DE3710569C2 - - Google Patents

Description

The present invention relates to cyclodextrin servers bindings with a cylindrical structure and their use.

It is known that thin films of organic verbin on solid substrates using the Langmuir-Trough process let form. Furthermore, DE-A1-35 45 984 describes the training monomolecular layers after Langmuir-Blodgette procedure. Thin films you like this can produce, can be used and are versatile 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 you can include connections of different connections using  create a "host-guest effect". This inclusion ver You can, for example, bindings

• (1) for catalytic reactions (which shows cyclodextrin a catalytic effect),
• (2) to protect compounds against light or acid are sensitive to fabric,
• (3) to suppress volatile compound evaporation fertilize,
• (4) to protect against toxic substances,
• (5) for chromatography, using organic molecules can be separated according to their molecular weight,
• (6) for chromatography, in the optically active Substances are separated from each other,
• (7) as a separation membrane in which each molecule has a passage has cavity, 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 forms connections as thin films, they offer on the mentioned technical advantages.

Cyclodextrin derivatives are described in EP-A2-01 97 571. 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 solution reach medium if the inclusion connection is open is spread out on a surface of water, it tends to open break;
• (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 above be sore.  

Other objects, features and advantages of the invention result from the following description and the figures. It shows

Fig. 1 to 6 graphical representations of surface pressure-area curves (FA) of cyclodextrin with hydrocarbon groups, with abscissa and ordinate each indicating the area per cyclodextrin molecule (nm²) and the surface pressure (mNm ^-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 is a hydrocarbon group points, forming 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 can be meaningful. The cyclodextrin according to the invention connection can be represented by the following general formula will give:

wherein
R is a hydrophobic alkyl group having 4 to 22 carbon atoms, preferably 6 to 22 carbon atoms, in particular 8 to 22 carbon atoms;
X represents a divalent functional group, namely -S-, -S (O) - or -NH-;
Y represents a hydrogen atom or an acetyl group; and
n is an integer from 6 to 8.

Ultrathin films of cyclodextrin or its inclusion connection 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 a selectively permeable membrane 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 cyclo is particularly suitable dextrins

• (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) as an 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 Anthra zenen, and
• (3) as a material to provide higher secondary harmonies, by including large polarity organic molecules.

Below we describe the invention in more detail with examples. The specific cyclodextrins used in the examples have been used according to the above general my formula specified, being their structures and abbreviations from the examples and Table 1 below surrender. 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 in 100 parts of anhydrous dimethylformamide suspen dated; 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. The mixture was then stirred for 16 hours at room temperature puts. The resulting reaction liquid became in 2000 Parts of ice water poured; the separating white low Impact 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 butanethiol 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% aqueous sodium carbonate solution, water and a saturated saline solution in the order given washed. The organic layer was then washed with water free sodium sulfate dried and concentrated, 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), ent speaking 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% aqueous 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.  

The other compounds (3a), (3b) and (3d) were obtained in the same way.

Example 4 Preparation of heptakis (6-alkylsulfinyl-6-dexoy) 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 resul The residue was then dissolved in CH₂Cl₂. The formed solution was poured into methanol to the Rohpro get duct. 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 hexa Obtain decanthiol or 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 of hexadecylamine.

Application example 1

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 (FA) 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 cadmium stearylate which had previously been applied to a glass plate ( FIG. 1).

Example of use 2

For the compounds (3a) to (3c) prepared according to Example 3, FA curves were obtained in the same manner as in Example 10, and it was found that the compounds (3b) and (3c) were stable 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

It was a solution of 1.0 × 10 ^-3 mol beta-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 Application example 1 spread. The surface pressure-area curve (FA) is determined , 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 of use 3

For the compounds (4a) to (4c), which had been prepared according to Example 4, FA curves were determined in the same manner as in Application Example 1; it was found that the compounds (4b) and (4c) could 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 application examples 1 to 3 show that that the cyclodextrin molecules, each a long chain Wear hydrocarbon group, side by side in such a way arranges that the cylindrical base of the Cyclodex trin 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), the area of the cylindrical Calculate the footprint per beta CD molecule. After this The areas of the cylindrical base area are calculated 1.77 to 1.96 cm² per beta CD molecule.

