JPH0434995B2 - - Google Patents

Description

[Detailed description of the invention]

(a) Industrial Application Field The present invention relates to bis-macrocyclic polyether diamide derivatives and their uses, particularly to calcium ion-selective electrodes and sensitive membranes for calcium ion-selective field-effect transistors. (b) Prior art In general, an ion-selective electrode is an electrode that indicates the activity of a specific ion in a solution by the membrane potential shown by the membrane electrode, and a glass electrode for pH measurement is a typical example. It is. In addition, ion-selective field-effect transistors have a structure in which the gate metal of the field-effect transistor is removed and an ion-sensitive film is attached thereto. It measures changes in the value of the current flowing through it, and can be made ultra-small. By the way, calcium in body fluids can be divided into those that exist in the form of calcium ions (Ca ²⁺ ) and those that are bound to proteins, etc., but especially those that exist in the form of free calcium.
Ca ²⁺ plays an extremely important role in maintaining biological functions, such as adjusting cell osmotic pressure, blood coagulation, activation of enzymes, and activation of cellular respiration. In addition, the Ca ²⁺ concentration in body fluids, especially in blood, is within a certain narrow range (approximately 4.4 to 5.1 meq/L) under normal conditions.
Changes in this concentration are associated with myeloma, acute bone atrophy, bone tuberculosis, cancer bone metastasis, hyperparathyroidism, uremia, nephrosclerosis, renal edema, nephrosis, acute pancreatitis, rickets, and osteomalacia. Since information is important in many diseases such as, the significance of measurement is extremely large. Currently, the methods for analyzing calcium are titration method, o
- Colorimetric method using cresolphthalein complexone, etc., flame method, and atomic absorption method are used, but all of these methods measure the total amount of calcium, and only free Ca ²⁺ can be measured. Deproteinization,
It requires complicated treatments such as dialysis, is time-consuming, and must be performed under anaerobic conditions, making it extremely difficult. On the other hand, methods using ion sensors such as ion-selective electrodes and ion-selective field-effect transistors can rapidly quantify the concentration of only this free Ca ²⁺ , which has extremely significant measurement significance as mentioned earlier. With these advantages, it is thought that it will make an extremely large contribution to diagnosis and treatment. For this reason, calcium ion-selective electrodes that use glass membranes as sensitive membranes, liquid membrane type and solid membrane type ion-selective electrodes that use phosphate esters as ion-sensitive substances, etc., have been developed, but all of them have Measurement of Ca ²⁺ in actual samples such as serum is difficult due to significant interference from coexisting ions. Therefore, in order to obtain practical calcium ion-selective electrodes and calcium ion-selective field effect transistors, there is a need for calcium ion-sensitive materials with higher calcium ion selectivity. (c) Purpose The present invention was made to solve these problems, and uses a bis-macrocyclic polyether diamide derivative as a unitary carrier to easily, rapidly and highly selectively transport calcium ions. The main object of the present invention is to provide a calcium ion-selective electrode that can perform measurements with high precision and good reproducibility over a long period of time, and a calcium ion-selective sensitive membrane for field effect transistors. (d) Structure Thus, according to the present invention, general formula (I): (In the formula, n is an integer from 1 to 7, R ₁ to R ₄ each represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ₅ and R ₆ each represent an alkyl group having 5 to 20 carbon atoms.) A sensitive membrane for an ion sensor is provided comprising the bis-macrocyclic polyether diamide derivative shown below. The bis-macrocyclic polyether diamide derivatives used in the present invention are a novel group of compounds that have not been described in any literature. Accordingly, the present invention also provides a bis-macrocyclic polyether diamide derivative represented by general formula (I). Such compounds can also be used in phase transfer catalyst applications. The compound represented by the general formula (I) is, for example, a compound represented by the general formula Ia (wherein each R is a hydrogen atom or has 1 to 3 carbon atoms).
alkyl group, X ₁ means a halogen atom)
dicarboxylic acid halide represented by and 1,17-
Compound Ib is synthesized by reacting dihydroxy-3,15-diaza-6,9,12-trioxaheptadecane in dehydrated benzene in the presence of triethylamine, This was reacted with an acid halide represented by the following general formula Ic (in the formula, R' is an alkyl group having 5 to 20 carbon atoms, and X ₂ is a halogen atom) in dehydrated chloroform in the presence of triethylamine to obtain Id. Synthesize alkyl substituted Id, Furthermore, any one of this Id and the following general formula
