Real-time voltage-changing in-situ detection device for nuclear magnetic resonance spectrometer and its application

Abstract

The present invention discloses a real-time voltage-changing in-situ detection device and application for a nuclear magnetic resonance spectrometer. The real-time voltage-changing device comprises a four-way module, and the connection relationship of the openings of the four-way module is as follows: opening A is connected to an air-driven gas booster pump; opening B is connected to a pressure sensor and an exhaust valve; opening C is connected to a nuclear magnetic tube through a weak magnetic tube and an adapter; a plug is provided inside one end of the four-way module opposite to opening C, and an internal magneton and a titanium alloy extension rod are provided inside the plug, and an external magneton is coaxially arranged outside the plug, and the rotation of the external magneton is controlled by a rotating stepper motor; one end of the titanium alloy extension rod is connected to a stirring rod, and the other end of the stirring rod extends into the nuclear magnetic tube. The real-time voltage-changing detection device of the present invention cooperates with a nuclear magnetic resonance spectrometer for high-pressure in-situ NMR detection of samples, and the applicable samples can be the characterization of material synthesis in complex fluids, the evidence of systems with conformational isomers, and the real-time observation of some gas inclusion reactions.

Description

Technical Field

[0001] The invention relates to a real-time voltage-changing in-situ detection device for a nuclear magnetic resonance spectrometer and application thereof, belonging to the technical field of nuclear magnetic resonance spectroscopy. Background Art

[0002] Nuclear Magnetic Resonance spectroscopy (NMR spectroscopy), also known as nuclear magnetic resonance spectroscopy, is a spectroscopic technique that applies nuclear magnetic resonance phenomena to molecular structure, intermolecular interactions, dynamics and thermodynamic characterization. It can obtain information such as chemical shift, coupling constant, interatomic connection, spatial orientation, relaxation time, etc. It is widely used in many fields such as chemistry, physics, and life sciences. Pressure is a basic thermodynamic variable. Changes in pressure will change the distribution of electrons in molecules, thereby causing changes in molecular structure. Changes in molecular structure can be reflected in changes in NMR parameters such as shielding, spin-spin coupling, and relaxation time. At present, nuclear magnetic resonance spectrometers can only provide detection under atmospheric pressure conditions. For in-situ tracking of the evolution of molecular structure and kinetic transformation processes under temperature and pressure conditions, there is a lack of in-situ characterization experimental technology with variable pressure. At present, there are commercial high-pressure nuclear magnetic tubes in China that are applied to the detection of nuclear magnetic resonance spectra, but their pressure resistance is low (up to 1.4MPa) and their scope of application is very limited, so there are few users who purchase them. Summary of the invention

[0003] The purpose of the present invention is to provide a real-time voltage-variable in-situ detection device for a nuclear magnetic resonance spectrometer, so as to solve the problem that the existing equipment cannot perform in-situ detection under high-pressure environment.

[0004] The real-time voltage conversion device for a nuclear magnetic resonance spectrometer provided by the present invention comprises a four-way module, and the connection relationship of the openings of the four-way module is as follows:

[0005] Opening A is connected to the air-driven air booster pump;

[0006] Port B is connected to the pressure sensor and the exhaust valve;

[0007] Opening C is connected to the nuclear magnetic tube through a weak magnetic tube and a titanium alloy adapter;

[0008] A plug is provided inside one end of the cross-way opposite to the opening C, an inner magnet and a titanium alloy extension rod are provided inside the plug, an outer magnet is coaxially provided outside the plug, and the rotation of the outer magnet is controlled by a rotating stepping motor;

[0009] One end of the titanium alloy extension rod is connected to a stirring rod, and the other end of the stirring rod extends into the nuclear magnetic tube.

[0010] In the above-mentioned real-time pressure conversion device, the air-driven pump is connected to the air inlet needle valve on the cross-way through a high-pressure resistant hose;

[0011] The inner diameter of the gas inlet in the four-way connected to the high-pressure hose is 0.1-0.5 mm. A hole of this size can both play a throttling role and will not make the pressurization speed too slow. This hole is to prevent the nuclear magnetic tube from accidentally bursting, and the external booster pump (with a gas storage tank inside) will quickly enter the nuclear magnetic tube with a large amount of pressurization to cause further damage.

[0012] In the above-mentioned real-time voltage conversion device, the opening A is also connected to a cleaning port;

[0013] The opening B is also connected to an exhaust port.

