JP2500329B2 - ALPHA.-Amino acid polymer having crown compound residue and method for producing the same - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an .alpha.-amino acid polymer having a crown compound residue on at least one of its main chain, side chain and terminal, and a process for producing the same. The α-amino acid polymer having a crown compound residue in the main chain or the like of the present invention is used as, for example, a chemical analysis reagent, a sensor-sensitive substance, an element for electronics, or the like.

[0002]

2. Description of the Related Art Crown compounds are known to selectively form complexes with various metal ions such as alkali metal ions and alkaline earth metal ions. Therefore, a new analysis method for detecting metal ions by utilizing crown compounds as a sensitive substance by utilizing this characteristic has been considered. For example, using a crown compound that emits fluorescence by forming a complex with a specific metal ion, a method of identifying a metal ion by fluorescence spectroscopy, or a membrane potential using a polymer thin film embedded with a crown compound. Methods for identifying metal ions are known. Furthermore, new detection methods are desired, and development of new crown compounds for them is needed.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel crown compound derivative used for detecting metal ions and the like and a method for producing the same.

[0004]

Means for Solving the Problems As a result of earnest studies, the present inventors have conducted earnest studies to economically obtain an α-amino acid polymer having a crown compound residue in the main chain, etc. The present invention has been completed.

That is, according to the present invention, there is provided an α-amino acid polymer having a crown compound residue on at least one of the main chain, side chain and terminal. Further, according to the present invention, a crown compound having an amino group is used as an initiator, and α
-Providing a method for producing an α-amino acid polymer having the above-mentioned crown compound residue, which comprises polymerizing an amino acid. Furthermore, according to the present invention, an α-amino acid is polymerized to synthesize an α-amino acid polymer, and then at least one kind selected from an amino group, an isocyanate group, a carboxyl group and a formyl group is added to the polymer. Provided is a method for producing an α-amino acid polymer having a crown compound residue, which comprises reacting a crown compound having a functional group.

The crown compound in the present invention has a function of "having a hetero atom such as O, N and S as an electron-donating donor atom in a part of the ring-constituting atoms and incorporating a cation into a ring hole. Macrocycles, or 2 of these
A bicyclic compound consisting of at least one ring, which is an amino group,
A compound having one or more of at least one of an isocyanate group, a carboxyl group and an aldehyde group "(see" Crown Compound "by Michio Hiraoka, Kodansha, Scientific, p4). That is, the crown compound of the present invention includes not only a crown ether having oxygen as an electron-donating donor atom, but also a large ring compound having a donor atom such as nitrogen or sulfur as a ring structure-constituting atom as an analog thereof. Also included are multicyclic crown compounds consisting of two or more rings, which are representative of clybutand.

Specific examples of the crown compound include 4-aminocyclohexyl-12-crown-4,
4,4'-diaminodibenzo-14-crown-4,3
-Amino-5- (t-butyl) benzo-15-crown-5,4,4'-diaminodibenzo-18-crown-
6,4,4'-diisocyanate dicyclohexyl-1
8-crown-6,4,4'-diisocyanate dibenzo-18-crown-6,4,4 ', 4''-tricarboxytribenzo-18-crown-6,4,4',
4 ″, 4 ′ ″-tetraaminotetrabenzo-24-crown-8, 4,4-formyldibenzo-26-crown-6 and the like can be mentioned.

Further, the α-amino acid of the present invention includes not only α-amino acids such as alanine, glutamic acid, leucine and lysine, but also α-amino acid derivatives in which the side chain portion thereof is modified.

The method for producing the polymer of the present invention includes:
The following methods can be shown. (1) A method of polymerizing an α-amino acid using a crown compound having an amino group as an initiator. In the crown compound having an amino group used in this method, the number of the amino groups may be one or plural, for example, 2 to 3. The amino group can be bonded to a carbon atom constituting the crown compound, and any conventionally known method can be adopted as a method for introducing the amino group into the crown compound. In this way,
An amino acid is bound to the amino group of the crown compound, and another amino acid is sequentially bound to this amino acid to form a polymer. This polymerization reaction can be represented by the following formula. X (NH ₂ ) m + HOOCRNH ₂ → X [-NH (CORNH) nH] m (1) In the above formula, X (NH ₂ ) m represents a crown compound having m amino groups, and X is a crown compound. Residue, m is 1
To an integer of 3 and n represents a degree of polymerization, and usually 10 to 5000.
Is. HOOCRNH ₂ represents an α-amino acid, R is a linear or branched alkylene group which may have a substituent, and the carbon number thereof may be 1 to 10. As the substituent, an alkoxy group, an aryloxy group, an alalkyloxy group, an acyl group, an acyloxy group, an ester group (R ¹ OCO-, R ¹ ; an alkyl group, an aryl group or an aralkyl group), a carboxyl group, an amino group Etc. In HOOCRNH ₂ representing an α-amino group, the carboxyl group may be a salt such as sodium salt, potassium salt, ammonium salt, or organic ammonium salt. The amino group bonded to the crown compound is bonded to the carbon atom constituting the crown compound,
Preferably, it is bonded to a carbon atom forming a carbon ring such as a benzene ring or a cyclohexane ring. The amino group-containing crown compound preferably used in the present invention is a benzocrown compound having 1 to 4 benzene rings with an amino group introduced into at least one benzene ring thereof.

