POROUS RUBBER MATERIALS

Abstract: The present invention provides a material comprising pores with a diameter which allows the passage of water through the material but excludes molecules larger than water. The pores are typically less than 10A DEG in diameter and exclude the passage of hazardous chemicals across the material. The material preferably comprises a polymeric matrix, e.g. natural or synthetic rubber, and the pores are provided by a chemical compound included within the polymeric matrix, e.g. by cyclodextrins. The materials may be used to provide water permeable chemically resistant material useful for preparing e.g. protective clothing. The invention also provides methods for preparing the materials described above and novel chemical compounds suitable for incorporation into polymers to provide pores. It also provides methods and apparatus for separating compounds comprising immobilised cyclodextrins.

Description: POROUS RUBBER MATERIALS The present invention relates to the provision of materials comprising pores capable of allowing the passage of water molecules, items made from such materials and compounds which may be included into materials to provide pores. The pores are preferably provided by inverted cyclodextrins. This invention also relates to the use of inverted cyclodextrins to separate polar compounds from apolar compounds, particularly in the fields of effluent treatment, ultrafiltration and the separation of chiral compounds. Chemically resistant materials are used in many fields, eg. in the chemical industry, the petroleum industry and in the defence industry, in order to provide protection for personnel working in these areas, particularly they are used to manufacture protective clothing. These materials are also used in warfare scenarios and by international teams set up to ensure that international controls of the use of chemical substances are enforced. Garments manufactured from chemically resistant materials are generally unpleasant to wear because as well as preventing chemicals from permeating them they also prevent the passage of water vapour. The perspiration of the wearer is thus trapped within the garments, resulting in an increase of heat and discomfort to the wearer. When the garments are worn for considerable periods of time or are worn while performing difficult manual tasks they may cause skin problems or heat exhaustion of the wearer as well as hindering him in the performance of his tasks. It ib an aim of the present invention to provide materials capable of allowing the passage of water vapour through them while excluding the passage of larger molecules. Preferred materials can be used to manufacture chemical resistant suits or other wearable items such as gloves, and are capable of allowing perspiration to pass through them while maintaining their resistance to hazardous chemicals. A first aspect of the present invention provides a polymeric material comprising pores with diameters which allow the passage of water but exclude molecules substantially larger than water characterised in that the material comprises a polymeric matrix wherein the pores art- provided by inverted cyclodextrins included within the polymeric matrix. Preferably the pores have a diameter of less than 10 A°, more preferably 7 A°. The polymeric material preferably comprises natural or synthetic rubber, more preferably butyl rubber or polyisoprene. The pores are provided by cyclodextrins, cyclic oligomers of several alpha-1,4-linked glucose units, used extensively as inclusion complexes because they have a hydrophilic exterior and a hydrophobic interior. The applicant has carried out molecular modelling experiments which have indicated that the inner cavity of these oligomers is too hydrophobic to allow the passage of water vapour, all the hydroxyl groups being on the outer surface of the cyclodextrin. However, X-ray crystallographic and neutron diffraction studies of cyclodextrins have indicated that the inner face of the beta-cyclodextrin molecule is capable of accommodating up to eight molecules of water of crystallisation being present in the structure of beta-cyclodextrin crystals (Klar et al, Acta Cryst Sect B, B36, 115 4 * (1980); Lindner et al Acta Cryt Sect B B38. 203 (1982); Chacko et al J Amer Chem Soc 103, 1708 (1981)). These studies have also indicated that alpha-cyclodextrin also contains molecules of water crystallisation. The cyclodextrins included in the material are modified to have a hydrophilic interior eg. inverted cyclodextrins in which inversion of the anomeric glucosidic links to a beta-l,*.