Production method of coordination compound, crystal of porous compound, inclusion compound, and sample for crystal structure analysis

Abstract

To provide a coordinating compound that gives a porous compound having hydrophilicity and including pores of a size sufficient to accommodate guest molecules regularly; crystal of the porous compound containing the coordinating compound; an inclusion complex including the porous compound serving as a host molecule; and a method for making a sample for crystal structure analysis.SOLUTION: The present invention provides: a coordinating compound represented by the formula (I); crystal of the porous compound containing the coordinating compound; an inclusion complex including the porous compound serving as a host molecule; and a method for making a sample for crystal structure analysis. In the formula (I), X1 and X2 each denote a specific group having a coordination atom, and -A1-A2-A3- denotes a specific tripeptide skeleton.SELECTED DRAWING: Figure 4

Description

Technical Field

[0001] The present invention relates to a coordination compound, a crystal of a porous compound, an inclusion compound, and a method for producing a sample for crystal structure analysis.

Background Art

[0002] A porous compound is a compound having pores inside. Among porous compounds, there are those that can accommodate guest molecules in their pores, and various utilization methods have been proposed so far.

[0003] For example, Patent Document 1 describes a method of regularly arranging molecules of a compound to be analyzed in the pores of a single crystal of a polymer complex and performing crystal structure analysis using the obtained inclusion compound as a measurement sample.

[0004] In addition, in relation to the present invention, Non-Patent Document 1 describes a coordination compound having a skeleton of (glycine)-(L-proline)-(L-proline) and a crystal of a porous compound containing this coordination compound.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Documents

[0006]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0007] The pores of the polymer complex described in Patent Document 1 are highly hydrophobic. Therefore, the pores of this polymer complex tend to be difficult to accommodate hydrophilic molecules having polar groups. On the one hand, the coordination compound described in Non-Patent Document 1 has a tripeptide skeleton, and the crystal of the porous compound containing this coordination compound has hydrophilic pores. However, since the pores of the crystal of the porous compound described in Non-Patent Document 1 had a considerably large pore diameter, these pores tended to accommodate small guest molecules disorderly. Therefore, even when a guest molecule was accommodated in the pores of the crystal of the porous compound described in Non-Patent Document 1, it was sometimes difficult to confirm the presence of the guest molecule by crystal structure analysis. Therefore, there has been a demand for a porous compound that is hydrophilic and has pores of a size capable of regularly accommodating guest molecules.

[0008] An object of the present invention is to provide a coordination compound that gives a porous compound having hydrophilic pores and a size capable of regularly accommodating guest molecules, a crystal of a porous compound containing the coordination compound, an inclusion compound in which the porous compound functions as a host molecule, and a method for producing a sample for crystal structure analysis.

Means for Solving the Problems

[0009] The present inventor earnestly studied a coordination compound having a tripeptide skeleton in order to solve the above problems. As a result, (1) By introducing a ring structure or a substituent into the tripeptide skeleton, a coordination compound with restricted conformational freedom can be obtained, and (2) A coordination compound having a tripeptide skeleton and restricted conformational freedom coordinates to metal ions, thereby easily forming a porous compound having pores of a size capable of regularly accommodating guest molecules, were found, and the present invention was completed.

[0010] Thus, according to the present invention, the coordination compounds of the following [1] and [2], the crystals of the porous compounds of [3] and [4], the inclusion compounds of [5] to [7], and the method for producing a sample for crystal structure analysis of [8] are provided.

[0011] 〔1〕The coordination compound represented by the following formula (I).

[0012]

Chem.

[0013] In formula (I), X 1 is a group represented by the following formula (II)

[0014]

Chem.

[0015] (R 1 represents a group having a coordinating atom, and *1 represents a bond to A 1 .). is a group represented by, and A 1 is a group represented by the following formula (III)

[0016]

Chem.

[0017] (R 2 , R 3 each independently represents an alkyl group having 1 to 5 carbon atoms (provided that R 2 -C-R 3 includes a ring structure formed by the bonding of R 2 and R 3 ). *2 represents a bond to X 1 , and *3 represents a bond to A 2 .). is a group represented by, and A 2 is a group represented by the following formula (IV-1) to (VI-12)

[0018]

Chem.

[0019] (*4 represents a bond to A 1 , and *5 represents a bond to A 3 . R4 is a group or atom having 1 to 5 atoms (excluding the number of hydrogen atoms). "R 4 -" represents that R 4 is bonded to any carbon atom constituting a 4-membered ring, 5-membered ring or 6-membered ring. A 2 when having R 4 , the number of R 4 is 1 or 2 or more. A 2 when having a plurality of R 4 , the plurality of R 4 may be the same as or different from each other. ) is a group represented by any of 3 and A

[0020]

Chemical formula

[0021] (*6 represents a bond to A 2 , and *7 represents a bond to X 2 . R 5 is a group or atom having 1 to 5 atoms (excluding the number of hydrogen atoms). "R 5 -" represents that R 5 is bonded to any carbon atom constituting a 4-membered ring, 5-membered ring or 6-membered ring. A 3 when having R 5 , the number of R 5 is 1 or 2 or more. A 3 when having a plurality of R 5 , the plurality of R 5 may be the same as or different from each other. ) is a group represented by any of 2 and X

[0022]

Chemical formula

[0023] (R 6 represents a group having a coordination atom, and *8 represents A3 represents a bonding hand with...) is a group represented by... [2] R 1 is a pyridyl group with or without substituents, and R 6 is a pyridyl group with or without substituents, the coordination compound according to [1]. [3] A crystal of a porous compound having a three-dimensional skeleton composed of one or two or more molecular chains and three-dimensionally regularly arranged pores formed by being partitioned by the three-dimensional skeleton, wherein the molecular chains constituting the three-dimensional skeleton contain the coordination compound according to [1] or [2] and ions of an element of Group 11 of the periodic table, a crystal of a porous compound. [4] The crystal of the porous compound according to [3], which has single crystallinity. [5] An inclusion compound in which guest molecules are accommodated in the pores of a crystalline host molecule, wherein the crystalline host molecule is the crystal of the porous compound according to [3] or [4]. [6] The inclusion compound according to [5], wherein the guest molecule is a compound having a polar group. [7] The inclusion compound according to [5] or [6], wherein the guest molecule is a chiral compound. [8] A method for preparing a sample for crystal structure analysis, which comprises incorporating molecules of a compound to be analyzed into the pores of the crystal of the porous compound according to [4] and regularly arranging the molecules of the compound to be analyzed, a method for preparing a sample for crystal structure analysis. [Advantages of the Invention]

