DE3710569A1 - Cyclodextrin compound, ultrathin film using it, and process for the preparation - Google Patents

Abstract

The invention relates to a cyclodextrin compound and inclusion compounds comprising it. This cyclodextrin compound or its inclusion compound can be used to form ultrathin films on a solid substrate. These ultrathin films are used, for example, as protective film for compounds which are sensitive to light or oxygen or as chromatographic support with which organic molecules can be separated.

Description

The present invention relates to a cyclodextrin compound with a cylindrical structure, an inclusion connection based on the cyclodextrin compound, an organic ultra-thin film that deals with the cyclodextrin compound can produce, and a method for producing the film.

It is known that thin films of organic compounds on solid substrates using the Langmuir-Trough process let form. Thin films that can be made in this way can, can be used in a variety of ways especially in the fields of the chemical industry, electronics and biology interesting. For example are various basic applications of thin films by Hiroo Nakahara, Oil Chemistry, vol. 34, pages 774-783, 1985.

Cyclodextrin has a uniform cyclic structure, in which several glucose units are linked together; there is a cylindrical one for each molecule of cyclodextrin Cage with a diameter of 0.45 nm (4.5 Å) or more in front. With these cavities or cages, inclusion connections can be made using various connections  create a "host-guest effect". These inclusion connections you can, for example

• (1) for catalytic reactions (which shows cyclodextrin a catalytic effect),
• (2) to protect compounds against light or oxygen are sensitive
• (3) to suppress the evaporation of volatile compounds,
• (4) to protect against toxic substances,
• (5) for chromatography, using organic molecules can be separated according to their molecular weight,
• (6) for chromatography, using optically active substances be separated from each other
• (7) as a separation membrane in which each molecule has a through cavity owns, d. H. as a selectively permeable membrane Tunnel structure,
• (8) as electronic material, for example as not linear optical material that has a higher secondary order offers and can be manufactured by one includes organic molecule of large polarity, and
• Use (9) as the optical recording material can be made by reversibly one includes photosensitive substance.

So if you have cyclodextrin compounds or their inclusion compounds trained as thin films, they offer on the mentioned technical advantages.

With conventional cyclodextrin derivatives, however, the formation thin films not easy and not easy either. One can form a Langmuir-Blodgett film by first  spreading organic molecules on a water surface, they transferred under pressure to a single layer and then apply the single layer to a substrate. At Cyclodextrin has therefore been worked with water, although it is undesirable to dissolve cyclodextrin in water. So are inclusion compounds of conventional cyclodextrin derivatives problematic.

• (1) One can have an inclusion in an organic solvent reach if the inclusion connection is however on is spread out on a surface of water, it tends to break open;
• (2) when the inclusion compound is on a substrate applies, it also tends to break open.

It is therefore an object of the invention to provide new cyclodextrin compounds provide with which the disadvantages mentioned are overcome will.

It is also an object of the invention to provide new organic ultra-thin To provide films made up of the new cyclodextrin compounds let form.

It is also an object of the invention to provide a method for manufacturing of organic ultra-thin films from the new ones To provide cyclodextrin compounds.

Furthermore, it is an object of the invention to organic ultra-thin To provide films of inclusion compounds derived from the mentioned cyclodextrin compounds and functional organic Molecules exist.

It is also an object of the invention to provide a method for manufacturing of organic ultra-thin films of inclusion compounds to be provided from the cyclodextrin compounds  and functional organic molecules.

Other objects, features and advantages of the invention will be apparent itself from the following description and the figures. It shows

Fig. 1 to 6 are graphs showing surface pressure-area curves (F - A) of cyclodextrins with hydrocarbon groups, wherein the abscissa and ordinate indicate respectively the area per cyclodextrin molecule (nm²) or the surface pressure (nm ^-1);

Fig. 7 is a graph showing a surface pressure-area curve, the solid curve and the dashed curve related to a mixed solution of cyclodextrin and methyl red and a solution of cyclodextrin alone, and each area is the area per cyclodextrin molecule;

Fig. 8 and 10 absorption spectra of applied films, the measurements of inclination of the substrate opposite the incident light at an angle of 45 ° were performed and s-polarized or affect the solid and the dashed curve p-polarized light light; and

Fig. 9 shows a circular dichroism spectrum of a coated film, wherein the dotted curve and the solid curve representing values, which were measured by inclination of the substrate from incident light at an angle of 90 ° or 45 °.