-configuration has resulted in the molecule being effectively turned inside out and therefore having hydroxyl groups on the inner face. Initial calculations indicated that the cavity of this 'inverted' cyclodextrin would be too small to allow the passage of water if it was based on alpha-cyclo-dextrin but that it would be ideal if based on beta-cyclodextrin. Cyclodextrins may be inverted by forming beta-l,4-links between the sugars by chemical reaction or by forming a 3,6-ether-bond on several of the sugar residues within the oligomer, ie. by forming anhydro-sugars. Using this latter technique the ideal cavity size is provided by the alpha-cyclodextrin. Preferred embodiments comprise at least three 3.6-anhydro-sugars, the most preferred embodiments comprising A,B,D,E-tetra-3.6-anhydro- cyclodextrins. Per-3.6-anhydro-alpha- and beta-cyclodextrins have been prepared (Stoddart et al Angew Chem Int Ed Engl 30, 80 (1991); Defaye et al Angew Chem Int Ed Engl 30, 78 (1991)). The formation of the ether bridge between the C-6 and C-3 causes the chair conformation to flip resulting in the alpha-substituent becoming equatorial rather than axial. Molecular modelling of per-3.6-anhydro-alpha-cyclodextrin revealed that on changing the conformation of the chair all the C-2 hydroxyls take up a position on the inner phase of the cyclodextrin. Modelling experiments have also indicated that the size of the pore of the cyclodextrin increased from 4.9 A° to between 5 and 7 A°, a diameter which would allow the passage of a water molecule. Inversion may also be performed on a suitable support, such as those used for peptide synthesis, eg. per-chloromethylated styrene resins. The cyclodextrin component preferably comprises a substituted cyclodextrin, in which a number of the sugar rings may be substituted. Substitution at the primary hydoroxyl functions of alpha-cyclodextrin is however limited to a maximum of three glucose units if the ring is subsequently to be inverted. Preferred cyclodextrins are those comprising 6-substituted-sugars, more preferably C,F-6-substituted-cyclodextrins. Suitable cyclodextrin derivatives include ethers, esters and abides and various methods of preparing these are known. The formation of ether derivatives for inclusion in the materials of the present invention is particularly suitable as they are inert and the degree of substitution is more easily controlled than in the preparation of esters or amides. The cyclodextrin preferably comprises an optionally substituted alkenyl, aryl, alkenylaryl or arylalkenyl ether, ester or amide group eg. an allyl, vinyl, styryl, cinnamyl, geranyl, but-3-enyl or methoxy-vinyl-phenyl ether, ester or amide. Di-, tri and tetra-6-O-tritylated derivatives of cyclodextrins are relatively easy to make with a high degree of symmetry, (Knowles et al, J Amer Chem Soc 101, 7630 (2979)). This is useful in characterising the products, a task which is difficult bearing in mind the relative insolubility of cyclodextrins in organic solvents. The trityl group may also be used as a protecting group. Benzyl and allyl ethers of cyclodextrin have previously been prepared. Allyl derivatives are particularly useful in the present invention because they can be cross-linked into butyl rubber type polymers. Further suitable derivatives include geranyl ethers prepared using the cheap and readily available geranyl chloride, and vinylphenyl ethers prepared from eugenol. Alternatively, the cyclodextrins may be acetylated to provide esters eg. the acetate, benzoate, acrylate, pentenoate or cinnamate. The acrylate may be copolymerised with a number of materials eg. styrene or divinylbenzene. The cyclodextrin may be incorporated into the polymeric matrix in various ways eg. by copolymerising unsaturated derivatives of cyclodextrins with monomers to produce the polymer or by cross linking unsaturated derivatives of the cyclodextrins to a polymer by standard methods, eg. by free radical initiation using benzoyl peroxide or AIBN. The presence of several monomers on the cyclodextrin ring renders it susceptible to extensive crosslinking when polymerised. It will be apparent to a person skilled in the art that careful control of the monomer concentrations and reaction conditions will allow the regulation of the way in which the monomers are incorporated into the polymer chain. The properties of the resulting polymer or copolymer will be determined by the composition, configuration and stereochemistry of these chains and by the amount of each monomer incorporated. The material of this first aspect of the present invention is preferably formed from the copolymerisation of an monomer and a cyclodextrin comprising an unsaturated moiety; preferably an optionally substituted alkenyl, aryl, alkenylaryl or arylalkenyl ether, ester or amide group eg. an allyl, vinyl, styryl, cinnamyl, geranyl, but-3-enyl or methoxy-vinyl-phenyl ether, ester or amide. Preferred embodiments of this first aspect of the present invention provide materials which comprise cyclodextrins arranged to provide channels through the material. Random incorporation of cyclodextrin derivatives may provide some such channels due the formation of hydrogen bonds between cyclodextrin molecules but more structured channels can be formed by first oligomerising or polymerising the cyclodextrin derivatives. The formation of oligomers or short polymers of cyclodextrin derivatives may be achieved by limiting the starting materials or reaction conditions to terminate polymerisation when only short