[0024] According to the present invention, there are provided a coordination compound that gives a porous compound having hydrophilicity and pores of a size capable of regularly accommodating guest molecules, a crystal of a porous compound containing the coordination compound, an inclusion compound in which the porous compound functions as a host molecule, and a method for preparing a sample for crystal structure analysis. [Brief Description of the Drawings]

[0025]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

Figure 13

BEST MODE FOR CARRYING OUT THE INVENTION

[0026] Hereinafter, the present invention will be described in detail by dividing it into 1) coordination compound, 2) crystal of porous compound, 3) inclusion compound, and 4) method for preparing a sample for crystal structure analysis.

[0027] 1) Coordination compound The coordination compound of the present invention is a compound represented by the following formula (I).

[0028]

Chem.

[0029] In formula (I), X 1 is a group represented by the following formula (II).

[0030]

Chem.

[0031] In formula (II), R 1 represents a group having a coordinating atom, and *1 represents a bond to A 1 .

[0032] R 1 is a group having a coordinating atom. R 1 Examples of the coordinating atom contained in R include a nitrogen atom constituting an amino group, a nitrogen atom constituting a heterocyclic group, an oxygen atom constituting a carboxylate ion, an oxygen atom constituting a phenoxide ion, an oxygen atom constituting an alkoxide ion, a sulfur atom constituting a thiolate ion, and the like. 1 The number of atoms in R

[0033] excluding hydrogen atoms is usually 1 to 20, preferably 1 to 10. 1 Since a stable porous compound is easily obtained, R is preferably a heterocyclic group, more preferably a nitrogen-containing heterocyclic group.

[0034] Examples of the pyridine ring-containing group include a 2-pyridyl group, a 3-pyridyl group, and a 4-pyridyl group. Examples of the pyridazine ring-containing group include a 3-pyridazinyl group and a 4-pyridazinyl group. Examples of the pyrimidine ring-containing group include a 2-pyrimidinyl group, a 4-pyrimidinyl group, and a 5-pyrimidinyl group. Examples of the pyrazine ring-containing group include a 2-pyrazinyl group. Examples of the imidazole ring-containing group include a 2-imidazolyl group, a 4-imidazolyl group, and a 5-imidazolyl group. Examples of the pyrazole ring-containing group include a 3-pyrazolyl group, a 4-pyrazolyl group, and a 5-pyrazolyl group.

[0035] The heterocyclic ring-containing group may have a substituent. Examples of the substituent contained in the heterocyclic ring-containing group include an alkyl group, an alkoxy group, a carbonyl group-containing group, a hydroxy group, a halogen atom, and the like.

[0036] The number of carbon atoms of the alkyl group contained in the heterocyclic ring-containing group is preferably 1 to 10, more preferably 1 to 5. Examples of the alkyl group contained in the heterocyclic ring-containing group include a methyl group, an ethyl group, a 1-propyl group, an isopropyl group, and the like.

[0037] The number of carbon atoms of the alkoxy group contained in the heterocyclic ring-containing group is preferably 1 to 10, more preferably 1 to 5. Examples of the alkoxy group contained in the heterocyclic ring-containing group include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, and the like.

[0038] The number of carbon atoms of the carbonyl group-containing group contained in the heterocyclic ring-containing group is preferably 1 to 20, more preferably 1 to 10. Examples of the carbonyl group-containing group contained in the heterocyclic ring-containing group include oxycarbonyl group-containing groups such as an alkyloxycarbonyl group, an aryloxycarbonyl group, and an aralkyloxycarbonyl group; a formyl group; a carbamoyl group; and the like.

[0039] Examples of the halogen atom contained in the heterocyclic ring-containing group include a fluorine atom, a chlorine atom, a bromine atom, and the like.

[0040] Since a stable porous compound is easily obtained, R 1 is preferably a pyridyl group with or without a substituent.

[0041] In formula (I), A 1 is a group represented by the following formula (III).

[0042]

Chemical formula

[0043] In formula (III), R 2 , R 3 each independently represents an alkyl group having 1 to 5 carbon atoms (however, R 2 -C-R 3 includes a ring structure formed by the bonding of R 2 and R 3 ). *2 represents a bond with X 1 , and *3 represents a bond with A 2 .

[0044] R 2 , R 3 has 1 to 5 carbon atoms in the alkyl group, and 1 to 3 are preferred. Examples of the alkyl group of R 2 , R 3 include a methyl group, an ethyl group, a 1-propyl group, an isopropyl group, etc. Examples of the ring structure formed by the bonding of R 2 and R 3 include a cyclobutane ring, a cyclopentane ring, a cyclohexane ring, etc.

[0045] Since a stable porous compound is easily obtained, R 2 and R 3 are both preferably methyl groups.

[0046] In formula (I), A 2 is a group represented by any of the following formulas (IV-1) to (VI-12).

[0047]

Chemical formula

[0048] In formulas (IV-1) to (VI-12), *4 represents a bond with A 1 and *5 represents a bond with A 3 and. R 4 is a group or atom having 1 to 5 atoms (excluding the number of hydrogen atoms). "R 4 -" represents that R 4 is bonded to any carbon atom constituting a 4-membered ring, 5-membered ring or 6-membered ring. A 2 When A has R 4 , the number of R 4 is 1 or 2 or more. A 2 When A has a plurality of R 4 , the plurality of R 4 may be the same as or different from each other.

[0049] R 4 is a group or atom having 1 to 5 atoms (excluding the number of hydrogen atoms), and a group or atom having 1 to 3 atoms is preferred. R 4 Examples of R include alkyl groups having 1 to 5 carbon atoms such as methyl group, ethyl group, 1-propyl group, isopropyl group, etc.; alkoxy groups having 1 to 4 carbon atoms such as methoxy group, ethoxy group, propoxy group, isopropoxy group, etc.; hydroxy group; halogen atoms such as fluorine atom, chlorine atom, bromine atom, etc.

