EP1232018A2

EP1232018A2 - Method for applying a polymer on a carrier

Info

Publication number: EP1232018A2
Application number: EP00979625A
Authority: EP
Inventors: Klaus Gottschall
Original assignee: Instraction GmbH
Current assignee: Instraction GmbH
Priority date: 1999-11-26
Filing date: 2000-11-27
Publication date: 2002-08-21
Anticipated expiration: 2020-11-27
Also published as: DE50002864D1; WO2001038009A3; CA2390628A1; WO2001038009A2; EP1232018B1; AU1704901A; ES2203533T3; CA2390628C; ATE244610T1; DK1232018T3; JP2003534393A; DE19957018A1

Abstract

The invention relates to a method for applying at least two layers of at least one polymer on a carrier material. The inventive method is characterised in that at least one layer of the at least one polymer is bound to the carrier material in at least one step and in that, in at least one additional step, at least one additional layer of the at least one polymer is applied to the at least one polymer layer which is bound to the carrier material.

Description

Process for applying a polymer to a support

The present invention relates to a method in which one or more polymers are applied in layers to a carrier material. The present invention likewise relates to the polymer network which can be obtained by the process according to the invention, the polymer network being produced in a preferred embodiment in such a way that its conformation is adapted to one or more template compounds. Another aspect of the present invention relates to the use of the polymeric network produced according to the invention in processes in which substances are produced, separated, detected or converted into other substances.

In processes in which polymers are applied to a carrier according to the known prior art, polymer solutions are normally spun onto the carrier. By concentrating the polymer solution, however, polymer coatings are obtained which generally have no satisfactory properties. If the polymer networks produced in this way are used, for example, for material separation processes, the loadability with a substrate has insufficient values, or the retention time of the substrate is generally so short that insufficient material selectivity is achieved in these material separation processes. Likewise, the reproducibility of the characteristic data of the polymer network and of the carrier used, for example with regard to its polymer content, is generally insufficient.

Coatings with polymers are described, for example, in Wilfried Plum, dissertation, D 82 (RWTH Aachen), Verlag Shaker, Aachen 1995, G. Schomburg et al, Chromatographia, 18 (1984) 265 and in A. Kurganov et al, Journal of Chromatography A, 660 (1994) 97-111.

Suitable polymers are described, inter alia, in German patent applications DE-A 198 55 173.8 and DE-A 199 28 236.6.

It was accordingly an object of the present invention to provide a process which makes it possible to apply a polymer to a support in such a way that the disadvantages mentioned above are avoided.

Accordingly, the present invention relates to a method for applying at least two layers of at least one polymer to a carrier material, characterized in that at least one layer of the at least one polymer is bound to the carrier material in at least one step and at least one in at least one further step another layer of the at least one polymer is applied to the at least one polymer layer bonded to the carrier material.

The step-by-step application of the at least one polymer can be carried out in accordance with any suitable method which ensures that at least one layer of the polymer is applied per step, so that a layered polymer structure is applied to the carrier material.

In a preferred embodiment, the present invention relates to a process as described above, characterized in that in the at least one step in which the at least one layer of the at least one polymer is bonded to the support material,

(i) a solution of the at least one polymer with the carrier material

Reaction conditions are brought into contact, in which the at least one polymer is not bound to the support material and then the reaction conditions are varied such that the at least one polymer is bound to the support material, or (ii) a solution of the at least one polymer is brought into contact with the support material under reaction conditions in which the solution of the at least one polymer is present under theta conditions ,

Here, the solution which is brought into contact with the carrier material according to (i) may have one or more suitable solvents, the at least one polymer being dissolved or also colloidally dissolved or suspended, for example in the form of a nanosuspension, in the solvent or solvent mixture , can be.

According to (i), the reaction conditions are chosen such that when the solution is brought into contact with the support material, the at least one polymer is not bound to the support material. These reaction conditions are set, for example, by one or more suitable solvents. In this regard, preference is given to using solvents in which the at least one polymer is so readily soluble that there is no binding to the support material.

In the context of the present invention, the term “the polymer is not bound to the support material” means that essentially no binding can be determined by measuring the distribution coefficient.

These reaction conditions can also be achieved by a suitable choice of temperature, for example by bringing the solution into contact with the support material at such high temperatures that the at least one polymer does not bind to the support material.

Furthermore, these reaction conditions can be achieved by suitably adjusting the pH of the polymer solution if the binding of the at least one polymer to the support material is dependent on the pH. It is also conceivable that the binding of the at least one polymer to the carrier material is prevented by a suitable combination of two or more of these methods.

This specific type of reaction control ensures, among other things, that reaction conditions under which the at least one polymer contained in the solution precipitates are avoided.

With regard to the contacting of the solution of the at least one polymer with the at least one carrier material, in principle all suitable procedures are conceivable.

For example, it is possible to bring a solution comprising the at least one polymer into contact with the carrier material. It is also conceivable to first bring the carrier material into contact with the at least one solvent and then to introduce the at least one polymer into the at least one solvent. It is also possible to first bring the support material into contact with at least one solvent and then to add a solution comprising the at least one polymer. If two or more polymers are used, it is conceivable to dissolve each separately or together with one or more other polymers in a respective solvent or solvent mixture and to separate the individual solutions, each of which comprises at least one polymer, together or separately with the carrier material, which is already dissolved or colloidally dissolved or suspended in at least one solvent.

In principle, all carrier materials to which the at least one polymer can be applied by bonding are suitable in the context of the present invention. If two or more different polymers are used, it is sufficient in the process according to the invention if one of the Polymers can be applied to the carrier material by binding. Of course, it is of course also conceivable that two or more different polymers can be applied to the carrier material by bonding.

If two or more different polymers and two or more different support materials are used, it is conceivable, among other things, that all of the polymers can be applied to all of the support materials. It is also conceivable that one or more polymers can be applied to one or more carrier materials and one or more different polymers can be applied to one or more different carrier materials.

If two or more different carrier materials are used, no polymer can be applied to one or more of them as long as polymer is applied to at least one of the carrier materials. Furthermore, further polymers and compounds, such as, for example, customary auxiliaries, can be applied, it being possible for the polymer to be bound to the carrier material by other interactions and / or processes. Furthermore, the polymers and / or compounds present in the solution cannot be applied to the support and, for example, remain in the solution. Among other things, it is conceivable that at least one of these polymers is applied in a further step to, for example, a carrier material which is brought into contact with the solution comprising this polymer before this further step.