chains of have been formed. These chains will contain cyclodextrins in very close proximity, which will tend to hydrogen bond to one another. Thus a hydrophilic channel can be formed from the chains of cyclodextrins. The provision of such a channel within a hydrophobic material will allow hydrophilic molecules, particularly water vapour, to pass through the material. When the materials are used in chemically resistant clothing they will allow perspiration to pass from inside the clothing to the environment, preventing the build up of heat. This will be encouraged by the high concentration of water within the garment resulting in loss of water vapour through the channel to the environment because of the concentration gradient. The formation of channels may also be performed by the photolysis of cyclodextrins comprising a branched chain unsaturated moiety, eg. cinnamyl derivatives may be polymerised via photolysis to form cyclobutanes between adjacent cinnamyl groups leading to the formation of intermolecular bonds between the cyclodextrin molecules. This photolysis results in stacking to form hydrophobic tubules suitable to allow the passage of water vapour. A second aspect of the present invention provides an item comprising a material as described above, preferably being a garment such as a chemical protection suit, wearable apparel such as gloves, or a body bag. Alternatively the item may be a semipermeable membrane, eg. a membrane suitable for use as an osmotic membrane, for use in ultrafiltration or the treatment of effluent. A third aspect of the present invention provides an apparatus for the resolution of compounds comprising inverted cyclodextrin immobilised on a polymer support, preferably a column. This aspect of the invention also provides a method of separating compounds using such an apparatus; the method comprises applying the compounds to be separated to a support on which inverted cyclodextrin is immobilised, allowing the compounds to form inclusion complexes with the inverted cyclodextrin and eluting the different compounds in different fractions of eluant. The apparatus and methods are particularly useful for the resolution of chiral compounds. The hydrophilic interior of the inverted cyclodextrins allows it to form inclusion complexes with the polar part of the compound to be separated. Different enantiomers can then be eluted at different rates facilitating separation. Columns having immobilised cyclodextrins are already known for the separation of chiral compounds but they bind the chiral compound by its apolar part rather than its polar part. Thus improved resolution of those, compounds in which the polar is closer to the chiral carbon is provided by the use of inverted cyclodextrins, the separation of compounds such as amino acids is improved. Conventional polymeric supports such as polystyrene may conveniently be used in this aspect of the invention. A fourth aspect of the present invention provides the use of a material as described above to allow the selective permeation of water vapour through it while excluding the permeation of chemicals having a molecular diameter larger than 10A°, preferably larger than 7A°. A fifth aspect of the present invention provides a method for the production of a material as described in the first aspect comprising reacting a cyclodextrin with a reactive moiety to produce a cyclodextrin derivative; inverting the derivative product; and incorporating the inverted derivative into a polymer. The cyclodextrin derivative produced is preferably an ester, amide or ether. Preferred embodiments of this aspect provide an optionally substituted alkenyl, aryl, alkenylaryl or arylalkenyl ether, ester or amide group eg. an allyl, vinyl, styryl, cinnamyl, geranyl, but-3-enyl or methoxy-vinyl-phenyl ether, ester or amide. Further preferred embodiments of this aspect of the invention provide a method for the production of cyclodextrin derivatives comprising one to three derivatised sugars; more preferably mono or di-substituted cyclodextrins are produced. Preferably at least 50% of the cyclodextrin derivatives are substituted at one to three units, more preferably at least 70%, most preferably at least 90 . The cyclodextrin product is preferably inverted by the formation of 3,6-anhydro-sugars. Preferred embodiments provide the formation of at least three anhydrous sugars resulting in the inversion of the cyclodextrin. The inverted derivative produced may be incorporated into a polymer by being polymerised, by copolymerisation with an unsaturated monomer or by crosslinking to a polymer. Preferred embodiments are those in which the inverted derivative comprises an unsaturated moiety and this is copoly erised with an unsaturated monomer to provide a material having pores capable of allowing the passage of water while excluding larger molecules. Further preferred embodiments are those in which the cyclodextrin is oligomerised or polymerised to provide a hydrophobic channel before being incorporated into a polymer or copolymer. A further aspect of the present