In the context of the present invention, it was found that by making an ultra-thin film of cyclodextrin can produce that first the primary alcohol residue (the Hydroxyl group in the C₆ position) of the cyclodextrin by a functional group which has a hydrocarbon group, to form a molecule with a hydrophilic  Cyclodextrin skeleton and the hydrophobic hydrocarbon group replaced, then a stable monomolecular film the connection created forms on a water surface and the formed monomolecular film on a substrate applies. The cyclodextrin molecule is said to be hydrophobic and have hydrophilic groups of a size and strength, that stable monomolecular films on water surfaces let form, the balance of these groups meaningful can be. The cyclodextrin compound according to the invention can be represented by the following general formula will:

wherein

Pure hydrophobic higher alkyl group having 4 or more carbon atoms, preferably 6 to 22 carbon atoms, in particular 8 to 22 carbon atoms; X represents a divalent functional group, for example -O-, -S-, -S (O) - or -NH-; Y represents a hydrogen atom, an acyl group (e.g. a C _2-22 aliphatic acyl group or a C _7-22 aromatic acyl group) or an alkyl group (preferably having 1 to 20 carbon atoms); and n represents an integer of 6 or more, preferably 6 to 12.

The organic ultrathin film of the new cyclodextrin compound or its inclusion compound can be produced as follows:
A suitable amount of a solution, namely the cyclodextrin compound or its inclusion compound dissolved in a volatile solvent which is immiscible with the carrier liquid, can be applied extensively to the surface of a carrier liquid and a thin film of the cyclodextrin compound or its inclusion compound can be formed. A solid substrate is then passed through the thin film, after which the solvent is allowed to evaporate. Preferably, the carrier liquid is not a solvent for the cyclodextrin compound or its inclusion compound, and water is conveniently generally used as the carrier liquid. A water-immiscible organic solvent of suitable density is generally used as the volatile solvent for the cyclodextrin compound or its inclusion compound.

Examples of solvents for the cyclodextrin compound or their inclusion compound are chloroform, hexane, Toluene, xylene, benzene and methylene chloride.

The concentration of the cyclodextrin compound or its inclusion compound in the solution is in the range of generally 10 ^-1 to 10 ^-6 mol / l, and preferably 10 ^-3 to 10 ^-4 mol / l.

Water is generally used as the carrier liquid, but you can also use an organic solvent for example glycerin. If water is chosen, can Water containing suitable metal ions is used or added to pure water. If water with a content of suitable metal ions of suitable concentration can be used at a suitable pH good ultra thin films can be obtained.

Examples of solid substrates are ordinary plates  Glass, glass plates on which monomolecular films are higher Fatty acids (e.g. stearic acid or arachidic acid) quartz plates, aluminum plates, Calcium fluoride plates and porous plates such as percoal glass or percolatin glass, and membrane filter.

According to the invention can be used as compounds in the cyclodextrin compounds included, nitrophenol, Benzene derivatives, such as azobenzene derivatives, naphthalene derivatives, like Congo red, polycyclic compounds like anthracene, and aliphatic acids with long hydrocarbon chains be used. Dyes are preferably used and especially azo dyes.

Ultrathin films of cyclodextrin or its inclusion compound according to the invention are excellent

• (1) as a protective film for connections against light or Are sensitive to oxygen
• (2) as a support in chromatography, in organic To separate molecules
• (3) as a carrier in chromatography, in optical Activators are to be separated, and
• (4) as selectively permeable membranes with which the Structure of the film is exploited on a porous substrate is applied.

The ultrathin film of the cyclodextrin compound according to the Invention is very powerful because of the monomolecular Film with a thickness corresponding to a molecular layer can be stacked and the cages of the applied film can be regulated in a certain direction are oriented.  