It can be obtained by reacting a dibasic acid halide represented by Ie (in the formula, n is an integer of 1 to 7, and X ₃ means a halogen atom) in dehydrated chloroform in the presence of triethylamine. The sensitive membrane according to the invention can be used as a solid membrane or a liquid membrane. The solid membrane is formed by uniformly dispersing the bis-macrocyclic polyether diamide derivative in a water-insoluble solid organic polymer as a support. This polymer forms a matrix to support the neutral carrier bis-macrocyclic polyether diamide derivative in the form of a film, and prevents the neutral carrier from eluting into the sample aqueous solution. It is necessary that the calcium ions contained therein have properties that allow appropriate diffusion within the matrix, and polyvinyl chloride, silicone rubber, polymethacrylic acid ester (for example, polymethyl methacrylate), etc. are usually used. Sensitive membranes based on polyvinyl chloride are usually prepared by dissolving polyvinyl chloride, a plasticizer, and a bis-macrocyclic polyether diamide derivative in a suitable low-boiling organic solvent, such as tetrahydrofuran, and then dissolving the solvent in a Petri dish, for example. It is formed into a film by gradual evaporation. The plasticizer is used to impart appropriate flexibility to the resulting sensitive membrane and to prevent the bis-macrocyclic polyether diamide derivative from eluting into the measurement solution, such as dioctyl phthalate, o-nitrophenyl octyl ether, etc. is used. In addition, as in the case of sensitive membranes using silicone rubber as a support, bis-macrocyclic polyether diamide derivatives,
It can also be produced by dissolving silicone rubber alone and a silane compound for crosslinking the membrane in an appropriate organic solvent, polymerizing it into a membrane, and removing the solvent from the molded product. The content of bis macrocyclic polyether diamide derivative in the solid film is 0.5 to 20% by weight, preferably 1
It is desirable that the content be ~15% by weight. If the content is too small, the response will be poor; if the content is too large, it will be difficult to uniformly disperse it in the polymer, and it will be uneconomical. When a plasticizer is used in combination, such as when polyvinyl chloride is used as a support, the appropriate amount of plasticizer is 50 to 70% by weight. The liquid film is formed by dissolving a bis-macrocyclic polyether diamide derivative in a water-insoluble polar organic solvent. aromatic ethers, aromatic ethers, etc. A preferred specific example is 1-decano-
Examples include chlorine, nitrobenzene, chlorobenzene, diphenyl ether, and 1,2-dichloroethane. The content of bis macrocyclic polyether diamide derivative in the liquid film is 0.5 for the same reason as above.
-20% by weight, preferably 1-10% by weight. The liquid membrane is usually held in a porous support such as ceramics or cellulose. A porous film made of fluororesin is also one of the preferred supports. The bis macrocyclic polyether diamide derivative represented by the general formula (I) of the present invention is stably retained in a solid film or liquid film because B ₅ and R ₆ in the formula have long chain alkyl groups, It shows excellent performance as a calcium ion selective electrode and a neutral carrier for a calcium ion selective field effect transistor. As described above, the sensitive membrane according to the present invention uses a bis-macrocyclic polyether diamide derivative having a linking portion of a certain chain length as a neutral carrier, and the above-mentioned derivative is free from interfering ions such as sodium ions and potassium ions. Regardless of the presence of can be measured with high selectivity, and has a short response time and excellent reproducibility, making it a highly practical calcium ion-selective electrode and sensitive membrane for calcium ion-selective field-effect transistors. It is something. When the compound of general formula (I) of the present invention is used as a sensitive film, n is 4 to 6, particularly preferably 5. It is believed that compounds having such a value of n create a spacing between two macrocyclic polyether diamide rings that is advantageous for forming a stable 2:1 sandwich complex with Ca ⁺² . The method for producing a compound in which n is 5 was exemplified above, but a compound in which n is 4 or 6 can be obtained by using adipic acid dihalide or suberic acid dihalide instead of the raw material pimelic acid dichloride. . Another desirable group of compounds are those where n has 1-3 or 7. In this case as well, dicarboxylic acid dihalide having a predetermined number of carbon atoms can be used instead of pimelic acid dichloride. The alkyl groups represented by R ₅ and R ₆ in the general formula (I) are considered to influence the fat solubility of the bis macrocyclic polyether diamide derivative and its retention in the sensitive membrane. That is, the bis-macrocyclic polyether diamide derivative is prevented from being eluted from the sensitive membrane into the sample, increasing the stability of the membrane, suppressing deterioration, and extending its life. In order to bring about this effect, it is undesirable if the alkyl group is too short, and if it is too long, it may be difficult to obtain raw materials, and the solubility of the bis macrocyclic polyether itself in the solvent may decrease, making it difficult to fabricate a sensitive film. It is not suitable as it may become difficult. From this point of view, the number of carbon atoms in the alkyl groups of R ₅ and R ₆ is 5 to 5.