invention provides a cyclodextrin comprising at least three 3.6-anhydro-sugars and at least one 6-substituted-sugar, preferably a cyclodextrin comprising at least two 6-substituted-sugars. The substituted sugars are preferably ester, amide or ether derivatives, preferably comprising an optionally substituted alkenyl, aryl, alkenylaryl or arylalkenyl ether, ester or amide group eg. an allyl, vinyl, styryl, cinnamyl, geranyl, but-3-enyl or methoxy-vinyl-phenyl ether, ester or amide group. A preferred embodiment of this aspect comprises A,B,D,E-tetra-3.6- -anhydro-C.F-di-substituted-cyclodextrins; a particularly preferred embodiment is A,B,D,E-tetra-3,6-anhydro-C,F-di-vinylbenzyl-alpha- -cyclodextrin. EJJΔMELES EXPERIMENTAL DETAILS HPLC was performed using a Novapak Carbon 185um (8 x 100mm) reverse phase column and water/methanol as eluant. Capillary gas chromatography was performed on a 5m χ 0.22 mm 0.25u BP-1 29a column using hydrogen as carrier gas at lml/min between 50 and 300°C at 5°C/min with an injector temperature of 200°C. Proton n.m.r. was performed at 200 MHz on a Varian Gemini 200, at 300 MHz on a Bruker AC 300 and at 500 MHz on a Varian Unity 500 instrument. Carbon-13 n.m.r. was performed at 50 Hz on a Varian Gemini 200, 75 MHz on a Bruker AC 300 and at 125 MHz on a Varian Unity instrument. Mass spectrometry was performed on Kratos Concept IS instrument. Infra red spectroscopy was performed on a Perkin-Elmer FT 1710 instrument using KBr disc. General Iodination Procedure Cyclodextrin (l.Og), triphenylphosphine (4.86g) and iodine (4.68g) were heated in DMF for 18 hours at 80°C with stirring. Half the solvent was removed under reduced pressure, 30 ml dry methanol added and the reaction cooled to 0°C with stirring. Sodium methoxide was added at 0°C, with stirring until the solution reached pH 10. The solution was left overnight with stirring to reach room temperature. The precipitated product was then isolated by filtration. General Inversion Procedure 6-iodocyclodextrin (l.Og) derivative and 1M sodium hydroxide (10 ml) were heated overnight in 30 ml DMS0, at 60 °C with stirring. The reaction was allowed to cool to room temperature and six lumps of solid carbon dioxide added. The solvent was removed under reduced pressure and the residue was taken up in OCM/ethanol (10:1) and percolated through a column of silica to afford the product on evaporation. One-pot Inversion Procedure The cyclodextrin derivative (l.Og), triphenylphosphine (4.86g) and iodine (4.68g) were heated overnight in DMF (100ml) at 8θ°C, with stirring. The solvent was then removed under reduced pressure and the residue dissolved in DMSO (30 ml) . 2M sodium hydroxide (lOmls) was added and the reaction heated for two days at 60 °C with stirring. The solution was then poured directly into a length of Visking tube and dialysed against a constant flow of water for two days. The contents of the Visking tube were filtered and the filtrate freeze dried to afford the product. General Acetvlation Procedure The cyclodextrin derivative (100 mg) was dissolved in 15 ml of a 2:1 mixture of acetic anhydride/pyridine and stirred overnight. The solvent was removed under reduced pressure and the residue dissolved in chloroform (25 ml), washed with 5% hydrochloric acid (2 x 10 ml), sodium bicarbonate (2 x 10 ml) and brine (10 ml). It was then dried over anhydrous sodium sulphate and evaporated under reduced pressure to afford the product. General Alkylation Procedure Cyclodextrin l.Og, barium hydroxide (648g) and two molar equivalents of alkyl halide were stirred in 50 ml 1:1 DMF/DMSO overnight, poured into a sealed length of Visking tube and allowed to undergo dialysis against a continuous flow of water overnight. The contents of the Visking tube was then freeze dried to afford the product. General Tritvlatinn/Acvlation Procedure Cyclodextrin (l.Og) was dissolved in 50 ml pyridine and trityl/ acid chloride (X eq.) added. The reaction was heated at 60°C overnight with stirring. The solvent was then removed under reduced pressure to afford the product. EXAMPLE 1: PREPARATION OF INVERTED CYCLODEXTRINS Per-iodo-alpha-cvclodextrin The preparation was carried out in accordance with the general iodination procedure described by DeFaye (Defaye and Gadelle, Angew. Chem. Int. Ed. Eng. , 30, 80, (1991)) giving 80% yield. Problems were encountered in the work up and purification due to the large amount of triphenylphosphine used in the reaction. Initially attempts were made to cut down the amount of triphenylphosphine used in the reaction however this only resulted in the reaction failing to go to completion. Attempts to remove triphenylphosphine oxide by use of iron exchange resin also proved to be fruitless as did extraction with petroleum ether (bp 40/60) of the reaction mixture after slurrying in water. Alternative methods of iodination were attempted as follows: i) Lil. TMSC1. CH 3 CN, 0°C - RT ii) NIS, Ph 3 . DCM, 0°C - RT iii) MsCl, collidine, DMF, Lil. 0°C - RT All the above reactions failed to give the desired product and in the case of the