According to (i), after the contacting, the reaction conditions are changed such that the at least one polymer binds to the support material. As described above, it is of course conceivable within the scope of the present invention that in the case that two or more different polymers and / or two or more different carrier materials are used, a polymer is bound to a carrier material. As far as the variation of the reaction conditions is concerned, all changes are conceivable which are suitable for enabling the binding of at least one of the polymers to the support material.

In the event that the binding is dependent on the temperature, it is conceivable, for example, to either increase or decrease the temperature, depending on which change favors the binding. In also preferred embodiments, the composition of the solution containing the at least one polymer is changed or this solution is slowly concentrated.

The present invention therefore also relates to a process as described above, characterized in that the reaction conditions according to (i) are varied in that (a) the composition of the solution by varying the at least one

Solvent or by adding at least one other compound is changed, or

(b) the solution is concentrated in such a way that the concentration of the at least one polymer in the solution is kept largely constant when concentrated, or

(c) at least one method according to (a) and method (b) are combined appropriately.

As far as the change in the composition of the solution containing the at least one polymer is concerned, in principle all methods are conceivable which are suitable for enabling the binding by means of this change.

In a preferred embodiment, at least one further solvent is added to the solution in which the at least one polymer is present, which solvent has poorer solvent properties with respect to at least one of the polymers. In a likewise preferred embodiment, the composition of the solution is changed such that at least one acidic or at least one basic compound or a mixture of two or more thereof is added, by means of which the pH of the solution is changed so that the binding of at least one the polymer is made possible. Of course, it is also possible to add one or more buffer solutions, by means of which the pH of the solution is changed so that the binding of at least one of the polymers is made possible.

In an equally preferred embodiment, suitable compounds, for example salts, comprising, for example, metal cations, or suitable organic compounds are added in accordance with the process of the invention, the addition of which bonds at least one of the polymers.

In a likewise preferred embodiment, the solution which contains the at least one polymer is concentrated in such a way that the concentration of the at least one polymer which is to be bound to the support material remains largely constant in the solution. In a very particularly preferred embodiment, this concentration of the solution is carried out by a correspondingly slow procedure, by means of which the polymer concentration is kept largely constant.

It is also possible to evaporate the solution containing the at least one polymer to dryness in the presence of a non-specific or non-selective crosslinking reagent. In this embodiment, which is generally carried out in such a way that the polymer is deposited on the support from the solution more quickly than it is depleted from the solution, deposits during spinning off are avoided in particular.

In a further preferred embodiment, the method according to the invention can be carried out in such a way that a solution which contains the at least one polymer lymer contains, is passed through a device filled with carrier material, preferably a packed column, is preferably pumped, then a non-specific or non-selective crosslinking reagent is passed through the device filled with carrier material, then again a solution with at least one polymer which may be the same or different from the polymer carried out first, through which the device filled with carrier material is passed, etc.. This embodiment is outstandingly suitable for the continuous, comparatively time-effective application of polymer layers, in particular when the polymer solutions and the crosslinking agent are passed through in succession from the respective storage containers.

In a further preferred embodiment of the method according to the invention, two or more of the above-mentioned methods can be combined in a suitable manner, including the change in temperature. For example, it is conceivable both to vary the composition of the solution as described and to slowly narrow the solution to support it and / or to vary the temperature in a suitable manner.

Depending on the reaction conditions chosen, it is conceivable in the context of the process according to the invention that one polymer or several different polymers are applied to the support material. Among other things, it is conceivable to choose the reaction conditions in such a way that two or more different polymers are applied simultaneously to the support material, a layer being formed on the support material which comprises the two or more different polymers. If two or more different support materials are used, it is conceivable that a layer of a polymer is applied to each support material, which layer can comprise a polymer or two or more different polymers.

Of course, it is also possible for two or more layers of at least one polymer to be applied to the support material in one step, wherein the first layer of the polymer is bound to the carrier material, the second layer of the polymer is bound to the first layer and, if appropriate, every further layer of the polymer is bound to the respectively preceding layer. In principle, each layer can comprise a single type of polymer or two or more different polymers.

In a further embodiment, according to (ii), a solution of the at least one polymer is brought into contact with the support material under reaction conditions in which the solution of the at least one polymer is present under theta conditions. With regard to this embodiment, the at least one polymer is very particularly preferably applied to the support material while the solution is brought into contact with the support material. Regarding the term “theta condition”, reference is made inter alia to M. Yamakawa, Modern Theory of Polymer Solutions, Harper & Row, New York (1971), p. 72 f.

According to the method described above, a layer of at least one polymer is preferably applied to the carrier material in a first step, and a second layer is applied to this first layer in a second step and, if necessary, a third layer to the second layer and so on. With regard to the suitable methods of application, reference is made to the detailed discussion above.

The term "bond" as used in the context of the present invention is understood to mean all covalently reversible, covalently irreversible and non-covalent interactions via which the at least one polymer with the carrier material and / or with one, if applicable, already occurs the carrier material applied or, if appropriate, applied to a polymer layer can interact. Possible non-covalent interactions of a first polymer with the carrier material and / or a second polymer, which may be the same or different from the first polymer, include the following:

Hydrogen bonds; - Dipole-dipole interactions;

Van der Waals interactions;

Hydrophobic interactions;

Charge transfer interactions, e.g. π-π interaction;

Ionic interactions; - coordination, e.g. on transition metals;

Combinations of these interactions.

Accordingly, essentially all polymers can be used in the process according to the invention which are capable of forming such non-covalent interactions, for example. It is conceivable here, inter alia, that the at least one functional group via which the polymer forms at least one of these non-covalent interactions lies in the polymer strand itself and / or in at least one side chain of the polymer strand.

The term “functional group” as used in the context of the present invention accordingly encompasses all chemical structures by means of which non-covalent, but also covalently reversible or covalently irreversible interactions can take place. In particular, hydrocarbon chains and other structural units also fall, through which Van der Waals interactions can be built up under the term functional group.

With regard to the covalently reversible interaction, examples include binding via disulfide bridges or via labile esters or imines such as Schiff bases or enamines. In principle, all polymers which are capable of forming these interactions can be used in the process according to the invention. These can be commercially available or those polymers which are produced specifically for the process according to the invention. In the latter embodiment, it is conceivable, among other things, to derivatize a commercially available polymer in such a way that it has side groups which are required for the formation of the desired interaction. It is also possible to prepare the polymer from suitable monomers in such a way that such functional groups are present in the polymer strand and / or in the side chains of the polymer via which the desired interactions can take place.