20 is desirable, and 7-15 is preferable. The above production method is for the case in which caprylic acid chloride has 7 carbon atoms, but in the case of obtaining an alkyl group having 8 to 15 carbon atoms, pelargonic acid, capric acid, n-undecylene A halide of acid, lauric acid, n-tridecylenic acid, myristic acid or palmitic acid may be used. In addition,
Although the alkyl group has been explained using a linear one, it may be branched. Further, R ₁ to _{R 4} in general formula (I) are preferably hydrogen, a methyl group, or an n-propyl group, and preferably a methyl group. Thus, a preferred group of compounds of general formula (I) according to the invention is one in which n is 4 to 7 and R ₅ and R ₆ are 7 to 7.
It is a compound in which an alkyl group having 15 carbon atoms and R ₁ to _{R 4} are methyl groups. Another preferred group is n
is 1 to 3, R ₅ and R ₆ are alkyl groups having 7 to 15 carbon atoms, and R ₁ to _{R 4} are methyl groups.
A further group is compounds in which n is 7 and R ₁ to R ₆ are as described above. Note that when constructing an ion sensor using the sensitive membrane of the present invention, structures known in the fields of ion-selective electrodes and ion-selective field-effect transistors can be appropriately adopted as the structure. (e) Examples The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples. First, production examples of the bis-macrocyclic polyether diamide derivative represented by the general formula (I) of the present invention and representative examples of its physical properties will be shown. Production Example 1 Bis-macrocyclic polyether diamide derivative in general formula (I) where n=5, R ₁ to R ₄ are methyl groups, and R ₅ and R ₆ are n-C ₇ H ₁₅ or n-C ₁₁ H ₂₃ was synthesized. 10 mmol of 4,5-dimethyl-3,6-dioxaoctanedicarboxylic acid chloride (2.5 g) and 10 mmol of 1,17-dihydroxy-3,15-diaza-6,9,12-trioxaheptadecane (2.8 g) and 30 mmol of triethylamine (3 g) very slowly for 4 hours. It dripped. After continuing stirring for 2 hours, the generated triethylamine hydrochloride was removed by filtration, washed with a small amount of dehydrated benzene, the benzene was distilled off from the liquid under reduced pressure, and the remaining oil was extracted with chloroform:methanol = 5:1. The mixture was purified using silica gel column chromatography using a mixed solvent as a developing solvent to obtain a macrocyclic polyether diamide as shown below. Next, 5 mmol (2.3 g) of the obtained macrocyclic polyether diamide and 5 mmol of triethylamine (0.5 g) were dissolved in 20 ml of dehydrated chloroform.
While cooling on ice and stirring well, a solution of 5 mmol of caprylyl chloride (0.8 g) dissolved in 15 ml of dehydrated chloroform was added dropwise. After stirring and refluxing for 24 hours,
Chloroform was distilled off under reduced pressure, and 70 ml of dehydrated benzene was added to the residue, the resulting triethylamine hydrochloride was removed by filtration, and washed with a small amount of dehydrated benzene.
Benzene was distilled off from the liquid under reduced pressure. The residue was purified using silica gel column chromatography using a mixed solvent of chloroform:methanol=10:1 as a developing solution to obtain an alkyl-substituted macrocyclic polyether diamide. Next, 1 mmol (0.6 g) of this alkyl-substituted macrocyclic polyether diamide and 3 mmol (0.3 g) of triethylamine were dissolved in 10 ml of dehydrated chloroform, and while stirring at room temperature, 0.5 mmol of pimelic acid dichloride (0.1 g) was added to 5 ml of the alkyl-substituted macrocyclic polyether diamide. was dissolved in dehydrated chloroform and slowly added dropwise. After stirring and refluxing for 48 hours, chloroform was distilled off under reduced pressure.
The residue was separated by GPC, n = 5, R ₁ - _{R 4} =
The target product in which CH ₃ , R ₅ =R ₆ =C ₇ H ₁₅ was purified. The physical properties of this compound were as follows. ₍ 1) (n=5, _R1 ~ _R4 = _CH3 , _R5 = _R6 = _C7H15
) Properties Colorless and transparent oil Elemental analysis Actual values C = 58.83%, H = 8.88%,
N=4.04% Calculated value C=59.23%, H=8.84%,
N=4.39% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(amide C=O) 1HNMR (δ-ppm, in CDCl ₃ ) 0.90 (t, 6H,
CH ₃ CH ₂ ), 1.05-1.40 (m, 28H, CH ₂ (CH ₂ ) ₄
CH ₃ , CH ₃ CH), 1.40~1.80 (m, 10H,