[0014] In the above-mentioned real-time voltage conversion device, the weak magnetic tube is a 316L weak magnetic stainless steel tube, which is arranged at the opening C end of the cross-way;

[0015] A high-pressure resistant sealing ring is provided at the connection between the 316L weak magnetic stainless steel tube and the nuclear magnetic tube.

[0016] In the above-mentioned real-time voltage conversion device, the stirring rod is a polytetrafluoroethylene rod;

[0017] The stirring rod is connected to the titanium alloy extension rod via a titanium alloy adapter joint;

[0018] The material of the nuclear magnetic tube is zirconium oxide.

[0019] In the above-mentioned real-time voltage conversion device, a lifting stepping motor is arranged on the four-way module to control the up and down movement of the stirring rod.

[0020] The real-time voltage transformation device also includes a lifting bracket,

[0021] The lifting bracket comprises an aluminum profile bracket, a linear guide rail, a steel wire rope, a hand crank and a slide block;

[0022] The slide block that can be lifted and lowered along the linear guide rail is fixed on the aluminum profile bracket, and the four-way module is fixed on the slide block;

[0023] After the steel wire rope passes through the fixed pulley arranged on the top of the aluminum profile bracket, one end of the steel wire rope is connected to the slider, and the other end is connected to the hand crank. The lifting and lowering of the steel wire rope is controlled by the hand crank: the hand crank is rotated clockwise to lift the slider through the steel wire rope. Conversely, the slider is lowered due to the influence of gravity. When it does not rotate, the hand crank is automatically locked.

[0024] The present invention also provides a high-voltage in-situ detection device for a nuclear magnetic resonance spectrometer, comprising a nuclear magnetic resonance spectrometer and the real-time voltage transformation device;

[0025] The real-time voltage transformer is fixed on the upper part of the nuclear magnetic resonance spectrometer, and the nuclear magnetic tube extends into the interior of the nuclear magnetic resonance spectrometer.

[0026] The high-pressure in-situ detection device can be used for high-pressure in-situ NMR detection of samples, such as detecting the effect of pressure on supramolecular structure and the effect of pressure on amide bond substrates;

[0027] Applicable samples include the characterization of material synthesis in complex fluids, the evidence of the existence of conformational isomers, and the real-time observation of some gas inclusion reactions.

[0028] The high-pressure in-situ detection device is easy to install, has strong pressure resistance, and has a sample stirring function.

[0029] The present invention has the following beneficial technical effects:

[0030] (1) Coupling of real-time pressure-changing device and nuclear magnetic resonance spectrometer: The variable pressure solution requires that the booster pipeline, valve and nuclear magnetic resonance tube be connected in real time, which will inevitably cause problems such as complicated sample injection and large device mass. To this end, the present invention provides a support frame that is firmly combined with the NMR and ensures that the nuclear magnetic resonance tube accurately enters the magnet.

[0031] (2) In-situ high-pressure stirring: In order to achieve the compatibility of stirring and real-time voltage transformation functions, a four-way module is used. The in-situ stirring device includes a stirring rod, an extension rod, internal and external magnets, and a stepper motor device. The stirring rod is a low-magnetic susceptibility, corrosion-resistant polytetrafluoroethylene rod with a length slightly longer than the length of the nuclear magnetic tube; the stirring rod is connected to the titanium alloy extension rod through an adapter joint, and the length of the extension rod extends to the inner magnet (strip neodymium magnet) of the magnetic transmission stirring at the top of the four-way module. The inner and outer magnets attract each other and are airtightly isolated by weak magnetic steel. The rotation of the rotary stepper motor drives the rotation of the external magnet to achieve in-situ high-pressure stirring; the rotary stepper motor is placed on a lifting slide. After stirring, the stirring rod can be lifted to prevent the stirring rod from interfering with the uniform field.

[0032] (3) The gas inlet in the pressure-resistant four-way module is set as a 0.3 mm small hole. In the event of an accidental explosion, it can effectively throttle the gas stored in the booster pump and reduce damage.

[0033] (4) The main body of the device is made of titanium alloy, stainless steel and other materials that have both compressive strength and non-magnetic requirements. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 The figure is a schematic diagram of the overall structure of the high-pressure in-situ detection device for a nuclear magnetic resonance spectrometer according to the present invention.

[0035] Figure 2 The figure is a schematic structural diagram of a real-time voltage transformer for a nuclear magnetic resonance spectrometer according to the present invention.

[0036] Figure 3 The present invention is a schematic structural diagram of a lifting bracket in a real-time voltage transformer for a nuclear magnetic resonance spectrometer.

