Method for changing the inclusion ability of a host molecule, method for producing an inclusion complex, inclusion complex, single crystal, complex, and kit for capturing a target molecule

Abstract

To provide a method for changing the clathrate ability of a host molecule, a method for synthesizing a clathrate, a clathrate, a single crystal, a complex body, and a kit for capturing a target molecule.SOLUTION: The present invention relates to a method for changing the clathrate ability of a host molecule, which molecule has an internal space and one or more openings, and the charge of which molecule is positive, negative, or uncharged in its entirety, the method comprising a step of having a specific lid-like molecule, the host molecule, and a molecule to be included in the internal space of the host molecule coexist in the same system. The invention also relates to a method for synthesizing a clathrate, a clathrate, a single crystal, a complex body, and a kit for capturing a target molecule, in association with the method.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a method for changing the inclusion ability of a host molecule, a method for producing an inclusion complex, an inclusion complex, a single crystal, a complex, and a kit for capturing a target molecule. [Background technology]

[0002] Molecules that have an internal space and have the property of encapsulating molecules or ions within that space (hereinafter, these molecules are referred to as "host molecules," and the molecules or ions encapsulated within the internal space of the host molecule are sometimes referred to as "guest molecules") are known. In particular, some host molecules selectively encapsulate guest molecules within their internal space, and various methods for using them have been proposed.

[0003] For example, Patent Document 1 describes a method for determining the molecular structure of a guest molecule by obtaining a single crystal of an inclusion complex formed by including a guest molecule in the internal space of a polynuclear metal complex, and then performing crystal structure analysis using the obtained single crystal as a sample.

[0004] Furthermore, Patent Document 2 describes a technique for selectively separating alcohols using a polymer complex that is capable of selectively incorporating guest molecules. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2018 / 159692 [Patent Document 2] International Publication No. 2007 / 102594 Summary of the Invention [Problem to be solved by the invention]

[0006] As described above, the selective inclusion ability of host molecules has the advantage of enabling the preparation of samples for crystal structure analysis and separation and purification treatments, but it has also sometimes led to the problem that the target molecule cannot be incorporated into the internal space of the host molecule, making it impossible to form the desired inclusion complex. In such cases, it has been necessary to prepare a different host molecule capable of inclusion of the target molecule, which requires extra time and cost.

[0007] The present invention solves this problem and aims to provide a method for incorporating target molecules, which have previously been difficult to incorporate, into the internal space of a host molecule by changing the inclusion ability of the host molecule in a simple manner. That is, an object of the present invention is to provide a method for changing the inclusion ability of a host molecule, a method for producing an inclusion complex, an inclusion complex, a single crystal, a complex, and a kit for capturing a target molecule. [Means for solving the problem]

[0008] In order to solve the above problems, the present inventors have conducted extensive research into host molecules having an internal space and an opening, and have found that when the host molecule and the target molecule have the same type of charge, the target molecule is less likely to be included in the internal space of the host molecule. Furthermore, the present inventors have found that the inclusion ability of a host molecule can be changed by allowing a specific molecule having a charge different from that of the host molecule to coexist with the host molecule, and have thus completed the present invention.

[0009] Thus, according to the present invention, there are provided the following methods for changing the inclusion ability of a host molecule (1) to (5), a method for producing an inclusion complex (6), an inclusion complex (7), a single crystal (8), a complex (9), and a kit for capturing a target molecule (10).

[0010] [1] A method for changing the inclusion ability of a host molecule, the method comprising the steps of: (a) allowing a lid-shaped molecule, the host molecule having an internal space and one or more openings, the overall molecular charge of which is positive, negative, or uncharged, to satisfy the following requirements 1, 2, and 3, the host molecule, and a molecule (target molecule) to be inclosed in the internal space of the host molecule to coexist in the same system: (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule. [2] The method for changing the inclusion ability of a host molecule according to [1], wherein the affinity interaction between the lid-like molecule and the opening of the host molecule is a Coulomb interaction. [3] A method for changing the inclusion ability of a host molecule according to [1] or [2], wherein the affinity interaction between the lid-shaped molecule and the target molecule is a Coulomb interaction, a hydrogen bond, a hydrophobic interaction, a π-π interaction, or a CH-π interaction. [4] The method for changing the inclusion ability of a host molecule according to any one of [1] to [3], wherein the host molecule is a polynuclear metal complex having a metal ion at the opening, and the lid-shaped molecule is a molecule having an anionic group capable of Coulomb interaction with the metal ion at the opening of the host molecule. [5] The polynuclear metal complex is a compound represented by the following formula (1):

[0011] [ka]

[0012] (A is an m-valent group having aromaticity. X is a divalent organic group or a single bond directly connecting A and Y. Y is a coordinating atom or a monovalent group containing a coordinating atom. m represents an integer of 2 to 6. Multiple Xs may be different from each other, and multiple Ys may be different from each other.) The method for changing the inclusion ability of a host molecule according to [4], wherein the host molecule contains a ligand represented by the formula: [6] A method for producing an inclusion complex in which a target molecule is encapsulated in the internal space of a host molecule, the method comprising the steps of: modifying the inclusion ability of the host molecule by using the method described in any one of [1] to [5], and incorporating the target molecule into the internal space of the host molecule. [7] An inclusion complex comprising a host molecule, a lid-like molecule, and a guest molecule, wherein the guest molecule is enclosed within the internal space of the host molecule, wherein the host molecule has an internal space and one or more openings, and the overall charge of the molecule is positive, negative, or uncharged, and the lid-like molecule satisfies the following requirements 1, 2, and 3, and the lid-like molecule covers at least one of the openings of the host molecule. (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of forming an affinity interaction with the guest molecule. [8] A single crystal obtained by crystallizing the inclusion complex according to [7] above. [9] A complex for inclusion of a target molecule, comprising a host molecule and a lid molecule associated therewith, A complex for inclusion of a target molecule, characterized in that the host molecule has an internal space and one or more openings, and the overall charge of the molecule is positively charged, negatively charged, or uncharged, and the lid molecule is a molecule that satisfies the following requirements 1, 2, and 3, and the lid molecule covers at least one of the openings of the host molecule. (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

[10] A kit for capturing a target molecule, comprising as components a host molecule having an internal space and one or more openings, the host molecule having a positive, negative, or uncharged overall molecular charge, and a lid-shaped molecule that satisfies the following requirements 1, 2, and 3: (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule. [Effects of the Invention]