【formula】

【formula】) 2.25(t, 8H,

[Formula]), 360(m, 44H, O(CH ₂ ) ₂ O, N(CH ₂ ) ₂ O,

[Formula] CHCH ₃ ), 4.05~4.50 (m, 16H,

【formula】

[Formula]) Production Example 2 n = 5, R ₁ - R ₄ = CH ₃ , R ₅ = R ₆ = C ₁₁ The compound of H ₂₃ was prepared in exactly the same way except that caprylyl chloride was changed to dodecanoyl chloride. Obtained. Examples of these physical property values are shown in the table below. ₍ 2) (n=5, _R1 ~ _R4 = _CH3 , _R5 = _R6 = _C11H23
) Properties Colorless and transparent oil Elemental analysis Actual values C = 61.21% H = 9.53%
N=4.05% Calculated value C=61.36% H=9.28%
N=4.03% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(Amide C=O) 1H-NMR (δ-ppm, in CDCl ₃ ) 0.90 (t, 6H, CH ₃ CH ₂ ), 1.05-1.40 (m, 44H, (CH ₂ (CH ₂ ) ₈
CH ₃ , CH ₃ CH) 1.40 to 1.80 (m, 10H,

【formula】

【formula】) 2.25(t, 8H,

[Formula]) 3.60 (m, 44H, O(CH ₂ ) ₂ O, N
(CH ₂ ) ₂ O,

[Formula], CHCH ₃ 4.05~4.50 (m, 16H,

【formula】

[Formula]) Production Examples 3 to 8 Bis-macrocyclic polyether diamide derivatives having the following physical properties were obtained in the same manner as Production Examples 1 and 2, respectively. (3) (n= ₁ , R1~ _R4 =H, _R5 = _R6 =n- _C5
In the case of H ₁₁ ) Properties Colorless and transparent oil Elemental analysis, measured values C = 55.50% H = 7.95%
N=5.03% Calculated value C=55.21% H=8.01%
N=5.05% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(Amide C=O) 1H-NMR (δ-ppm, in CDCl ₃ ) δ = 0.90 (t, 6H, CH ₃ CH ₂ ) 1.05-1.40 (m, 8H, CH ₂ (CH ₂ ) ₂
CH ₃ ) 1.40~1.80 (m, 4H,

【formula】) 2.25(t, 6H,

[Formula]) 3.60 (m, 48H, O(CH ₂ ) ₂ O, N
(CH ₂ ) ₂ O,

【formula】) 4.05~4.50 (m, 16H,

【formula】

[Formula]) (4) (n=1, R ₁ ~ _{R 4} = n-C ₃ H ₇ , R ₅ = R ₆ = n
-C ₂₀ H ₄₁ ) Properties Colorless and transparent sticky oil Elemental analysis, actual values C = 65.48% H = 10.11%
N=3.40% Calculated value C=65.75% H=10.23%
N=3.30% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(Amide C=O) 1H-NMR (δ-ppm, in CDCl ₃ ) δ = 0.90 (t, 18H, CH ₃ CH ₂ ) 1.05-1.40 (m, 84H, CH ₂ (CH ₂ ) ₁₇
CH ₃ , CH (CH ₂ ) ₂ CH ₃ ) 1.40 to 1.80 (m, 4H,

【formula】) 2.25(t, 6H,

【formula】

[Formula]) 3.60 (m, 44H, O(CH ₂ ) ₂ O, N
(CH ₂ ) ₂ O,

[Formula] CHCH ₂ ) 4.05~4.50 (m, 16H,

【formula】

[Formula]) (5) (When n = 5, R ₁ to R ₄ = H, R ₅ = R ₆ = nC ₅ H ₁₁ ) Properties Colorless and transparent oil Elemental analysis, actual value C = 56.78% H = 8.51%
N=4.78% Calculated value C=56.67% H=8.32%
N=4.81% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(Amide C=O) 1H-NMR (δ-ppm, in CDCl ₃ ) δ = 0.90 (t, 6H, CH ₃ CH ₂ ) 1.05-1.40 (m, 8H, CH ₂ (CH ₂ ) ₂
CH ₃ ) 1.40~1.80 (m, 10H,