[0050] Since a stable porous compound is easily obtained, A 2 is preferably a group represented by formula (IV-2), formula (IV-5), formula (IV-8), or formula (IV-11).

[0051] In formula (I), A 3 is a group represented by any one of the following formulas (V-1) to (V-12).

[0052]

Chemical formula

[0053] In formulas (V-1) to (V-12), *6 represents a bond with A 2 and *7 represents a bond with X 2 . R 5 is a group or atom having 1 to 5 atoms (excluding the number of hydrogen atoms). "R 5 -" represents that R 5 is bonded to any carbon atom constituting a 4-membered ring, 5-membered ring, or 6-membered ring. A 3 When A has R 5 , the number of R 5 is 1 or 2 or more. A 3 When A has a plurality of R 5 , the plurality of R 5 may be the same as or different from each other.

[0054] R 5 is a group or atom having 1 to 5 atoms (excluding the number of hydrogen atoms), and a group or atom having 1 to 3 atoms is preferred. Examples of R 5 include alkyl groups having 1 to 5 carbon atoms such as methyl group, ethyl group, 1-propyl group, and isopropyl group; alkoxy groups having 1 to 4 carbon atoms such as methoxy group, ethoxy group, propoxy group, and isopropoxy group; hydroxy group; halogen atoms such as fluorine atom, chlorine atom, and bromine atom; and the like.

[0055] Since a stable porous compound is easily obtained, A 3 is preferably a group represented by formula (V-2), formula (V-5), formula (V-8), or formula (V-11).

[0056] In formula (I), X 2 is a group represented by the following formula (VI).

[0057] [Chemical formula]

[0058] In formula (VI), R 6 represents a group having a coordinating atom, and *8 represents A 3represents a bonding hand with [object].

[0059] R 6 is a group having a coordinating atom. R 6 Examples of the coordinating atoms contained in R 6 include a nitrogen atom constituting an amino group, a nitrogen atom constituting a heterocyclic group, an oxygen atom constituting a carboxylic acid ion, an oxygen atom constituting a phenoxide ion, an oxygen atom constituting an alkoxide ion, a sulfur atom constituting a thiolate ion, and the like. R 6 The number of atoms (excluding hydrogen atoms) in R 6 is usually 1 to 20, preferably 1 to 10.

[0060] Since a stable porous compound is easily obtained, R 6 is preferably a heterocyclic group, more preferably a nitrogen-containing heterocyclic group. Examples of the heterocyclic ring include a pyridine ring, a pyridazine ring, a pyrimidine ring, a pyrazine ring, an imidazole ring, a pyrazole ring, and the like. Examples of the heterocyclic group include the same ones as those described for the heterocyclic group of R 1 . Since a stable porous compound is easily obtained, R 6 is preferably a pyridyl group with or without substituents.

[0061] The coordination compound of the present invention has a group having a coordinating atom at both ends (R in X 1 , R in X 1 , X 2 , R in X 6 ). Therefore, by combining the coordination compound of the present invention with a metal ion, a polymer metal complex such as a porous compound can be efficiently obtained.

[0062] The coordination compound of the present invention has a tripeptide skeleton represented by -A 1 -A 2 -A 3 . Since the coordination compound of the present invention has a tripeptide backbone, by using the coordination compound of the present invention, crystals of a porous compound having hydrophilic pores can be efficiently obtained.

[0063] A 1 In, rotation around the N-C α bond and the C α -C bond is possible, respectively. However, due to the steric hindrance of R 1 and R 2 in A 3 , the stable state of A 1 is limited to the following state α or state β. Here, C α means the α-carbon (the carbon adjacent to the carboxy group in the corresponding amino acid).

[0064] State α: The dihedral angle φ is usually -20 to -70°, and the dihedral angle ψ is usually -35 to -55°. State β: The dihedral angle φ is usually 20 to 70°, and the dihedral angle ψ is usually 25 to 45°.

[0065]

Chemical formula

[0066] On the other hand, since A 2 and A 3 in the above tripeptide backbone have a ring structure containing atoms constituting the main chain, in the part of "A 2 -A 3 ", the rotational movement around the main chain is hindered, and it has a rigid structure.

[0067] Thus, in the coordination compound of the present invention, as a result of the restricted rotational movement around the main chain, as stable molecules, there are two types: a molecule in which A 1 is in state α (a molecule having the conformation represented in FIG. 1, hereinafter sometimes referred to as conformational isomer (α)), and a molecule in which A 1 is in state β (a molecule having the conformation represented in FIG. 2, hereinafter sometimes referred to as conformational isomer (β)).

[0068] Since the coordination compound of the present invention has the above structural characteristics, by using the coordination compound of the present invention, crystals of a porous compound having pores of a size capable of regularly accommodating guest molecules can be efficiently obtained. In the present specification, the "guest molecule" means a molecule included in the pores or the hollow of the crystal of the porous compound.

[0069] The coordination compound of the present invention can be synthesized by using known reactions. For example, "H-A 2 -A 3 -X 2 " where the nitrogen atom in A 2 is protected by a protecting group, and a compound where the carboxy group (A 1 -A 1 -OH) in "X 1 -A -OH]" is protected by a protecting group are each synthesized, and then these are deprotected and reacted to obtain the coordination compound of the present invention. Examples of the protecting group for the nitrogen atom include a t-butoxycarbonyl group and the like.

[0070] 2) Crystals of the porous compound The crystal of the porous compound of the present invention is a crystal of a porous compound having a three-dimensional skeleton composed of one or two or more molecular chains and three-dimensionally regularly arranged pores formed by being partitioned by the three-dimensional skeleton, wherein the molecular chains constituting the three-dimensional skeleton contain the coordination compound of the present invention and ions of an element of Group 11 of the periodic table.

[0071] The three-dimensional skeleton refers to a skeletal structure having a three-dimensional spread inside the crystal. The three-dimensional skeleton is usually composed of one or two or more molecular chains. The "molecular chain" refers to an organized body organized by covalent bonds and / or coordination bonds. There may be a branched structure or a cyclic structure in this molecular chain. Examples of the three-dimensional skeleton composed of the molecular chain of 1 include a skeleton organized in a "jungle gym" shape. The three-dimensional skeleton composed of two or more molecular chains refers to a skeleton in which two or more molecular chains are organized as a whole by interactions such as hydrogen bonds, π-π stacking interactions, and van der Waals forces. The "three-dimensionally regularly aligned pores" refer to pores that are regularly aligned without being disordered to the extent that they can be confirmed by crystal structure analysis. The "pores" refer to the internal space extending in a cylindrical shape within the crystal. The porous compound of the present invention may have an internal space other than the pores. In this specification, the internal space other than the pores is referred to as "hollow".