[0037] Figure 4 It is the appearance and cross-sectional diagram of the temperature and pressure resistance test device.

[0038] Figure 5 The figure is a schematic diagram of the external structure of a high-voltage nuclear magnetic resonance tube in a real-time voltage transformation device for a nuclear magnetic resonance spectrometer according to the present invention.

[0039] Figure 6 The present invention is a cross-sectional view of a high-voltage nuclear magnetic resonance tube in a real-time voltage transformer for a nuclear magnetic resonance spectrometer.

[0040] Figure 7 Figure 3 is the variation of chemical shifts of phenol OH and water peaks with pressure, where (a) and (c) are the hydrogen spectra of the phenol OH peak tracked by the high-pressure in-situ monitoring system as it varies with pressure and the corresponding linear relationship diagrams of the chemical shift value and pressure, (b) and (d) are the hydrogen spectra of the phenol water peak tracked by the high-pressure in-situ monitoring system as it varies with pressure and the corresponding linear relationship diagrams of the chemical shift value and pressure.

[0041] Figure 8 DMA under different pressure nitrogen atmosphere 1 H NMR spectrum at 373 K.

[0042] The marks in the figure are as follows:

[0043] 1 Nuclear magnetic resonance spectrometer, 2 Real-time voltage transformer, 3 316L weak magnetic stainless steel pipe, 4 Titanium alloy adapter, 5 High-pressure sealing ring, 6 Nuclear magnetic tube, 7 High-pressure air intake needle valve, 8 High-pressure hose, 9 Air-driven air booster pump, 10 Pressure sensor, 11 Exhaust valve, 12 Internal magnet, 13 Titanium alloy extension rod, 14 External magnet, 15 Rotary stepper motor, 16 Lifting stepper motor, 17 Aluminum profile bracket, 18 Linear guide rail, 19 Hand crank, 20 Slider, 21 Steel wire rope, 22 Fixed pulley. DETAILED DESCRIPTION

[0044] The present invention is further described below in conjunction with the accompanying drawings, but the present invention is not limited to the following embodiments.

[0045] like Figure 1As shown, the high-pressure in-situ detection device for a nuclear magnetic resonance spectrometer provided by the present invention comprises a nuclear magnetic resonance spectrometer 1 and a real-time voltage transformer 2. The nuclear magnetic resonance spectrometer is an existing commercial instrument and does not have the functions of pressurizing, transforming and stirring the sample; the real-time voltage transformer 2 is coupled to the spectrometer. The real-time voltage transformer 2 can realize the functions of pressurizing, transforming and stirring the sample, and the nuclear magnetic resonance spectrometer 1 can detect the chemical shift of the sample in the pressurized state, so the coupled systems jointly realize the high-pressure in-situ NMR detection of the sample.

[0046] like Figure 2 As shown, it is a structural schematic diagram of the real-time voltage conversion device 2 provided by the present invention, including a four-way module. The structure of the four-way module is as follows:

[0047] The four-way module is a customized 316L stainless steel module, and the four sides are designed with high-pressure resistant nuts and screw sleeves. The 316L weak magnetic stainless steel tube 3 at the bottom of the four-way module is connected to the nuclear magnetic tube 6 through a titanium alloy adapter 4 and a high-pressure resistant sealing ring 5; the left side is connected to a high-pressure hose 8 (pressure resistance>60MPa, 10 meters long) through a high-pressure air inlet needle valve 7, and the hose is connected to an air-driven air booster pump 9. When the needle valve is opened, the pressurized gas can enter the four-way to achieve real-time pressure change (pressure change range 0-30MPa); the right side is connected to a pressure sensor 10 and an exhaust valve 11. The pressure sensor 10 is used to detect the pressure inside the four-way (approximately equal to the pressure inside the nuclear magnetic tube), and the exhaust valve 11 is used to exhaust the high-pressure gas in the system after the experiment is completed; in addition, in order to ensure the safety of the device, the air inlet hole of the four-way is set to 0.3mm. This current limiting design can reduce the impact and damage of the residual gas in the booster pump on the nuclear magnetic resonance spectrometer when the nuclear magnetic tube explodes.

[0048] Among them, the air-driven gas booster pump 9 has a fixed boost ratio (1:60). By adjusting the pressure of the driving gas (nitrogen), the pressure of the boosted gas (the boosted gas can be carbon oxygen, carbon-hydrogen small molecule gas, inert gas, hydrogen, oxygen, etc.) can be adjusted.