The monomolecular film of cyclodextrin is particularly suitable as

• (1) as a sensor for the selective determination of substances, the in the cavities with a diameter of 0.5 to 1.0 nm (5 to 10 Å) can penetrate,
• (2) optical recording material in which the change of the absorption spectrum due to a photo reversal reaction exploits, for example a photoisomerization reaction of azobenzene or photodimerization reaction of anthracenes, and
• (3) as a material to provide higher secondary harmonies, by including large polarity organic molecules.
• The invention is described in more detail below with examples. The specific cyclodextrins used in the examples have been used according to the above general Formula specified in more detail, with their structures and abbreviations from the examples and the following table 1 result. All quantities are parts by weight, provided nothing else is specified.

example 1 Production of heptakis (6-alkylthio-6-deoxy) beta-cyclodextrin (1)

Under a nitrogen atmosphere, 2.2 parts of sodium hydride suspended in 100 parts of anhydrous dimethylformamide; 5.3 parts of butanethiol were also converted of the thiol added in a sodium salt. To the resulting A solution was then added dropwise to the mixture, in the 11.0 parts of heptakis (6-bromo-6-deoxy) beta cyclodextrin (prepared according to K. Takeo, "Starch", 26 (1974) 111) in 100 parts of anhydrous dimethylformamide had been dissolved. Thereafter, the reaction was carried out at room temperature for 16 hours. The resulting reaction liquid became in 2000 Parts of ice water poured; the precipitating white precipitate was collected by filtration. This rainfall was washed with water and then with acetone and then Dried over phosphorus pentoxide under reduced pressure. The crude yield of the desired product (1a) was 40 g (Yield 96%).

Instead of the buthandiol used, octanethiol, Dodecanethiol, hexadecanethiol and octadecanethiol independently implemented in the same way so that the corresponding Compounds (1b), (1c), (1d) and (1e) in one yield of 97% or more were obtained.

Example 2 Preparation of heptakis (6-alkylthio-6-deoxy-2,3-di-O-acetyl) beta-cyclodextrin (2)

To a solution mixture of 0.3 parts of compound (1a) and 15 parts of pyridine became 5 parts of acetic anhydride added, then the reaction was stirred in  Room temperature for 16 h. The resulting one The reaction solution was then washed sufficiently; the resulting oily residue was dissolved in methylene chloride. The organic layer formed was then washed with water, a 10 percent. aqueous sodium carbonate solution, water and a saturated saline solution in the order given washed. The organic layer was then washed with anhydrous Dried and concentrated sodium sulfate, whereby an acetylated crude product was obtained. This product was further purified by recrystallization received a product (2a) in an amount of 0.32 parts (Yield 79%, FP 103 ° C).

For the other derivatives (2b), (2c) and (2d), corresponding Results achieved.

Example 3 Preparation of heptakis (6-alkylsulfinyl-6-deoxy-2,3-di-O-acetyl) beta-cyclodextrin (3)

In a solvent mixture of dioxane / methanol (5: 3) 4.5 parts of compound (2c) were dissolved, after which chilled with ice. An aqueous solution (25 parts) Containing 3.55 parts of sodium metaperiodate (NaIO₄) slowly added dropwise so that the reaction temperature could be kept at 2 ° C or below. After reacting overnight, the resulting was Concentrated reaction solution. The residue formed was dissolved in chloroform and then with 5 percent. watery Sodium carbonate, water and a saturated saline solution washed. After that, it was made with anhydrous sodium sulfate dried and then concentrated to the desired product (3c). The yield was 3.9 parts (83%). The melting point of the product was 107 ° C.  

In the same way, the other compounds (3a), (3b) and (3d) obtained.

Example 4 Preparation of heptakis (6-alkylsulfinyl-6-deoxy) beta-cyclodextrin (4)

In a small amount of dioxane, 3.0 parts of the compound (3c) solved; the resulting mixture became one Given ethanol solution containing 1.4 parts of KOH. After that, the mixture was left overnight at room temperature touched. After the implementation was concentrated; the resulting The residue was then dissolved in CH₂Cl₂. The educated Solution was poured into methanol to make the crude product to obtain. The crude product was washed with water and then dried, after which on a silica column has been cleaned; 1.0 part (43%) of the desired was obtained Product (4c) (FP 210 ° C).