If one or more polymers are first derivatized in the process according to the invention and then used in the process according to the invention, the derivatization can be carried out by all processes known from the prior art. In this regard, reference is made to DE-A 198 55 173.8 and the prior art cited therein.

Another possibility for derivatizing polymers is the polymer-analogous reaction of functional groups-containing polymers with derivatization compounds.

In a preferred embodiment, a derivatized polymer can be provided in the process according to the invention, which is produced by reacting a polymer having at least one functional group with at least one activation reagent or a derivative of an activation reagent, this reaction being homogeneous or heterogeneous, preferably homogeneous can be done.

The activation reagent will usually be chosen so that the at least one functional group of the polymer during the reaction with reacts with the activation reagent and thus improves its reactivity in a subsequent reaction with a derivatization reagent.

In the context of this embodiment of the method according to the invention, the polymer having at least one functional group can be treated with at least one activated and / or at least one non-activated derivatization reagent and / or one activation reagent simultaneously, i.e. in the sense of a "one-pot reaction".

A desired residue can be introduced into the polymer via this reaction of the activated polymer having at least one functional group with a derivatization reagent.

If a polymer was reacted with different activation reagents, these activated functional groups can have different reactivities to one or more derivatization reagents. Accordingly, it is conceivable in the context of the method according to the invention to selectively derivatize functional groups in this way. In this context, the term “selective” means that a polymer which has, for example, two or more functional groups which are different from one another, is reacted with, for example, two different activation reagents, so that a subsequent reaction with a derivatization reagent for derivatization predominantly to exclusively on the or the activated functional groups, which is or are activated with one of these two activation reagents, generally on the activated functional group (s) which are more reactive with respect to the derivatization reagent.

In the process according to the invention, it is also possible to react the activation reagent with the derivatization reagent before the reaction with the polymer having at least one functional group, and then to react the latter Reacting the reaction product with the polymer having at least one functional group.

Another conceivable embodiment of the present invention consists in reacting the polymer having at least one functional group with different products from reactions of activation reagents and derivatization reagents. For example, a mixture of compounds can be reacted with the polymer, the mixture comprising reaction products from an activation reagent and two or more different derivatization reagents. A mixture is also conceivable which comprises reaction products of a derivatization reagent and two or more different activation reagents. Of course, if it is necessary, it is also possible to use a mixture which comprises reaction products of two or more different activation reagents and two or more different derivatization reagents. Of course, it is also possible within the scope of the present invention not to react the various reaction products of activation reagent and derivatization reagent in a mixture, but individually and in the desired order with the polymer having at least one functional group.

In principle, all activation reagents known from the literature can be used as the activation reagent. An overview of a whole series of activation reagents that can be used to activate different functional groups is given, for example, by the article cited above by P. Mohr, M. Holtzhauer, G. Kaiser, which in this regard is fully referenced in the context of the present Patent application is included. Chloroformic acid esters and chloroformic acid esters with electron-withdrawing radicals should be mentioned in particular.

In particular, the present invention describes a method in which the activation reagent is derived from a compound of the following structure (I):

wherein R \ and R _{2 are the} same or different and can be straight-chain, branched-chain or bridged to a carbocycle or a heterocycle and are chosen so that the activating reagent or the derivative of the activating reagent with the polymer having at least one functional group in a homogeneous phase can be implemented.

R 1 and R _{2 can be,} for example, cycloalkyl, cycloalkenyl, alkyl, aryl or aralkyl radicals having up to 30 carbon atoms, f

In a preferred embodiment, the present invention describes a process in which the activating reagent is derived from a compound of the following structure (I ¹ ),

where R ₃ to R _{10 may be the} same or different and may represent hydrogen, straight-chain or branched-chain alkyl, aryl, cycloalkyl, heterocyclic and aralkyl radicals having up to 30 carbon atoms, or more of the R ₃ to Rio in turn can be bridged to a carbocycle or heterocycle and are chosen so that the activating reagent or the derivative of the activating reagent with the polymer having at least one functional group can be reacted in a homogeneous phase.

The present invention further describes a method in which the activation reagent has the following structure (II),

wherein R ₃ to R _{10 are} as defined above.

In a likewise preferred embodiment, the present invention describes a process in which the activation reagent is derived from a compound of structure (II), as indicated above, where R ₃ to R _{10 are} each hydrogen.

The compounds having the structures (I), (I ') and (II) can be prepared by all customary processes known from the prior art. Such a method for ONB-Cl is described, for example, in P. Henklein et al., Z. Chem. 9 (1986), p. 329 f. specified.

In principle, all of the polymers which have at least one functional group which is reactive with the activation reagents can be reacted with the activation reagents or derivatives of activation reagents as described above.

Among other things, preference is given to using polymers in the process according to the invention which, as at least one functional group, have a group which has at least one nucleophilic unit. Preferred functional groups of the polymer having at least one functional group include OH groups, optionally substituted amine groups, SH groups, OSO ₃ H groups, SO ₃ H groups, OPO ₃ H ₂ groups, OPO ₃ HR _π -Groups, PO ₃ H ₂ groups, PO ₃ HR _n groups, COOH groups and mixtures of two or more thereof, each with R- _. ι is selected so that the activation reagent or the derivative of the activation reagent can be reacted with the polymer having at least one functional group in a homogeneous and / or heterogeneous phase. Likewise, the polymers having at least one functional group can also contain further polar groups, such as, for example, -CN.

Both natural and synthetic polymers can be used as the polymer having at least one functional group. Possible restrictions in the selection of the polymers result only from the fact that the implementation of the polymer in the process according to the invention is carried out in a homogeneous phase and from the later intended use of the derivatized polymer.

In the context of this invention, the term “polymer” naturally also includes higher molecular weight compounds which are referred to in polymer chemistry as “oligomers”.