[0049] Stirring during the reaction can fully mix the reactants and significantly increase the reaction efficiency. Stirring under ordinary high-pressure conditions uses a pair of mutually attractive magnetons, and the rotation of the internal magnetons is achieved by rotating the external magnetons to stir the sample. However, there are two problems when this method is applied to stirring under NMR in-situ high-pressure conditions: first, any magnetons with different magnetic susceptibility from the sample will affect the magnetic field distortion, affecting the uniform field effect (the magnetic susceptibility of the stirring rod is different from that of the sample, resulting in magnetic field distortion, thereby affecting the resolution), and second, the nuclear magnetic resonance spectrometer itself has an ultra-strong magnetic field, which is incompatible with external magnetons. The present invention realizes in-situ stirring through the following structure: a stirring rod, an extension rod, an internal and external magnetons and a stepper motor device: a plug is set at the top of the four-way, an internal magneton 12 and a titanium alloy extension rod 13 are placed in the plug, and an external magneton 14 is coaxially set outside the plug, and the external magneton 14 is driven by the top rotating stepper motor 15, and the internal magneton 12 drives the titanium alloy extension rod 13 and the stirring rod 15 to realize the stirring function. The stirring rod 15 is a low magnetic susceptibility, corrosion-resistant PTFE rod, and its length is slightly longer than the length of the nuclear magnetic tube; the stirring rod 15 is connected to the titanium alloy extension rod 13 through an adapter joint. In addition, the lifting stepper motor 16 can also be used to drive the external magneton 14 to move up and down, so as to realize the lifting and lowering movement of the internal stirring rod. When necessary, the stirring rod can be inserted into the sample to achieve stirring; when not needed, the stirring rod is lifted upward to avoid affecting the uniform field.

[0050] like Figure 3 As shown, the present invention also includes a lifting bracket: it includes an aluminum profile bracket 17, a linear guide rail 18, a hand crank 19, a slider 20 and a wire rope 21, etc.; the lifting bracket can be stably installed on the spectrometer, and the liftable slider 20 is fixed on the aluminum profile bracket 17, and can slide up and down along the linear guide rail 18, and at the same time, a high-pressure resistant four-way module is fixed on the slider 20. The hand crank 19 has a built-in wire rope 21, and the wire rope 21 is pulled out to the fixed pulley 22 at the top of the aluminum profile bracket 17, and then connected downward to the fixed block on the slider 20 for fixing. The hand crank 19 is rotated clockwise to lift the slider 20 through the wire rope 21. On the contrary, under the influence of gravity, the slider 20 drops. When it does not rotate, the hand crank 19 is automatically locked, so that the sample can be easily and quickly entered and exited.

[0051] The appearance diagram of the NMR tube is shown in the figure below: Figure 5 It is a high-pressure nuclear magnetic tube, the cross-section diagram is as follows Figure 6 As shown, it is a non-magnetic or weakly magnetic tube that can withstand high pressure and high and low temperatures. Preferably, the high-pressure resistant nuclear magnetic tube is made of aluminum oxide, zirconium oxide, or sapphire.

[0052] The actual processing and explosion test results show that: the actual test shows that the explosion pressure of the alumina NMR tube is less than 60MPa, and the safety margin is insufficient; the explosion pressure of the zirconium oxide NMR tube is 140MPa, which meets the requirements; sapphire has a higher pressure resistance, but the processing cost is extremely high; the NMR background signal of zirconium oxide is extremely low, so it can fully meet the project requirements. The explosion test results show that the explosion pressure of the zirconium oxide NMR tube is still greater than 100MPa under high (+100℃) and low (-100℃) temperature conditions, which has sufficient experimental safety margin.

[0053] Since the NMR tube is made of zirconium oxide, there are two problems with using gas for burst testing: first, it is difficult to pressurize the gas when the burst pressure requirement is high; second, the gas is compressible, and the burst will produce a huge impact force, which is very dangerous. For this reason, a hydraulic method with lower cost and higher pressure (up to 300MPa) is used for burst pressure testing. In order to fully simulate the high-pressure test under NMR variable temperature conditions, an atmosphere temperature control device is coupled in the burst test. The low-temperature (using liquid nitrogen refrigeration) or room-temperature gas is heated by a heater, and the gas temperature is controlled by a temperature controller (-100℃~+100℃). The temperature-controlled gas is passed through a semi-closed pipe to cool or heat the pressurized NMR tube to obtain the true pressure resistance performance of the NMR tube under variable temperature conditions.