(2) A method of reacting a previously synthesized α-amino acid polymer with a crown compound having reactivity with the α-amino acid polymer. The crown compound used in this method has introduced a functional group capable of reacting with the α-amino acid polymer. Examples of the functional group in this case include an isocyanate group, an amino group, a carboxyl group, and an aldehyde group. The number of functional groups in the crown compound can be one or more, for example 2-3. In this method, the functional group of the crown compound reacts with the amino acid polymer to obtain a reaction product in which both are bound.
This reaction is shown below when the functional group bonded to the crown compound is an isocyanate group. X (NCO) m + HO- (CORNH) n-H-> X [NHCO- (NHRCO) nOH] m (2) In the formula, X, R, m and n are the same as described above. In the above reaction, alkylamine (R ²
When NH ₂ ) is used, the terminal OH of the resulting reaction product reacts with this alkylamine and is converted to NHR ² . The isocyanate group (NCO) bonded to the crown compound is bonded to a carbon atom constituting the crown compound, and preferably bonded to a carbon atom constituting a carbon ring such as a benzene ring or a cyclohexane ring. The crown compound having an isocyanate group preferably used in the present invention is a benzocrown compound having 1 to 4 benzene rings with an isocyanate group introduced into at least one of the benzene rings.

(3) A method of reacting the polymer obtained by the method (1) with a dibasic acid. In this reaction, the carboxyl group of the dibasic acid reacts with the terminal amino group of the polymer and the polymer is attached via the dibasic acid. This reaction is represented by the following equation. X [-NH (CORNH) n-H] ^{m + HOOCR 3 COOH (3)} → X [-NH (CORNH) n] p-qCOR ³ CO - [(NHRCO) n-NH-] In Xp Formula, X , R, m and n are the same as above, p is mq, and q is an integer of 1 or more, which is smaller than m.
In the dibasic acid (HCOOR ³ COOH) used in this method, the carbon number of R ³ is usually 1 to 12,
It is preferably 2-8. The dibasic acid can also be its reactive derivative, such as an acid halide.

The α-amino acid polymer of the present invention has a crown compound residue on at least one of its main chain, side chain and terminal.
-The number of bonded amino acids (average degree of polymerization) is 10 to 100.
The range is 00.

[0013]

EFFECTS OF THE INVENTION The α-amino acid polymer of the present invention has a structure in which a crown compound residue is bound to at least one of its main chain, side chain, and terminal, and is used as a chemical analysis reagent or a sensor-sensitive substance. Used as an element for electronics.

[0014]

Next, the present invention will be described in more detail with reference to examples.

Example 1 L-glutamic acid-γ-benzyl was reacted with phosgene by a conventional method to obtain L-glutamic acid-γ-benzyl anhydride (hereinafter abbreviated as BLG-NCA). Benzo-15-
To obtain poly (L-glutamate-γ-benzyl) having a crown-5 at the end of the main chain (hereinafter abbreviated as [A]), BLG-NCA was dissolved in dioxane (concentration 6%), Aminobenzo-15-crown-5 was used as an initiator for polymerization at 25 ° C., and the polymerization solution was poured into a large excess of methanol to dry the precipitate. In this case, the charging ratio of BLG-NCA to the initiator was 25. Using a vapor pressure osmosis method, the molecular weight of [A] was measured using 1,2-dichloroethane as a solvent. As a result, 2.48 x 1
0 ⁴ and Motomari, the average molecular weight L- glutamic acid -
The average degree of polymerization of γ-benzyl was 112. The infrared absorption spectrum of [A] has an absorption peak of 16
50 cm ^-1 (amide 11), 1545cm ^-1 (amide I
I) and 610 cm ⁻¹ (amide V) were observed. Judging from this peak, the polypeptide chain portion of [A] was α-
It was found that the main structure is the helix structure. Furthermore, the presence of a valley at 222 nm in the circular dichroism spectrum of a solution of [A] in 1,2-dichloroethane indicates that the polypeptide chain portion of [A] forms an α-helix structure. I confirmed that.