The other compounds (4a) and (4b) received.

Example 5 Preparation of hexakis (6-alkylthio-6-deoxy) alpha-cyclodextrin (5)

According to the procedure of Example 1, the Compounds (5d) and (5c) from alpha-cyclodextrin and hexadecanethiol or get octadecanethiol.

Example 6 Production of hexakis (6-alkylthio-6-deoxy-2,3-di-O-acetyl) -alpha-cyclodextrin (6)

Following the procedure of Example 2, the compounds (6d) and (6e) from the previously prepared derivatives (5d) and (5e) obtained.

Example 7 Production of heptakis (6-alkylamino-6-deoxy) beta-cyclodextrin (7)

According to a method of the inventor (bulletin, publisher: Osaka City University, 26 (1985) 93-99) became the connection (7c). In the same way the connections were made (7a) and (7b) synthesized.

Example 8 Production of hexakis (6-alkylamino-6-deoxy) -alpha-cyclodextrin (8)

Following the procedure of Example 7, the compound (8d) obtained from alpha-cyclodextrin and hexadecylamine.

Example 9 Preparation of octakis (6-alkylamino-6-deoxy) gamma cyclodextrin (9)

Following the procedure of Example 7, the compound (9d) obtained from gamma-cyclodextrin and hexadecylamine.

Example 10

Each of the compounds (2a) to (2c), which had been prepared by the method of Example 2, was dissolved in chloroform; a monomolecular film was formed from the resulting solution in a Langmuir trough using water as a carrier liquid according to a conventional procedure. A surface pressure-area curve ( F - A) was then determined for each monomolecular film. It was found that the compounds (2b) and 2c) were able to form a stable monomolecular film with a limit range of about 2.2 nm². All monomolecular films could be applied as a Y-type film on a glass plate or as an application film on cadmium arachidate or kadium stearylate which had previously been applied on a glass plate ( FIG. 1).

Example 11

For the compounds (3a) to (3c), which had been prepared according to Example 3, F - A curves were determined in the same manner as in Example 10, it being found that the compounds (3b) and (3c) were stable could form monomolecular films with a limit range of about 2.53 nm². Compound (3c) could be applied as a Y-type film on a solid substrate ( Fig. 2).

Comparative Example 1

There was a solution of 1.0 × 10 ^-3 mol of cyclodextrin (10) (R = CH₃, X = O and Y = CH₃ in formula (I)) in chloroform on pure water as a carrier in the same manner as in Example 10 spread out. The surface pressure-area curve ( F - A) was found , but even if the area was small, the surface pressure did not increase. This result shows that a stable monomolecular film was not formed.

Comparative Example 2

There was a solution of beta-cyclodextrin in the same  Spread out as in Comparative Example 1 except that usual beta-cyclodextrin instead of beta-cyclodextrin (10) was used. beta-cyclodextrin, dissolved in water as a support, did not form a stable monomolecular film.

Example 12

for the compounds (4a) to (4c), which had been prepared according to Example 4, F - A curves were determined in the same manner as in Example 10; it was found that the compounds (4b) and (4c) were able to form stable monomolecular films with an interface of about 2.2 nm². Compound (4c) could be applied as a Y-type film on a solid substrate ( Fig. 3).

The results of Examples 10 to 12 show that the cyclodextrin molecules, each a long chain Wear hydrocarbon group, arranged side by side in this way are that the cylindrical base of the cyclodextrin molecules is parallel to the water surface. Known there is that the outside diameter and height of unsubstituted beta-cyclodextrin (beta-CD) 1.54 ± 0.04 nm or 0.80 nm (Sanger, Angewandte Chemie, Internationale Ed., 19 (1980) 344), one can see the area of the cylindrical Calculate the footprint per beta CD molecule. According to this calculation are the areas of the cylindrical base 1.77 to 1.96 cm² per beta CD molecule.

