Highly polarized object, method for producing same, high polarization method, and high polarization device

Abstract

A highly polarized object 100 includes first molecules 102, second molecules 104, and a polarization source 108. At least one of the first molecules and the second molecules are target molecules, for which the atomic nucleus spin is to be highly polarized by a triplet DNP. Among the first molecules and the second molecules, the molecules that are not target molecules are coformer molecules. The first molecules and the second molecules constitute a crystal structure of a co-crystal including a coupling part 106 that is a supramolecular shynthon having a hexagonal structure. The polarization source is arranged at a position where part of the crystal structure is replaced.

Description

Highly polarized object, its manufacturing method, highly polarized method, and highly polarized device

[0001] The present invention relates to a highly polarized object in which atomic nuclear spins are highly polarized, as well as a manufacturing method, a highly polarizing method, and a highly polarizing device for the same. This application claims priority to Japanese Application No. 2023-201230, filed November 29, 2023. The entire contents of the Japanese application are incorporated herein by reference.

[0002] NMR (Nuclear Magnetic Resonance) spectroscopy and MRI (Magnetic Resonance Imaging) are indispensable tools in chemical analysis and medical diagnosis, respectively. Dynamic nuclear polarization (hereinafter referred to as DNP), which is one method that can improve the sensitivity of these spectroscopy and MRI, has been actively researched in recent years.

[0003] In NMR spectroscopy and MRI, atomic nuclear spins (hereinafter simply referred to as nuclear spins) in a substance are precisely controlled under a strong static magnetic field, and a wealth of molecular-level information is read out from electromagnetic signals (NMR signals) modulated by interactions between nuclear spins. The sensitivity of NMR signals is proportional to the polarization rate, but even under strong magnetic fields of several to several tens of teslas applied by superconducting magnets, the Zeeman energy of nuclear spins is very low. This Zeeman energy is five orders of magnitude smaller than the thermal energy at room temperature, so the degree to which the direction of nuclear spins is biased toward the static magnetic field (polarization rate) is 10 －５ ~10 －６ The polarization rate of nuclear spins is extremely low (about 0.001% to 0.0001%), and the proportion of resonating nuclear spins that contribute to the detection signal is extremely small. Therefore, in order to improve the sensitivity of NMR spectroscopy and MRI, it is important to increase the polarization rate of nuclear spins. In this specification, "high polarization" means a state in which the polarization rate of atomic nuclear spins exceeds the polarization rate at room temperature.

[0004] By performing DNP at extremely low temperatures near 1 K and in a high magnetic field exceeding 3 T, it is possible to achieve a nuclear spin polarization rate of several percent to several tens of percent. However, the equipment required for this purpose is expensive and large. In response to this problem, Patent Document 1 and Non-Patent Document 1 below disclose a method for performing triplet DNP by mixing benzoic acid doped with pentacene as a polarization source with target molecules to form a eutectic, which is then used to perform triplet DNP. This method allows for high polarization at room temperature without cooling the sample to extremely low temperatures.

[0005] International Publication No. 2019 / 039477

[0006] Akinori Kagawa, et al., “Dynamic Nuclear Polarization using Photoexcited Triplet Electron Spins in Eutectic Mixtures”, Phys. Chem. A, 2018, 122, 50, 9670-9675

[0007] For polarization to diffuse within a solid to which a polarization source is added, the longitudinal relaxation time must be sufficiently long (e.g., 10 to 100 seconds or more). Furthermore, highly polarizing various molecules used in active pharmaceutical ingredients would be useful for pharmaceutical development. However, pentacene, the polarization source, is poorly soluble, limiting the types of molecules that can be added.

[0008] Therefore, an object of the present invention is to provide a highly polarized object including a molecule to be highly polarized by triplet DNP, to which a polarization source can be added and which can realize a sufficient longitudinal relaxation time, as well as a method for producing the same, a method for highly polarizing the same, and an apparatus for highly polarizing the same.

[0009] (1) A first aspect of the present invention provides a highly polarized object comprising a first molecule, a second molecule, and a polarization source, wherein at least one of the first and second molecules is a target molecule whose nuclear spins are to be highly polarized by triplet DNP; the non-target molecule of the first and second molecules is a coformer molecule; the first and second molecules constitute a cocrystal crystal structure containing a supramolecular synthon having a hexagonal structure; and the polarization source is positioned so as to replace a portion of the crystal structure. This allows the polarization source to be incorporated into the crystal structure. Therefore, the nuclear spins of the target molecule can be highly polarized by triplet DNP. Furthermore, a sufficient longitudinal relaxation time can be achieved.

[0010] (2) In the above (1), the supramolecular synthon can include an acid-acid, acid-amide, or amide-amide supramolecular synthon, which allows a polarization source such as pentacene to be easily incorporated into the crystal structure, and allows the nuclear spins of the target molecule to be efficiently highly polarized by triplet DNP.

[0011] (3) In the above (1), the target molecule may be benzoic acid, salicylic acid, 3-nitrobenzoic acid, pentafluorobenzoic acid, nicotinamide, isonicotinamide, 4-methylbenzamide, salicylamide, benzamide, picolinamide, aspirin, or ethenzamide. This allows the nuclear spins of these molecules to be highly polarized by triplet DNP.

[0012] (4) In the above (3), the supramolecular synthon may be an acid-amide supramolecular synthon, and the combination of the first molecule and the second molecule may be salicylic acid and benzamide, salicylic acid and picolinamide, or 3-nitrobenzoic acid and benzamide. By performing triplet DNP on the highly polarized object, the nuclear spins of each molecule can be highly polarized. For example, a high polarization rate of 0.015% to 0.146% can be achieved.

[0013] (5) In the above (3), the combination of the first molecule and the second molecule may be salicylic acid and salicylamide. By performing triplet DNP on the highly polarized object, the nuclear spins of each molecule can be highly polarized. For example, a high polarization rate of 0.349% can be achieved.

[0014] (6) In the above (3), the combination of the first molecule and the second molecule may be a combination of benzoic acid and 4-methylbenzamide, salicylamide, or pentafluorobenzoic acid, thereby performing triplet DNP on the highly polarized object to highly polarize the nuclear spins of each molecule.

[0015] (7) In the above (3), the target molecule may be aspirin and the coformer molecule may be pentafluorobenzoic acid, or the target molecule may be ethenzamide and the coformer molecule may be pentafluorobenzoic acid, 3-nitrobenzoic acid, or salicylic acid. By performing triplet DNP on the highly polarized object, the nuclear spins of aspirin or ethenzamide can be highly polarized.

[0016] (8) A second aspect of the present invention provides a highly polarized object comprising first and second coformer molecules, a target molecule whose nuclear spins are to be highly polarized by triplet DNP, and a polarization source. The first and second coformer molecules form a co-crystal crystalline structure containing a supramolecular synthon having a hexagonal structure. The target molecule is bonded to the first and second coformer molecules or to the first coformer molecule by intermolecular forces. The polarization source is positioned at a position where it replaces a part of the crystalline structure. This allows the polarization source to be incorporated into the crystalline structure. Therefore, the nuclear spins of the target molecule can be highly polarized by triplet DNP. Furthermore, a sufficient longitudinal relaxation time can be achieved.

[0017] (9) In the above (8), the supramolecular synthon can include an acid-acid, acid-amide, or amide-amide supramolecular synthon, which allows a polarization source to be easily incorporated into the crystal structure, and allows the nuclear spins of the target molecule to be efficiently highly polarized by triplet DNP.

[0018] (10) In the above (8), the target molecule may be picolinic acid, acetic acid, succinic acid, sebacic acid, dodecanedioic acid, pyruvic acid, formic acid, urea, nicotinamide, or isonicotinamide, thereby allowing the nuclear spins of these molecules to be highly polarized by triplet DNP.

[0019] (11) In the above (10), the supramolecular synthon may be an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule may be isonicotinamide, and the target molecule may be benzoic acid, salicylic acid, or picolinic acid. Thus, by performing triplet DNP on a highly polarized object, the nuclear spins of the target molecule can be highly polarized.

[0020] (12) In the above (10), the supramolecular synthon may be an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule may be nicotinamide, and the target molecule may be succinic acid, sebacic acid, or dodecanedioic acid. By performing triplet DNP on highly polarized objects, the nuclear spins of these molecules can be highly polarized. For example, high polarization rates of 0.0079% for succinic acid and nicotinamide and 0.00405% for sebacic acid and nicotinamide can be achieved.

[0021] (13) In the above (10), the supramolecular synthon may be an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule may be isonicotinamide, and the target molecule may be sebacic acid, dodecanedioic acid, or acetic acid. This allows the nuclear spins of sebacic acid, dodecanedioic acid, or acetic acid to be highly polarized by triplet DNP. For example, a high polarization rate of 0.00685% can be achieved for dodecanedioic acid.

[0022] (14) In the above (10), the supramolecular synthon may be an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule may be nicotinamide, and the target molecule may be urea. By performing triplet DNP on a highly polarized object, a high polarization rate of 0.0135% can be achieved for urea.

[0023] (15) In the above (1), the first molecule is a coformer molecule, the second molecule is a target molecule, the first molecule and the second molecule form an acid-amide supramolecular synthon, and two first molecules and two second molecules further form an (acid-amide)-(acid-amide) supramolecular synthon. The polarization source may be located in the cocrystal at a position that replaces two first molecules that form a portion of the (acid-amide)-(acid-amide) supramolecular synthon among the multiple (acid-amide)-(acid-amide) supramolecular synthons. This allows the polarization source to be incorporated into the crystal structure. Therefore, the nuclear spins of the target molecule can be highly polarized by triplet DNP. Furthermore, a sufficient longitudinal relaxation time can be achieved.