former totally destroyed the cyclodextrin system. Due to the problems encountered it was decided to by-pass die purification of the product and to attempt a one pot synthesis. The yield was 60-80% and the product obtained had the following characteristics: m/z (FAB); 1655 (M+Na * ); delta *H nmr (D 6 DMS0, 200 MHz); 5-85 (2H. m) 4.95 (1H, m) 3-9~3.2 (4H, m) ; delta 13 C nmr (D 6 DMSO, 75 MHz); 102, 86.4, 72.4, 71.6 (remaining peaks lost in baseline). Per-2.4-act-tyl-per-6-iodo-alpha-cyclodextrin The preparation was carried out in accordance with the standard acetylation procedure in 90% yield in order to verify the results from the iodination reaction and as an aid to the quantification of the amount of triphenylphosphine residues being carried through (§ 3:1 PPh 3 P/product) . A product having the following characteristics was obtained: m/z (FAB); 2159 (M+Na * ); delta *H n.m.r. (CDC1 3 , 200 MHz); 5.5 (1H, br s) 5.15 (1H, br d, J=8 Hz), 4.85 (1H. br t, J=8 Hz); 4.15 (1H. br s), 3.9-3.5 (3H m). 2.15 (3H. s) . 2.05 (3H. s). Per- .6-an ydro-alpha-cyclodextrin The preparation was carried out in accordance with the method described by DeFaye whereby the iodo-derivative was heated in DMSO containing aqueous sodium hydroxide. The reaction product proceeded in ca 80% yield after allowing for residual triphenylphosphine present. In order to by-pass the need for a large quantity of triphenyl phosphine a one pot synthesis was performed. The cyclodextrin was iodinated via the standard method of heating in a solution of DMF containing a large excess of triphenylphosphine and iodine, but the work up was then modified. The DMF was removed under reduced pressure and the residual dissolved in DMSO to which a large excess of concentrated aqueous sodium hydroxide was added. After heating at 80°C for three days the reaction mixture was poured directly into a length of Visking tube and the reaction dialysed against a constant flow of water for two days. The aqueous contents of the Visking tube. containing a precipitate of residual triphenylphosphine was then filtered and the filtrate freeze-dried to give the product in 85% overall yield. The product obtained had the following characteristics: m/z (FAB); 887 (M+Na * ); 864 (M * ); delta 13 C n.m.r. (D 2 0, 75 MHz); 102.29. 82.29. 77-14, 74.29. 72.00, 71.43. EXAMPLE 2: PREPARATION OF CYCLODEXTRIN ETHERS 6-Benzvl-alpha-cvclodextrin The reaction was carried out by the general alkylation procedure. Mass spectroscopy (FAB) revealed that a mixture of mono-, di-, tri-, tetra, penta- and hexabenzylated derivatives had been formed. The material was analysed by HPLC and mass spectroscopy and shown to contain more than six components, mainly due to varying substitution patterns. Attempts were made to try to minimise the amount of material with three or more substituents by reducing the quantities of alkyl halide (benzyl bromide) used and by using higher dilution. Eventually a standard of two molar equivalents of alkyl halide and two molar equivalents of barium hydroxide used at a dilution of l.Og cyclodextrin / 50 ml 1:1 DMSO / DMF was adopted. This general procedure was then used for most of the other alkylations. A further useful aid in purification was precipitation from water with acetone. The reaction was carried out on alpha-cyclodextrin in accordance with the general alkylation procedure using benzyl bromide in 95% yield. The product obtained had the following characteristics: m/z (FAB); 1535 (hexa subst. +Na) , 1445 (penta subst. ♦Na) , 1355 (tetra subst. +Na) , 1265 (tri subst. -t-Na) , 1175 (di subst. +Na) , 1085 (mono subst. ♦Na) , delta *H n.m.r. (D-,0, 200 MHz); 7.40 (1H, m) , 5.0 (1H, br s). 3-9 (4H, m). 3-55 (2H. m) , 2.80 (2H. s). 6-Trityl- lnha-cvclodextrin This compound was prepared in order to investigate the substitution patterns encountered when making cyclodextrin derivatives, since the reaction on alpha-cyclodextrin was known to give a variety of products. HPLC analysis revealed that several compounds were formed and mass spectroscopy showed that a range of polyalkylated products, ranging from mono- to tetra substituted, had been formed. The reaction was carried out on alpha-cyclodextrin in accordance with the general tritylation procedure using three equivalents of trityl chloride. The product obtained had the following characteristics: m/z (FAB); 1963 (tetra subst. +Na) . 1722 (tri subst. +Na) , l48l (di subst. *Na), delta *H n.m.r. (D 6 Acetone, 200 MHz); 7.5O-7.O5 (6H, m). 5.3 (1H. m). 5.05 <1H. m) . 4.70 (1H, m) . 4.37 (1H. m) , 3.80-3-30 (3H, m). 