【formula】

【formula】) 2.25(t, 8H,

[Formula]) 3.60 (m, 48H, O(CH ₂ ) ₂ O, N
(CH ₂ ) ₂ O,

【formula】) 4.05~4.50 (m, 16H,

【formula】

[Formula]) (6) (n=5, R ₁ ~ _{R 4} = n-C ₃ H ₇ , R ₅ = R ₆ = n
-C ₂₀ H ₄₁ ) Properties: Colorless, transparent and sticky oil Elemental analysis, measured values: C = 66.51% H = 10.23%
N=3.15% Calculated value C=66.39% H=10.36%
N=3.19% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(Amide C=O) 1H-NMR (δ-ppm, in CDCl ₃ ) δ = 0.90 (t, 18H, CH ₃ CH ₂ ) 1.05-1.40 (m, 84H, CH ₂ (CH ₂ ) ₁₇
CH ₃ , CH (CH ₂ ) ₂ CH ₃ ) 1.40 to 1.80 (m, 10H,

【formula】

【formula】) 2.25(t, 8H,

[Formula]) 3.60 (m, 44H, O(CH ₂ ) ₂ O, N
(CH ₂ ) ₂ O,

[Formula], CHCH ₂ ) 4.05-4.50 (m, 16H,

【formula】

[Formula]) (7) (n=7, R ₁ to R ₄ = H, R ₅ = R ₆ = n-C ₅
In the case of H ₁₁ ) Properties Colorless and transparent oil Elemental analysis, measured values C = 55.20% H = 8.31%
N=4.65% Calculated value C=55.35% H=8.46%
N=4.69% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(Amide C=O) 1H-NMR (δ-ppm, in CDCl ₃ ) δ = 0.90 (t, 6H, CH ₃ CH ₂ ) 1.05-1.40 (m, 8H, CH ₂ (CH ₂ ) ₂
CH ₃ ) 1.40~1.80 (m, 14H,

【formula】

【formula】) 2.25(t, 8H,

[Formula]) 3.60 (m, 48H, O(CH ₂ ) ₂ O, N
(CH ₂ ) ₂ O,

【formula】) 4.05~4.50 (m, 16H,

【formula】

[Formula]) (8) (n=7, R ₁ ~ _{R 4} = n-C ₃ H ₇ , R ₅ = R ₆ = n
-C ₂₀ H ₄₁ ) Properties: Colorless, transparent, sticky oil Elemental analysis, measured values: C = 66.75% H = 11.53%
N=3.20% Calculated value C=66.69% H=11.42%
N=3.14% IR (cm ^-1 , neat) 1730 (ester C=O), 1640
(Amide C=O) 1H-NMR (δ-ppm, in CDCl ₃ ) δ = 0.90 (t, 18H, CH ₃ CH ₂ ) 1.05-1.40 (m, 84H, CH ₂ (CH ₂ ) ₁₇
CH ₃ , CH (CH ₂ ) ₂ CH ₃ ) 1.40 to 1.80 (m, 14H,