[0072] The crystal of the porous compound of the present invention contains the coordination compound of the present invention (hereinafter, may be referred to as "coordination compound (i)") as a part of the molecular chain constituting the three-dimensional skeleton. By the crystal of the porous compound of the present invention containing the coordination compound (i), hydrophilic pores are formed. The crystal of the porous compound of the present invention preferably contains both the conformational isomer (α) and the conformational isomer (β) as the coordination compound (i). By the porous compound of the present invention containing both the conformational isomer (α) and the conformational isomer (β), pores more suitable for accommodating guest molecules are easily formed.

[0073] The crystal of the porous compound of the present invention contains ions of an element of Group 11 of the periodic table as a part of the molecular chain constituting the three-dimensional skeleton. By the crystal of the porous compound of the present invention containing ions of an element of Group 11 of the periodic table, pores of a size capable of regularly accommodating guest molecules are formed. Examples of the ions of the element of Group 11 of the periodic table include Cu + , Ag + , Au + .

[0074] The crystal of the porous compound of the present invention may have anions or electrically neutral compounds in the pores or the hollow.

[0075] The molecular chains that make up the three-dimensional skeleton in the crystal of the porous compound of the present invention usually have a positive charge. Therefore, due to the presence of anions in the pores or the hollow inside the crystal of the porous compound, the electrical balance of the crystal of the porous compound of the present invention is maintained. Examples of the anion include hydroxide ion (OH - ), chloride ion (Cl - ), bromide ion (Br - ), iodide ion (I - ), thiocyanate ion (SCN - ), nitrate ion (NO3 - ), perchlorate ion (ClO4 - ), tetrafluoroborate ion (BF4 - ), hexafluoroantimonate ion (SbF6 - ), hexafluorophosphate ion (PF6 - ), hexafluoroarsenate ion (AsF6 - ), acetate ion (CH3CO2 - ), trifluoroacetate ion (CF3CO2 - ), triflate ion (CF3SO3 - ), bis(trifluoromethanesulfonyl)imide ion ((CF3SO2)2N - ) and other monovalent anions; oxide ion (O 2- ), sulfate ion (SO4 2- ) and other divalent anions; and the like.

[0076] Examples of the electrically neutral compound include the compound used as a solvent and coordinating compounds such as ammonia, monoalkylamine, dialkylamine, trialkylamine, ethylenediamine, and pyridine. Examples of the solvent include nitriles such as acetonitrile and benzonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); amides such as N,N-dimethylformamide and n-methylpyrrolidone; ethers such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropyl alcohol; ketones such as acetone, methyl ethyl ketone, and cyclohexanone; cellosolves such as ethyl cellosolve; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, and 1,2-dichloroethane; nitros such as nitromethane and nitroethane; esters such as methyl acetate, ethyl acetate, ethyl lactate, and ethyl propionate; water; and the like.

[0077] In addition, the above anions and electrically neutral compounds may not only be present in the pores and the interior of the hollow, but may also be included as part of the molecular chain constituting the three-dimensional skeleton.

[0078] Examples of the porous compound of the present invention include those whose repeating unit is represented by the following formula.

[0079]

Chemical formula

[0080] In the formula, M represents an ion of an element in Group 11 of the periodic table, L represents a coordinating compound (i), X represents a monovalent anion, Y represents an electrically neutral compound, a is an arbitrary number, X may be the same as or different from each other, and Y may be one kind or two or more kinds.

[0081] The porous compound of the present invention preferably has a repeating unit represented by the following formula.

[0082]

Chemical formula

[0083] In the formula, L represents the coordination compound (i). Two Ls are preferably the conformational isomers (α) and (β). m and n are arbitrary numbers.

[0084] The pores of the crystal of the porous compound of the present invention preferably have a rectangular or parallelogram cross-sectional shape. By having a rectangular or parallelogram cross-sectional shape, the interaction with guest molecules becomes easier, and the guest molecules can be more stably accommodated. When the cross-sectional shape of the pore is rectangular or parallelogram, the length of the long side is preferably 2.0 to 4.0 nm, more preferably 2.5 to 3.5 nm, and the length of the short side is preferably 0.5 to 2.5 nm, more preferably 1.0 to 2.0 nm. Note that the lengths of these sides are the shortest metal ion distances in the relationship of opposite sides in the pore cross-section when the pore thickness is not constant.

[0085] The cross-sectional shape and thickness of the pore can be determined by drawing a cross-sectional view of the pore in a plane (hereinafter sometimes referred to as a parallel plane) that is parallel to the crystal plane closest to perpendicular to the direction in which the pore extends. The "direction in which the pore extends" can be determined by the following method. That is, first, select a crystal plane X (such as plane A, plane B, plane C, or their diagonal planes) in an appropriate direction that crosses the target pore. Then, represent the atoms existing on the crystal plane X and constituting the three-dimensional framework using the van der Waals radius, and draw a cross-sectional view of the pore with the crystal plane X as the cut surface. Similarly, draw a cross-sectional view of the pore with the crystal plane Y that is displaced by one unit cell from the crystal plane X as the cut surface. Next, connect the centers of the cross-sectional shapes of the pores in each crystal plane with a straight line (dashed line) in a three-dimensional view (see Figure 3). The direction of the straight line obtained at this time is the direction in which the pore extends. Also, the "cross-sectional shape and thickness of the pore" can be obtained by the following method. That is, first, in the same manner as described above, a cross-sectional view of the pores with the parallel plane as the cut surface is drawn. Next, while gradually translating the parallel plane by one unit cell, by drawing cross-sectional views of the pores on each parallel plane, the shape of the cross-section of the pores in which metal ions are arranged on the sides of a rectangle or a parallelogram and its thickness (the shortest distance between metal ions in the relationship of the opposite sides represented in the cross-sectional view) can be determined.