6-Geranyl-alpha-cyclodextrin Geranyl chloride was prepared by a standard procedure of heating geraniol and triphenylphosphine at reflux in carbon tetrachloride. Although effect, this method had the drawback that it utilised the toxic and expensive carbon tetrachloride and so an alternative route was sought. Attempts at chlorination using TMSCl (two equivalents) and calcium carbonate in DCM, although successful were seen to contain a large quantity of by-products when analysed by GC/MS. Attempts at chlorination via the mesylate using MsCl, LiCl and collidine in DMF also proved unsuccessful. An effective alternative synthesis eventually proved to be the use of N-chlorosuccinimide and triphenylphosphine in DCM at 0°C which provided geranyl chloride in over 80% yield. N-chlorosuccinimide (l4.0g, 105mmol) was dissolved in DCM (150 ml) and cooled to 0°C with stirring triphenyl phosphine (27-5g. 105 mmol) was added dropwise over 15 minutes. Geraniol (15.4 g, 17-3 ml, mmol) was added to the stirred, cooled solution in ca. lg portions over ten minutes and the reaction stirred at 0°C for an hour. The solvent was removed under reduced pressure and the solid residue crushed in petroleum ether (b.p. 4θ-6θ°C, 100 ml) and the slurry was heated to boiling point. The petroleum slurry was then filtered through silica (50g) and the silica washed with 3 x 100 ml petrol. The combined filtrate was then evaporated under reduced pressure to afford the product in 80% yield (85% purity by G.C.), having the following characteristics: m/z (El); 174/2 (M * ). >H n.m.r. (CDC1 3 , 200 MHz); 7-50-7-05 (6H, m). 5-45 (1H. t. J= 7-5 Hz). 5-08 (1H. m). 4.10 (2H. d. J=8 Hz), 2.08 (4H. m), 1.72 (3H. s), 1.67 (3H. s), 1.6. (3H. s) . The preparation of 6-geranyl-alpha-cyclodextrin was then carried out by the standard alkylation procedure. However, the quantity of alkylated material produced was low and proton n.m.r. spectroscopy failed to indicate any clear evidence of a geranyl group present in the product. Attempts to quantify the degree of alkylation by acetylation and subsequent column chromatography proved to be unsuccessful. 6-Vinvlbenzvl-alpha-cyclodextrin The preparation was carried out by the standard alkylation procedure with a 70:30 mix of m/p vinylbenzyl chloride. HPLC analysis revealed the expected mixture of products and mass spectroscopy (FAB) showed the presence of mono-, di-, and tri- substituted species, the di-substituted being the major product. Proton n.m.r. spectroscopy indicated an averdge of 1.5 styryl groups per cyclodextrin as did the spectrum of the per-acetate derivative. This product is likely to suitable to be polymerised by itself or as a co-polymer with styrene. The yield of product was 95% and it had the following characteristics: m/z (FAB); 1343 (tri subst. +Na) , 1227 (di subst. +Na) , 1111 (mono subst. +Na), *H n.m.r. (CDC1 3 200 MHz); 7-70-7.20 (Ar-H) , 7-0-6.8 (C-H olefin), 5-9-5-60 (C-H, olefin) , 5-45-5-20 (C-H, olefin) , 5.00 (6H, d, J =4 Hz), 4.00-3-65 (24H. m) , 3.60-3-45 (12H, ), 2.95 (1H, s). 2.85 (1H. s). 6-Cinnaayl-aloha-cyclodexTin The reaction was carried out by the standard alkylating procedure using cinnamyl bromide and HPLC analysis gave the expected mixture of products. FAB mass spectroscopy indicated that up to six cinnamyl groups had been added to the cyclodextrin, the most common being the di-substituted derivative. Proton n.m.r. spectroscopy indicated an average of 1.8 cinnamyl groups per cyclodextrin as did the spectrum of the per-acetate derivative. The yield of product was 95% and it had the following characteristics: m/z (FAB); 1691 (hexa subst. +Na) , 1577 (penta subst. +Na) , 149 (tetra subst. +Na) , 13 3 (tri subst. *Na) , 1227 (di subst. ♦Na) , 1111 (mono subst. +Na) ; »H n.m.r. (CDC1 3 200 MHz) ; 7-50-7-20 (Ar-H), 6.65 (C-H olefin. J=l8 Hz). 6.50-6.20 (C-H. olefin, m) , 4.95 (6H, m) , 4.95-4.75 (24H, m) , 3-65-3-45 (12H, ■) . This monomer may not only be polymerised by a free radical process in a similar way to the polymerisation of styrene. but also via photolysis to form cyclobutanes between adjacent cinnamyl groups, probably leading to the formation of inter olecular bonding between cyclodextrin moieties. The photolysis of the cinnamyl derivative of anhydrocyclodextrin is likely to result in stacking to form hydrophobic tubules. EXAMPLE : IODINATION AND INVERSION OF CYCLODEXTRINS ON A SUPPORT The ready availability and well documented use of per-chloromethylated styrene resins as a support for peptide synthesis indicates their potential value as a support on which the iodination and inversion of cyclodextrins may be performed. Cyclodextrin uptake of the resin during the standard alkylation procedure was investigated, the method being modified by using a 1:1 molar ratio of cyclodextrin : alkyl halide. Reaction overnight, followed by dialysis and filtration resulted in the uptake of approximately 6% of the available cyclodextrin by gravimetric analysis. 