[0013] According to the present invention, there are provided a method for changing the inclusion ability of a host molecule, a method for producing an inclusion complex, an inclusion complex, a single crystal, a complex, and a kit for capturing a target molecule. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 is a schematic diagram showing the process of generating a host molecule-lid-like molecule complex. [Figure 2] FIG. 1 shows the molecular structure of a host molecule 1-lid-like molecule 2 complex. [Figure 3] FIG. 1 is a diagram showing the molecular structure of the inclusion complex obtained in Example 4. [Figure 4] FIG. 1 is a diagram schematically showing the molecular structure of the inclusion complex obtained in Example 4. [Figure 5] FIG. 1 is a schematic diagram showing the interaction between a host molecule and a lid molecule, and the interaction between a target molecule and a lid molecule. [Figure 6] FIG. 1 is a diagram schematically showing the estimated structure of the inclusion complex obtained in Example 5. [Figure 7] FIG. 1 is a diagram showing the molecular structure of the inclusion complex obtained in Example 8 and a schematic diagram showing the molecular structure of the guest molecule that constitutes this inclusion complex. [Figure 8] FIG. 1 shows the molecular structure of the inclusion complex obtained in Example 10 and a schematic diagram of the molecular structure of the guest molecule that constitutes this inclusion complex. [Figure 9] FIG. 1 shows the molecular structure of the inclusion complex obtained in Example 11 and a schematic diagram of the molecular structure of the guest molecule that constitutes this inclusion complex. DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention will be described in detail below, divided into the following sections: 1) a method for changing the inclusion ability of a host molecule, 2) a method for producing an inclusion complex, 3) an inclusion complex and single crystal, 4) a complex, and 5) a kit for capturing a target molecule. The color drawings of Figures 1 to 9 will be submitted separately in a document submission form.

[0016] 1) Method for changing the inclusion ability of host molecules The "method for changing the inclusion ability of a host molecule" of the present invention (hereinafter sometimes abbreviated as "the method of the present invention") is a method for changing the inclusion ability of a host molecule, characterized in that the host molecule has an internal space and one or more openings, and the overall charge of the molecule is positively, negatively, or uncharged, and the host molecule satisfies the following requirements 1, 2, and 3, and the target molecule coexists in the same system. (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

[0017] In this specification, the term "molecule" includes not only electrically neutral substances composed of two or more atoms, but also electrically charged substances (ions) composed of two or more atoms. The term "host molecule" refers to a molecule that has an internal space and an opening, and that has the ability to encapsulate a guest molecule within the internal space. The "internal space" refers to the space within the host molecule. There are no limitations on the shape of the space as long as it can encapsulate the guest molecule, and it may be elongated, for example, like a "pore." "Opening" means a part that functions as an entrance or exit to an interior space. The term "guest molecule" refers to a molecule that is enclosed within the internal space of a host molecule. Note that guest molecules (target molecules) include metal ions and metal complexes.

[0018] The term "lid-shaped molecule" refers to a molecule that is large enough to cover the opening of the host molecule and has a partial structure that allows affinity interaction with the opening of the host molecule. The term "target molecule" refers to a molecule to be included in the internal space of a host molecule. In this specification, after the target molecule is included in the internal space of the host molecule, it may be referred to as a "target molecule" or a "guest molecule." "Having the lid-shaped molecule, host molecule, and target molecule coexist in the same system" means that these three components are placed in a state where they can come into contact with each other. The entire system does not necessarily have to be a single-phase system; for example, even if the system is a two-phase system of an aqueous solvent and an oil-based solvent, it falls under the category of "having the lid-shaped molecule, host molecule, and target molecule coexist in the same system" as long as these three components can come into contact with each other at the interface between the solvents.

[0019] [Host molecule] The host molecule used in the method of the present invention is a molecule having an internal space and one or more openings. The internal space is used as a space for encapsulating guest molecules. The size of the internal space is not particularly limited as long as it is possible to encapsulate guest molecules. The internal space may be partitioned by molecular chains or the like to have a plurality of independent small spaces.

[0020] The opening serves as a gateway for the target molecule to enter and exit the internal space. The shape and size of the opening are not particularly limited as long as it allows the guest molecule to pass through. When the largest circle inscribed in the opening is assumed, the diameter thereof is, for example, 0.1 to 5 nm, and preferably 0.3 to 3 nm. The number of openings is usually 1 to 10, preferably 1 to 5.

[0021] The host molecule used in the method of the present invention is a molecule whose overall charge is positively charged, negatively charged, or uncharged. As described below, the method of the present invention changes the electrical properties of a host molecule by allowing a lid-shaped molecule having a charge different from that of the host molecule to interact with the host molecule. The method of the present invention can change the inclusion ability of the host molecule regardless of the type of charge (positive, negative, or neutral) of the host molecule.

[0022] The size of the host molecule is not particularly limited. When the smallest rectangular parallelepiped capable of accommodating the host molecule is assumed, the length of the longest side of the rectangular parallelepiped is, for example, 0.3 to 15 nm, preferably 1 to 10 nm, and the length of the shortest side is, for example, 0.3 to 15 nm, preferably 0.5 to 10 nm.

[0023] As the host molecule, a polynuclear metal complex is preferred because molecular design is relatively easy and a host molecule with relatively high symmetry is easily obtained. In addition, in recent years, attempts to use polynuclear metal complexes as host molecules have been actively made, and from the viewpoint of being able to fully utilize the knowledge obtained so far, it is preferable to use a polynuclear metal complex as the host molecule.

[0024] Polynuclear metal complexes are metal complexes containing two or more metal ions and ligands. For example, there is mentioned a polymeric metal complex containing a ligand having two or more coordinating sites and a metal ion as a central metal, which has a three-dimensional network structure formed by the ligand coordinating to the metal ion, and which has pores and hollows regularly arranged three-dimensionally within the three-dimensional network structure.

[0025] The metal ion is not particularly limited as long as it can constitute a polynuclear metal complex. The metal ion is preferably an ion of an element selected from the group consisting of Ti, Fe, Co, Ni, Cu, Zn, Ru, Rh, Pd, Cd, Os, Ir, and Pt, and more preferably an ion of an element of Group 8, 9, or 10 of the periodic table. The valence of the metal ion is not particularly limited, and is usually 1 to 4, preferably 1 to 3, and more preferably 2.

[0026] Examples of the ligand include a ligand that acts as a wall or pillar of the host molecule (hereinafter, sometimes referred to as "ligand (α)"), and a ligand that acts as another role (such as adjusting the charge of the polynuclear metal complex or occupying vacant coordination sites of metal ions to inhibit the polynuclear metal complex from polymerizing) (hereinafter, sometimes referred to as "ligand (β)").

[0027] The ligand (α) is preferably a multidentate ligand containing an aromatic group as a central skeleton. Multidentate ligands containing an aromatic group as a central skeleton are relatively rigid and have excellent planarity, so that the structure of the host molecule is easily maintained. The ligand (α) may be, for example, one represented by the following formula (1).