Without wishing to be restricted to certain polymers, the following are possible polymers which have at least one functional group and others. called:

Polysaccharides, e.g. Cellulose, amylose and dextrans;

Oligosaccharides such as e.g. cyclodextrins;

chitosan;

Polyvinyl alcohol, poly-thr, poly-ser; - Polyethyleneimine, polyallylamine, polyvinylamine, polyvinylimidazole, polyaniline, polypyrrole, poly-lys; Poly (meth) acrylic acid (ester), polyitaconic acid, poly-Asp; Poly-Cys;

Likewise, not only homopolymers, but also copolymers and in particular block copolymers and statistical copolymers are in principle suitable for use in the present process. Both copolymers with non-functionalizable fractions such as co-styrene or co-ethylene or copolymers such as co-pyrrolidone should be mentioned.

If the polymers are derivatized in a homogeneous liquid phase in the process according to the invention, mixed-functional or even pre-derivatized polymers are preferably used in order to achieve optimum solubility. Examples include: partially or fully alkylated or acylated cellulose; - polyvinyl acetate / polyvinyl alcohol; Polyvinyl ether / polyvinyl alcohol; N-butyl polyvinylamine / polyvinylamine.

Polymer / copolymer mixtures can also be used. All suitable polymer / copolymer mixtures can be used here, for example mixtures of the above-mentioned polymers and copolymers, among which is to be mentioned here, among others: poly (acrylic acid) -covinyl acetate; Polyvinyl alcohol-co-ethylene; - polyoxymethylene-co-ethylene; modified polystyrenes, e.g. Copolymers of styrene with

(Meth) acrylic acid (esters);

Polyvinyl pyrrolidone and its copolymers with poly (meth) acrylates.

All of the above-described polymers and / or copolymers or their mixtures can of course also be underivatized in the Processes according to the invention are used as long as it is ensured that, as described in the context of the present application, they can form covalent and / or non-covalent interactions with at least one support material and / or with at least one further polymer used in the process according to the invention.

If, as described above, the polymer having at least one functional group is reacted with an activation reagent such as, for example, a compound of structure (II), this reaction product can also be reacted with a derivatization reagent, as also described above.

In principle, all reagents that can react with the activated polymer and lead directly or indirectly to the desired derivatized polymer can be used. Among other things, compounds which have at least one nucleophilic group are used as derivatization reagents in the process according to the invention.

For example, derivatization reagents are used which have the general composition HY-Rj ₂ . Y stands for example for O, NH, NR ₁₃ or S, where R ₁₂ and Rι ₃ can generally be chosen freely. For example, they represent an optionally suitable substituted alkyl or aryl radical.

In addition, it is also possible to react the activated polymer with nucleophilic chiral compounds. Examples of such chiral nucleophiles include:

Borneol, (-) - menthol, (-) - ephedrine, α-phenylethylamine, adrenaline, dopamine.

Another possibility is to activate the activated in the inventive method

Implement polymer with a mono- or polyhydric alcohol or thiol containing amino groups. Will that contain at least one functional group

Activated polymer, for example with ONB-Cl, the amino group-containing mono- or polyhydric alcohol or the mono- or polyhydric thiol containing amino groups, selectively with the amino group. The OH or SH groups thus introduced into the polymer can then be reactivated in a further step with, for example, one of the activation reagents described above, which enables chain extensions and branching, depending on the value of the alcohols or thiols originally used.

In another embodiment of the method according to the invention already described above, the polymer having at least one functional group is reacted with an activated derivatization reagent, the latter being obtained from the reaction of an activation reagent with the derivatization reagent.

Derivatives of amines, alcohols, thiols, carboxylic acids, sulfonic acids, sulfates, phosphates or phosphonic acids activated in the process according to the invention are preferably reacted with the polymer having at least one functional group, the compounds being activated with ONB-Cl, again in a preferred embodiment.

Among other things, these activated derivatization reagents, which can be reacted with the polymer having at least one functional group, have the following general structures (πi) to (IX):

where R ₃ to R _{10 are} as defined above and R ₁₄ to R ₂ ι are generally not subject to any restrictions, for example may also have chirality, and be selected in the process according to the invention in such a way that the reaction with the polymer having at least one functional group is homogeneous Phase can be carried out. The substituents R ₁₄ to R _{21 are} generally chosen as a function of the desired interaction with the substrate. R ₁₄ to R _{21 may be the} same or different and represent hydrogen, a straight-chain or branched-chain alkyl, aryl or aralkyl radical having up to 30 C atoms or radicals containing corresponding heteroatoms.

Likewise, polyvalent amines, alcohols, thiols, carboxylic acids, sulfonic acids, sulfates, phosphates or phosphonic acids can be reacted with an activation reagent and this reaction product can be reacted with the polymer having at least one functional group, polyols in particular being mentioned here.

Of course, it is also conceivable to activate derivatization reagents and react them with the polymer having at least one functional group, which have two or more different types of the above-mentioned functional groups. Examples include amino alcohols. In the context of the present invention, such multivalent derivatization reagents can be selectively partially or completely activated with an activation reagent and reacted with the polymer having at least one functional group.

Both the reaction of the polymer having at least one functional group with an activated derivatization reagent and the reaction of the polymer having at least one functional group with an activation reagent and subsequent reaction of the product with a derivatization reagent according to the process of the invention makes it possible to prepare polymer derivatives which are very diverse have spatial arrangements.

In a likewise preferred embodiment, the present invention describes a derivative of the type in question here which has at least one receptor group which has a binding unit which is decisive for the binding of a biological substrate.

Such a derivative, which is tailor-made for biological substrates, then has corresponding receptor groups which, for example, can also have structures which occur in nature or parts of such structures which are responsible for binding, and which can then interact with a biological substrate. Enzyme, amino acid, peptide, sugar, amino sugar, sugar acid and oligosaccharide groups or derivatives thereof are to be mentioned here in particular. It is essential for the above receptor groups that the naturally occurring binding principle of a receptor with a substrate is maintained so that, for example, synthetic enzymes, binding domains of antibodies or other physiological epitopes can be obtained by means of this embodiment. Among other things, in the context of the present invention, preference is given here to a derivative of a polymer having at least three functional groups, as described above, in which at least one group is an amino acid residue or an amino acid derivative residue. Examples of possible amino acids are:

Amino acids with aliphatic residues such as e.g. Glycine, alanine, valine,

Leucine, isoleucine; Amino acids with an aliphatic side chain comprising one or more hydroxyl groups, e.g. Serine, threonine;

Amino acids that have an aromatic side chain, e.g. Phenylalanine, tyrosine, tryptophan;

Amino acids comprising basic side chains, e.g. Lysine, arginine, histidine;

Amino acids that have acidic side chains, e.g. aspartic acid,

glutamic acid;

Amino acids that have amide side chains, e.g. Asparagine, glutamine; Amino acids which have sulfur-containing side chains, e.g. cysteine,

methionine;

Modified amino acids, e.g. Hydroxyproline, γ-carboxylglutamate, O-

phosphoserine;

Derivatives of the amino acids mentioned or of optionally further amino acids, for example on the or optionally the carboxyl groups with, for example, alkyl or aryl radicals, which may optionally be substituted, esterified amino acids.