50% chloromethylated resin may also be useful as a support for the iodination and inversion of cyclodextrins. Inversion of cyclodextrin on a styrene support would lead to the formation of a hydrophilic tubule. Hydrogenation of an inverted cyclodextrin from its polymer support would produce a free C-6 primary alcohol which could be modified to incorporate various substituents, ie. unsaturated moieties suitable for crosslinking the cyclodextrin into a polymer or susceptible of polymerisation. EXAMPLE 4. PREPARATION OF ESTERS OF INVERTED CYCLODEXTRINS Inverted 6-benzvl-alDha-cvclodextrin The benzylated material was inverted as a model for the styrene derivative. The inverted benzyl derivative could also be hydrogenolysed to free the benzyl protected primary alcohol in order to make a vinylbenzyl derivative if the styrene derivative proved not to be suitable for inversion . Initial attempts at inverting the benzyl derivative were ineffective but by increasing the amount of base used and heating the reaction for a longer period of time more satisfactory results are expected. A reaction was observed to have occurred by changes in the proton n.m.r. but no peaks attributable to the desired product were observed in the FAB mass spectrum. Inverted ά-vinvl-benzvl-alpha-cvclodextrin Inversion of the styrene was attempted using the standard on pot method. A change in the proton n.m.r. spectrum reaction indicated that a reaction had occurred but this could not be attributed to the formation of the desired product, although the olefinic protons were still present. EXAMPI55: POLYMERISATION OF CYCLODEXTRIN ETHERS Polv-6-vinvl-benzvl-alDha-cyclodextrin Method 1: 6-vinylbenzyl-alpha-cyclodextrin (0.476g, ca. 0.395 mmol) and benzoyl peroxide (47 mg, 0.2 mmol) were heated at reflux in 1:1 water/methanol (50 ml) for 12 hours. The resultant white precipitate was filtered, washed with methanol/water (1:1) (3 x 1 ul) and dried under vacuum to yield the product in 58% yield as an insoluble white solid. The product obtained absorbed at 1638 cm '1 of its infra red spectrum and acetylation of the material via the standard method resulted in a material having absorptions at 1746cm '1 and 2936 cm '1 in its infrared spectrum. Method 2: 6-vinylbenzyl-alpha-cyclodextrin (0.366g, ca. 0.303 mmol) and AIBN (50 mg, 0.3 mmol) were heated at reflux in methanol (50 ml) for two days. The resultant white precipitate was filtered, washed with methanol/water (1:1) (3 x 1 ml) and dried under vacuum to yield the product in 32 yield as an insoluble white solid. The product obtained was found to have the same characteristics as the product obtained from Method 1. The 6-vinylbenzyl-alpha-cyclodextrin was successfully polymerised using both AIBN and benzoyl peroxide in methanol/water (1:1) at reflux. The polymeric material formed proved difficult to characterise due to a high degree of cross linking creating insolubility problems. Styrene/poly-6-vinvl-benzvl-alpha-cvclodextrin copolvmer The 6-vinyl-benzyl-alpha-cyclodextrin was copolymerised with styrene in methanol using benzoyl peroxide as an initiator. This proved easier to characterise than the product described above. The 6:1 styrene/cyclodextrin derivative ratio used in the reaction mix was mirrored in the resultant polymer when analysed by solid state 13 C n.m.r. The solid state n.m.r. studies also revealed that the copolymer consisted mainly of higher substituted cyclodextrins with an average of 2.9 vinylbenzyl groups per cyclodextrin. 6-vinylbenzyl-alpha-cyclodextrin (0.3δ5g, ca. 0.326 mmol), styrene (0.17 ml. 0.1926 g, 1.85 mmol) and benzoyl peroxide (lOmg 0.04 mmol) were heated at reflux in methanol (50 ml) for 12 hours. The resultant white precipitate was filtered, washed with methanol (3 x 10ml ) and dried under vacuum to yield the product in 28% yield as an insoluble white solid. The product obtained had the following characteristics: ir.: 1652 cm *1 : delta 13C (125 MHz, solid state): 147-120 (broad band, aromatic), 105-48 (broad band, cyclodextrin), 48-28 (broad band, polystyrene backbone) . EXAMPLE 6; PREPARATION OF CYCLODEXTRIN ESTERS 6-AcrγlQvl-alpha-cyclodextrin Cyclodextrin and acryloyl chloride were reacted in pyridine in a variety of ratios to provide mixtures of polysubstituted cyclodextrin derivatives, n.m.r. spectroscopy, mass spectroscopy and infra-red spectroscopy all provided evidence that esters had been formed. Using 1, 2 and 6 equivalents of acryloyl chloride the yields were over 90% and the products having the following characteristics were obtained: ir.: 1743 cm '1 : m/z (FAB): delta ^(D j O, 200 MHz): 5-10-4.90 (6H, m), 4.05-3-75 (24H. D). 3.65-3. 5 (12H. m) . 6-Cinnamovl-alpha-cyclodextrin Cyclodextrin was reacted with one equivalent cinnamoyl chloride in pyridine to form a mixture of polycinnamate derivatives, as evidenced by mass spectroscopy. The yield was 80% and the product obtained had the following characteristics: ir.: 1700 cm '1 : m/z (FAB): delta ^(D- j O, 200 MHz): 7-70-7.30 (Ar-H), 6.5 (d. » CH-), 6.4 (d, =CH-) 5-05-4.95 (6H. m) , 3-95-3-75 (24H, m), 3.6-3.45 (12H, m) . 6-PentenQvl-alpha-cyclpde χ trin Pentenoyl chloride (2 equivalents) was reacted with alpha-cyclodextrin in pyridine to produce a pent-4-enoate ester. Addition of the pentenoyl group was proved by proton n.m.r. spectroscopy and infra red spectroscopy. All reactions resulted in a mixture of poly substituted cyclodextrin derivatives from di- to hexa-, as evidenced by mass spectroscopy. The product obtained had the following characteristics: m/z (FAB): delta ^(D j O, 200 MHz): 6.75 (=CH). 5.85 (=CH), 5.45 (=CH). 5.10-4.90 (6H. m), 4.00-3.70 (24H, m) 3-55~3.45 (12H. m) 2.42-2.30 (CH 2 CH 2 ).