[A] and N in 1,2-dichloroethane
By knowing the complex forming function with a or K,
The molecular association state of [A] was estimated. The complex forming ability of [A] with Na or K was measured as follows.
That is, a solution of [A] in 1,2-dichloroethane (4 m
g / 5 ml) with an excess of sodium picrate (0.5 m
g) or potassium picrate (0.8 mg) was added and the concentration of picrate was determined by UV spectroscopy. As a result, 1 mol of [A] was extracted with 1.30 mol of sodium picrate and 0.598 mol of potassium picrate (in this case, the average molecular weight of [A] was extracted). As 2.48 × 10 ⁴ ). This suggests that [A] forms a one-to-one complex with Na, while with K, [A] forms a sandwich type complex with two molecules. The viscosity of the 1,2-dichloroethane solution in which [A] was complexed with Na or K was measured using a Ubbelohde viscometer in a constant temperature water bath at 25 ° C. In FIG. 1, the horizontal axis shows the concentration C of the solution, and the vertical axis shows the value obtained by dividing the viscosity ηsp of the solution with respect to the solvent by the concentration C. When [A] forms a complex with K, it is more N
It can be seen that the viscosity is higher than in the case of forming a complex with a. This result means that it is possible to distinguish whether [A] forms a complex with Na or forms a complex with K by measuring the viscosity of the solution. Using this principle, Na and K And can be identified.

Example 2 The α-amino acid polymer [A] obtained in Example 1 was added to a mixed solution of methanol, 2-propanol and 5M aqueous sodium hydroxide solution (volume ratio 2: 2: 1). 25 in
The reaction was carried out at 0 ° C for 3 days. The reaction solution was acidified to pH 3 with 1M hydrochloric acid and the precipitate was collected. In the infrared absorption spectrum of this precipitate, the absorption peak due to the ester bond at 1730 cm ^-1 disappeared. In this way, benzo-15
-Poly (L- having a crown-5 structure at one end of the main chain
Glutamic acid) was obtained.

Example 3 0.2 g of the amino acid polymer [A] obtained in Example 1
(0.008 mmol) of 1,2-dichloroethane 40
Dissolve in 0.7 ml, 0.7 mg of adipic acid dichloride (0.
004 mmol) and reacted at room temperature for 3 days,
An [alpha] -amino acid polymer having a crown ether structure at both ends was obtained in a form in which two molecules of [A] were bound together.

Example 4 L-leucine was reacted with phosgene by a conventional method to obtain an anhydrous L-leucine (abbreviated as LL-NCA). LL-NC using aminobenzo-15-crown 5 as an initiator
A was polymerized in benzene for 10 days at room temperature. The precipitate obtained by throwing this polymerization solution into a large excess of methanol was dried. The charge ratio of LL-NCA to the initiator is 5
It was set to 0. Thus, poly (L-leucine) having a crown ether structure at the end of the main chain was obtained.

Example 5 BLG-NCA was polymerized in dioxane at room temperature for 10 days using 4,4'-diaminodibenzo-18-crown-6 as an initiator. This polymer solution was poured into a large excess of methanol, and the resulting precipitate was dried. BL for initiator
The charging ratio of G-NCA was 25. In this way,
Poly (L-glutamate-γ-benzyl) having a crown ether structure in the center of the main chain was obtained.

Example 6 4,4'-Diaminodibenzo-18-crown-6 was suspended in ortho-dichlorobenzene and phosgene was passed through at 100 ° C. to obtain 4,4'-diisocyanate dibenzo-.
18-Crown-6 was obtained. BLG-N obtained in Example 1
CA was dissolved in dioxane (concentration: 6%), polymerized with n-butylamine as an initiator at room temperature for 5 days, and the polymer solution was poured into a large excess of methanol to dry a precipitate obtained. The charge ratio of BLG-NCA to the initiator is 2
It was set to 5. The precipitate was found to be poly (L-glutamate-γ-benzyl) from the infrared absorption spectrum. 0.2 g (0.016 mmol) of this precipitate was dissolved in 50 ml of benzene, and 3.4 mg of 4,4′-diisocyanate dibenzo-18-crown-6 was dissolved therein.
(0.016 mmol) was added and reacted at 80 ° C. for 20 hours. The reaction solution was poured into a large excess of methanol to obtain a precipitate, which was dried. Thus, poly (L-glutamate-γ-benzyl) having a crown ether structure in the center of the main chain was obtained.

[Brief description of drawings]

FIG. 1 is a relationship diagram between the concentration and viscosity of a solution of an α-amino acid polymer having a crown compound residue in its main chain.

[Explanation of symbols]

● An α-amino acid polymer complexed with potassium ion. O An α-amino acid polymer complexed with sodium ions. Δ An α-amino acid polymer that does not form a complex with a metal ion.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References POLYM. PREPR. (AM. C HEM., DIV. POLY. CHE M.) (1988), 29 (1), 248-9.

Claims (3)

(57) [Claims] 1. An α-amino acid polymer having a crown compound residue on at least one of a main chain, a side chain and a terminal. 2. The method for producing an α-amino acid polymer having a crown compound residue according to claim 1, wherein the α-amino acid is polymerized using a crown compound having an amino group as an initiator. 3. An α-amino acid is polymerized to synthesize an α-amino acid polymer, and then at least one functional group selected from an amino group, an isocyanate group, a carboxyl group and a formyl group is added to the polymer. The method for producing an α-amino acid polymer having a crown compound residue according to claim 1, wherein the crown compound is reacted.