[0024] (16) In the above (15), the coformer molecule may be picolinamide or 4-methylbenzamide, and the target molecule may be pyruvic acid. By performing triplet DNP on a highly polarized object, the nuclear spins of pyruvic acid can be highly polarized.

[0025] (17) In the above (15), the coformer molecule may be picolinamide and the target molecule may be mandelic acid, whereby the nuclear spins of the mandelic acid can be highly polarized by performing triplet DNP on the highly polarized object.

[0026] (18) In the above (1), the cocrystal may further include a third molecule, the first and third molecules being coformer molecules, the second molecule being a target molecule, the first and second molecules forming an acid-amide supramolecular synthon, the first and third molecules forming an acid-amide supramolecular synthon, and two first molecules, one second molecule, and one molecule forming a further (acid-amide)-(acid-amide) supramolecular synthon, and the polarization source may be located in the cocrystal at a position substituting the first and third molecules forming some of the (acid-amide)-(acid-amide) supramolecular synthons. This allows the polarization source to be incorporated into the crystal structure. Therefore, the nuclear spins of the target molecules can be highly polarized by triplet DNP, and sufficient longitudinal relaxation times can be achieved.

[0027] (19) In the above (18), the first molecule may be picolinamide, the third molecule may be salicylic acid, and the target molecule may be pyruvic acid, acetic acid, or formic acid. By performing triplet DNP on the highly polarized object, the nuclear spins of pyruvic acid, acetic acid, or formic acid can be highly polarized.

[0028] (20) In the above (18), the first molecule may be picolinamide, the third molecule may be 4-chlorosalicylic acid, and the target molecule may be pyruvic acid. In this way, by performing triplet DNP on the highly polarized object, the nuclear spins of pyruvic acid can be highly polarized.

[0029] (21) In the above (18), the first molecule may be 4-methylbenzamide, the third molecule may be benzoic acid, and the target molecule may be pyruvic acid. Thus, by performing triplet DNP on the highly polarized object, the nuclear spins of pyruvic acid can be highly polarized.

[0030] (22) A third aspect of the present invention provides a method for producing a highly polarized object, comprising: a step of generating a molten mixture containing a first molecule, a second molecule, and a polarization source by heating; and a step of cooling the molten mixture, wherein at least one of the first molecule and the second molecule is a target molecule whose nuclear spins are to be highly polarized by triplet DNP; and the non-target molecule of the first molecule and the second molecule is a coformer molecule. Through the cooling step, the first molecule and the second molecule form a cocrystal crystal structure containing a supramolecular synthon having a hexagonal structure, and the polarization source is positioned to replace a portion of the crystal structure. This allows the polarization source to be incorporated into the crystal structure. Therefore, the nuclear spins of the target molecule can be highly polarized by triplet DNP. Furthermore, a sufficient longitudinal relaxation time can be achieved.

[0031] (23) A fourth aspect of the present invention provides a method for producing a highly polarized object, comprising: generating a molten mixture containing first and second coformer molecules; a target molecule whose nuclear spins are to be highly polarized by triplet DNP; and a polarization source; and cooling the molten mixture, wherein the first and second coformer molecules form a co-crystal crystal structure containing a supramolecular synthon having a hexagonal structure by the cooling step; the target molecule is bound to the first and second coformer molecules or to the first coformer molecule by intermolecular forces; and the polarization source is positioned at a position that replaces a part of the crystal structure. This allows the polarization source to be incorporated into the crystal structure. Therefore, the nuclear spins of the target molecule can be highly polarized by triplet DNP. Furthermore, a sufficient longitudinal relaxation time can be achieved.

[0032] (24) A method for highly polarizing nuclear spins according to a fifth aspect of the present invention includes a light irradiation step of irradiating light onto a sample placed in a space in which a uniform static magnetic field is formed, and a microwave irradiation step of irradiating microwaves onto the sample while a sweeping magnetic field is being applied to the sample, the sample including the highly polarized object described in (1) above, and further includes a dissolving step of dissolving target molecules in the sample to produce a solution after repeating the light irradiation step and the microwave irradiation step, thereby producing a solution of target molecules whose nuclear spins are highly polarized.

[0033] (25) A sixth aspect of the present invention provides an apparatus for highly polarizing nuclear spins in a sample by triplet DNP, the apparatus comprising: a magnetic field generating unit for generating a static magnetic field; a light irradiating unit for irradiating light onto a sample placed in the region where the static magnetic field is formed; a microwave irradiating unit for irradiating microwave pulses onto the sample placed in the region where the static magnetic field is formed; and a control unit for controlling the light irradiating unit and the microwave irradiating unit, the sample including the highly polarized object described in (1) above; and the control unit controls the light irradiating unit and the microwave irradiating unit to highly polarize the nuclear spins in the highly polarized object by triplet DNP, thereby enabling the nuclear spins of target molecules to be highly polarized.

[0034] The present invention provides a highly polarized object containing a molecule to be highly polarized by triplet DNP, which can be added with a polarization source and achieves a sufficient longitudinal relaxation time, as well as a manufacturing method, a highly polarizing method, and a highly polarizing device. That is, a target molecule with highly polarized nuclear spins can be realized in a room temperature environment without cooling the sample containing the target molecule. For example, molecules used for active pharmaceutical ingredients, ligands, metabolic molecular probes, etc. can be used as target molecules. Using an aqueous solution containing a target molecule with highly polarized nuclear spins in an NMR spectrometer or MRI device enables ultrasensitive chemical analysis or ultrasensitive metabolic imaging.

[0035] Furthermore, a compact, low-cost nuclear spin hyperpolarizer capable of highly polarizing nuclear spins at room temperature, which can be used for chemical analysis or medical applications, can be realized. By attaching this hyperpolarizer to a commercially available NMR spectrometer or MRI device, ultrasensitive chemical analysis or ultrasensitive metabolic imaging becomes possible.

[0036] FIG. 1 is a schematic diagram showing a highly polarized object (cocrystal) according to a first embodiment of the present invention. FIG. 2 is a schematic diagram showing the configuration of components of the cocrystal shown in FIG. 1. FIG. 3 is a chemical formula showing an acid-acid supramolecular synthon. FIG. 4 is a chemical formula showing an amide-amide supramolecular synthon. FIG. 5 is a chemical formula showing an acid-amide supramolecular synthon. FIG. 6 is a chemical formula showing pentacene. FIG. 7 is a chemical formula showing a pentacene derivative. FIG. 8 is a diagram showing the chemical formula of benzoic acid. FIG. 9 is a diagram showing the chemical formula of 4-methylbenzamide. FIG. 10 is a diagram showing the chemical formula of d5-benzoic acid. FIG. 11 is a diagram showing the chemical formula of salicylic amide. FIG. 12 is a diagram showing the chemical formula of salicylic acid. FIG. 13 is a diagram showing the chemical formula of benzamide. FIG. 14 is a diagram showing the chemical formula of picolinamide. FIG. 15 is a diagram showing the chemical formula of 3-nitrobenzoic acid. FIG. 16 is a diagram showing the chemical formula of pentafluorobenzoic acid. FIG. 17 is a diagram showing the chemical formula of aspirin. FIG. 18 is a diagram showing the chemical formula of ethenzamide. FIG. 19 is a flowchart showing a method for producing the highly polarized object shown in FIG. 1. FIG. 20 is a block diagram showing a schematic configuration of an apparatus for highly polarizing atomic nuclear spins. FIG. 21 is a schematic diagram showing the periphery of the cavity shown in FIG. 20. FIG. 22 is a flowchart showing a method for highly polarizing atomic nuclear spins using the apparatus for highly polarizing atomic nuclear spins shown in FIG. 20. FIG. 23 is a timing chart showing the sequences of laser light irradiation, microwave irradiation, and sweep magnetic field application used in the apparatus shown in FIG. 20. FIG. 24 is a schematic diagram showing the configuration of components of a co-crystal constituting a highly polarized object according to a second embodiment of the present invention. FIG. 25 is a diagram showing the chemical formula of isonicotinamide. FIG. 26 is a diagram showing the chemical formula of picolinic acid. FIG. 27 is a diagram showing the chemical formula of nicotinamide. Fig. 28 is a diagram showing the chemical formula of succinic acid. Fig. 29 is a diagram showing the chemical formula of sebacic acid. Fig. 30 is a diagram showing the chemical formula of dodecanedioic acid. Fig. 31 is a diagram showing the chemical formula of acetic acid. Fig. 32 is a diagram showing the chemical formula of urea. Fig. 33 is a schematic diagram showing the configuration of components of a co-crystal that constitutes a highly polarized object according to a third embodiment of the present invention.FIG. 34 is a chemical formula showing the (acid-amide)-(acid-amide) supramolecular synthon. FIG. 35 is a diagram showing the chemical formula of pyruvic acid. FIG. 36 is a diagram showing the chemical formula of mandelic acid. FIG. 37 is a schematic diagram showing the configuration of components of a cocrystal constituting a highly polarized object according to a modified example of the present invention. FIG. 38 is a diagram showing the chemical formula of 4-chlorosalicylic acid. FIG. 39 is a diagram showing the chemical formula of formic acid. FIG. 40 is a graph of an NMR signal showing a highly polarized state of a cocrystal containing benzoic acid and 4-methylbenzamide. FIG. 41 is a graph of an NMR signal showing a highly polarized state of a cocrystal containing salicylic acid and benzamide. FIG. 42 is a graph of an NMR signal showing a highly polarized state of a cocrystal containing salicylic acid and picolinamide. FIG. 43 is a graph of an NMR signal showing a highly polarized state of a cocrystal containing salicylic acid and salicylamide. Figure 44 is a graph of the NMR signal showing a highly polarized state of a co-crystal containing 3-nitrobenzoic acid and benzamide. Figure 45 is a graph of the NMR signal showing a highly polarized state of a co-crystal containing nicotinamide and succinic acid. Figure 46 is a graph of the NMR signal showing a highly polarized state of a co-crystal containing nicotinamide and sebacic acid. Figure 47 is a graph of the NMR signal showing a highly polarized state of a co-crystal containing isonicotinamide and dodecanedioic acid. Figure 48 is a graph of the NMR signal showing a highly polarized state of a co-crystal containing urea and nicotinamide. Figure 49 is a graph of the NMR signal showing a highly polarized state of a co-crystal containing pyruvic acid, salicylic acid, and picolinamide. Figure 50 is a graph of the NMR signal showing a highly polarized state of a co-crystal containing pyruvic acid and picolinamide. FIG. 51 is a graph of the NMR signal showing the highly polarized state of a co-crystal containing pyruvic acid and 4-methylbenzamide.