[0086] The crystal of the porous compound of the present invention preferably has single crystallinity. In the present invention, "having single crystallinity" means being able to serve as a measurement sample for crystal structure analysis.

[0087] The crystal of the porous compound having single crystallinity is preferably one in which the molecular structure can be determined with a resolution of at least 1.5 Å when irradiated with MoKα rays (wavelength: 0.71 Å) generated at a tube voltage of 24 kV and a tube current of 50 mA and the diffracted X-rays are detected by a CCD detector. By using a crystal having such characteristics, the presence of guest molecules can be easily confirmed by crystal structure analysis.

[0088] The method for synthesizing the crystal of the porous compound of the present invention is not particularly limited, and known methods can be used. For example, the porous compound of the present invention can be synthesized using the method described in the Sigma-Aldrich pamphlet (Fundamentals of Materials Science, No. 7 - Fundamentals of Porous Coordination Polymers (PCP) / Metal-Organic Frameworks (MOF)) issued in September 2012. More specifically, a solution method in which a solution containing a polydentate ligand or the like and a solution containing metal ions or the like are mixed; a hydrothermal method in which a solvent, a polydentate ligand, metal ions, etc. are placed in a pressure-resistant container, the pressure-resistant container is sealed, and then heated to a temperature above the boiling point of the solvent to perform a hydrothermal reaction; a microwave method in which a solvent, a polydentate ligand, metal ions, etc. are placed in a container and irradiated with microwaves; an ultrasonic method in which a solvent, a polydentate ligand, metal ions, etc. are placed in a container and irradiated with ultrasonic waves; a solid-phase synthesis method in which a polydentate ligand, metal ions, etc. are mechanically mixed without using a solvent; and the like.

[0089] Among these, the solution method is preferably used because no special device or the like is required. As the solution method, for example, there is a method in which a solution of the coordination compound (i) and a solution of a salt of a Group 11 metal of the periodic table are stacked in layers and allowed to stand. Further, a layer of only a solvent may be provided between these layers. The solvent to be used can be appropriately determined in consideration of the solubility of the coordination compound (i), the salt of the Group 11 metal of the periodic table, the crystal of the porous compound, etc. Since the coordination compound (i) and the salt of the Group 11 metal of the periodic table are hydrophilic compounds, it is preferable to use a combination of water, an alcohol-based solvent, a ketone-based solvent, an ester-based solvent, etc. as appropriate. The temperature at the time of standing is usually 0 to 60°C, preferably 10 to 35°C. The standing time is usually 1 to 500 days, preferably 100 to 180 days. Note that crystals may be precipitated more efficiently by adding seed crystals or the like.

[0090] Since the crystal of the porous compound of the present invention has a three-dimensional skeleton composed of a molecular chain containing a coordination compound (i) and an ion of a Group 11 element of the periodic table, the inside of the pores is highly hydrophilic. Therefore, the crystal of the porous compound of the present invention can stably accommodate a hydrophilic compound in its pores.

[0091] The crystal of the porous compound of the present invention contains a coordination compound (i) having a relatively rigid structure, and pores of a size suitable for accommodating guest molecules are easily formed. Further, since the coordination compound (i) has a tripeptide skeleton, affinity interactions such as hydrogen bonds and ionic bonds may occur with guest molecules. Therefore, the crystal of the porous compound of the present invention tends to regularly accommodate guest molecules in its pores.

[0092] The coordination compound (i) contained in the crystal of the porous compound of the present invention is a chiral compound. Therefore, the pores of the crystal of the porous compound of the present invention can provide a chiral environment for guest molecules that can interact.

[0093] Since the pores of the crystals of the porous compound of the present invention have these characteristics, as shown in the examples, the crystals of the porous compound of the present invention have various functions.

[0094] Example 5 is an experiment using 1,4-anhydroerythritol as a guest molecule. Mesomers such as 1,4-anhydroerythritol are achiral compounds, but the two stable conformations (conformations shown in the following figure) are not equivalent in a chiral environment. In Example 5, 1,4-anhydroerythritol tended to adopt a more suitable conformation depending on the nature of the accommodation site. Thus, the crystals of the porous compound of the present invention have the function of determining the conformation of guest molecules.

[0095]

Chemical formula

[0096] Example 6 is an experiment using methyl acetoacetate as a guest molecule. 1,3-diketone compounds such as methyl acetoacetate are usually in an equilibrium state between the keto form and the enol form in solution. In Example 6, methyl acetoacetate was accommodated as the keto form. Furthermore, all the torsional directions of the accommodated methyl acetoacetate were the same. Thus, the crystals of the porous compound of the present invention have the function of expressing chirality to guest molecules.

[0097] Example 7 is an experiment using methyl pyruvate as a guest molecule. In Example 7, together with methyl pyruvate, the ethanol adduct (hemiacetal) of methyl pyruvate was accommodated. Also, all the accommodated hemiacetals were in the S form. Thus, the crystals of the porous compound of the present invention have the functions of stabilizing usually unstable compounds and promoting asymmetric reactions.

[0098] Example 8 is an experiment using cyclohexanol as a guest molecule. The most stable conformation of cyclohexanol is the chair form, and the twist-boat form is an unstable conformation. In Example 8, the twist-boat form of cyclohexanol was accommodated together with the chair form of cyclohexanol. Thus, the crystal of the porous compound of the present invention has a function of stably accommodating a guest molecule in an unstable conformation.

[0099] As shown in the examples, the crystal of the porous compound of the present invention is not only used for confirming the molecular structure of the guest molecule (crystal sponge method), but also as a reaction apparatus for performing an asymmetric reaction or the like, and as an observation apparatus for observing a molecule in an unstable state.

[0100] 3) Inclusion compound The inclusion compound of the present invention is an inclusion compound in which a guest molecule is accommodated in the pores of a crystalline host molecule, and the crystalline host molecule is a crystal of the porous compound.

[0101] The crystalline host molecule constituting the inclusion compound of the present invention is a crystal of the porous compound of the present invention (hereinafter, may be referred to as "crystal (ii) of the porous compound"). By using the crystal (ii) of the porous compound as the crystalline host molecule, a relatively small guest molecule can be efficiently accommodated in its pores.