Instead of the amino acid, the use of one or more di- or oligopeptides is also conceivable, in particular homopeptides which are composed only of the same amino acids. An example of a dipeptide is hippuric acid. Furthermore, beta, gamma or other structural isomeric amino acids and peptides derived therefrom, such as, for example, desipeptides, can also be used. Very generally, compounds of the general structure (X)

are used, which are characterized in that R represents a halogen atom or a radical (X ¹ )

stands and R _\ , R ₂ '; Ri "and R ₂ " are the same or different and represent hydrogen, straight-chain or branched-chain alkyl, aryl, cycloalkyl, heterocyclic or aralkyl radicals having up to 30 carbon atoms or either R and R ₂ 'or R-, "and R ₂ "or both Ri 'and R ₂ ' and R _\ " and R ₂ "are linked to at least one carbocycle or to at least one heterocycle or to at least one carbocycle and to at least one heterocycle. In particular, compounds which include the following structures (Xι) to (X ₃₉ ) are to be mentioned as examples:

where R '"is hydrogen or a straight-chain or branched-chain, optionally substituted alkyl, aryl or aralkyl radical having up to 30 carbon atoms. In the context of the present invention, it is in particular possible to design the derivatization reagent with regard to its chemical nature already during derivatization, inter alia with regard to the subsequent binding of the polymer to the carrier material and / or to a further polymer and / or a further polymer layer. In particular, the derivatization reagent can contain groups that are selective or specific for the covalent and / or non-covalent interaction.

In a further embodiment of the process according to the invention, the polymers can be prepared from suitable monomers by a suitable method, this polymer then optionally being derivatized in accordance with the process described above.

In principle, any method which leads to this polymer is suitable for producing a suitable polymer which has the functional groups required for binding to the carrier material or binding to a polymer layer.

Among other things, a method for producing the polymer is preferably used in which a condensation compound by reacting at least one functional group of a first low molecular compound having at least two functional groups with at least one functional group of at least one further second low molecular compound having at least two functional groups , which may be the same as or different from the first low molecular weight compound, is obtained to give a condensation compound, the process being characterized in that at least one of the functional groups involved in this reaction is reacted with a compound structure (X ) as defined above

In a particularly preferred embodiment, the first layer, which is applied to the at least one carrier material, is bound in such a way that non-covalent interactions of the type described above are formed between the polymer layer and the carrier material.

In a further preferred embodiment of the method according to the invention, the individual polymer layers, which in turn are preferably applied in individual steps, are connected to one another by covalent crosslinking.

Accordingly, the present invention also relates to a method as described above, characterized in that the binding of the at least one layer of the at least one polymer to the carrier material takes place through non-covalent interaction of the at least one polymer with the carrier material and the application of the at least one further Position of the at least one polymer is carried out by covalent crosslinking.

With regard to the covalent crosslinking, which, as described, is particularly preferably formed between the individual polymer layers, all suitable, covalently reversible and / or covalently irreversible interactions are possible.

With regard to the covalently reversible interaction, examples include binding via disulfide bridges or via labile esters or imines such as Schiff bases or enamines. Take, for example Formation of a non-covalent interaction by shifting the pH value if at least one basic and at least one acidic group interact with each other.

With regard to the covalent interaction, inter alia, ester, amide, carbonate, hydrazide, urethane or urea bonds or thio-analogous or nitrogen-homologous bonds can be formed.

The covalent or / and non-covalent interactions mentioned can take place between the carrier material and the first polymer layer or between the individual polymer layers in such a way that functional groups which are present in the polymer strand of the at least one polymer used and / or in at least one side chain of the at least one polymer , interact with the carrier material or at least one functional group of a further polymer, which in turn is present in the polymer strand and / or in at least one side chain of this polymer.

In a further preferred embodiment of the present invention, it is conceivable to bind the first polymer layer to the carrier material and / or to bind further polymer layers, in each case one polymer layer being bound to an already applied polymer layer using at least one crosslinking reagent. In the context of the present invention, the term “crosslinking reagent” is understood to mean all compounds which have at least two functional groups via which this compound is non-covalently and / or covalently reversible or / and covalently irreversible with either the carrier material and interacts with at least one polymer or with at least two polymers, which may be the same or different from one another.

In principle, all suitable compounds known from the prior art are suitable as crosslinking reagents. Accordingly, the network tion, for example, in a covalently reversible manner, in a covalently irreversible manner or in a non-covalent manner, in the case of crosslinking in a noncovalent manner, for example, crosslinking via ionic interaction or via charge transfer interaction may be mentioned. Crosslinking methods or reagents of this type are described, inter alia, in Han, KK, et al., Int. J. Biochem., 16, 129 (1984), Ji, TH, et al., Meth. Enzymol., 91, 580 (1983) and Means, G. and Feeney, RE, Bioconj. Chem., 1, 2 (1990). In this context, possible non-covalent interactions should also be referred to all the non-covalent interactions already described in detail above. The same applies to covalently reversible interactions, which have also been described as examples above. As there, all suitable non-covalent interactions are also conceivable with regard to the cross-linking reagents.

Likewise, the formation of a non-covalent crosslinking can take place if, in the event that two basic groups of, for example, polyallylamine are crosslinked with one another, a dibasic acid such as, for example, glutaric acid is added, or in the case that two acidic groups, for example polyacrylic acid, are added to one another to be crosslinked, a divalent base such as ethylenediamine is added. A non-covalent crosslinking can also be formed, for example, by complex-forming metal ions or by metal complexes with free coordination points. In general, with regard to non-covalent crosslinking, reference can be made to all possible interactions that have already been presented above.