When the cyclodextrin molecules in the densest two-dimensional Pack was brought, the cylindrical Base area 1.95 to 2.16 nm², so that these values the observed To come close to values. If the sec alcohol part of the beta-CD was acetylated [(4c) → (3c)], the limit increased from 2.2 to 2.53 nm²; if a sulfinyl group  [-S (O) -] has been replaced by a sulfide group (-S-) [(3c) → (2c)], the border area did not change. These results show that the border area through the cylindrical The area or proportion of the cyclodextrin was determined. The Cyclodextrin derivative with a long hydrocarbon chain can a stable monomolecular film on the water surface form, the long chain hydrocarbon groups are oriented upwards and parallel; by one the film on a substrate according to the Langmuir-Blodgett method applies an ultra-thin organic Make film in which the cavities of cyclodextrin regularly formed on the Y-type film applied are so that they are oriented in one direction.

Example 13

For alpha, beta and gamma cyclodextrin compounds with different long-chain hydrocarbon groups, the surface pressure-area curves ( F - A) are shown in FIGS. 4 to 6. In each case, a stable monomolecular film was formed. Furthermore, each monomolecular film could be applied to a solid substrate as a Y-type or Z-type film according to the application conditions.

Example 14

The cyclodextrin compound (7c) was mixed with methyl red; the resulting mixture was then dissolved in chloroform so that both the compound and methyl red were at a concentration of 2.0 × 10 ^-4 mol / l. The resulting solution was then spread on pure water at 17 ° C according to the usual Langmuir-Blodgett method to form a film; the surface pressure-area curve ( F - A) was then determined. The result is shown in Fig. 7 (dashed curve). For comparison, the F - A curve (solid curve) of compound (7c) alone and the F - A curve (dash-dotted curve) of methyl red alone are also given. The solid curve and the dashed curve largely overlap. The limit of the film mentioned was about 2.5 nm². This result shows that the cyclodextrin molecules with their cylindrical bases align on and parallel to the water surface and that the orientation does not change even when a dye is added. By keeping the surface pressure at 30 mNm ^-2 and using a quartz plate as the substrate, the opposite surfaces of which had been covered with 5 layers of cadmium arachidate film, a Y-type film could be obtained on the substrate both when placed in water , as well as when it was pulled out of the water. The commissioned film was yellow in color when viewed from the side. A UV spectrum of 50 layers of film applied in this way is shown in FIG. 8. When the substrate was inclined at an angle of 45 ° and polarized light was used, the direction of the longitudinal axis of the dipole of the azo dye was measured (lambda _max about 400 nm; EE Polymeropoulos, D. Mobius and H. Kuhn, J. Chem. Phys. , 68 (1978) 3918). It was found that the azo dye molecules were almost oriented to the substrate.

From the fact that the F - A isotherm did not change even in the presence of the dye and that the dye molecule contained in the application films was oriented in the same direction as the cavities of the cyclodextrin, it can be assumed with great probability that the dye is included in the cyclodextrin. In order to further clarify whether the dye was included, an induced circular dichroism spectrum was measured ( FIG. 9). During the measurement, the substrate was placed perpendicular to the incident light, but no absorption of the circular dichroism was found. When the measurement was carried out when the substrate was inclined at 45 °, no absorption according to the positive Cotton effect was found. These results show that the azo dye was enclosed in the cavities of the cyclodextrin and that the long dipole axis of the dye molecules in the application films was oriented vertically to the substrate.

Example 15

To 5 ml of a solution containing 2.0 × 1.0 ^-4 mol / l beta-cyclodextrin / compound (7c) was added 10 mg of methyl orange; after that it was stirred. 1 part of methyl orange was dissolved in chloroform, so that a yellow color developed. A monomolecular film with the resulting solution was prepared on a water surface according to Example 14. This film could be applied under constant pressure of 30 mNm ^-1 as a Y-type film on a quartz substrate which had been coated with 5 layers of a monomolecular film of cadmium arachidate. Measurements of the UV spectrum ( Fig. 10) confirmed that the methyl orange had been included in the application film and that the methyl orange molecules were practically vertical to the substrate.