[0102] The guest molecule constituting the inclusion compound of the present invention is not particularly limited as long as it can be accommodated in the pores of the crystal (ii) of the porous compound. The molecular weight of the guest molecule is usually 20 to 1200, preferably 50 to 300.

[0103] The guest molecule constituting the inclusion compound of the present invention may be a compound having a polar group. The molecular chains constituting the crystal (ii) of the porous compound contain a coordination compound (i) or a metal ion. Therefore, an affinity interaction is likely to occur between the molecular chains constituting the crystal (ii) of the porous compound and the polar groups of the guest molecule, and the guest molecule tends to be regularly accommodated.

[0104] Examples of the polar group include a hydroxyl group, a carboxy group, a carbonyl group, an ester group, an amino group, an amide group, and the like.

[0105] The guest molecule constituting the inclusion compound of the present invention may be a chiral compound. When the guest molecule is a chiral compound, the absolute configuration of the guest molecule can be determined by synthesizing the inclusion compound of the present invention. That is, since the molecular chains constituting the crystal (ii) of the porous compound contain a coordination compound (i) that is a chiral compound, if the absolute configuration of the coordination compound (i) is known, based on the relative positional relationship with the coordination compound (i), the absolute configuration of the chiral guest molecule can be easily determined.

[0106] The method for synthesizing the inclusion compound of the present invention is not particularly limited. For example, a method of preparing a solution containing a guest molecule and bringing the crystal (ii) of the porous compound into contact with this solution, or when the guest molecule is a liquid or a gas, a method of directly bringing the crystal (ii) of the porous compound into contact with the guest molecule can be used to incorporate the guest molecule into the pores of the crystal (ii) of the porous compound. Among them, when the inclusion compound is used as a sample for crystal structure analysis, a method of preparing a solution containing a guest molecule and bringing the crystal (ii) of the porous compound into contact with this solution is preferable.

[0107] The solvent of the solution containing the guest molecule is appropriately selected from those that do not dissolve the crystal (ii) of the porous compound used and dissolve the guest molecule. Specific examples of the solvent to be used include aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene, nitrobenzene; aliphatic hydrocarbons such as n-butane, n-pentane, n-hexane, n-heptane; alicyclic hydrocarbons such as cyclopentane, cyclohexane, cycloheptane; nitriles such as acetonitrile, benzonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); amides such as N,N-dimethylformamide, n-methylpyrrolidone; ethers such as diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane; alcohols such as methanol, ethanol, isopropyl alcohol; ketones such as acetone, methyl ethyl ketone, cyclohexanone; cellosolves such as ethyl cellosolve; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane; nitros such as nitromethane, nitroethane; esters such as methyl acetate, ethyl acetate, ethyl lactate, ethyl propionate; water; and the like. These solvents can be used alone or in combination of two or more.

[0108] The amount of the guest molecule to be used is not particularly limited. The time for contacting the crystal (ii) of the porous compound with the guest molecule is not particularly limited, but is usually from 1 minute to 50 days, preferably from 6 hours to 7 days. The temperature for contacting the crystal (ii) of the porous compound with the guest molecule is not particularly limited, but is usually -20 to 150 °C, preferably 0 to 50 °C.

[0109] 4) Method for preparing a sample for crystal structure analysis The method for preparing a sample for crystal structure analysis of the present invention is characterized in that molecules of the compound to be analyzed are incorporated into the pores of the crystal of the porous compound having single crystallinity, and the molecules of the compound to be analyzed are regularly arranged.

[0110] The phrase "the molecules of the compound to be analyzed are regularly arranged" means that the molecules of the compound to be analyzed are regularly accommodated in the pores of the crystal of the porous compound without being disordered to the extent that the structure can be determined by crystal structure analysis.

[0111] The method for preparing a sample for crystal structure analysis of the present invention performs the same operations as the above-described method for synthesizing the inclusion compound, except that a requirement of using a crystal of a porous compound having single crystallinity is imposed, to prepare a sample for crystal structure analysis.

[0112] The sample for crystal structure analysis preferably has a resolution of at least 1.5 Å and can determine the molecular structure when irradiated with MoKα rays (wavelength: 0.71 Å) generated at a tube voltage of 24 kV and a tube current of 50 mA, and the diffracted X-rays are detected by a CCD detector.

[0113] The sample for crystal structure analysis does not need to have the molecules of the compound to be analyzed accommodated in all the accommodation sites in the crystal of the porous compound as long as it can determine the molecular structure of the compound to be analyzed. For example, a part of the accommodation sites may contain the solvent used in the solution containing the compound to be analyzed.

[0114] The sample for crystal structure analysis preferably has an occupancy of 10% or more of the molecules of the compound to be analyzed, more preferably 50% or more, and even more preferably 70% or more. The occupancy is a value obtained by crystal structure analysis and represents the amount of guest molecules (molecules of the compound to be analyzed) actually present in the sample for crystal structure analysis when the amount of guest molecules in the ideal inclusion state is set to 100%.

Examples

[0115] Hereinafter, the present invention will be described in more detail with reference to examples. Note that the present invention is not limited to the following examples at all.

[0116] 〔Single crystal X-ray crystal structure analysis〕 Single-crystal X-ray crystallographic analysis was performed using a Bruker APEX-II / CCD diffractometer [Mo-Kα radiation (wavelength 0.71073 Å)].

[0117] The abbreviations of the reagents used in the examples are as follows. H-Aib-OEt·HCl: 2-Amino-2-methyl-propionic acid ethyl ester hydrochloride EDCI: EDCI·HCl; 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride HOBt: HOBt·H2O; 1-hydroxylbenzotriazole monohydrate DIEA: N,N-diisopropylethylamine boc: t-butoxycarbonyl group Boc-L-Pro-OH: N-boc-L-Proline H-Aib-OEt·HCl: α-Aminoisobutyric acid ethyl ester hydrochloride DMF: N,N-dimethylformamide

[0118] Example 1: Synthesis of Coordination Compound (1) As shown in the following scheme, Compound (2) and Compound (3) were reacted to synthesize Coordination Compound (1). The details are shown below.

[0119]

Chemical formula

[0120] (Step 1) Synthesis of N-(3-Pyridyl)-N’-boc-prolylprolineamide [(Compound (2)] Compound (2) was synthesized according to the method described in Angew. Chem. Int. Ed. 2016, 55, 4519 - 4522.