A covalently reversible crosslinking can be achieved, for example, by forming a sulfur-sulfur bond to form a disulfide bridge between two groups attached to one or two polymer strands or by forming a Schif base. Crosslinking via ionic interaction can occur, for example, via two residues, one of which is a Structural unit a quaternary ammonium ion and the other as a structural unit for example

COO ^{- or} - so ₃ ^_ . Crosslinking via hydrogen bonds can, for example, be formed between two complementary base pairs, for example via the following structure:

In very general terms, non-covalently crosslinkable polymers can have a complementary structure with respect to the crosslinking sites, structural units which are complementary to one another being, for example, acid / triamine or uracil / melamine. Likewise, in the case of non-covalent crosslinking, the crosslinking reagent can be complementary to the crosslinking sites on the polymer strand. An example of this would be an amine group on the polymer strand and a dicarboxylic acid as crosslinking reagent.

If it is necessary within the scope of the method according to the invention to activate at least one of the functional groups which are involved in the crosslinking with regard to a crosslinking step, this is essentially conceivable by all methods which are known from the prior art. In particular, the activation of a functional group can be carried out according to a method as described in detail above for the activation and derivatization of polymers. Crosslinking reagents which can lead to covalently irreversible crosslinking include, inter alia, two or more functional compounds such as, for example, diols, diamines or dicarboxylic acids. For example, divalent crosslinking agents are reacted with the activated polymer derivative or the at least divalent activated crosslinking reagent with the non-activated fourth polymer derivative.

If, in the process according to the invention, crosslinking is carried out using at least one crosslinking reagent, this crosslinking reagent can in particular be a condensation compound which, by reacting at least one functional group of a first low molecular weight compound having at least two functional groups, with at least one functional group of at least one further, at least one the second low-molecular compound having two functional groups, which may be the same as or different from the first low-molecular compound, is produced to obtain a condensation compound, the process being characterized in that at least one of the functional groups involved in this reaction is preceded by the reaction Reaction with a connection structure

(X)

as defined above

Compounds of the following structures (XL) to (XI ₁ ) are mentioned as examples of (activated) crosslinking reagents:

As an example of a crosslinking agent to be used according to the invention, a dimeric crosslinker is listed below, which is prepared from phenylalanine and leucine by the process described above:

leucine

dimer

Phe-Leu-crosslinker

The following reaction routes (A) and (B), in which the rest BNO represents the following structural unit (XII), are listed as examples of the structure of a condensation compound to be used as a crosslinking reagent by the process according to the invention:

Reaction path (A):

etc. Reaction path (B):

ETC.

Accordingly, all materials which can form the covalent and / or non-covalent interactions with the at least one polymer as described above are suitable as carrier materials. In particular, it is conceivable that the carrier material is dissolved or colloidally dissolved or suspended. In this context, it is particularly conceivable that the carrier material is a polymer or a polymer network, as is produced, inter alia, in the process according to the invention, as described below.

If the carrier material is a solid, its surface can be flat, such as plates made of glass or metal, or curved or embedded in porous bodies, for example tubular or sponge-like, such as zeolites, silica gel or cellulose beads , The carrier materials can furthermore be of natural origin or synthetic nature. Examples include gelatin, collagen or agarose.

In a preferred embodiment of the present invention, the first polymer layer, which is applied to the carrier material, is bound to the carrier material via non-covalent interaction without using a crosslinking reagent, and the polymer layers are crosslinked to one another by covalent crosslinking using at least one crosslinking reagent.

With regard to the crosslinking reagents, it is conceivable within the scope of the present invention that either non-selective / non-specific or / and selective / specific crosslinking reagents are used. In the context of the present invention, the term “selective / specific crosslinking reagent” is understood to mean a crosslinking reagent which has two or more different functional groups, of which at least one group, in comparison with at least one group different from one another, under given reaction conditions with one functional group of another Polymer or the carrier material preferably reacts. The term furthermore encompasses crosslinking reagents which have two or more identical functional groups, but whose chemical environment differs or / and which are sterically different are arranged and therefore at least one of them reacts preferentially with a functional group of a further polymer or the support material under given reaction conditions. This term also encompasses those crosslinking reagents which have the same or different functional groups and differ in their selectivity / specificity because part of the functional groups is activated with an activation reagent by a process as described above. Of course, in the case of the compounds which have two or more different functional groups, one or more of the functional groups with optionally different reactive groups can be activated, so that the reactivity of some of the optionally activated groups differs from the reactivity of the other part of the any activated groups. Combinations of two or more of the influences described, which affect the specificity / selectivity, are of course also conceivable.

Accordingly, the present invention also relates to a method as described above, characterized in that the covalent crosslinking is carried out by at least one non-specific or non-selective crosslinking reagent or at least one specific or selective crosslinking reagent or by a mixture of two or more thereof.

As far as the use of these crosslinking reagents is concerned, all processes are conceivable which are suitable for applying at least one layer of at least one polymer to the support material according to the invention, which, as described, is preferably carried out step by step.

If in the process according to the invention a polymer layer is applied to the carrier material or a polymer layer applied to the carrier material or to a polymer layer using a selective / specific cross-linking reagent, a preferred embodiment proceeds in such a way that the starting material to which the Polymer layer is to be brought into contact with a solution which brings the at least one crosslinking reagent and the at least one polymer which is to be applied as a polymer layer into contact. Here, reaction conditions are chosen under which the crosslinking reagent preferably reacts with the starting material or with the polymer to be applied. By varying the reaction conditions, the crosslinking takes place in a next step, for example by reacting the reaction product from the polymer to be applied and crosslinking reagent with the starting material via at least one functional group of the crosslinking reagent or by reacting the reaction product from starting material and crosslinking reagent with the polymer to be applied.

Selective / specific crosslinking reagents are preferably used in the process according to the invention when the support material and polymer or polymer and polymer are crosslinked to one another via functional groups which have the same or similar reactivity. Examples of selective / specific activation reagents include, for example, polyvalent carboxylic acids, diamines or diols which are activated with different reactive groups or of which only some of the functional groups are activated. Further examples include compounds which have at least two different functional groups, such as, for example, amino acids, hydroxy acids or amino alcohols, the different functional groups having different reactivity under given reaction conditions. Of course, in the case of the compounds which have two or more different functional groups, one or more of the functional groups with optionally different reactive groups can be activated, so that the reactivity of some of the optionally activated groups is different from the reactivity of the other part of the optionally activated Groups differ, as already described above.