【formula】

【formula】) 2.25(t, 8H,

[Formula]) 3.60 (m, 44H, O(CH ₂ ) ₂ O, N
(CH ₂ ) ₂ O,

[Formula], CHCH ₂ ) 4.05-4.50 (m, 16H,

【formula】

[Formula]) Example 1 In general formula (1), n=5, R ₁ to _{R 4} =CH ₃ ,
3% by weight of a bis-macrocyclic polyether diamide derivative with R ₅ = R ₆ = C ₇ H ₁₅ , 1.1% by weight of potassium tetrakis(p-chlorophenyl)borate and 65.9% of o-nitrophenyl octyl ether as a plasticizer. A polyvinyl chloride membrane containing % by weight was prepared. Cut this sensitive film into a circle with a diameter of 5 mm.
Attached to the bottom of the philips-IS561 electrode, Ag・
Agcl/10 ^-3 MCaCl ₂ /Membrane/Sample solution/0.1MNH ₄
Calcium ion activity (ac _a ) in the measurement sample solution with the electrode configuration of NO ₃ /KCl (saturated) /Hg ₂ Cl ₂・Hg
and the interelectrode potential difference (EMF/mV) were measured, and a calibration curve was created. In addition, the measurement was conducted using Corning pH.
The test was carried out using a meter 130 model at 25℃±0.1℃. As a result, the calibration curve had linearity over a wide range of _aca from 3×10 ⁻⁵ to 3×10 ⁻² and showed a Nernst response. An example is shown in FIG. Furthermore, virtually no influence by pH was observed over the pH range of 4 to 10. Next, various interfering ions M (M ⁺ are Li ⁺ , Na ⁺ ,
The selectivity coefficient K _caM for K ⁺ , Mg ²⁺ , Sr ²⁺ , Ba ²⁺ ) is determined by the mixed solution method, that is, by keeping the activity of the interfering ion M in the measurement sample solution at a constant a _M ;
Measure the interelectrode potential by varying a _ca , find the a _ca that no longer shows a Nernst response, and calculate a _ca / (a _M ) ^2/m
(where m is the valence of M). The selectivity coefficient K _caMg for magnesium ions was 1×10 ⁻⁵ . This means that the sensitive membrane is approximately 100,000 times more sensitive to calcium ions than to magnesium ions. Example 2 Petra'nek et al. have reported on monocyclic macrocyclic polyether diamide (Analytica Chimica Acta, 128, 129 (1981)).
Comparison of selectivity coefficients between similar compounds (compounds 1 and 2 below) and the bis macrocyclic polyether diamide derivative of the present invention was carried out in the same manner as in Example 1. Compound 3 has general formula (I) where n=5, R ₁
~ _R4 = _CH3 , _R5 = _R6 = _C7H15 , Compound 4 has n=5 in general formula (I ₎ , _R1 ~ _R4 = _CH3 , _R5 =
R ₆ =C ₁₁ H ₂₃ .

[Formula] Compound 1 R=C ₇ H ₁₅ Compound 2 R=C ₁₁ H ₂₃ As a result, as shown in FIG. It was revealed that the selectivity coefficient for each interfering ion was improved by 5 to 10 times compared to ether. Ca ²⁺ is a macrocyclic polyether diamide ring.
It is thought that a stable complex is formed in which the cation is sandwiched between the rings in a sandwich-like manner with a ratio of 2:1 (ring: cation), but the two macrocyclic polyether diamide rings involved in the complex formation are inside 2
The bis-macrocyclic polyether diamide derivative of the individual invention can form a stable complex much more easily than monocyclic macrocyclic polyether diamide, which is why it exhibits such an excellent selectivity coefficient. Seem. Example 3 Using various bis-macrocyclic polyether diamide derivatives of the present invention as neutral carriers, solid films were prepared in the same manner as in Example 1, and K _caM was measured. Table 1 shows the logarithmic values of K _caM obtained as a result. Example 4 0.5ml of 150mg of sensitive membrane prepared in the same manner as Example 1
was dissolved in THF, and the solution was dip-coated on the Si ₃ N ₄ gate film of the FET, and the THF was evaporated to form a sensitive film, thereby fabricating a calcium ion-selective field-effect transistor (Ca-ISFET). Similar to the ion-selective electrode in Example 1, this Ca-ISFET exhibited a Nernst response over a wide range of a _ca from 3 × 10 ^-5 to 3 × 10 ^-2 , and had similar selectivity. .

【table】

[Table] (F) Effects As described above, according to the bis-macrocyclic polyether diamide derivative of the present invention, a calcium ion-sensitive membrane having excellent responsiveness, selectivity, reproducibility, etc. to calcium ions can be obtained.

[Brief explanation of drawings]

FIG. 1 is a graph illustrating a calibration curve of a Ca ²⁺ selective electrode using the sensitive membrane of the present invention. Figure 2 illustrates a comparison of log values of selectivity coefficients for various ions between an electrode using the sensitive membrane of the present invention and an electrode using a sensitive membrane using monocyclic macrocyclic polyether diamide as a neutral carrier. It is a graph.

Claims (1)

[Claims] 1 General formula (I): (In the formula, n is an integer from 1 to 7, R ₁ to R ₄ each represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ₅ and R ₆ each represent an alkyl group having 5 to 20 carbon atoms.) A bis-macrocyclic polyether diamide derivative represented by: 2 General formula (I): (In the formula, n is an integer from 1 to 7, R ₁ to R ₄ each represent a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and R ₅ and R ₆ each represent an alkyl group having 5 to 20 carbon atoms.) A neutral carrier for an ion sensor comprising the bis-macrocyclic polyether diamide derivative shown below.