[0037] In the following embodiments, the same components are denoted by the same reference numerals, and their names and functions are also the same, so detailed descriptions thereof will not be repeated.

[0038] First Embodiment Referring to FIG. 1 , a highly polarized object 100 according to a first embodiment of the present invention includes a first molecule 102, a second molecule 104, and a polarization source 108. The first molecule 102 and the second molecule 104 are bonded to each other to form a bonded portion 106, thereby constituting a cocrystal. At least one of the first molecule 102 and the second molecule 104 is a molecule (hereinafter referred to as a target molecule) whose nuclear spins are to be highly polarized by triplet DNP. Of the first molecule 102 and the second molecule 104, the one that is not a target molecule is a molecule (hereinafter referred to as a coformer molecule) that forms a cocrystal together with the target molecule. One first molecule 102 and one second molecule 104 form one component that constitutes the cocrystal. Both a cocrystal and a eutectic are composed of multiple types of non-ionized molecules. While eutectics maintain the crystalline phase of each type of molecule, cocrystals are composed of multiple types of molecules existing within the same crystal lattice.

[0039] The polarization sources 108 are arranged in a dispersed manner at positions in the crystal structure of the co-crystal of the first molecule 102 and the second molecule 104 so as to replace parts (i.e., components) of the co-crystal. The polarization sources 108 are molecules with electrons in a photoexcited triplet state, and are the first molecules to be highly polarized in triplet DNP. The highly polarized nuclear spins of the polarization sources 108 are transferred to the first molecule 102 and the second molecule 104, thereby achieving highly polarized nuclear spins of the target molecules.

[0040] To form a co-crystal of the first molecule 102 and the second molecule 104, for example, powdered first molecule 102 and second molecule 104 are mixed, melted by heating, and then cooled. As a result, as shown in FIG. 2 , the group 112 of the first molecule 102 and the group 114 of the second molecule 104 bond to form a bond 106, thereby forming a co-crystal component 110. The groups 112 and 114 are groups (specifically, functional groups) in organic chemistry. The bond 106 is formed by a bond other than a covalent bond, such as a hydrogen bond, and the co-crystal component 110 is a supramolecule. The highly polarized object 100 is formed by replacing a portion of the multiple co-crystal components 110 with a polarization source 108. In FIG. 2 , the polygons (i.e., hexagons) included in the first molecule 102 and the second molecule 104 represent aromatic rings, such as benzene rings. 2 represent atoms or atomic groups (such as nitrogen atoms, hydroxyl groups, or carboxylic acids) that form non-covalent bonds such as hydrogen bonds. Dashed lines between the white circles represent non-covalent bonds such as hydrogen bonds.

[0041] The bond 106 is a basic framework of non-covalent bonds such as hydrogen bonds formed in the supramolecule (cocrystal component 110), and is a supramolecular synthon. Each of the groups 112 and 114 is, for example, a carboxyl group (—COOH) or an amide group (—CO—NH ２ ) For example, when the groups 112 and 114 are both carboxyl groups, an acid-acid supramolecular synthon (homodimer) shown in FIG. 3 is formed as the bond 106. In FIG. 3, dashed lines represent non-covalent bonds (the same applies below). When the groups 112 and 114 are both amide groups, an amide-amide supramolecular synthon (homodimer) is formed as the bond 106, as shown in FIG. 4. When one of the groups 112 and 114 is a carboxyl group and the other is an amide group, an acid-amide supramolecular synthon (heterodimer) shown in FIG. 5 is formed as the bond 106. The basic shape of all of these supramolecular synthons is hexagonal.

[0042] The polarization source 108 can be pentacene or a pentacene derivative, as shown in FIG. 6 . A pentacene derivative refers to a molecule represented by the chemical formula shown in FIG. 7 . In the chemical formula shown in FIG. 7 , multiple Rs each represent a hydrocarbon group having 1 to 20 carbon atoms and may independently contain a hydrogen atom (H), a deuterium atom (D), or at least one atom selected from the group consisting of oxygen, nitrogen, sulfur, and silicon. At least one of the multiple Rs is a hydrocarbon group having 1 to 20 carbon atoms and may contain at least one atom selected from the group consisting of oxygen, nitrogen, sulfur, and silicon. In addition, derivatives in the chemical formula shown in FIG. 7 include those in which a portion of the aromatic ring is replaced with a nitrogen atom or the like (e.g., 6,13-diazapentacene). The polarization source 108 is not limited to pentacene derivatives; acene-based molecules can also be used. Acene refers to a hydrocarbon having a structure in which multiple benzene rings are linearly fused. Acene molecules are naphthalene (molecular formula C １０ H ８ ), anthracene (molecular formula C １４ H １０ ), tetracene (molecular formula C １８ H １２ ), pentacene (molecular formula C ２２ H １４ ), hexacene (molecular formula C ２６ H １６ ) and heptacene (molecular formula C ３０ H １８ ), and derivatives thereof.

[0043] Specific examples of combinations of the first molecule 102 and the second molecule 104 are given below. For example, as a combination of the first molecule 102 and the second molecule 104, benzoic acid (molecular formula C ７ H ６ O ２ ) and 4-methylbenzamide (molecular formula C ８ H ９ As shown in FIG. 10, benzoic acid can be deuterated (i.e., hydrogen atoms ( １ H) is a deuterium atom ( ２ d) substituted by H) ５-benzoic acid (molecular formula C ７ D ５ O ２ 10, D represents a deuterium atom. The combination of the first molecule 102 and the second molecule 104 may be benzoic acid (see FIGS. 8 and 10) and salicylamide (molecular formula C ７ H ７ NO ２ ) may also be used.

[0044] As a combination of the first molecule 102 and the second molecule 104, salicylic acid (molecular formula C ７ H ６ O ３ ) and benzamide (molecular formula C ７ H ７ The combination of the first molecule 102 and the second molecule 104 is a combination of salicylic acid (see FIG. 12) and picolinamide (molecular formula C ６ H ６ N ２ The combination of the first molecule 102 and the second molecule 104 may be 3-nitrobenzoic acid (molecular formula C ７ H ５ NO ４ ) and benzamide (see FIG. 13). In these cases, an acid-amide supramolecular synthon is formed as the bond 106.

[0045] As a combination of the first molecule 102 and the second molecule 104, salicylic acid (see FIG. 12) and salicylamide (see FIG. 11) can be used.

[0046] The combination of the first molecule 102 and the second molecule 104 is benzoic acid (see FIGS. 8 and 10) and pentafluorobenzoic acid (molecular formula C ７ F ５ O ２ H).

[0047] As a combination of the first molecule 102 and the second molecule 104, aspirin (i.e., acetylsalicylic acid) (molecular formula C ９ H ８ O ４) and pentafluorobenzoic acid (see FIG. 16 ). Also, as a combination of the first molecule 102 and the second molecule 104, ethenzamide (molecular formula C ９ H １１ NO ２ ) and pentafluorobenzoic acid (see FIG. 16) can be used. The combination of the first molecule 102 and the second molecule 104 may be ethenzamide (see FIG. 18) and 3-nitrobenzoic acid (see FIG. 15). The combination of the first molecule 102 and the second molecule 104 may be ethenzamide (see FIG. 18) and salicylic acid (see FIG. 12). Aspirin and ethenzamide are used as drugs or ligands and are target molecules for triplet DNP.

[0048] (Method for Manufacturing a Highly Polarized Object) A method for manufacturing a highly polarized object 100 will be specifically described with reference to FIG. 19 . In step 200, first molecules and second molecules are mixed. For example, the first molecules and second molecules (at a molar ratio of, for example, 1:1) are placed in a mortar, mechanically crushed into powder, and then mixed. Note that the mixing ratio of the first molecules and the second molecules is not limited to a molar ratio of 1:1, and any appropriate molar ratio can be determined.

[0049] In step 202, the mixture produced in step 200 is heated to melt it. For example, the mixture is heated to a temperature in the range of 150°C to 200°C.