[0121] (Step 2) Synthesis of 2 - Methyl - N-(3 - pyridinylcarbonyl)-alanine ethyl ester [Compound (3)]

[0122] 1.2 g (10 mmol) of nicotinic acid, 1.7 g (10 mmol) of H - Aib - OEt·HCl, 2.3 g (12 mmol) of EDCI, and 1.8 g (12 mmol) of HOBt were dissolved in dichloromethane. After slowly adding 2.6 mL (15 mmol) of DIEA to the resulting solution, the solution was stirred at room temperature (25 °C, the same hereinafter) for 2 days to carry out the reaction. Subsequently, the reaction mixture was washed twice with saturated aqueous NaHCO3 solution and once with brine, and then the organic layer was taken out. The obtained organic layer was dried over MgSO4. After filtering off MgSO4, the organic layer was evaporated to concentrate, and then the concentrate was dried under vacuum to obtain 1.9 g of a pale - yellow solid [Compound (3)] (yield 76%).

[0123] (Step 3) Compound (3) obtained in Step 2 was dissolved in an aqueous methanol solution. After slowly adding 1.6 g (38 mmol) of LiOH·H2O to the resulting solution, the solution was stirred at room temperature for 5 hours. Subsequently, the solution was neutralized with 5N HCl aqueous solution (5 mL). The solvent was distilled off from the reaction solution, and the residue was dried under vacuum to obtain a pale - yellow oily substance. This oily substance contains the deprotected Compound (3) and LiCl salt.

[0124] (Step 4) 1.3 g (6.6 mmol) of Compound (2) obtained in Step 1 was dissolved in methanol (5 mL). After slowly adding 8.3 mL (33 mmol) of 4N HCl (1,4 - dioxane solvent) to the resulting solution, the solution was stirred for 2 hours. The solvent was distilled off from the reaction solution, and the residue was dried under vacuum to obtain a white solid. This white solid is the deprotected compound (2).

[0125] (Step 5) 2.4 g (6.6 mmol) of the pale yellow oily substance obtained in Step 3, 1.3 g (6.6 mmol) of the white solid obtained in Step 4, 1.2 g (7.9 mmol) of HOBt, 1.5 g (7.9 mmol) of EDCI and 2.9 mL (16.5 mmol) of DIEA were dissolved in DMF. The resulting solution was stirred at room temperature for 2 days, and then the solvent was distilled off under reduced pressure. The residue was dissolved in a small amount of solvent (ethyl acetate:methanol = 1:2). Using the resulting solution as a sample solution, silica gel column chromatography (ethyl acetate:methanol = 10:1 → 2:1) was performed. The fractions containing the target product were collected, evaporated to dryness, and a yellow oily substance was obtained. The obtained oily substance was dissolved in methanol (about 20 mL). Using the resulting solution as a sample solution, preparative SEC (Size Exclusion Chromatography) (methanol) was performed. The fractions containing the target product were collected, evaporated to dryness, and an oily substance was obtained. This oily substance was dissolved in about 5 mL of CHCl3, and the resulting solution was poured into a diethyl ether layer (100 mL) on ice to obtain a white powder. This was collected by filtration and dried under vacuum to obtain 1.6 g of a white powder [coordination compound (1)]. (Yield 51%).

[0126] [Example 2] Synthesis of porous compound (4) In a test tube with a diameter of 6 mm, the following solutions were layered as follows. Upper layer: Ethanol solution of coordination compound (1) (12 μmol), 150 μL Middle layer: Mixed solvent [ethanol / water = 1 / 1 (v / v)], 150 μL Lower layer: Aqueous solution with AgBF4 and AgPF6 (17 mol%) as solutes (the amount of silver ions is 12 μmol), 150 μL

[0127] By leaving it standing at 30 °C for 5 months as it was, rod-shaped crystals [porous compound (4)] were obtained. Elemental analysis was performed on the obtained crystals. The results are shown below.

[0128]

Table 1

[0129] In addition, single crystal X-ray crystallographic analysis was performed using the obtained crystals. The results are shown in FIGS. 4, 5, and 6.

[0130] In the single crystal X-ray crystallographic analysis, the molecular chains constituting the three-dimensional skeleton, water molecules, ethanol molecules, and hexafluorophosphate ions could be confirmed, but hydroxide ions could not be found. As shown in FIGS. 4 and 5(a), the porous compound (4) has pores with a parallelogram cross-sectional shape composed of two molecules of conformational isomer (α) and two molecules of conformational isomer (β). The length of the long side of this parallelogram is 3.0 nm, and the length of the short side is 1.4 nm. As shown in FIG. 5(b), the anion (PF6 - ) is accommodated at a specific position. In FIG. 5(a), the anion and solvent molecules are removed, and in FIG. 5(b), the solvent molecules are removed. As shown in FIG. 6, the three-dimensional skeleton of the porous compound (4) is formed by the entanglement of the molecular chains containing the coordination compound (3) and silver ions.

[0131] Note that the solution in which the crystals precipitated is considered to contain crystal nuclei. Therefore, the supernatant (100 μL) after the crystals precipitated was transferred to another test tube and allowed to stand at 15 °C for about one week, whereby a large amount of crystals could be obtained.

[0132] 〔Method for storing crystals〕 The crystals obtained in Example 2 were transferred to a 1.5 mL microtube and washed 5 times with ethanol. The washed crystals were immersed in ethanol and stored at room temperature. By this method, the crystals can be stored stably for several months. The "crystals obtained in Example 2" used in Examples 3 to 7 are the crystals preserved by this method.

[0133] [Example 3] Synthesis of an inclusion compound containing (S)-1,2-propanediol (5) as a guest molecule The crystals obtained in Example 2 were transferred together with 20 μL of ethanol to 100 μL of (S)-1,2-propanediol (5) and allowed to stand at room temperature for 4 days as it was. As a result of crystal structure analysis, (S)-1,2-propanediol (5) was confirmed (Figure 7). The primary hydroxyl group of (S)-1,2-propanediol (5) is weakly coordinated to silver ions. Furthermore, there are attractive interactions such as van der Waals interactions and hydrogen bonds between (S)-1,2-propanediol (5) and the molecular chain of the porous compound (4) (Figure 8). Due to these intermolecular interactions, (S)-1,2-propanediol (5) is stabilized. In this case, although an inclusion compound was synthesized using a guest molecule whose absolute configuration was known, even if the absolute configuration of the guest molecule is unknown, the absolute configuration of the guest molecule can be determined based on the absolute configuration of the coordination compound (3).