[0028] [ka]

[0029] In formula (1), A is an m-valent group having aromaticity. X is a divalent organic group or a single bond directly connecting A and Y. Y is a coordinating atom or a monovalent group containing a coordinating atom. m represents an integer of 2 to 6. Multiple Xs may be different from each other, and multiple Ys may be different from each other.

[0030] The group represented by A usually has 6 to 100 atoms (excluding hydrogen atoms), preferably 6 to 60 atoms, and more preferably 6 to 30 atoms. Examples of the group represented by A include a six-membered aromatic group, a group in which a plurality of six-membered aromatic groups are linked by single bonds, and a group having a porphyrin skeleton.

[0031] Examples of the six-membered aromatic group include groups having an aromatic ring such as a benzene ring, a triazine ring, a pyridine ring, and a pyrazine ring. The six-membered aromatic group may have a substituent other than -(-XY). Examples of the substituent include an alkyl group having 1 to 10 carbon atoms; and a halogen atom such as a fluorine atom, a bromine atom, or a chlorine atom.

[0032] Examples of the group represented by A include, but are not limited to, the following: In addition, "*" represents a bond (position of bonding to X).

[0033] [ka]

[0034] [ka]

[0035] In the above formula, M represents a metal ion. Examples of the metal ion include the same ions as those exemplified as metal ions constituting the polynuclear metal complex. Among these, zinc ions are preferred.

[0036] The group represented by X usually has 2 to 30 atoms (excluding hydrogen atoms), preferably 2 to 20 atoms, and more preferably 2 to 10 atoms. Examples of the group represented by X include, but are not limited to, the divalent group represented by A, hydrocarbon groups such as methylene, ethylene, 1,2-ethenediyl, 1,2-ethynediyl (acetylene), p-phenylene, and m-phenylene, amide groups (-C(=O)-NH-), ester groups (-C(=O)-O-), oxymethylene groups (-O-CH-), and oxyethylene groups (-O-CHCH-). The group represented by X may also be a group formed by bonding two or more of these groups. Examples of such groups include, but are not limited to, the following:

[0037] [ka]

[0038] Examples of the coordinating atom represented by Y include an oxygen atom, a sulfur atom, a nitrogen atom, and a phosphorus atom. The monovalent group represented by Y usually has 1-20 atoms (excluding hydrogen atoms), preferably 1-15 atoms, and more preferably 1-10 atoms. Examples of the monovalent group represented by Y include a pyridyl group, an amino group, a hydroxyl group, a deprotonated amide group, a carboxylate group, a sulfonate group, a phosphonate group, a dithiocarboxylate group, a cyano group, and groups containing these groups as substituents. Examples of the monovalent group represented by Y include the following.

[0039] [ka]

[0040] Examples of the ligand (α) include, but are not limited to, the following:

[0041] [ka]

[0042] [ka]

[0043] [ka]

[0044] As the ligand (α), a ligand other than that represented by formula (1) can also be used. Examples of such a ligand include the following.

[0045] [ka]

[0046] The ligand (β) is preferably a ligand with a relatively low molecular weight, since a low molecular weight ligand is less likely to have adverse effects such as steric hindrance on the coordination of the ligand (α). The ligand (β) may be a monodentate ligand or a chelating ligand.

[0047] The monodentate ligand used as the ligand (β) is an oxide ion (O 2- ) and other divalent anions; hydroxide ions (OH - ), chloride ions (Cl - ), bromide ion (Br - ), iodide ion (I - ), thiocyanate ion (SCN - ) and other monovalent anions; electrically neutral coordinating compounds such as water, ammonia, monoalkylamines, dialkylamines, and trialkylamines; and the like.

[0048] Examples of chelating ligands used as ligand (β) include bidentate chelating ligands such as ethylenediamine, N,N'-dimethylethylenediamine, N,N,N',N'-tetramethylethylenediamine, 2,2'-bipyridyl, and 1,2-cyclohexanediamine, but are not limited to these.

[0049] By appropriately selecting a metal ion, a ligand (α), and a ligand (β) and utilizing a conventionally known method, a polynuclear metal complex that can be used as a host molecule can be synthesized. In the method of the present invention, known polynuclear metal complexes having inclusion ability can be used as host molecules. An example of such a polynuclear metal complex is shown below, along with the ligand (α) that constitutes the polynuclear metal complex. When expressing the quantitative ratio of the metal ion and the ligand (α) that constitute the polynuclear metal complex, the metal ion is represented as "M", the ligand (α) as "L", and, if necessary, the second ligand (α) as "X".

[0050] [ka]

[0051] In the above formula, Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., 2,2'-bipyridyl). The main component ratio of this polynuclear metal complex is [M6L4], and this polynuclear metal complex has four openings. M represents a metal ion, such as a Pd ion or a Pt ion, coordinated with a bidentate chelating ligand.

[0052] [ka]

[0053] In the formula (L), Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M6L3], and this polynuclear metal complex has two openings. In formula (L), M represents a metal ion such as a Zn ion.

[0054] [ka]

[0055] In the above formula, Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M6L2X3], and this polynuclear metal complex has three openings.

[0056] [ka]

[0057] In the above formula, Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M6L1], and this polynuclear metal complex has one opening.

[0058] [ka]

[0059] In the above formula, Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M 12 L2], and this polynuclear metal complex has two openings.

[0060] [ka]

[0061] In the above formula, Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M 12 L4], and this polynuclear metal complex has two openings.

[0062] [ka]

[0063] In the above formula, Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of the polynuclear metal complex on the left is [M 10 The main component ratio of the polynuclear metal complex on the right is [M8L4], and both of these polynuclear metal complexes have two openings.

[0064] [ka]

[0065] In the above formula, Pd represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of the polynuclear metal complex on the left is [M8L4], and the main component ratio of the polynuclear metal complex on the right is [M6L4]. Both of these polynuclear metal complexes have two openings.

[0066] [ka]

[0067] In the above formula, Pt represents a platinum ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M4L4], and this polynuclear metal complex has two openings.

[0068] [ka]

[0069] In the above diagram, the sphere represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M6L2], and this polynuclear metal complex has six openings.

[0070] [ka]

[0071] In the above schematic diagram, the sphere represents a palladium ion coordinated with a bidentate chelating ligand (e.g., ethylenediamine). The main component ratio of this polynuclear metal complex is [M 12 L4], and this polynuclear metal complex has eight openings.

[0072] Details of the synthesis methods of these polynuclear metal complexes are described in WO 2018 / 159692.

[0073] [Led molecule] The lid-shaped molecule used in the method of the present invention satisfies the following requirements 1, 2 and 3. (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

[0074] The lid-shaped molecule used in the method of the present invention satisfies the above requirement 1. That is, since the lid molecule and the host molecule have different electric charges, when the lid molecule approaches the host molecule, the electrical properties of the host molecule change.