When the cyclodextrin molecules in the closest two dimen were brought in package, the cylindrical Base area 1.95 to 2.16 nm², so that these values the observed values. If the sec alcohol part of the beta-CD was acetylated / (4c) → (3c) /, the Grenzbe increased ranges 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 area, the long chain hydrocarbon groups are oriented upwards and in parallel; by one the film on a substrate according to the Langmuir-Blodgett Ver is an ultra-thin organic one 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 of use 4

For alpha, beta and gamma cyclodextrin compounds with different long-chain hydrocarbon groups, the surface pressure-area curves (FA) 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.

Application example 5

The cyclodextrin compound (7c) was mixed with methyl red; the resulting mixture was then so in chloroform dissolved so that both the compound and methyl red in a concentration of 2.0 × 10^-4 mol / l templates. The solution obtained was then on pure water at 17 ° C. according to the usual Langmuir-Blodgett method of formation elaborated a film; after that the surface pressure Area curve(FA) determined. The result is inFig. 7 reproduced (dashed curve). Also for comparison  theFACurve (solid curve) of connection (7c) alone and theFA-Curve (dash-dotted curve) of methyl indicated in red alone. The solid curve and the dashed curve largely overlap. The border area said film was about 2.5 nm². This result shows that the cyclodextrin molecules with their zylin drische base areas on the water surface and parallel to align and that even with the addition of a dye the orientation is not changed. By the waiter surface pressure at 30 mNm^-2 stopped and as a substrate a quartz plate took, its opposite surfaces with 5 layers of film had been coated with cadmium arachidate then obtained a Y-type film on the substrate both if it was put in water as well as if it was was withdrawn from the water. The commissioned film had one yellow color when viewed from the side. A UV spectrum of 50 layers of film applied in this way has been inFig. 8 shown. If you look at the substrate light inclined at an angle of 45 ° and polarized the direction of the longitudinal axis of the dipole of the Azo dye measured (λ _Max about 400 nm; E. E. Polymeropoulous, D. Mobius and H. Kuhn, J. Chem. Phys., 68 [1978] 3918). It was found that the azo dye molecules were oriented almost vertically to the substrate.

From the fact that the FA isotherm did not change even in the presence of the dye and that the dye molecule contained in the commissioned 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, measurements were carried out in the induced circular dichroism spectrum ( 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 of use 6

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 produced on a water surface in accordance with Application Example 5. This film could be applied as a Y-type film under constant pressure of 30 mNm ^-1 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) confirm that the methyl orange had been included in the application film and that the methyl orange molecules were arranged practically vertically to the substrate.

Application example 7

With beta-cyclodextrin / compound (7d) / and methyl orange was an experiment in the same manner as in Application Example 5 carried out. In this case too, it was found that the methyl orange molecules are inserted in the application film were closed.

Application example 8

With alpha-cyclodextrin / compound (8d) / and methyl red, an experiment was carried out in the same manner as in application example 5. On the basis of 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) / Application Examples 6 and 7 were used. This result is probably due to the fact that the cavities of the alpha-cyclodextrin are narrower than those of the beta-cyclodextrins.

Application example 9

The same procedure as in Application Example 5 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 application film. However, from the UV spectrum ( Fig. 12) with polarized light, it was found 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 of use 10

The same procedure as in application example 5 was used repeated except that gamma-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 in the Ver Use of alpha-cyclodextrin (8d) or beta-cyclo dextrins (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 (2)

1. Cyclodextrin compound of the general formula wherein
R is a C _4-22 alkyl group,
X is a divalent functional radical from the group formed by -S-, -S (O) - and -NH-,
Y is a hydrogen atom or an acetyl group and
n is an integer from 6 to 8. 2. Use of a cyclodextrin compound according to claim 1 to produce an ultra-thin film, one after the other another thin on the surface of a carrier liquid Film of the cyclodextrin compound forms and a solid Passes through the thin film and substrate on the thin film the solid substrate.