[0054] The high-pressure in-situ NMR detection of samples was carried out using the high-pressure in-situ detection device of the present invention, and the changes in the solution state of organic small molecules and supramolecular structures under an inert gas atmosphere were investigated. The experimental process proved that the high-pressure in-situ detection device of the present invention was successfully operated and met the relevant technical indicator requirements.

[0055] 1. Effect of pressure on supramolecular structure

[0056] The mechanism of action within drug molecules under different pressure nitrogen atmospheres and its relationship with pressure changes were studied, such as Figure 7 As shown, during the process of increasing the pressure to 30 MPa, it can be seen that the chemical shifts of active hydrogen and H2O peaks are basically linearly related to the pressure, and there are different degrees of deshielding phenomena, which provides evidence for studying the molecular mechanism and proves the feasibility of the high-pressure device of the present invention.

[0057] 2. Effect of pressure on amide bond substrates

[0058] The hydrogen spectrum of DMA in nitrogen atmosphere at different pressures and high temperatures was studied. The temperature investigated was the fusion temperature of 373K. At this temperature, the two methyl groups on N exchanged quickly and almost merged into one broad peak on the hydrogen spectrum. As the pressure gradually increased, the two methyl peaks on N gradually separated. Figure 8 It can be seen that the increase in pressure can lead to the hindrance of amide bond rotation and slow down the exchange of methyl groups.

Claims

1. A real-time voltage transformer for a nuclear magnetic resonance spectrometer, comprising a four-way module, wherein the connection relationship of the openings of the four-way module is as follows: Opening A is connected to the air-driven air booster pump; Opening B is connected to the pressure sensor and the exhaust valve; Opening C is connected to the nuclear magnetic tube through a weak magnetic tube and an adapter; A plug is provided inside one end of the cross-way opposite to the opening C, an inner magnet and a titanium alloy extension rod are provided inside the plug, an outer magnet is coaxially provided outside the plug, and the rotation of the outer magnet is controlled by a rotating stepping motor; One end of the titanium alloy extension rod is connected to a stirring rod, and the other end of the stirring rod extends into the nuclear magnetic tube; A lifting stepping motor is provided on the four-way module to control the up and down movement of the stirring rod; The real-time voltage transformation device also includes a lifting bracket, The lifting bracket comprises an aluminum profile bracket, a linear guide rail, a hand crank and a slide block; The slide block that can be lifted and lowered along the linear guide rail is fixed on the aluminum profile bracket, and the four-way module is fixed on the slide block; After the steel wire rope passes through the fixed pulley arranged on the top of the aluminum profile bracket, one end of the steel wire rope is connected to the sliding block, and the other end is connected to the hand crank, and the lifting and lowering of the steel wire rope is controlled by the hand crank.

2. The real-time voltage transformation device according to claim 1, characterized in that: The air-driven air booster pump is connected to the air inlet needle valve on the cross-way through a high-pressure hose; The inner diameter of the gas inlet in the four-way pipe connected to the high-pressure hose is 0.1-0.5 mm.

3. The real-time voltage transformation device according to claim 1 or 2, characterized in that: The opening A is also connected to a cleaning port; The opening B is also connected to an exhaust port.

4. The real-time voltage transformation device according to claim 1 or 2, characterized in that: The weak magnetic tube is a 316L weak magnetic stainless steel tube, which is arranged at the open C end of the cross-way; A high-pressure resistant sealing ring is provided at the connection between the 316L weak magnetic stainless steel tube and the nuclear magnetic tube.

5. The real-time voltage transformation device according to claim 1 or 2, characterized in that: The stirring rod is a polytetrafluoroethylene rod; The stirring rod is connected to the titanium alloy extension rod via a titanium alloy adapter joint; The material of the nuclear magnetic tube is zirconium oxide.

6. A high-voltage in-situ detection device for a nuclear magnetic resonance spectrometer, comprising a nuclear magnetic resonance spectrometer and the real-time voltage transformation device according to any one of claims 1 to 5; The real-time voltage transformer is fixed on the upper part of the nuclear magnetic resonance spectrometer, and the nuclear magnetic tube extends into the interior of the nuclear magnetic resonance spectrometer.

7. Use of the high-pressure in-situ detection device according to claim 6 in high-pressure in-situ NMR detection of samples.

8. The use according to claim 7, characterized in that: The high-pressure in-situ NMR detection includes characterization of material synthesis in complex fluids, evidence of the existence of conformational isomers, and real-time observation of some gas inclusion reactions.

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