[0075] The lid-shaped molecule used in the method of the present invention satisfies requirement 2 above. By satisfying requirement 2, the lid molecule can remain in the opening of the host molecule, thereby maintaining the change in the electrical properties of the host molecule for a long period of time.

[0076] The affinity interaction between the lid molecule and the opening of the host molecule includes Coulomb interaction. Coulomb interaction can occur when the opening of the host molecule has a partial negative charge and a lid molecule with a positive charge is added to the position corresponding to the negative charge, or when the opening of the host molecule has a partial positive charge and a lid molecule with a negative charge is added to the position corresponding to the positive charge.

[0077] The lid-shaped molecule used in the method of the present invention satisfies requirement 3 above. When the lid-shaped molecule satisfies requirement 3, it can stabilize the guest molecule enclosed in the inner space of the host molecule.

[0078] Affinity interactions between the lid molecule and the target molecule include Coulomb interactions, hydrogen bonds, hydrophobic interactions, π-π interactions, and CH-π interactions.

[0079] The lid molecule is preferably a relatively rigid compound from the viewpoint of maintaining the structure. Such a lid-like molecule is preferably a molecule that contains an aromatic group as a central skeleton and further contains a group that can interact with an affinity to a host molecule or a target molecule.

[0080] Examples of the aromatic group include the same groups as those exemplified above as "A" constituting the ligand (α).

[0081] Examples of groups capable of affinity interaction with host molecules or target molecules include anionic groups such as carboxylate groups, sulfonate groups, and phosphonate groups; cationic groups such as ammonium groups, phosphonium groups, and pyridinium groups; and electrically neutral groups such as aromatic groups, amide groups, and ester groups. These can be appropriately selected depending on the charges of the host molecule and the target molecule and the type of affinity interaction to be generated.

[0082] When a polynuclear metal complex is used as a host molecule, metal ions may be present in the opening of the host molecule, and because these metal ions have a positive charge, they can be used to generate an affinity interaction with the lid molecule. In this case, the lid molecule is preferably a molecule having an anionic group at a position corresponding to the metal ion in the opening of the host molecule.

[0083] For example, [{(2,2'-bipyridyl)palladium}6(2,4,6-tris(4-pyridyl)-1,3,5-triazine)4] obtained in Synthesis Example 1 described later has an opening in the shape of an equilateral triangle, with a palladium ion at each vertex of the triangle. The average distance from the center of gravity of the triangle to the palladium ion is 0.8 nm. Therefore, for example, compounds having a three-fold rotation axis as a symmetry element with respect to the anionic group, and in which the distance from the center to the anionic group is close to 0.8 nm, are suitable as lid molecules for [{(2,2'-bipyridyl)palladium}6(2,4,6-tris(4-pyridyl)-1,3,5-triazine)4]. Examples of such compounds include, but are not limited to, the following:

[0084] [ka]

[0085] In the above formula, Z is —SO3 - , -COO - , -O - , -COOH, -OH, etc. R represents an alkyl group such as a methyl group. The three Rs may be the same or different. Among these, the following compounds are preferred from the viewpoints of ease of availability and ability to obtain the excellent effects of the present invention.

[0086] [ka]

[0087] Thus, if the structure of the opening of the host molecule is known by crystal structure analysis or the like, it is relatively easy to find a lid-shaped molecule suitable for that opening. For example, in the above formula (19), the group connecting the benzene ring and the group represented by Z is a methylene group (-CH2-). However, by replacing this with another group, the length (e.g., the length of the carbon chain) can be changed, thereby changing the size of the lid-shaped compound. Therefore, depending on the structure of the opening of the host molecule, a lid-shaped molecule suitable for that opening can be appropriately selected.

[0088] For example, in the inclusion complex obtained in Example 4, there is an affinity interaction (Coulomb interaction) between the sulfonate group of the lid molecule (1,3,5-benzenetrimethanesulfonate) and the palladium ion at the opening of the host molecule ([{(2,2'-bipyridyl)palladium}6(2,4,6-tris(4-pyridyl)-1,3,5-triazine)4]). Furthermore, there is also an affinity interaction (Coulomb interaction) between the sulfonate group of the lid molecule and the ammonium group of the guest molecule (1-adamantylammonium). Thus, 1,3,5-benzenetrimethanesulfonate satisfies requirements 2 and 3.

[0089] The amount of the lid molecule used is usually 0.5 to 10 moles, preferably 1 to 6 moles, per mole of the host molecule, from the viewpoint of easily achieving the effects of the present invention. When the lid molecule is a salt, the term "lid molecule" may be used herein to refer to both the salt state and the cationic or anionic state. That is, as described in the Examples, the term "lid molecule" may refer to 1,3,5-benzenetrimethanesulfonic acid sodium salt or 1,3,5-benzenetrimethanesulfonate ion.

[0090] [Target molecule] The target molecule used in the method of the present invention is a molecule to be included in the internal space of the host molecule. The state of the target molecule is not particularly limited as long as it is included in the internal space of the host molecule, and it may be in a solid state at room temperature (20°C), a liquid state at room temperature, or a gaseous state at room temperature.

[0091] The target molecule is a molecule capable of affinity interaction with the lid molecule, and therefore preferably contains a group or site capable of affinity interaction with the lid molecule.

[0092] Examples of groups or moieties that can form an affinity interaction with the lid molecule include anionic groups such as carboxylate groups, sulfonate groups, and phosphonate groups; cationic groups such as ammonium groups, phosphonium groups, pyridinium groups, iminium groups, and pyrylium groups; metal ions; electrically neutral groups such as aromatic groups, amide groups, and ester groups; and oxygen or hydrogen atoms in water molecules. These can be appropriately selected depending on the type of affinity interaction to be induced. The amount of the lid molecule used is usually 0.5 to 10 moles, preferably 1 to 6 moles, per mole of the host molecule, from the viewpoint of easily achieving the effects of the present invention.

[0093] [Method for changing the inclusion ability of a host molecule] The method of the present invention includes a step of allowing the lid molecule, the host molecule, and the target molecule to coexist in the same system. In the present invention, "changing the inclusion ability of a host molecule" means changing the ease with which a target molecule is included in the internal space of a host molecule. In the present invention, the presence of a lid molecule usually makes it easier for a target molecule to be included in the internal space of a host molecule.

[0094] The method of the present invention is usually carried out in the presence of a solvent. The reaction system may be in a state where all components are completely dissolved (solution) or in a state where some components remain undissolved (suspension).

[0095] The solvent can be appropriately selected depending on the solubility of the host molecule, lid molecule, target molecule, etc., and the stability of these molecules in the solvent. For example, when the host molecule is a water-soluble polynuclear metal complex, the solvent is preferably an aqueous solvent such as water or a water-alcohol mixture.