[0134] [Example 4] Synthesis of an inclusion compound containing (R)-1,2-propanediol (5) as a guest molecule The crystals obtained in Example 2 were transferred together with 20 μL of ethanol to 100 μL of (R)-1,2-propanediol (5) and allowed to stand at room temperature for 4 days as it was. As a result of crystal structure analysis, (R)-1,2-propanediol (5) was confirmed (Figure 9).

[0135] [Example 5] Synthesis of an inclusion compound containing 1,4-anhydroerythritol (6) as a guest molecule The crystals obtained in Example 2 were transferred together with 20 μL of ethanol to 100 μL of 1,4-anhydroerythritol (6) and allowed to stand at room temperature for 4 days as it was. As a result of crystal structure analysis, two conformational isomers were confirmed (Figure 10).

[0136] Example 5: Synthesis of an inclusion compound containing methyl acetoacetate (7) as a guest molecule The crystals obtained in Example 2 were transferred together with 20 μL of ethanol to 100 μL of methyl acetoacetate (7), and left standing at room temperature for 4 days as it was. As a result of crystal structure analysis, it was confirmed that all of the methyl acetoacetate was in the keto form (Fig. 11). The dihedral angle (τ) between the two carbonyl groups was 68 - 108°, and all the molecules were twisted in the same direction.

[0137]

Chemical formula

[0138] Example 6: Synthesis of an inclusion compound containing methyl pyruvate (8) as a guest molecule The crystals obtained in Example 2 were transferred together with 20 μL of ethanol to 100 μL of methyl pyruvate (8), and left standing at room temperature for 4 days as it was. As a result of crystal structure analysis, together with methyl pyruvate (8), an ethanol adduct (hemiacetal) (9) of methyl pyruvate was confirmed (Fig. 12). Incidentally, all of this hemiacetal (9) was in the S form.

[0139] Example 7: Synthesis of an inclusion compound containing cyclohexanol (10) as a guest molecule The crystals obtained in Example 2 were transferred together with 20 μL of ethanol to 100 μL of cyclohexanol (10), and left standing at room temperature for 4 days as it was. As a result of crystal structure analysis, both a chair-shaped molecule (10a) and a twisted boat-shaped molecule (10b) were confirmed (Fig. 13).

Explanation of symbols

[0140] 1: Crystal plane X 2: Crystal plane Y 3: Pore 4: Direction in which the pore extends

Claims

1. A coordination compound represented by the following formula (I). 【Chemical 1】 In formula (I), X １ is the following formula (II) 【Chemical 2】 (R １ represents a nitrogen-containing heterocyclic group having a substituent or being unsubstituted, and the unsubstituted nitrogen-containing heterocyclic group has the following formula [Chemical Formula 3] is a group represented by any of them. *1 represents a bond with A １ represents a bond with). is a group represented by, and A １ is the following formula (III) 【Chemical Formula 4】 (R ２ , R ３ are each independently an alkyl group having 1 to 5 carbon atoms (provided that R ２ -C-R ３ contains a ring structure formed by the bonding of R ２ and R ３ ). *2 represents a bond with X １ , and *3 represents a bond with A ２ ).) is a group represented by, and A ２ is the following formulas (IV-1) to (VI-12) 【Chemical Formula 5】 (*4 represents a bond with A １ and *5 represents a bond with A ３ . R ４ is the number of atoms (excluding the number of hydrogen atoms). is a group or atom of 1 to 5. "R ４ -" means that R ４ is bonded to any carbon atom constituting a 4-membered ring, 5-membered ring or 6-membered ring. A ２ has R ４ , the number of R ４ is 1 or 2 or more. A ２ has a plurality of R ４ , when a plurality of R ４ are present, the plurality of R ４ may be the same as each other or different from each other. ) is a group represented by any of them, and A ３ is represented by the following formulas (V-1) to (V-12) 【Chemical Formula 6】 (*6 represents a bond with A ２ and *7 represents a bond with X ２ . R ５ is the number of atoms (excluding the number of hydrogen atoms). is a group or atom of 1 to 5. "R ５ -" means that R ５ is bonded to any carbon atom constituting a 4-membered ring, 5-membered ring or 6-membered ring. A ３ When A has R ５ , the number of R ５ is 1 or 2 or more. A ３ When A has a plurality of R ５ , the plurality of R ５ may be the same as each other or different from each other.) is a group represented by any of, and X ２ is represented by the following formula (VI) 【Chemical Formula 7】 (R ６ represents a nitrogen-containing heterocyclic group which has a substituent or is unsubstituted, and the unsubstituted nitrogen-containing heterocyclic group has the following formula 【Chemical 8】 is a group represented by any of them. *8 represents a bond with A ３ ). is a group represented by.

2. R １ is a pyridyl group having a substituent or unsubstituted, and R ６ is a pyridyl group having a substituent or unsubstituted, the coordination compound according to claim 1.

3. A crystal of a porous compound having a three-dimensional skeleton composed of one or two or more molecular chains and three-dimensionally regularly arranged pores formed by being partitioned by the three-dimensional skeleton, The crystal of the porous compound, wherein the molecular chain constituting the three-dimensional skeleton contains the coordination compound according to Claim 1 or 2 and ions of an element of Group 11 of the periodic table.

4. The crystal of the porous compound according to Claim 3, which has single crystallinity.

5. An inclusion compound in which guest molecules are accommodated in the pores of a crystalline host molecule, The inclusion compound, wherein the crystalline host molecule is the crystal of the porous compound according to Claim 3 or 4.

6. The inclusion compound according to Claim 5, wherein the guest molecule is a compound having a polar group.

7. The inclusion compound according to Claim 5 or 6, wherein the guest molecule is a chiral compound.

8. A method for preparing a sample for crystal structure analysis, characterized by incorporating molecules of a compound to be analyzed into the pores of the crystal of the porous compound according to Claim 4 and regularly arranging the molecules of the compound to be analyzed.

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