oxalate solutions at different pH values

[0051] Test method:

[0052] S1. Dissolve oxalic acid in water to prepare an oxalic acid solution with a 2 M oxalic acid concentration. Dissolve iron (III) oxalate hexahydrate (Fe2(C2O4)3.6H2O) in a 1.6 wt% hydrochloric acid solution to prepare a ferric oxalate solution with a 15 mM ferric oxalate concentration. Dissolve oxalic acid and iron (III) oxalate hexahydrate in water to obtain an oxalic acid-ferric oxalate mixed solution, wherein the concentration of oxalic acid is 2 M and the concentration of ferric oxalate is 15 mM, resulting in an actual ferric oxalate concentration of 15 mM* (11%-12.5%). Dissolve sodium hydroxide in water to prepare a 2 M sodium hydroxide solution. Dilute concentrated hydrochloric acid with water to prepare a 0.1 M hydrochloric acid solution.

[0053] S2. To simulate the dissolution process during melt polarization, 150 μL of ferric oxalate solution was added to 6.5 mL of water to obtain a simulated melt solution. The pH of the simulated melt solution was then adjusted to 6 using 2 M sodium hydroxide solution to obtain the sample solution. 2 mL of the sample solution was filtered through a filter to obtain clear solution A1. The remaining sample solution was further adjusted to pH 9 using 2 M sodium hydroxide solution and filtered to obtain clear solution A2. 2 mL of A2 was adjusted to pH approximately 7 using 0.1 M hydrochloric acid solution and filtered to obtain clear solution A3. Clear solutions A1, A2, and A3 were used for subsequent relaxation time determination.

[0054] S3. Treat the oxalic acid solution according to the method of step S2 to obtain clear solutions B1, B2, and B3. Treat the oxalic acid-ferric oxalate mixed solution according to the method of step S2 to obtain clear solutions C1, C2, and C3.

[0055] S4. Use time-domain NMR technology to measure the relaxation time of the clear solutions A1, A2, A3, B1, B2, B3, C1, C2, and C3, and compare them with the relaxation time of pure water.

[0056] Test results:

[0057] The relaxation time of the above-mentioned Jiufen clear solution and the relaxation time of pure water are as follows Figure 2 As shown. Figure 2As can be seen, when the simulated melts containing ferric oxalate, oxalic acid, and oxalic acid-ferric oxalate were adjusted to pH 6 using sodium hydroxide solution, the relaxation times of clear solutions A1, B1, and C1 were all short, with A1 and C1 experiencing even shorter relaxation times due to the influence of iron ions. When the pH was adjusted to pH 9, the relaxation times of clear solutions A2, B2, and C2 were close to that of pure water, indicating that the oxalic acid and / or ferric oxalate in the simulated melts were almost completely removed. Subsequently, when the pH of clear solutions A2, B2, and C2 was adjusted to pH 7, a slight decrease in the relaxation times of clear solutions A3, B3, and C3 was observed, likely due to the redissolution of a small amount of ferric oxalate precipitate that was not completely filtered. However, clear solutions A3, B3, and C3 still maintained long relaxation times. This demonstrates that the introduction of excess sodium hydroxide and a pressurized filtration-type impurity removal device can effectively remove oxalic acid and oxalate-complexed iron from the melts.

[0058] Test 2: Determination of oxalic acid content in oxalic acid-ferric oxalate solution when adjusted to neutral

[0059] Test method:

[0060] S1. Dissolve 2 M oxalic acid and 15 mM iron (III) oxalate hexahydrate in water to obtain an oxalic acid-ferric oxalate mixed solution, where the actual concentration of ferric oxalate is 15 mM* (11%-12.5%). Dissolve sodium hydroxide in water to prepare a 2 M sodium hydroxide solution. Dilute concentrated hydrochloric acid with water to prepare a 0.1 M hydrochloric acid solution.

[0061] S2. Add 150 μL of the oxalic acid-ferric oxalate mixture to 6.5 mL of water to create a simulated solution. Adjust the pH of the simulated solution to 9 with 2 M sodium hydroxide solution and filter to obtain a filtrate. Adjust the pH of the filtrate to approximately pH 7 with 0.1 M hydrochloric acid solution and filter to obtain the supernatant for subsequent determination of oxalic acid content.

[0062] S3. Take 0.12174 g of the supernatant and dilute to 10 mL with a dilution factor of 2. Determine the peak area of ​​oxalic acid in the supernatant by HPLC and convert it to obtain the oxalic acid content in the supernatant.

[0063] Test results:

[0064] The HPLC spectrum of the clear solution is as follows Figure 3 As shown, after converting the peak areas of the HPLC spectrum, it was determined that after removing oxalic acid and ferric oxalate from the simulated solution, the oxalic acid content in the supernatant was 0.4 wt%, which is a safe concentration for humans. This indicates that by introducing excess sodium hydroxide and using a pressurized filtration-based impurity removal device to remove oxalic acid and oxalate-complexed iron from the solution, the residual oxalic acid concentration in the resulting polarized supernatant is not harmful to the human body.

Claims

1. A method for removing oxalic acid and iron oxalate complexes from a molten solution, characterized in that The steps include: S1. treating a solution containing a target metabolic small molecule, oxalic acid, and an iron oxalate complex with UV light at a low temperature not higher than 77 K, and then placing the solution in a dDNP spectrometer for polarization and melting to obtain a melt solution; S2. Rapidly add sodium hydroxide solution to the melt to adjust the pH of the melt to alkaline, and precipitation begins to appear; S3. After the precipitation is complete, the precipitate is removed by rapid filtration to obtain a filtrate; S4. Rapidly add hydrochloric acid solution to the filtrate to adjust the pH of the filtrate to neutral, and precipitation begins to appear; S5. After the precipitation is complete, the precipitate is quickly filtered to remove it, and a polarized clear solution is obtained from which oxalic acid and the iron oxalate complex are removed. The polarized clear solution is injected into the magnet to be detected in the dDNP spectrometer.

2. The method for removing oxalic acid and ferric oxalate complexes from a melt according to claim 1, wherein: The target metabolic small molecule is selected from [1- 13 C]-pyruvic acid, 13 C-urea and 15 At least one of N-glycine.

3. The method for removing oxalic acid and ferric oxalate complexes from a melt according to claim 1, wherein: In step S2, the pH of the melt is adjusted to pH ≥ 9.

4. The method for removing oxalic acid and ferric oxalate complexes from a melt according to claim 1, wherein: The concentration of the sodium hydroxide solution is 1 M~4 M.

5. The method for removing oxalic acid and ferric oxalate complex from a melt according to claim 1, wherein: The concentration of the hydrochloric acid solution is 0.05M~0.15M.

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