[0096] When the method of the present invention is carried out in the presence of a solvent, the lid molecule is usually in an equilibrium state between a free state and a state in which it blocks the opening of the host molecule. Therefore, even if the host molecule has one opening and that opening is already blocked by the lid molecule, the target molecule is encapsulated after the lid molecule leaves the opening.

[0097] In the "complex formed by association of a host molecule and a lid molecule" described below, the host molecule has already been affected by the lid molecule, and its electrical properties have been changed. Therefore, when this complex is obtained as a solid, the target molecule in the gas phase can be encapsulated in the internal space of the host molecule by contacting the obtained solid with the target molecule in the gas phase in the absence of a solvent.

[0098] The reason why the inclusion ability of the host molecule changes according to the method of the present invention is thought to be as follows. (1) The lid-shaped molecule is a molecule that can interact with the opening of the host molecule through an affinity, and also with the target molecule through an affinity. Therefore, the target molecule encapsulated in the internal space of the host molecule is stabilized compared to a state in which the lid molecule is not present, and thus the formation of an inclusion complex is promoted. (2) When a host molecule has two or more openings and is a combination of a host molecule with an overall positive charge and a lid-like molecule with an overall negative charge, or vice versa, the openings of the host molecule are partially covered by the lid-like molecule, thereby canceling out the charges of the host molecule and making it easier for the target molecule to pass through another opening of the host molecule. (3) When the method of the present invention is carried out in the presence of a solvent and a target molecule having an overall positive charge is combined with a lid molecule having an overall negative charge, or vice versa, Coulomb interaction occurs between the free target molecule and the free lid molecule, canceling out the charges of the target molecule and making it easier for the target molecule to pass through the opening of the host molecule.

[0099] The primary objective of the method of the present invention is to reduce the influence of an exclusive interaction between a host molecule and a target molecule that have the same type of charge and that encapsulate the target molecule within the internal space of the host molecule. Therefore, in the method of the present invention, it is generally preferable that the host molecule and the target molecule have the same type of charge.

[0100] The method of the present invention is also suitable for use when the host molecule and the target molecule have different electric charges, or when it has already been confirmed that an inclusion complex can be obtained using only the host molecule and the target molecule. That is, by using the method of the present invention, the disorder of guest molecules in the internal space of the host molecule is reduced, and the orientation of the guest molecules is aligned, and the mobility of the guest molecules in the internal space of the host molecule is reduced.

[0101] Thus, according to the method of the present invention, the inclusion ability of the host molecule can be changed by using the lid-shaped molecule, and target molecules that have previously been difficult to inclusion can be included in the internal space of the host molecule, thereby greatly expanding the range of applications of the host molecule. Furthermore, as described above, by carrying out the method of the present invention, guest molecules can be regularly included, making it easier to obtain high-quality samples for crystal structure analysis. Furthermore, unstable guest molecules are stabilized within the internal space of the host molecule, and all openings in the host molecule are blocked to block external influences, enabling long-term storage of unstable guest molecules.

[0102] 2) Method for producing the inclusion complex The "method for producing an inclusion complex" of the present invention is a method for synthesizing an inclusion complex in which a target molecule is encapsulated within the internal space of a host molecule, and is characterized by comprising a step of using the above-mentioned invention (method for changing the inclusion ability of a host molecule) to change the inclusion ability of the host molecule and incorporate the target molecule into the internal space of the host molecule.

[0103] Generally, an "inclusion complex" refers to a compound in which a guest molecule is enclosed within the internal space of a host molecule, and is composed of two components: a "host molecule" and a "guest molecule." However, in the inclusion complex obtained by the synthesis method of the present invention, the host molecule has its inclusion ability modified by the lid molecule, and therefore the "inclusion complex" obtained by the production method of the present invention essentially comprises three components: a host molecule, a guest molecule, and a lid molecule.

[0104] As explained above, the electrical properties of the host molecule change due to the interaction between the lid molecule and the host molecule. When a target molecule is present in the system, it easily passes through the opening of the host molecule, and the target molecule remains in the internal space of the host molecule because the internal space is in a state suitable for the inclusion of the target molecule. In this way, by utilizing the invention of the "method for changing the inclusion ability of a host molecule," the host molecule is changed to a state suitable for inclusion of the target molecule, and the desired inclusion complex can be synthesized by leaving the reaction system to stand without any special manipulation.

[0105] The time for standing is not particularly limited, but is usually from 10 seconds to 1 day, preferably from 1 minute to 2 hours. The temperature of the reaction system when left standing is not particularly limited, but is usually 4 to 100°C, preferably 15 to 60°C.

[0106] 3) Inclusion complexes and single crystals The inclusion complex of the present invention comprises a host molecule, a lid-like molecule, and a guest molecule, with the guest molecule being enclosed within the internal space of the host molecule, wherein the host molecule has an internal space and one or more openings, and the overall molecular charge is positive, negative, or uncharged; the lid-like molecule is a molecule that satisfies the following requirements 1, 2, and 3, and the lid-like molecule covers at least one of the openings of the host molecule. (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of forming an affinity interaction with the guest molecule.

[0107] The "host molecule" and "lid-like molecule" that constitute the inclusion complex of the present invention are the same as those explained in the invention of the "method for changing the inclusion ability of a host molecule." The "guest molecule" constituting the inclusion complex of the present invention is the "target molecule" in the invention of the "method for changing the inclusion ability of a host molecule" that is enclosed within the internal space of the host molecule.

[0108] The lid-shaped molecule constituting the inclusion complex of the present invention has a charge different from that of the host molecule (Requirement 1) and is capable of affinity interaction with the opening of the host molecule (Requirement 2). Therefore, in the inclusion complex of the present invention, the lid-shaped molecule remains covering the opening of the host molecule, and the electrical properties of the host molecule remain changed. Furthermore, an affinity interaction occurs between the lid-like molecule and the guest molecule. In this way, the lid-like molecule continues to cover the opening of the host molecule, and the internal space of the inclusion body of the present invention is changed to one that is more suitable for the inclusion of guest molecules than the internal space of the original host molecule, and the guest molecules are stably inclusive.

[0109] On the other hand, for the lid-shaped molecule, the stable presence of the guest molecule within the internal space of the host molecule stabilizes the association state with the host molecule. That is, due to the affinity interaction that occurs between the lid molecule and the guest molecule, the lid molecule is less likely to leave the opening of the host molecule. In fact, when the complex obtained in Example 2 (which is formed by association of a host molecule with a lid molecule and does not contain a guest molecule) is dissolved in a solvent, some of the lid molecules dissociate, generating free lid molecules. However, the inclusion complex obtained in Example 4 was highly stable, and no dissociation of the lid molecules was observed even in the presence of a solvent.