If non-selective / non-specific crosslinking reagents are used in the method according to the invention, two preferred methods are among others to name tour guides. Just as in the process described above, in which the intramolecular crosslinking is avoided and a polymer layer is applied to the carrier material or a further polymer layer, these preferred process guides are carried out in such a way that the intramolecular crosslinking and / or the intermolecular crosslinking within a polymer layer are largely avoided and a polymer layer is applied. Small cross-links within a polymer layer can contribute to additional stabilization of the polymer network.

Accordingly, the present invention also relates to a method as described above, wherein at least one non-specific or one non-selective crosslinking reagent is used, characterized in that the crosslinking takes place in such a way that

(aa) the at least one crosslinking reagent reacts in a first step with the last applied layer of the at least one polymer and the

Reaction product in a further step with a solution comprising the at least one polymer is brought into contact and by reaction of the at least one polymer contained in the solution with the reaction product at least one further layer of the at least one polymer is applied to the reaction product, or

(bb) a solution comprising the at least one crosslinking reagent and the at least one polymer is brought into contact with the last applied layer of the at least one polymer under reaction conditions in which the reaction of the at least one crosslinking reagent with both the last applied layer of the at least one Polymer as well as with the at least one polymer contained in the solution, or (cc) the methods according to (aa) and (bb) are combined in a suitable manner.

In a very particularly preferred embodiment, method (aa) is carried out in such a way that the crosslinking reagent is brought into contact with the last applied polymer layer at temperatures at which the crosslinking agent tion reagent statistically evenly distributed over the already existing polymer layer and at which a reaction of the cross-linking reagent with the already existing polymer layer largely. The temperatures at which this work is carried out are generally in the range from 0 to -70 ° C.

When choosing the other reaction conditions, such as pH, type of solvent, concentration of the crosslinking reagent in the solvent, care is taken in this preferred embodiment of the method that the reaction of the crosslinking reagent with the polymer layer present is largely avoided until the crosslinking reagent is statistically evenly distributed over the existing polymer layer.

In a next step, the statistically uniformly distributed crosslinking reagent is reacted with the already existing polymer layer by appropriate variation of the reaction conditions in such a way that the crosslinking reagent predominantly reacts via one or more functional groups and at least one functional group of the crosslinking reagent via which the crosslinking to the next polymer layer, does not react with the existing polymer layer. As a rule, this takes place at low temperatures, which are generally in the range from 0 to -10 ° C. This is further promoted by the use of short-chain cross-linking reagents and / or the immobilization of the polymer layer. Possible ways in which this crosslinking can be induced include the use of ultrasound or photochemical crosslinking.

Of course, it is also possible, with appropriate crosslinking reagents and / or with a corresponding, already existing polymer layer, to control the reaction described above by varying the pH or / and varying the solvents or / and by adding modifiers, naturally also combinations of some or all methods are conceivable. In this context, reference can also be made to the specific methods which can be used as described above in order first to prevent the binding of a polymer and to stimulate it in a further step.

According to method (aa), in a next step, a solution comprising the at least one polymer that is to be applied as the next polymer layer is brought into contact with the reaction product of crosslinking reagent and already existing polymer layer. The reaction conditions are then changed so that the reaction takes place particularly preferably between the unreacted functional groups of the crosslinking reagent bound to the already existing polymer layer and the polymers to be applied as the next polymer layer. Among other things, it is also conceivable here that the reaction conditions are influenced by adding the solution which comprises the at least one polymer which is to be applied as the next polymer layer in such a way that a further change in the reaction conditions no longer has to take place.

With regard to this step of applying the next polymer layer, reference can also be made, inter alia, to the specific methods which can be used, as described above, in order first to prevent the binding of a polymer and to stimulate it in a further step.

In a likewise particularly preferred embodiment, the method according to (bb) is carried out in such a way that the solution comprising the at least one crosslinking reagent and the at least one polymer is brought into contact with the last applied layer of the at least one polymer under reaction conditions in which initially no reaction takes place, but both crosslinking reagent and polymer to be applied are statistically evenly distributed over the already existing polymer layer. As already described in connection with method (aa), this contacting takes place in a preferred embodiment at low temperatures, generally in the range from 0 to -70 ° C.

When selecting the other reaction conditions, such as pH, type of solvent, concentration of the crosslinking reagent in the solvent or concentration of the polymer to be applied in the solvent, care is taken in this preferred embodiment of the process to ensure that the reaction of the crosslinking reagent with the polymer layer present and the reaction of the polymer to be applied with the crosslinking reagent is largely absent and the crosslinking reagent and the polymer to be applied are statistically uniformly distributed over the already existing polymer layer.

In a next step, the reaction conditions are then changed such that the crosslinking reagent reacts both with the polymer layer already present and with the polymer which is applied as the next layer. It is conceivable here, among other things, that the crosslinking reagent first reacts with the already existing polymer layer and then with the polymer to be applied to form the new polymer layer. It is also conceivable that the crosslinking reagent reacts simultaneously with the already existing polymer layer and the polymer to be applied to form the new polymer layer. It is also possible that the statistically uniformly distributed crosslinking reagent first reacts with the statistically uniformly distributed polymer and the reaction product then reacts with the already existing polymer layer to form the new polymer layer. If the reactions of the crosslinking reagent with the already existing polymer layer on the one hand and the polymer to be applied on the other hand do not take place simultaneously, it is possible to first carry out one of the reactions by varying the reaction conditions and the other reaction by further varying the reaction conditions. With regard to the change in the reaction conditions, reference is made here to all the possibilities and combinations already described above. In particular, with regard to this step of applying the next polymer layer, reference can also be made, inter alia, to the specific methods which can be used as described above in order to initially prevent the binding of a polymer and to stimulate it in a further step. Possible ways in which this crosslinking can be induced include the use of ultrasound or photochemical crosslinking.

The use of ultrasound or photochemical crosslinking are, of course, methods which can be used in principle for any crosslinking step as is carried out in the context of the present invention.

Examples of non-selective / non-specific crosslinking reagents include divalent epoxides, isocyanates, chlorotriazines, amidines or aldehydes. Succinimide-activated, particularly preferably ONB- and N-hydroxy-phthalimide-activated compounds should also be mentioned. Among other things, they also refer here to the crosslinking reagents already explicitly listed above. In a preferred embodiment of the method according to the invention, symmetrical, as a rule bivalent crosslinking reagents and very particularly preferably activated dicarboxylic acids are used.