[0050] In step 204, a polarization source (see FIGS. 6 and 7) is added to the molten mixture. For example, a small amount (e.g., about 0.1 mol % or less of the total mixture) of a powder polarization source is added to the molten mixture and stirred.

[0051] In step 206, the molten mixture to which the polarization source has been added is rapidly cooled using a cooling material such as liquid nitrogen or ice water. For example, the container containing the molten mixture to which the polarization source has been added is brought into contact with (e.g., immersed in) liquid nitrogen or ice water. This results in the formation of a highly polarized object 100, as shown in FIG. 1 , in a co-crystal formed by first molecules 102 and second molecules 104, with some components replaced by the polarization source 108. During melting, bonds between molecules (e.g., hydrogen bonds or π-π interactions) are broken, and the component molecules move in the liquid. During cooling, bonds are formed and broken, resulting in the formation of a stable crystal structure. During this process, the polarization source can easily penetrate into the positions where the co-crystal components would normally be located. The cooling material may be a cryogen (e.g., dry ice and methanol, or ice and salt) or liquid water.

[0052] The first and second molecules in the above combination are mixed and melted, and then a pentacene derivative (see FIGS. 6 and 7) is added and quenched to produce a highly polarized object 100 in which a portion of the cocrystal is replaced by a polarization source 108, as shown in FIG. 1 . Both the first and second molecules contain aromatic rings, and the supramolecular synthon formed by the groups of the first and second molecules has a hexagonal shape. Pentacene (see FIG. 6) or a pentacene derivative (see FIG. 7) used as the polarization source has five benzene rings. Therefore, some of the components of the cocrystal formed by the first molecule 102 and the second molecule 104 can be easily replaced by the polarization source, pentacene (see FIG. 6) or a pentacene derivative (see FIG. 7). That is, during the cocrystal formation process, the polarization source can easily be inserted into the position where the cocrystal components would normally be located. As a result, as described below, the nuclear spins of the highly polarized object 100 (i.e., either the first or second molecule) can be highly polarized by triplet DNP.

[0053] In the above description, a polarization source is added to a mixture of the first and second molecules after heating and melting the mixture. However, this is not limiting. A mixture of the first and second molecules with a polarization source added may also be heated and melted. In either case, a molten mixture containing the first and second molecules and the polarization source is produced, and then the molten mixture is rapidly cooled.

[0054] The fact that the highly polarized object 100 is a cocrystal can be confirmed by, for example, powder X-ray diffraction or solid-state NMR, etc. For example, the formation of a cocrystal can be confirmed by comparing an XRD (X-ray diffraction) pattern obtained by X-ray diffracting the synthesized highly polarized object 100 with a known XRD pattern.

[0055] (High-Polarization Apparatus) To highly polarize the nuclear spins of the highly polarized object 100 shown in Fig. 1, triplet DNP is performed using a high-polarization apparatus. Referring to Fig. 20, the high-polarization apparatus 300 includes a main magnetic field generating unit 302, a cavity 304, a laser light source 308, a microwave source 310, and an amplifier unit 312. The cavity 304 is disposed between the magnetic poles of the main magnetic field generating unit 302. The laser light source 308 generates laser light to be irradiated onto a sample 306 disposed within the cavity 304. The microwave source 310 generates microwaves. The amplifier unit 312 amplifies the microwaves output from the microwave source 310 and irradiates the microwaves onto the sample 306.

[0056] Furthermore, the nuclear spin high polarization device 300 includes a sweep magnetic field generating unit 314, a power supply unit 316, an NMR signal detecting unit 318, an NMR analyzing unit 320, and a control unit 322. The sweep magnetic field generating unit 314 is disposed within the cavity 304. The power supply unit 316 supplies current to the sweep magnetic field generating unit 314. As a result, the sweep magnetic field generating unit 314 generates a sweep magnetic field to be irradiated onto the sample 306, as will be described later. The NMR signal detecting unit 318 detects the NMR signal. The NMR analyzing unit 320 analyzes the NMR signal detected by the NMR signal detecting unit 318. The control unit 322 controls each of these units.

[0057] An example of the configuration of the cavity 304 and its surroundings is shown in Figure 21. In Figure 21, the cavity 304 and the waveguide 334 are shown cut away.

[0058] Referring to FIG. 20 , the main magnetic field generating unit 302 is an electromagnet that receives current from a power supply (not shown) and generates a static magnetic field with uniform direction and strength in a region where the sample 306 is placed. The sample 306 is the highly polarized object 100 shown in FIG. 1 . In FIG. 20 , two main magnetic field generating units 302 are provided, each of which is an electromagnet with two opposing magnetic poles (e.g., opposing Helmholtz coils). Because the polarization rate of photoexcited triplet electron spins is not proportional to temperature and magnetic field strength, it is not necessary to use a magnet that generates a high magnetic field, such as a superconducting magnet, for the main magnetic field generating unit 302. Therefore, a relatively inexpensive resistive magnet can be used as the main magnetic field generating unit 302.

[0059] The main magnetic field generating unit 302 may be an electromagnet without opposing magnetic poles, for example, an electromagnet using an air-core solenoid coil. When a solenoid coil is used, the cavity 304 is disposed inside the space surrounded by the solenoid coil. The main magnetic field generating unit 302 may also be a permanent magnet.

[0060] The cavity 304 functions as a resonator for microwaves supplied from the microwave source 310 via the amplifier section 312 and the waveguide 334 (see FIG. 21). The cavity 304 is formed of an electric conductor that is not a magnetic material. The cavity 304 is formed so that its resonant frequency is equal to the frequency of the microwaves output from the microwave source 310. The junction between the cavity 304 and the waveguide 334 is preferably coupled by a known iris to suppress reflection of the supplied microwaves.

[0061] The laser light source 308 shown in Fig. 20 is controlled by the control unit 322 to output laser light of a predetermined wavelength at a predetermined timing for a predetermined period of time. The output laser light is transmitted to the cavity 304 via an optical transmission unit 330 (see Fig. 21). A light collecting unit 332 is provided within the cavity 304, and collects the laser light emitted from the optical transmission unit 330 and irradiates the sample 306 with the collected light. For example, a flash lamp pumped dye laser can be used as the laser light source 308. The optical transmission unit 330 is, for example, an optical fiber, and the light collecting unit 332 is, for example, a lens.

[0062] The microwave source 310 is controlled by the control unit 322 to generate and output microwaves of a predetermined frequency for a predetermined period at a predetermined timing. A microwave generator can be used as the microwave source 310. In DNP, to supply microwave pulses to the sample, a pulse wave is generated by a switch (not shown) from the microwaves continuously output from the microwave source 310.

[0063] The power supply unit 316 supplies current to the sweep magnetic field generator 314 under the control of the control unit 322. The sweep magnetic field is used to excite a set of spins with a range of resonant frequencies. The magnetic field strength is changed, i.e., the magnetic field is swept, by temporally varying the value of the current flowing through the sweep magnetic field generator 314. The strength of the sweep magnetic field is sufficiently smaller than that of the main magnetic field. The direction of the sweep magnetic field is the same as or opposite to the main magnetic field. FIG. 21 illustrates a case in which a saddle coil is used as the sweep magnetic field generator 314. FIG. 21 shows two of the four parallel straight lines constituting the sweep magnetic field generator 314 (i.e., the saddle coil). In FIG. 21, the main magnetic field direction is perpendicular to the paper surface. Therefore, by supplying currents in opposite directions to the two straight lines (as well as to the remaining two straight lines not shown), a sweep magnetic field in the same direction or opposite to the main magnetic field can be generated in the region where the sample 306 is placed.

[0064] The NMR signal detection unit 318 is a coil for detecting NMR signals (e.g., FID (Free Induction Decay) signals) due to spins precessing around the main magnetic field. The coils constituting the NMR signal detection unit 318 can detect magnetic field changes in a direction perpendicular to the main magnetic field. Under the control of the control unit 322, the NMR analysis unit 320 measures NMR signals using the NMR signal detection unit 318 and performs NMR analysis. The resonant frequency of the NMR signal detection unit 318 is adjusted by an adjustment component (not shown), such as a capacitor, so that it becomes equal to the NMR frequency corresponding to the strength of the main magnetic field.

[0065] 21 , the sample holder 336 holds the sample 306. The sample holder 336 is formed of a material that transmits the supplied laser light and microwaves, such as a glass tube. The sample holder 336 and the NMR signal detection unit 318 are preferably held so as to be displaceable relative to the cavity 304. That is, it is preferable to provide a mechanism that can move the sample holder 336 to the outside of the cavity 304, allow the sample 306 to be introduced into the sample holder 336, and position the sample holder 336 with the sample 306 introduced at a predetermined position within the cavity 304. Similarly, it is preferable to provide a mechanism that can move the NMR signal detection unit 318 to the outside of the cavity 304 and position the NMR signal detection unit 318 at a predetermined position within the cavity 304 (around the sample 306).

[0066] The solvent supply unit 338 holds a solvent (solution) 350 for dissolving the solid sample 306. In Figure 21, a dropper is shown as an example of the solvent supply unit 338. The solvent 350 held by the solvent supply unit 338 is dropped onto the sample 306 to generate a solution containing the sample 306.

[0067] (High Polarization of Nuclear Spins) Hereinafter, with reference to FIG. 22, a method for highly polarizing the nuclear spins of a sample 306 (i.e., the highly polarized object 100 shown in FIG. 1) using the high polarization device 300 shown in FIG. 20 will be described.