[0110] Thus, the inclusion complex of the present invention has high stability due to the presence of three components: a host molecule, a lid-like molecule, and a guest molecule.

[0111] The inclusion complex of the present invention can be produced, for example, by utilizing the invention of the "method for producing an inclusion complex" described above.

[0112] In the inclusion complex of the present invention, the guest molecules tend to be accommodated in an orderly manner due to the affinity interaction between the lid-like molecule and the guest molecules. Therefore, by forming the inclusion complex of the present invention into a single crystal, it is possible to obtain a single crystal that is more suitable as a sample for crystal structure analysis.

[0113] 4) Complex The complex of the present invention is a complex for inclusion of a target molecule, which is formed by association of a host molecule with a lid-shaped molecule, wherein the host molecule has an internal space and one or more openings, and the overall charge of the molecule is positively, negatively, or uncharged, and the lid-shaped molecule is a molecule that satisfies the following requirements 1, 2, and 3, and the lid-shaped molecule covers at least one of the openings of the host molecule. (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

[0114] In this specification, the "complex" of the present invention may be referred to as a "host molecule-lid-like molecule complex." The "host molecule," "lid-like molecule," and "target molecule" that constitute the complex of the present invention are the same as those described in the invention of the "method for changing the inclusion ability of a host molecule."

[0115] As explained above, the lid molecules that make up the complexes of the present invention are more susceptible to dissociation than the lid molecules that make up the inclusion complexes (which contain three components: a host molecule, a lid molecule, and a guest molecule), and some of the lid molecules dissociate in the presence of a solvent. Therefore, the complex of the present invention can be suitably used as a raw material compound when synthesizing the inclusion complex.

[0116] Furthermore, as explained above, when the complex of the present invention is obtained as a solid, this solid can be suitably used to encapsulate a target molecule present in the gas phase.

[0117] 5) Target molecule capture kit The target molecule capture kit of the present invention is a kit for capturing a target molecule, and comprises as its components a host molecule having an internal space and one or more openings, the entire molecule being positively, negatively, or uncharged, and a lid-shaped molecule that satisfies the following requirements 1, 2, and 3: (Requirement 1) The charge of the entire lid-shaped molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

[0118] The "host molecule" and "lid-like molecule" that make up the target molecule capturing kit of the present invention are the same as those explained in the invention of the "method for changing the inclusion ability of a host molecule." The "target molecule" in the target molecule capturing kit of the present invention is the same as that explained in the invention of the "method for changing the inclusion ability of a host molecule."

[0119] In the kit for capturing a target molecule of the present invention, the host molecule and the lid molecule may or may not exist independently.

[0120] When the host molecule and the lid molecule exist independently, the host molecule and the lid molecule may be in a solid state, or may be dissolved or dispersed in a solvent. When the host molecule and the lid molecule do not exist independently, the target molecule capture kit of the present invention may contain a mixture of a solid host molecule and a solid lid molecule, may contain a complex having a host molecule and a lid molecule, or may contain the host molecule and the lid molecule dissolved or dispersed in a solvent.

[0121] The kit for capturing a target molecule of the present invention is suitably used when carrying out the invention of the "method for synthesizing an inclusion complex" described above. Furthermore, in the kit for capturing a target molecule of the present invention, it is also possible to attempt to capture a target molecule using only the host molecule without adding a lid-shaped molecule to the reaction system. In this way, by either allowing or not allowing the lid molecule to be present in the system, the range of molecules that can be captured by the host molecule is expanded, allowing the target molecule to be captured efficiently. [Example]

[0122] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples in any way.

[0123] [Synthesis Example 1] Synthesis of the Octahedral Metal Complex [{(N,N,N',N'-tetramethylethylenediamine)palladium}6(2,4,6-tris(4-pyridyl)-1,3,5-triazine)4] The octahedral metal complex shown below (hereinafter, sometimes referred to as "host molecule 1") was synthesized according to the method described in J. Am. Chem. Soc. 2004, 126, 9172-9173.

[0124] [ka]

[0125] [Synthesis Example 2] Synthesis of 1,3,5-benzenetrimethanesulfonic acid sodium salt 1,3,5-benzenetrimethanesulfonic acid sodium salt (hereinafter sometimes referred to as "lid-shaped molecule 2") was synthesized according to the method described in Inorg. Chem. 2002, 41, 6986-6996.

[0126] [Synthesis Example 3] 1-Adamantylamine (0.102 g, 0.672 mmol) was suspended in water and then neutralized with 1 M HNO3. The precipitate was filtered off, and the resulting filtrate was concentrated under reduced pressure and further dried in vacuo to obtain 1-adamantylammonium nitrate (hereinafter sometimes referred to as "cationic target molecule 3") as a white powder (0.128 g, 0.5 99mmol, 89%).

[0127] [Synthesis Example 4] 1,ω-alkanediamine (0.196-0.285 mmol) was suspended in water and then neutralized with 1 M HNO3. The precipitate was collected by filtration and dried in vacuo to obtain 1,ω-alkanediammonium dinitrate as a white powder. Hereinafter, a molecule having an alkylene chain with 12 carbon atoms may be referred to as a "cationic target molecule 4a," and a molecule having an alkylene chain with 10 carbon atoms may be referred to as a "cationic target molecule 4b."

[0128] [NMR measurement] 1 H-NMR was measured under conditions of 500 MHz and 300 K using a measuring device (AVANCE III HD 500, manufactured by Bruker) equipped with a PABBO probe.

[0129] [Single-crystal X-ray crystallography] Single crystal X-ray crystal structure analysis was carried out using a Bruker APEX-II / CCD diffractometer (Mo-Kα radiation (wavelength 0.71073 Å)).

[0130] [Example 1] Synthesis of host molecule-lid-like molecule conjugate, and 1 H-NMR measurement The lid-shaped molecule 2 was added to a DO solution (1.67 mM, 0.75 mL) of the host molecule 1, and the mixture was stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1 H-NMR spectrum was measured. When the molar ratio of host molecule 1 to lid molecule 2 was 1:1, the signal derived from lid molecule 2 was significantly broadened compared to measurements using lid molecule 2 alone. This result suggests that there is some interaction between the host molecule 1 and the lid-like molecule 2. Furthermore, when the molar ratio of host molecule 1 to lid molecule 2 was 1:4, the broad signal was slightly shifted to the downfield side. These measurement results suggest that lid-shaped molecule 2 is not enclosed in the internal space of host molecule 1, but interacts with the opening of host molecule 1, forming a host molecule-lid-shaped molecule complex. Figure 1 shows a schematic diagram of the process of forming the host molecule-lid molecule complex.