Claims: CLAIMS 1. A polymeric material comprising pores having a diameter which allow the passage of water but exclude molecules larger than water characterised in that the material comprises a polymeric matrix and the pores are provided by inverted cyclodextrins included within the polymeric matrix. 2. A material as claimed in Claim 1 wherein the pores have a diameter of less than 10 A°. 3. A material as claimed in Claim 2 wherein the pores have a diameter of less than 7 A°. 4. A material as claimed in any one of Claims 1 to 3 or wherein the polymeric material comprises natural or synthetic rubber. 5. A material as claimed in Claim 4 wherein the rubber comprises butyl rubber or polyisoprene. 6. A material as claimed in any preceding claim wherein the cyclodextrin comprises at least three anhydrous sugars. 7. A material as claimed in Claim 6 wherein the cyclodextrin comprises A,B,D,E-tetra-3,6-anhydrous cyclodextrin. 8. A material as claimed in any preceding claim wherein the cyclodextrin comprises a 6-substituted-sugar. 9. A material as claimed in Claim 8 wherein the cyclodextrin comprises C,F-di-6-substituted-cyclodextrin. 10. A material as claimed in Claim 8 or Claim 9 wherein the cyclodextrin comprises a cyclodextrin ether, ester or amide. 11. A material as claimed in any one of Claims 9 to 10 wherein the cyclodextrin comprises an optionally substituted alkenyl, aryl, alkenylaryl, of arylalkenyl ether, ester or amide group. 12. A material as claimed in Claim 11 wherein the cyclodextrin comprises an allyl, vinyl, styryl, cinnamyl, geranyl, but-3-enyl or methoxy-vinyl-phenyl ether, ester or amide group. 13. A material as claimed in any preceding claim formed f om the copolymerisation of an addition monomer and a cyclodextrin comprising an unsaturated moiety. 14. A material as claimed in Claim 13 wherein the unsaturated moiety is an allyl, vinyl, styryl, cinnamyl, geranyl and but-3-enyl ether or ester group. 15. A material as claimed in any preceding claim wherein the cyclodextrin is arranged to provide a tubular channel through the material. 16. A chemically resistant garment comprising a material as claimed in any one of Claims 1 to 15 17. Use of a material as claimed in any one of Claims 1 to 15 to 21 to allow the selective permeation of water vapour through it while excluding the permeation of chemicals with a diameter larger than 10A° through it. 18. A method for the production of a material as claimed in any one of Claims 1 to 15 comprising reacting a cyclodextrin with a reactive moiety to produce a cyclodextrin derivative; inverting the derivative product; and incorporating the inverted derivative into a polymer. 19. A method as claimed In Claim 18 wherein the cyclodextrin derivative produced is an ether, ester or amide. 20. A method as claimed in Claim 19 wherein at least 50% of the cyclodextrin is di-substituted. 21. A method as claimed in Claim 20 wherein the cyclodextrin derivative comprises an unsaturated cyclodextrin ether. 22. A method as claimed in any one of Claims 18 to 21 wherein the cyclodextrin product is inverted by the formation of 3,6-anhydro- sugars. 23. A method as claimed in any one of Claims 18 to 22 wherein the inverted cylcodextrin is incorporated into a polymer by copolymerisation with an unsaturated monomer. 24. A method as claimed in Claim 23 wherein the inverted cyclodextrin is incorporated into a polymer by cross-linking. 25. A cyclodextrin comprising at least three 3,6-anhydro-sugars and at least one 6-substitued-sugar. 26. A cyclodextrin as claimed in Claim 25 comprising at least two 6- substituted-sugars. 27. A,B,D,E-tetra-3,6-anhydro-C,F-di-substituted-cyclodextri . 28. A,B,D,E-tetra-3,6-anhydro-C,F-di-vinylbenzy1-alpha-cyclodextrin. 29. An apparatus for the separation of compounds comprising inverted cyclodextrin immobilised on a polymer support. 30. An apparatus as claimed in Claim 29 wherein the support is a column. 31. A method of separating compounds comprising applying the compounds to a support on which inverted cyclodextrin is immobilised, allowing the compounds to form inclusion complexes with the inverted cyclodextrin and eluting the different compounds in different fractions of eluant. 32. A method as claimed in Claim 31 wherein chiral compounds are separated, the enantiomers eluting in different fractions of eluant.

Inventors: BROWN RICHARD TALBOT, JAMESON SIMON BRENT, RAHMAN HABIZUR, WILLIAMS CHARLES FRANCIS, BROWN, RICHARD, TALBOT, JAMESON, SIMON, BRENT, RAHMAN, HABIZUR, WILLIAMS, CHARLES, FRANCIS
Applicants: BROWN RICHARD TALBOT, JAMESON SIMON BRENT, RAHMAN HABIZUR, SECR DEFENCE BRIT, WILLIAMS CHARLES FRANCIS, BROWN, RICHARD, TALBOT, JAMESON, SIMON, BRENT, RAHMAN, HABIZUR, THE SECRETARY OF STATE FOR DEFENCE IN HER BRITANNI, WILLIAMS, CHARLES, FRANCIS
Application year: 1996
Main classification: C08B37
IPC codes: A41D31, A62B17, A62D5, B01D39, C08B37, C08L21