[0068] In step 400, a sample 306 is prepared as a highly polarized object. Specifically, the highly polarized object 100 shown in FIG. 1 is produced by the manufacturing method shown in FIG. 19. The NMR signal detection unit 318 is set in the sample holder 336 containing the sample 306, and the sample holder 336 is placed in the cavity 304 so that the sample 306 is located at the center of the cavity 304. Here, it is assumed that the polarization source included in the highly polarized object 100 is pentacene (see FIG. 6).

[0069] The amount of the sample 306 (i.e., the highly polarized object 100) can be determined depending on the capability (output power) of the laser light source used. If a laser light source capable of outputting a powerful laser beam is used, a larger amount of the sample 306 can be highly polarized.

[0070] In step 402, with the main magnetic field generating unit 302 energized to generate a static magnetic field, the control unit 322 controls the laser light source 308, the microwave source 310, and the sweep magnetic field generating unit 314 to perform triplet DNP on the sample 306. Specifically, with reference to Fig. 23 , while the magnetic field is swept by the sweep magnetic field generating unit 314, the laser light source 308 irradiates the sample 306 with laser light during a period T1, and then the microwave source 310 irradiates the sample 306 with microwaves during the following period T2. Note that the magnetic field may or may not be swept during the period T1.

[0071] In step 404, the control unit 322 determines whether or not triplet DNP is to be terminated. If it is determined that triplet DNP is to be terminated, control proceeds to step 406. Otherwise, after the period T3 has elapsed, control returns to step 402. As a result, the sequence shown in FIG. 23 is repeated with the period T3 being one cycle.

[0072] The end of triplet DNP can be determined, for example, by setting a predetermined number of executions N and determining whether laser light irradiation and microwave irradiation have been performed N times. Alternatively, an execution time ΔT can be set in advance, and the end of triplet DNP can be determined by determining whether time ΔT has elapsed since the first laser light irradiation and microwave irradiation.

[0073] The highly polarized object 100, which is the sample 306, includes pentacene (see FIG. 6) as a polarization source. When laser light is irradiated onto the pentacene, electrons of the pentacene are excited by the laser light and move to the ground state S ０ to the excited singlet state S １ After that, the electrons mainly emit light such as stimulated emission and transition to the ground state. In addition, the electrons also transition to an excited triplet state (T ３ ) due to the selection rule in this quantum process, the electron spin distribution is highly biased at about 70%. The excited triplet state transitions to the ground state S after about 100 microseconds. ０ However, before that, microwaves are irradiated to perform pulsed DNP. When pentacene is in a magnetic field, the excited triplet state level separates into three levels (denoted as |+1>, |0>, and |-1> in order of increasing energy level). Therefore, when microwaves with a frequency corresponding to the energy difference between the |-1> level and the |0> level, or the energy difference between the |0> level and the |+1> level are irradiated, the high polarization of the electron spin is transferred to the hydrogen nuclei ( １ The hydrogen nuclear spins of the pentacene are highly polarized, and the highly polarized spins are transferred to the hydrogen nuclear spins of the first molecule 102 and the second molecule 104 that make up the highly polarized object 100. Therefore, by repeating step 402 as described above, the hydrogen nuclear spins of the entire sample 306 can be highly polarized.

[0074] If it is determined that triplet DNP is to be completed, then in step 406, the control unit 322 stops the laser light source 308, the microwave source 310, and the power supply unit 316.

[0075] In step 408, the solvent 350 held by the solvent supply unit 338 is dropped onto the sample 306 to dissolve the first molecules 102 in the sample 306. This generates an aqueous solution in which the first molecules 102 in the sample are dissolved. By using a solvent that does not dissolve pentacene, the remaining undissolved pentacene can be easily removed using a filter or the like. As the solvent, for example, an aqueous solution containing a sodium carbonate solution, an alcohol containing methanol, or a solvent containing chloroform can be used.

[0076] As a result of the above, an aqueous solution containing a target molecule (either the first molecule 102 or the second molecule 104) with highly polarized proton nuclear spins can be produced. By using this aqueous solution in an NMR spectrometer and an MRI device, ultra-high sensitivity NMR spectroscopy and ultra-high sensitivity MRI can be achieved. If the target molecule is harmless to the human body and is metabolized in the body, the aqueous solution containing the target molecule, which does not contain pentacene, which is harmful to the human body, can be safely used in MRI examinations on the human body.

[0077] In the above, the case where the end of triplet DNP is determined using a preset number of repetitions N or a preset execution time ΔT has been described, but this is not limiting. For example, while repeatedly executing triplet DNP, NMR signals may be observed by the NMR signal detection unit 318, and when an NMR signal of a predetermined intensity is observed, it may be determined that triplet DNP is to be ended.

[0078] In the above description, the liquid that dissolves the target molecules is dropped onto the highly polarized object 100, but the present invention is not limited to this. For example, the liquid that dissolves the target molecules may be sprayed onto the highly polarized object 100 using a spray or the like. Alternatively, the highly polarized object 100 may be placed in the liquid that dissolves the target molecules that is contained in a container.

[0079] Although the above description has been given of the case where pentacene is added as a polarization source, the present invention is not limited to this, and pentacene derivatives other than pentacene (see FIG. 7) may also be used.

[0080] Second Embodiment In the above, a case where a target molecule to be highly polarized constitutes a supramolecular synthon has been described, but the present invention is not limited to this. In the second embodiment, a supramolecular synthon is formed by a molecule other than the target molecule.

[0081] A highly polarized object according to a second embodiment of the present invention is a cocrystal, similar to the highly polarized object 100 shown in FIG. 1 , with some of its components replaced by a polarization source. Referring to FIG. 24 , a cocrystal component 120, which is a component of the highly polarized object according to the second embodiment, is composed of a first molecule 122, a second molecule 124, and third molecules 136 and 138. At least one of the third molecules 136 and 138 is a target molecule whose nuclear spins are highly polarized by triplet DNP. Molecules other than the target molecule are coformer molecules that form a cocrystal together with the target molecule. The first molecule 122 has a group 132, and the second molecule 124 has a group 134. The groups 132 and 134 are groups (specifically, functional groups) in organic chemistry. The groups 132 and 134 are bonded to form a bond 126. The white circles shown in FIG. 24 represent atoms or atomic groups (such as nitrogen atoms, hydroxyl groups, or carboxylic acids) that form non-covalent bonds (see dashed lines) such as hydrogen bonds.

[0082] The bond 126 is a supramolecular synthon, similar to the bond 106 (see FIG. 2). Each of the groups 132 and 134 is, for example, a carboxyl group or an amide group, similar to the first molecule 102 and the second molecule 104 (see FIG. 2). Therefore, an acid-acid supramolecular synthon (see FIG. 3), an amide-amide supramolecular synthon (see FIG. 4), or an acid-amide supramolecular synthon (see FIG. 5) is formed as the bond 126.

[0083] The third molecules 136 and 138 are bonded to the first molecule 122 and the second molecule 124, respectively, by non-covalent bonds such as hydrogen bonds. In Figure 24, the polygons (i.e., hexagons) included in the first molecule 122 and the second molecule 124 represent aromatic rings such as benzene rings. Each of the third molecules 136 and 138 may or may not include an aromatic ring.

[0084] 24 shows a state in which third molecule 136 is non-covalently bound to the aromatic ring portion of first molecule 122, and third molecule 138 is non-covalently bound to the aromatic ring portion of second molecule 124. Third molecule 136 may be non-covalently bound to group 132 rather than to the aromatic ring portion of first molecule 122, and third molecule 138 may be non-covalently bound to group 134 rather than to the aromatic ring portion of second molecule 124. Each of third molecules 136 and 138 may be non-covalently bound to first molecule 122 and second molecule 124. Third molecules 136 and 138 may be molecules with the same name or different names. Also, one of third molecules 136 and 138 may be absent. 24, the third molecules 136 and 138 are shown separated, but the third molecules 136 and 138 may be bound by a non-covalent bond, or the third molecules 136 and 138 may form a supramolecular synthon. In addition, the molecule that is not the target molecule among the third molecules 136 and 138 may be a molecule having the same name as the first molecule 122 or the second molecule 124.

[0085] The polarization source is, for example, pentacene (see FIG. 6 ) or a pentacene derivative (see FIG. 7 ). The polarization sources are distributed in the crystal structure of the cocrystal, which is the highly polarized object, at positions where they substitute for some components of the cocrystal, i.e., the first molecules 122 and 124.

[0086] Specific examples of combinations of the first molecule 122, the second molecule 124, and the third molecules 136 and 138 are given below. For example, the first molecule 122 and the second molecule 124 may be isonicotinamide (molecular formula C ６ H ６ N ２ 0), and the third molecules 136 and 138 can be benzoic acid (see FIGS. 8 and 10). The first molecule 122 and the second molecule 124 can be isonicotinamide (see FIG. 25), and the third molecules 136 and 138 can be salicylic acid (see FIG. 12). The first molecule 122 and the second molecule 124 can be isonicotinamide (see FIG. 25), and the third molecules 136 and 138 can be picolinic acid (molecular formula C ６ H ５ NO ２In these cases, an amide-amide supramolecular synthon is formed as the bond 126.