[0131] [Example 2] Synthesis of host molecule-lid-shaped molecule complex and X-ray crystal structure analysis An aqueous solution containing host molecule 1 and lid-shaped molecule 2 (molar ratio 1:1) was left standing at 50°C to slowly evaporate the water, and single crystals were obtained after two weeks. This single crystal was used as a measurement sample for crystal structure analysis. The molecular structure of the host molecule 1-lid molecule 2 complex is shown in Figure 2.

[0132] [Example 3] Synthesis of inclusion complexes and 1 H-NMR measurement To a DO solution of host molecule 1 (0.50 mM, 2.0 mL), lid-shaped molecule 2 (5 equivalents relative to host molecule 1) and cationic target molecule 3 (10 equivalents relative to host molecule 1) were added and stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1 H-NMR spectrum was measured. As a result, a signal was observed originating from the cationic target molecule 3 accommodated in the internal space of the host molecule 1. The molar ratio of each molecule constituting this inclusion complex (host molecule 1:lid-like molecule 2:cationic target molecule 3) was 1:4:4.

[0133] Comparative Example 1 A cationic target molecule 3 (10 equivalents relative to the host molecule 1) was added to a DO solution (0.50 mM, 2.0 mL) of the host molecule 1, and the mixture was stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1 H-NMR spectrum was measured. As a result, no signal from the cationic target molecule 3 accommodated in the internal space of the host molecule 1 was observed.

[0134] [Example 4] Synthesis of inclusion complex and X-ray crystal structure analysis An aqueous solution containing host molecule 1, lid-like molecule 2, and cationic target molecule 3 (molar ratio 1:5:10) was left standing at 50°C to slowly evaporate the water, and single crystals were obtained after two weeks. This single crystal was used as a measurement sample for crystal structure analysis. The molecular structure of the inclusion complex is shown in Figure 3. Figures 4 and 5 show schematic diagrams of the molecular structure of the inclusion complex, as well as diagrams showing the interactions between the host molecule and the lid molecule and between the target molecule and the lid molecule, respectively.

[0135] [Example 5] Synthesis of inclusion complexes and 1 H-NMR measurement To a DO solution of host molecule 1 (1.0 mM, 1.0 mL), lid-shaped molecule 2 (5 equivalents relative to host molecule 1) and cationic target molecule 4a (5 equivalents relative to host molecule 1) were added and stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1 H-NMR spectrum was measured. As a result, a signal was observed originating from the cationic target molecule 4a accommodated in the internal space of the host molecule 1. The molar ratio of each molecule constituting this inclusion complex (host molecule 1:lid-like molecule 2:cationic target molecule 4a) was 1:4:2. The estimated structure of the inclusion complex estimated from the NMR peak splitting pattern is shown in Figure 6.

[0136] Comparative Example 2 A cationic target molecule 4a (5 equivalents relative to the host molecule 1) was added to a DO solution (1.0 mM, 1.0 mL) of the host molecule 1, and the mixture was stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1 H-NMR spectrum was measured. As a result, no signal from the cationic target molecule 4a accommodated in the internal space of the host molecule 1 was observed.

[0137] Example 6: Synthesis of inclusion complexes and 1 H-NMR measurement To a DO solution of host molecule 1 (1.0 mM, 1.0 mL), lid-shaped molecule 2 (5 equivalents relative to host molecule 1) and cationic target molecule 4b (5 equivalents relative to host molecule 1) were added and stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1 H-NMR spectrum was measured. As a result, a signal was observed originating from the cationic target molecule 4b accommodated in the internal space of the host molecule 1. The molar ratio of each molecule constituting this inclusion complex (host molecule 1:lid-like molecule 2:cationic target molecule 4b) was 1:4:2. From the NMR peak splitting pattern, it was estimated that the compound had the same structure as the inclusion compound obtained in Example 5.

[0138] Comparative Example 3 A cationic target molecule 4b (5 equivalents relative to the host molecule 1) was added to a DO solution (1.0 mM, 1.0 mL) of the host molecule 1, and the mixture was stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1 H-NMR spectrum was measured. As a result, no signal from the cationic target molecule 4b accommodated in the internal space of the host molecule 1 was observed.

[0139] [Example 7] Exchange of guest molecules To a DO solution (0.50 mM, 2.0 mL) of host molecule 1, cationic target molecule 3 (10 equivalents relative to host molecule 1) and 1-decanol (hereinafter sometimes referred to as "neutral target molecule 5") (10 equivalents relative to host molecule 1) were added, and the mixture was stirred at room temperature (25°C) for 1 hour. A portion of the resulting solution was used as a measurement sample. 1 Measurement of the 1 H-NMR spectrum revealed that the neutral target molecule 5 was accommodated in the internal space of the host molecule 1. Next, the lid-shaped molecule 2 (5 equivalents relative to the host molecule 1) was added to a DO solution containing the host molecule 1, cationic target molecule 3, and neutral target molecule 5, and the mixture was stirred at room temperature (25°C) for 1 hour. The resulting solution was used as a measurement sample. 1Measurement of the H-NMR spectrum revealed that the neutral target molecule 5 in the inner space of the host molecule 1 was replaced with the cationic target molecule 3.

[0140] [Example 8] Synthesis of inclusion complex and X-ray crystal structure analysis To 1.0 mL of an aqueous solution (1.0 mM) of host molecule 1, lid-shaped molecule 2 (2.07 mg, 4.86 μmol), lanthanum nitrate (14.2 mg, 32.9 μmol), and sodium benzoate (1.45 mg, 10.1 μmol) were added and stirred at room temperature (25°C) for 1 hour. The resulting solution was left to stand at 50°C, and the water was slowly evaporated. After 1 week, single crystals were obtained. Using this single crystal as a measurement sample, single-crystal structural analysis revealed that it was an inclusion complex consisting of host molecule 1, lid-like molecule 2, lanthanum ion, and benzoate anion. Figure 7 shows a diagram of the molecular structure of this inclusion complex and a schematic diagram of the molecular structure of the guest molecule contained in the complex.

[0141] [Synthesis Example 5] Synthesis of 2,4,6-trimethyl-1,3,5-benzenetrimethanesulfonic acid sodium salt 1,3,5-Trisbromomethyl-2,4,6-trimethylbenzene (1.00 g, 2.51 mmol), sodium sulfite (1.00 g, 7.94 mmol), and tetra-n-butylammonium iodide (83 mg, 0.22 mmol) were suspended in 15 mL of water and stirred under reflux for 24 hours. The solvent was evaporated under reduced pressure, and the precipitated solid was dissolved in 3 mL of water. 50 mL of acetone was added to the resulting solution, and the precipitated solid was washed successively with a methanol-water mixed solvent (methanol:water = 1:1 (volume ratio)), methanol, and acetone, and then vacuum dried to obtain 2,4,6-trimethyl-1,3,5-benzenetrimethanesulfonic acid sodium salt (hereinafter sometimes referred to as "lid-shaped molecule 6") as a white powder (0.609 g, 1.30 mmol, 52%). The molecular structure of the lid-shaped molecule 6 (anion part) is shown below.