Example 16

With beta-cyclodextrin / compound (7d) / and methyl orange was an experiment in the same way as in example 14 performed. In this case too, it was found that the methyl orange molecules are included in the application film were.

Example 17

With alpha-cyclodextrin / compound (8d) / and methyl red, an experiment was carried out in the same manner as in Example 14. From the UV spectrum ( Fig. 11) it was found with polarized light that the long axis of the transition moment of the dye was arranged rather vertically to the substrate in comparison with the cases in which the beta-cyclodextrins / compounds (7c) and (7d ) / Examples 15 and 16 were used. This result is believed to be due to the fact that the cavities of alpha-cyclodextrin are narrower than those of beta-cyclodextrins.

Example 18

The same procedure as in Example 14 was repeated except that beta-cyclodextrin (7c) and azobenzoic acid were used as the azo dye, and it was found that the azobenzoic acid was included in the coating film. However, it was found from the UV spectrum ( Fig. 12) with polarized light that the long axis of the transition moment of the dye was less oriented than that of the other azo dyes (methyl red and methyl orange).

Example 19

The same procedure as in Example 14 was used repeated except that cyclodextrin / compound (9d) / and methyl red were used, with a film on a Quartz substrate was applied. In this case it was Absorbance strength of methyl red lower than when used of alpha-cyclodextrin (8d) or the beta-cyclodextrins (7c) and (7d). It was found that for the Accumulation of the dye on the substrate the size of the Cavities in the cyclodextrin film play an important role and that the dye inclusion forces of cyclodextrin are one Cause the dye to accumulate on the substrate.  

Table 1

Structures and associated abbreviations of cyclodextrin compounds

Claims (11)

1. Cyclodextrin compound of the general formula whereinR is an alkyl group having 4 or more carbon atoms, X is a divalent functional residue from the group formed by -O-, -S-, -S (O) - and -NH-, Y is a hydrogen atom, an acyl group or an alkyl group and n is one means integer of 6 or more. 2. Cyclodextrin compound according to claim 1, characterized in that R in the general formula is a C _6-22 alkyl group, in particular a C _8-22 alkyl group. 3. Cyclodextrin compound according to claim 1 or 2, characterized in that n in the general formula is an integer from 6 to 8. 4. Cyclodextrin compound according to one of the preceding Claims, characterized in that Y means an acetyl group in the general formula.   5. Ultrathin film, characterized by a cyclodextrin compound of the general formula according to claim 1, in which R, X, Y and n have the meanings according to one of the preceding claims, or the inclusion compound of an azo dye in the cyclodextrin compound. 6. Ultra-thin film according to claim 5, characterized in that he has at least one monomolecular Film of the cyclodextrin compound or its inclusion compound includes. 7. A process for producing an ultra-thin film, characterized in that one successively on the surface of a carrier liquid a thin film of a cyclodextrin compound of the general formula according to claim 1, wherein R, X, Y and n have the meanings according to claims 1 to 4, or an inclusion compound in which an azo dye is included in the cyclodextrin compound, and passes a solid substrate through the thin film and deposits the thin film on the solid substrate. 8. A method of manufacturing an ultra-thin film according to Claim 7, characterized in that one the cyclodextrin compound or its inclusion compound dissolves in a solvent and with the help of the formed Solution the thin film on the surface of the carrier liquid forms. 9. A method for producing an ultra-thin film according to claim 7 or 8, characterized in that an aqueous medium or an aqueous solution is used as the carrier liquid and is preferably n in the general formula according to claim 1 6 to 8. 10. A method of manufacturing an ultra-thin film according to one of the preceding claims, characterized in that as a solid substrate, a glass plate, a quartz plate, an aluminum plate, a calcium fluoride plate or a porous plate made of, for example Percoal glass or percolation glass or a membrane filter used, one or more films on the substrate, in particular one or more monomolecular films of one higher fatty acid or a salt of a higher fatty acid can be applied. 11. A method for producing an ultra-thin film according to one of claims 7 to 10, characterized in that one uses a cyclodextrin compound of the general formula according to claim 1, wherein R is a C _8-22 alkyl group, X is a -NH group, Y a Hydrogen atom and n are an integer from 6 to 8.