[0087] The first molecule 122 and the second molecule 124 are nicotinamide (molecular formula C ６ H ６ N ２ 28. The third molecule 136 and 138 are succinic acid (molecular formula C ４ H ６ O ４ The first molecule 122 and the second molecule 124 can be nicotinamide (see FIG. 27), and the third molecules 136 and 138 can be sebacic acid (molecular formula C １０ H １８ O ４ ) may be used. The first molecule 122 and the second molecule 124 may be nicotinamide (see FIG. 27), and the third molecules 136 and 138 may be dodecanedioic acid (molecular formula C １２ H ２２ O ４ In these cases, the first molecule 122 and the second molecule 124 form an amide-amide supramolecular synthon as the bond 126.

[0088] The first molecule 122 and the second molecule 124 can be isonicotinamide (see FIG. 25), and the third molecules 136 and 138 can be sebacic acid (see FIG. 29). The first molecule 122 and the second molecule 124 can be isonicotinamide (see FIG. 25), and the third molecules 136 and 138 can be dodecanedioic acid (see FIG. 30). Alternatively, the first molecule 122 and the second molecule 124 can be isonicotinamide (see FIG. 25), and the third molecules 136 and 138 can be acetic acid (molecular formula C ) shown in FIG. 31. ２ H ４ O ２ In these cases, the first molecule 122 and the second molecule 124 form an amide-amide supramolecular synthon as the bond 126.

[0089] The first molecule 122 and the second molecule 124 are nicotinamide (see FIG. 27), and the third molecules 136 and 138 are urea (molecular formula CH) shown in FIG. ４N ２ The first molecule 122 and the second molecule 124 form an amide-amide supramolecular synthon as a bond 126. Urea, which is a target molecule, is used as a probe for MRI.

[0090] The highly polarized object according to the second embodiment can be manufactured in the same manner as the highly polarized object 100 (see FIG. 1). That is, a mixture of first, second, and third molecules is heated to melt, a polarization source (see FIGS. 6 and 7) is added to the melted mixture, stirred, and then rapidly cooled. Alternatively, a polarization source (see FIGS. 6 and 7) may be added to a mixture of the first, second, and third molecules, the mixture is heated to melt, and then rapidly cooled. This allows for the production of a highly polarized object in which a portion of the cocrystal is replaced by the polarization source, similar to the highly polarized object 100. To highly polarize the nuclear spins of the highly polarized object according to the second embodiment, triplet DNP may be performed (see FIG. 23) using the above-described high polarization device (see FIG. 20).

[0091] Both the first molecule 122 and the second molecule 124 contain aromatic rings, and the supramolecular synthon formed by the groups of the first molecule 122 and the second molecule 124 has a hexagonal shape. The pentacene (see FIG. 6) or pentacene derivative (see FIG. 7) used as the polarization source has five benzene rings. Therefore, some of the components constituting the cocrystal (i.e., the first molecule 122 and the second molecule 124) can be easily replaced by the polarization source, pentacene (see FIG. 6) or pentacene derivative (see FIG. 7). That is, during the cocrystal formation process, the polarization source can easily be inserted into the position where the cocrystal components would originally be located. As a result, the nuclear spins of the target molecule, which is the object of high polarization by triplet DNP, can be highly polarized.

[0092] Third Embodiment In the second embodiment, a case was described in which polarization sources were distributed in a cocrystal at positions substituting two coformer molecules (i.e., the first molecule 122 and the second molecule 124 in FIG. 24 ) that form a supramolecular synthon, but the present invention is not limited to this. In the third embodiment, polarization sources are distributed in positions substituting two coformer molecules in a cocrystal composed of components including a supramolecular synthon formed by four molecules including a target molecule and coformer molecules.

[0093] The highly polarized object according to the third embodiment is a co-crystal, similar to the highly polarized object 100 shown in FIG. 1 , with some of its components replaced by a polarization source. Referring to FIG. 33 , a co-crystal component 150 of the highly polarized object according to the third embodiment is composed of first molecules 152a and 152b and second molecules 154a and 154b. The second molecules 154a and 154b are target molecules whose nuclear spins are highly polarized by triplet DNP. The first molecules 152a and 152b are co-former molecules that form a co-crystal with the target molecules. The first molecules 152a and 152b have groups 162a and 162b, respectively. The second molecules 154a and 154b have groups 164a and 164b, respectively. For multiple elements (molecules and groups) with the same name, different letters are added to the end of the reference numeral to distinguish each element, and multiple elements are represented collectively without adding a letter. Groups 162a, 162b, 164a, and 164b are groups (specifically, functional groups) in organic chemistry. Groups 162a, 162b, 164a, and 164b are bonded to form bond 156. The open circles in Figure 33 represent atoms or atomic groups (such as nitrogen atoms, hydroxyl groups, or carboxylic acids) that form non-covalent bonds (see dashed lines) such as hydrogen bonds.

[0094] The bond 156 is a supramolecular synthon. Each of the groups 162a, 162b, 164a, and 164b is a carboxyl group or an amide group. For example, the groups 162a and 164a form an acid-amide supramolecular synthon (see FIG. 5), and the groups 162b and 164b form the same supramolecular synthon as the groups 162a and 164a. Furthermore, these groups form an (acid-amide)-(acid-amide) supramolecular synthon as the bond 156. The chemical formula of the (acid-amide)-(acid-amide) supramolecular synthon is shown in FIG. 34.

[0095] The polarization source may be, for example, pentacene (see FIG. 6) or a pentacene derivative (see FIG. 7). The polarization sources are distributed throughout the co-crystal at positions substituting additivity sites 166 (i.e., first molecules 152a and 152b) that are part of the co-crystal component 150.

[0096] For example, the first molecule 152 is picolinamide (see FIG. 14 ), and the second molecule 154 is pyruvic acid (molecular formula C ) shown in FIG. ３ H ４ O ３ The first molecule 152 may be 4-methylbenzamide (see FIG. 9), and the second molecule 154 may be pyruvic acid (see FIG. 35). The target molecule, pyruvic acid, is used as a probe for MRI.

[0097] The first molecule 152 is mandelic acid (molecular formula C ８ H ８ O ３ ), and the second molecule 154 may be picolinamide (see FIG. 14).

[0098] (Modification) In the above, the four molecules constituting the cocrystal component include two types of molecules, but the present invention is not limited to this. The four molecules constituting the cocrystal component may include three types of molecules.

[0099] The highly polarized object according to the modified example is a co-crystal similar to the highly polarized object 100 shown in FIG. 1 , with some of its components replaced by a polarization source. Referring to FIG. 37 , a co-crystal component 170 of the highly polarized object according to the modified example is composed of first molecules 172a and 172b, a second molecule 174, and a third molecule 176. The second molecule 174 is a target molecule whose nuclear spins are highly polarized by triplet DNP. The first molecules 172a and 172b and the third molecule 176 are co-former molecules that form a co-crystal with the target molecule. The first molecules 172a and 172b have groups 182a and 182b, respectively. The second molecule 174 and the third molecule 176 have groups 184 and 186, respectively. The groups 182a, 182b, 184, and 186 are groups (specifically, functional groups) in organic chemistry. Groups 182a, 182b, 184, and 186 are bonded to form bond 178. The open circles shown in Figure 37 represent atoms or atomic groups (such as nitrogen atoms, hydroxyl groups, or carboxylic acids) that form non-covalent bonds (see dashed lines) such as hydrogen bonds.

[0100] Bond 178 is a supramolecular synthon. Groups 182a, 182b, 184, and 186 are each a carboxyl group or an amide group. For example, groups 182a and 186 form an acid-amide supramolecular synthon (see FIG. 5), and groups 184 and 182b also form an acid-amide supramolecular synthon. Furthermore, these groups form an (acid-amide)-(acid-amide) supramolecular synthon (see FIG. 34) as bond 178.

[0101] The polarization source may be, for example, pentacene (see FIG. 6) or a pentacene derivative (see FIG. 7). The polarization sources are distributed throughout the co-crystal at positions substituting additivity sites 188 (i.e., first molecule 172a and third molecule 176) that are part of the co-crystal component 170.

[0102] For example, the first molecule 172 is picolinamide (see FIG. 14), the third molecule 176 is salicylic acid (see FIG. 12), and the second molecule 174 (target molecule) is pyruvic acid (see FIG. 35). The first molecule 172 may be picolinamide, the third molecule 176 may be 4-chlorosalicylic acid shown in FIG. 38, and the second molecule 174 (target molecule) may be pyruvic acid. Alternatively, the first molecule 172 may be 4-methylbenzamide (see FIG. 9), the third molecule 176 may be benzoic acid (see FIGS. 8 and 10), and the second molecule 174 (target molecule) may be pyruvic acid. The pyruvic acid target molecule is used as an MRI probe.

[0103] When the first molecule 172 is picolinamide (see FIG. 14) and the third molecule 176 is salicylic acid (see FIG. 12), the second molecule 174 (target molecule) is acetic acid (see FIG. 31) or formic acid (molecular formula CH) shown in FIG. ２ O ２ The target molecule, acetic acid, is used as a probe for MRI.

[0104] The highly polarized object according to the third embodiment and its modification can be manufactured in the same manner as the highly polarized object 100 (see FIG. 1 ). That is, a mixture of the first and second molecules, or the first to third molecules, is heated to melt, a polarization source (see FIGS. 6 and 7 ) is added to the melted mixture, stirred, and then rapidly cooled. Alternatively, a polarization source (see FIGS. 6 and 7 ) may be added to a mixture of the first and second molecules, or the first to third molecules, and the mixture may be heated to melt and then rapidly cooled. This allows for the production of a highly polarized object in which a portion of the cocrystal is replaced by the polarization source, similar to the highly polarized object 100. To highly polarize the nuclear spins of the highly polarized object according to the third embodiment and its modification, triplet DNP may be performed (see FIG. 23 ) using the above-described high polarization device (see FIG. 20 ).