[0142] [ka]

[0143] [Example 9] Synthesis of host molecule-lid-like molecule complex Lid-shaped molecule 6 (936.6 mg, 2.00 mmol) was added to 30 mL of an aqueous solution (20 mM) of host molecule 1, and the mixture was heated to 100 °C to dissolve the solid. The resulting solution was allowed to stand at room temperature (25 °C), resulting in the precipitation of a pale yellow solid. The precipitated solid was collected, washed with water, and then vacuum dried to obtain a complex containing host molecule 1 and lid-shaped molecule 6 in a molar ratio of 1:4 as a yellow powder (2.13 g, 5.09 mmol, 85%).

[0144] [Example 10] Synthesis of inclusion complex and X-ray crystal structure analysis Lid-shaped molecule 6 (1.80 mg, 3.84 μmol) and rhodamine 110 (1.83 mg, 5.0 μmol) were added to 2 mL of an aqueous solution (0.50 mM) of host molecule 1, and the mixture was heated and stirred at 60°C for 30 minutes. The resulting solution was left to stand at 50°C to slowly evaporate the water, and single crystals were obtained after one week. Using this single crystal as a measurement sample, single crystal structural analysis revealed that it was an inclusion complex composed of host molecule 1 and lid-like molecule 6-rhodamine 110. Figure 8 shows a diagram representing the molecular structure of this inclusion complex and a schematic diagram of the molecular structure of the guest molecule contained in the complex.

[0145] [Example 11] Synthesis of inclusion complex and X-ray crystal structure analysis 0.1 mL of an aqueous solution (10 mM) of host molecule 1, 0.1 mL of an aqueous solution (50 mM) of lid-shaped molecule 6, and 0.1 mL of an aqueous solution (100 mM) of lanthanum nitrate were mixed and heated and stirred at 60°C for 30 minutes. The resulting solution was left to stand at 50°C to slowly evaporate the water, and after one week, single crystals were obtained. Using this single crystal as a measurement sample, single-crystal structural analysis revealed that it was an inclusion complex consisting of host molecule 1, lid molecule 6, and lanthanum ion nonahydrate. Figure 9 shows a diagram of the molecular structure of this inclusion complex and a schematic diagram of the molecular structure of the guest molecule contained in the complex.

Claims

1. A method for changing the inclusion ability of a host molecule, comprising: the host molecule has an internal space and one or more openings, and the overall charge of the molecule is positively charged, negatively charged, or uncharged; A method for changing the inclusion ability of a host molecule, comprising the steps of: bringing a lid-shaped molecule that satisfies the following requirements 1, 2, and 3, the host molecule, and a molecule (target molecule) to be included in the internal space of the host molecule into the same system; and blocking at least one opening of the host molecule with the lid-shaped molecule. (Requirement 1) The charge of the entire lid-like molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule and blocking the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

2. The method for changing the inclusion ability of a host molecule according to claim 1 , wherein the affinity interaction between the lid molecule and the opening of the host molecule is a Coulomb interaction.

3. 3. The method for changing the inclusion ability of a host molecule according to claim 1 or 2, wherein the affinity interaction between the lid molecule and the target molecule is a Coulomb interaction, a hydrogen bond, a hydrophobic interaction, a π-π interaction, or a CH-π interaction.

4. the host molecule is a polynuclear metal complex having a metal ion in the opening, The method for changing the inclusion ability of a host molecule according to any one of claims 1 to 3, wherein the lid-like molecule is a molecule having an anionic group capable of Coulomb interaction with the metal ion at the opening of the host molecule.

5. The polynuclear metal complex is a compound represented by the following formula (1): 【Chemistry 1】 (A is an m-valent group having aromaticity. X is a divalent organic group or a single bond directly connecting A and Y. Y is a coordinating atom or a monovalent group containing a coordinating atom. m is an integer of 2 to 6. Multiple Xs may be different from each other, and multiple Ys may be different from each other.) The method for changing the inclusion ability of a host molecule according to claim 4, wherein the host molecule contains a ligand represented by the formula:

6. A method for producing an inclusion complex in which a target molecule is encapsulated in the inner space of a host molecule, comprising the steps of: A method for producing an inclusion complex, comprising the step of changing the inclusion ability of a host molecule by using the method according to any one of claims 1 to 5, and incorporating a target molecule into the internal space of the host molecule.

7. An inclusion complex comprising a host molecule, a lid-like molecule, and a guest molecule, the guest molecule being enclosed in the internal space of the host molecule, the host molecule has an internal space and one or more openings, and the overall charge of the molecule is positively charged, negatively charged, or uncharged; The lid-shaped molecule is a molecule that satisfies the following requirements 1, 2, and 3: An inclusion complex, characterized in that the lid molecule covers at least one opening of the host molecule. (Requirement 1) The charge of the entire lid-like molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule and blocking the opening of the host molecule. (Requirement 3) The molecule is capable of forming an affinity interaction with the guest molecule.

8. A single crystal obtained by crystallizing the inclusion compound according to claim 7.

9. A complex for inclusion of a target molecule, which is formed by association of a host molecule with a lid-like molecule, the host molecule has an internal space and one or more openings, and the overall charge of the molecule is positively charged, negatively charged, or uncharged; The host molecule is a molecule that encapsulates a target molecule in its internal space when the target molecule coexists with the host molecule in the same system, The lid-shaped molecule is a molecule that satisfies the following requirements 1, 2, and 3: A complex for inclusion of a target molecule, characterized in that the lid-like molecule covers at least one opening of the host molecule. (Requirement 1) The charge of the entire lid-like molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule and blocking the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

10. A kit for capturing a target molecule, comprising: a host molecule having an internal space and one or more openings, the host molecule having a positive charge, a negative charge, or no charge overall; and a lid-shaped molecule that satisfies the following requirements 1, 2, and 3 as a constituent component, A kit for capturing a target molecule, wherein the host molecule is a molecule that encapsulates the target molecule in its internal space when the target molecule is present in the same system. (Requirement 1) The charge of the entire lid-like molecule is positive, negative, or uncharged (however, when the charge of the entire host molecule is positive, it is not a positive charge; when the charge of the entire host molecule is negative, it is not a negative charge; and when the charge of the entire host molecule is uncharged, it is not uncharged). (Requirement 2) The molecule is capable of forming an affinity interaction with the opening of the host molecule and blocking the opening of the host molecule. (Requirement 3) The molecule is capable of affinity interaction with the target molecule.

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