[0105] Some of the components constituting the cocrystal, i.e., the first molecules 152 a and 152 b in the third embodiment, and the first molecule 172 a and the third molecule 176 in the modified example, can be easily replaced with pentacene (see FIG. 6 ) or a pentacene derivative (see FIG. 7 ), which is a polarization source. That is, during the process of forming the cocrystal, the polarization source can easily be inserted into the position where the cocrystal components would originally be located. As a result, the nuclear spins of the target molecule, which is the object to be highly polarized by triplet DNP, can be highly polarized.

[0106] The effectiveness of the present invention will be demonstrated by the following experimental results: A highly polarized object was produced as described above, and triplet DNP was carried out using the highly polarized apparatus shown in FIG.

[0107] (Highly Polarized Target 1) As described above in the first embodiment, a highly polarized target was synthesized as a co-crystal formed from benzoic acid (see FIG. 8) and 4-methylbenzamide (see FIG. 9) in a 1:1 molar ratio, with 0.06 mol % pentacene added to the entire mixture. The synthesized highly polarized target was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 40. The triplet DNP was performed for 90 seconds with a repetition frequency of 50 Hz for the sequence of laser light irradiation, microwave irradiation, and sweep magnetic field application shown in FIG. 23. In FIG. 40, the signal indicated by symbol A represents the NMR signal observed after triplet DNP, and the signal indicated by symbol B represents the NMR signal observed without triplet DNP. Comparing these, it can be seen that the synthesized highly polarized target was highly polarized by performing triplet DNP. A polarization rate P of 0.041% was achieved. The amplification factor relative to the thermal equilibrium state (see symbol B) was 310 times. The longitudinal relaxation time was 140 seconds, which was a sufficiently long time.

[0108] (Highly Polarized Object 2) As described in the first embodiment, a highly polarized object was synthesized as a cocrystal formed from salicylic acid (see FIG. 12) and benzamide (see FIG. 13) in a 1:1 molar ratio, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 41. As described above, triplet DNP was performed for 420 seconds with a sequence repetition frequency of 50 Hz. In FIG. 41, the symbols A and B have the same meanings as in FIG. 40. Comparing these results, it can be seen that the synthesized highly polarized object was highly polarized by triplet DNP. A polarization rate P of 0.146% was achieved. The amplification factor relative to the thermal equilibrium state (see symbol B) was 1095 times. The longitudinal relaxation time was 411.6 seconds, which was sufficiently long.

[0109] (Highly Polarized Object 3) As described in the first embodiment, a highly polarized object was synthesized as a cocrystal formed from salicylic acid (see FIG. 12) and picolinamide (see FIG. 14) in a 1:1 molar ratio, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 42. As described above, triplet DNP was performed for 420 seconds with a sequence repetition frequency of 50 Hz. In FIG. 42, the symbols A and B have the same meanings as in FIG. 40. Comparing these results, it can be seen that the synthesized highly polarized object was highly polarized by triplet DNP. A polarization ratio P of 0.093% was achieved. The amplification factor relative to the thermal equilibrium state was 700 times. The longitudinal relaxation time was 180 seconds, which was sufficiently long.

[0110] (Highly Polarized Object 4) As described in the first embodiment, a highly polarized object was synthesized as a cocrystal formed from salicylic acid (see FIG. 12) and salicylamide (see FIG. 11) in a 1:1 molar ratio, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 43. As described above, triplet DNP was performed for 420 seconds with a sequence repetition frequency of 50 Hz. In FIG. 43, the symbols A and B have the same meanings as in FIG. 40. Comparing these results, it can be seen that the synthesized highly polarized object was highly polarized by triplet DNP. A polarization ratio P of 0.349% was achieved. The amplification factor relative to the thermal equilibrium state was 2621 times. The longitudinal relaxation time was 303.9 seconds, which was a sufficiently long time.

[0111] (Highly Polarized Object 5) As described above in the first embodiment, a highly polarized object was synthesized as a cocrystal formed from 3-nitrobenzoic acid (see FIG. 15) and benzamide (see FIG. 13) in a 1:1 molar ratio, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 44. As described above, triplet DNP was performed for 420 seconds with a sequence repetition frequency of 50 Hz. In FIG. 44, the symbols A and B have the same meanings as in FIG. 40. Comparing these results, it can be seen that the synthesized highly polarized object was highly polarized by triplet DNP. A polarization rate P of 0.015% was achieved. The amplification factor relative to the thermal equilibrium state was 115 times. The longitudinal relaxation time was 43.5 seconds, which was a sufficiently long time.

[0112] (Highly Polarized Object 6) As described above in the second embodiment, a highly polarized object was synthesized as a cocrystal formed from nicotinamide (see FIG. 27) and succinic acid (see FIG. 28) in a molar ratio of 2:1, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 45. The repetition frequency of the sequence shown in FIG. 23 was set to 100 Hz, and triplet DNP was performed for 90 seconds. In FIG. 45, the symbols A and B have the same meanings as in FIG. 40. Comparing these, it can be seen that the synthesized highly polarized object was highly polarized by performing triplet DNP. A polarization rate P of 0.0079% was achieved. The amplification factor relative to the thermal equilibrium state was 60 times.

[0113] (Highly Polarized Object 7) As described above in the second embodiment, a highly polarized object was synthesized as a cocrystal formed from nicotinamide (see FIG. 27) and sebacic acid (see FIG. 29) in a molar ratio of 2:1, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 46. The repetition frequency of the sequence shown in FIG. 23 was set to 200 Hz, and triplet DNP was performed for 90 seconds. In FIG. 46, the symbols A and B have the same meanings as in FIG. 40. Comparing these, it can be seen that the synthesized highly polarized object was highly polarized by performing triplet DNP. A polarization rate P of 0.00405% was achieved. The amplification factor relative to the thermal equilibrium state was 30 times.

[0114] (Highly Polarized Object 8) As described above in the second embodiment, a highly polarized object was synthesized as a cocrystal formed from isonicotinamide (see FIG. 16) and dodecanedioic acid (see FIG. 30) in a molar ratio of 2:1, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 47. The repetition frequency of the sequence shown in FIG. 23 was set to 100 Hz, and triplet DNP was performed for 120 seconds. In FIG. 47, the symbols A and B have the same meanings as in FIG. 40. Comparing these, it can be seen that the synthesized highly polarized object was highly polarized by performing triplet DNP. A polarization rate P of 0.00685% was achieved. The amplification factor relative to the thermal equilibrium state was 51.4 times. The longitudinal relaxation time was 26.1 seconds, which was sufficiently long.

[0115] (Highly Polarized Object 9) As described above in the second embodiment, a highly polarized object was synthesized as a cocrystal formed from urea (see FIG. 32) and nicotinamide (see FIG. 27) in a molar ratio of 1:2, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 48. As above, triplet DNP was performed for 120 seconds with a sequence repetition frequency of 100 Hz. In FIG. 48, the symbols A and B have the same meanings as in FIG. 40. Comparing these, it can be seen that the synthesized highly polarized object was highly polarized by performing triplet DNP. A polarization rate P of 0.0135% was achieved. The amplification factor relative to the thermal equilibrium state was 101 times. The longitudinal relaxation time was 10 seconds, which was sufficiently long.

[0116] (Highly Polarized Object 10) As described above in the modified example, a highly polarized object was synthesized as a cocrystal formed from pyruvic acid (see FIG. 35), salicylic acid (see FIG. 12), and picolinamide (see FIG. 14) in a molar ratio of 1:1:2, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 49. The triplet DNP was performed for 90 seconds with a repetition frequency of 200 Hz, as in the sequence shown in FIG. 23. In FIG. 49, the symbols A and B have the same meanings as in FIG. 40. Comparing these, it can be seen that the synthesized highly polarized object was highly polarized by triplet DNP. A polarization rate P of 0.024% was achieved. The amplification factor relative to the thermal equilibrium state was 200 times. The longitudinal relaxation time was 67.8 seconds, which was sufficiently long.

[0117] (Highly Polarized Object 11) As described above in the third embodiment, a highly polarized object was synthesized as a cocrystal formed from pyruvic acid (see FIG. 35) and picolinamide (see FIG. 14) in a 1:1 stoichiometric ratio, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 50. The triplet DNP was performed for 90 seconds with a repetition frequency of 50 Hz, as in the sequence shown in FIG. 23. In FIG. 50, the symbols A and B have the same meanings as in FIG. 40. Comparing these, it can be seen that the synthesized highly polarized object was highly polarized by performing triplet DNP. A polarization rate P of 0.076% was achieved. The amplification factor relative to the thermal equilibrium state was 57 times.

[0118] (Highly Polarized Object 12) As described above in the third embodiment, a highly polarized object was synthesized as a cocrystal formed from pyruvic acid (see FIG. 35) and 4-methylbenzamide (see FIG. 9) in a 1:1 stoichiometric ratio, with 0.06 mol% pentacene added to the entire mixture. The synthesized highly polarized object was highly polarized by triplet DNP, and the observed NMR signal (a signal obtained by Fourier transform of the FID signal) is shown in FIG. 51. The triplet DNP was performed for 90 seconds with a repetition frequency of 200 Hz, as in the sequence shown in FIG. 23. In FIG. 51, the symbols A and B have the same meanings as in FIG. 40. Comparing these results, it can be seen that the synthesized highly polarized object was highly polarized by performing triplet DNP. A polarization rate P of 0.00487% was achieved. The amplification factor relative to the thermal equilibrium state was 36.6 times. The longitudinal relaxation time was 30.5 seconds, which was sufficiently long.

[0119] Although the present invention has been described above by explaining the embodiments, the above-described embodiments are merely examples, and the present invention is not limited to only the above-described embodiments. The scope of the present disclosure is defined by the claims in the scope of the claims, taking into consideration the description of the detailed description of the invention, and includes all modifications within the meaning and scope equivalent to the wordings described therein.

[0120] According to the present invention, it is possible to provide a highly polarized object including a molecule to be highly polarized by triplet DNP, to which a polarization source can be added and which can realize a sufficient longitudinal relaxation time, as well as a manufacturing method, a highly polarizing method, and a highly polarizing device for the same, and it is possible to realize a target molecule whose nuclear spins are highly polarized in a room temperature environment without cooling a sample containing the target molecule.

[0121] 100 Highly polarized object 102, 122, 152a, 152b, 172a, 172b First molecule 104, 124, 154a, 154b, 174 Second molecule 106, 126, 156, 178 Bonding portion 108 Polarization source 110, 120, 150, 170 Co-crystal component 112, 114, 132, 134, 162a, 162b, 164a, 164b, 182a, 182b, 184, 186 Group 136, 138, 176 Third molecule 166, 188 Additive site 300 Highly polarized device 302 Main magnetic field generating portion 304 Cavity 306 Sample 308 Laser light source 310 Microwave source 312 Amplification section 314 Sweep magnetic field generation section 316 Power supply section 318 NMR signal detection section 320 NMR analysis section 322 Control section 330 Light transmission section 332 Light collection section 334 Waveguide 336 Sample storage section 338 Solvent supply section 350 Solvent

Claims

1. An object to be highly polarized comprising a first molecule, a second molecule, and a polarization source, wherein at least one of the first molecule and the second molecule is a target molecule whose nuclear spin is to be highly polarized by triplet DNP, wherein the molecule which is not the target molecule of the first molecule and the second molecule is a coformer molecule, wherein the first molecule and the second molecule constitute a crystal structure of a cocrystal containing a supramolecular synthon having a hexagonal structure, and wherein the polarization source is positioned so as to replace a part of the crystal structure.

2. The highly polarized object according to claim 1, wherein the supramolecular synthon comprises an acid-acid, acid-amide, or amide-amide supramolecular synthon.

3. The highly polarized object of claim 1, wherein the target molecule is benzoic acid, salicylic acid, 3-nitrobenzoic acid, pentafluorobenzoic acid, isonicotinamide, 4-methylbenzamide, salicylamide, benzamide, picolinamide, aspirin, or ethenzamide.

4. The highly polarized object according to claim 3, wherein the supramolecular synthon is an acid-amide supramolecular synthon, and the combination of the first molecule and the second molecule is salicylic acid and benzamide, salicylic acid and picolinamide, or 3-nitrobenzoic acid and benzamide.

5. The highly polarized object of claim 3, wherein the combination of the first molecule and the second molecule is salicylic acid and salicylamide.

6. The highly polarized object according to claim 3, wherein the combination of the first molecule and the second molecule is a combination of benzoic acid and 4-methylbenzamide, salicylamide or pentafluorobenzoic acid.

7. The highly polarized object of claim 3, wherein the target molecule is aspirin and the coformer molecule is pentafluorobenzoic acid, or the target molecule is ethenzamide and the coformer molecule is pentafluorobenzoic acid, 3-nitrobenzoic acid, or salicylic acid.

8. An object to be highly polarized, comprising first and second coformer molecules, a target molecule whose nuclear spins are to be highly polarized by triplet DNP, and a polarization source, wherein the first and second coformer molecules form a co-crystal crystal structure including a supramolecular synthon having a hexagonal structure, the target molecule is bonded to the first and second coformer molecules or to the first coformer molecule by intermolecular forces, and the polarization source is positioned at a position to replace a part of the crystal structure.

9. The highly polarized object according to claim 8, wherein the supramolecular synthon comprises an acid-acid, acid-amide, or amide-amide supramolecular synthon.

10. The highly polarized object of claim 8, wherein the target molecule is benzoic acid, salicylic acid, picolinic acid, acetic acid, succinic acid, sebacic acid, dodecanedioic acid, pyruvic acid, formic acid, or urea.

11. The highly polarized object described in claim 10, wherein the supramolecular synthon is an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule are isonicotinamide, and the target molecule is benzoic acid, salicylic acid, or picolinic acid.

12. The highly polarized object described in claim 10, wherein the supramolecular synthon is an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule are nicotinamide, and the target molecule is succinic acid, sebacic acid, or dodecanedioic acid.

13. The highly polarized object described in claim 10, wherein the supramolecular synthon is an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule are isonicotinamide, and the target molecule is sebacic acid, dodecanedioic acid, or acetic acid.

14. The highly polarized object according to claim 10, wherein the supramolecular synthon is an amide-amide supramolecular synthon, the first coformer molecule and the second coformer molecule are nicotinamide, and the target molecule is urea.

15. The highly polarized object according to claim 1, wherein the first molecule is the coformer molecule, the second molecule is the target molecule, an acid-amide supramolecular synthon is formed by the first molecule and the second molecule, and an (acid-amide)-(acid-amide) supramolecular synthon is further formed by two of the first molecules and two of the second molecules, and the polarization source is arranged in the cocrystal at a position to replace two of the first molecules that form a part of the (acid-amide)-(acid-amide) supramolecular synthon of the multiple (acid-amide)-(acid-amide) supramolecular synthons.

16. The highly polarized object of claim 15, wherein the coformer molecule is picolinamide or 4-methylbenzamide, and the target molecule is pyruvic acid.

17. The highly polarized object of claim 15, wherein the coformer molecule is picolinamide and the target molecule is mandelic acid.

18. The highly polarized object according to claim 1, further comprising a third molecule, wherein the first molecule and the third molecule are the coformer molecule, the second molecule is the target molecule, an acid-amide supramolecular synthon is formed by the first molecule and the third molecule, an acid-amide supramolecular synthon is formed by the first molecule and the third molecule, and a further (acid-amide)-(acid-amide) supramolecular synthon is formed by two of the first molecules, one of the second molecule and one of the third molecule, and the polarization source is arranged at a position in the cocrystal to replace the first molecule and the third molecule that form a part of the (acid-amide) supramolecular synthon of the multiple (acid-amide)-(acid-amide) supramolecular synthons.

19. The highly polarized object of claim 18, wherein the first molecule is picolinamide; the third molecule is salicylic acid; and the target molecule is pyruvic acid, acetic acid, or formic acid.

20. The highly polarized object of claim 18, wherein the first molecule is picolinamide, the third molecule is 4-chlorosalicylic acid, and the target molecule is pyruvic acid.

21. The highly polarized object of claim 18, wherein the first molecule is 4-methylbenzamide, the third molecule is benzoic acid, and the target molecule is pyruvic acid.

22. A method for producing a highly polarized object, comprising: a step of generating a molten mixture containing a first molecule, a second molecule, and a polarization source by heating; and a cooling step of cooling the molten mixture, wherein at least one of the first molecule and the second molecule is a target molecule whose nuclear spin is to be highly polarized by triplet DNP, and of the first molecule and the second molecule, the molecule that is not the target molecule is a coformer molecule, and by the cooling step, the first molecule and the second molecule form a crystal structure of a cocrystal containing a supramolecular synthon having a hexagonal structure, and the polarization source is positioned at a position that replaces a part of the crystal structure.

23. A method for producing a highly polarized object, comprising: a step of generating a molten mixture containing first and second coformer molecules, a target molecule whose nuclear spins are to be highly polarized by triplet DNP, and a polarization source; and a cooling step of cooling the molten mixture, wherein by the cooling step, the first and second coformer molecules form a crystal structure of a co-crystal containing a supramolecular synthon having a hexagonal structure, the target molecule is bonded to the first and second coformer molecules, or to the first coformer molecule, by intermolecular forces, and the polarization source is positioned at a position that replaces a part of the crystal structure.

24. A method for highly polarizing atomic nuclear spins, comprising: a light irradiation step of irradiating light onto a sample placed in a space in which a uniform static magnetic field is formed; and a microwave irradiation step of irradiating microwaves onto the sample subsequent to the light irradiation step while a sweeping magnetic field is being applied to the sample, wherein the sample comprises a highly polarized object as described in claim 1; and after repeating the light irradiation step and the microwave irradiation step, further comprising a dissolution step of dissolving target molecules in the sample to generate a solution.

25. An apparatus for highly polarizing nuclear spins in a sample by triplet DNP, comprising: a magnetic field forming unit that forms a static magnetic field; a light irradiating unit that irradiates light onto the sample placed in the area where the static magnetic field is formed; a microwave irradiating unit that irradiates microwave pulses onto the sample placed in the area where the static magnetic field is formed; and a control unit that controls the light irradiating unit and the microwave irradiating unit, wherein the sample includes a highly polarized object as described in claim 1, and the control unit controls the light irradiating unit and the microwave irradiating unit to highly polarize the nuclear spins in the highly polarized object by triplet DNP. An apparatus for highly polarizing nuclear spins.

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