The chain length of the crosslinking reagents used in any of the embodiments of the method according to the invention is generally arbitrary and can be adapted to the requirements of the respective method. The chain itself can be aliphatic or aromatic or araliphatic. The chain can further comprise one or more functional groups which are capable of forming covalent or non-covalent interactions. The chain length for crosslinking reagents which have a carbon chain is preferably in the range from 2 to 24 C atoms, particularly preferably in the range from 4 to 24 C atoms and particularly preferably in the range from 8 to 12 C atoms.

The polymers which are used in the process according to the invention are essentially subject only to the restriction that they can be applied to a support material in at least one layer, forming the interactions as described above. Polymers with a poppy mass in the range of 2,000 to 100,000 g / mol are particularly preferably used. The molecular weights are determined by GPC.

Accordingly, the present invention also relates to a process as described above, characterized in that the at least one polymer has a molar mass in the range from 2,000 to 100,000 g / mol.

Three preferred embodiments of the method according to the invention can be mentioned here.

In a first embodiment, the at least one polymer is applied in such a way that it is brought into contact with the carrier material and / or already applied polymer layer in a largely uncoiled structure, but as close as possible above the theta point. In this embodiment, for the solution in which this at least one polymer is dissolved and brought into contact with the carrier material and / or polymer layer, a solvent or solvent mixture is chosen in which the polymer is largely uncoiled, naturally also by the specific choice other reaction conditions such as temperature, pressure or pH the uncoiled form of the polymer can be supported. In this case, there is preferably an optimization between polymer unfolding and the greatest possible distribution coefficient of the polymer. For this preferred embodiment, particular preference is given to used polymers that have a molecular weight of less than about 30,000 g / mol. This embodiment favors the application of largely monomolecular polymer layers.

In a second embodiment, the solvent or solvent mixture or other reaction conditions are chosen such that the at least one polymer in the solution is in the vicinity above the theta point. This special embodiment, which is particularly preferably favored by polymers with a molecular weight in the range of more than approximately 30,000 g / mol, makes it possible to favor the application of the polymer in loose polymer balls.

In a third embodiment, the solvent or solvent mixture or other reaction conditions are chosen such that the at least one polymer in the solution is in the vicinity below the theta point. Here it is possible, inter alia, to apply nanoparticles formed from the at least one polymer.

The individual crosslinking steps which are carried out in the process according to the invention can be carried out in such a way that an essentially arbitrary degree of crosslinking of the polymer layers with one another is achieved. However, the process is preferably carried out in such a way that the degree of crosslinking of a polymer chain which is crosslinked with two further polymers is in the range from 0.5 to 25%. This degree of crosslinking is based on the monomer units of a polymer chain which has been crosslinked with two adjacent polymer chains. This degree of crosslinking is particularly preferably in the range from 2 to 10%.

Accordingly, the present invention also relates to a process as described above, characterized in that the degree of crosslinking is in the range from 0.5 to 25%, based on the monomer units of a polymer chain crosslinked with two adjacent polymer chains. In the described method according to the invention, it is possible to apply a polymer network to a carrier material which, for example due to the covalent crosslinking of the polymer layers with one another, has a structure which consists of two- or three-dimensional cells. Such a cell of the polymer network is generally formed by at least one crosslinking reagent which crosslinks two polymer layers and a part of at least one polymer from which the polymer layers are formed. Depending on the chemical structure of the at least one crosslinking reagent or the at least one polymer used, it is conceivable, among other things, that the cells are constructed in such a way that the cell can interact with at least one template compound. Therefore, the present invention also describes a method, as described above, in which a polymer network is formed by applying at least one polymer layer to at least one carrier material, the polymer network comprising one or more interaction cells via which the polymer network connects with at least one template compound can interact covalently or / and non-covalently.

In a preferred embodiment, the process according to the invention can be carried out in such a way that the polymer structure, which is built up by applying at least one polymer in at least one layer on at least one support material, is adapted to at least one template compound with respect to the interaction cells.

In addition to the previously described embodiments, the present invention therefore also describes a method as described above, characterized in that the conformation of the polymeric structure, which results from interaction and crosslinking, during the application or after the application of at least one of the layers of the at least one polymer is adapted to at least one template connection on the carrier material. Furthermore, the present invention also describes a method in which the polymeric structure which has been applied and produced on the carrier material is detached from the carrier material and is then used in applications such as are described below, for example.

The present invention also encompasses the polymeric network itself, which can be obtained by a process as described above.

The present invention therefore also relates to a polymeric network which can be produced by a method as described above.

In a particularly preferred embodiment, the polymer network which can be produced by the process according to the invention is distinguished in particular by the fact that it is insoluble but nevertheless has swellability.

Accordingly, the present invention also relates to the use of a process as described above or a polymeric network, obtainable by a process as described above, for producing a polymeric network which is matched to at least one template compound.

Due to their structure, which, as described above, comprises interaction cells, the polymeric networks produced according to the invention can, in a preferred embodiment, be used in processes in which, for example, substances are produced, converted into other substances or separated from other substances. It is also conceivable that the polymeric networks produced according to the invention are used for the detection of optical, electrical or mechanical signals. The polymeric networks are particularly suitable for these processes if, as described above, they are adapted to at least one template compound.

The present invention is explained in more detail in the following example. example 1

Covering of silica gel SP 300-15 / 30 with poly (benzyl-N-allylcarbamate) with a degree of derivatization of 14% and subsequent crosslinking of the polymer with dodecanedioic acid bis (N-hydroxy-5-norbornene-2,3-dicarboximide) ester

Poly (benzyl-N-allyl carbamate) with a degree of derivatization of 14% (1.60 g) was dissolved in boiling glacial acetic acid (100 ml, approx. 117 ° C.) and, after cooling, diluted with dichloromethane (100 ml, 1.18 mol) and pyridine (112 mL, 1.42 mol) was added to degrade the solubility of the polymer. Subsequently, the cloudiness was removed with a few drops of glacial acetic acid. After the addition of silica gel 300 Ä, 20 μm (Daisogel SP 300-15 / 30) (10.02 g), the mixture was agitated on a shaker for 30 minutes and, after suction extraction, washed with dichloromethane (4 × 50 mL) over a glass frit.

For crosslinking, the coated silica gel was converted into a solution of dodecanedioic acid bis (N-hydroxy-5-norbornene-2,3-dicarboximide) ester (46 mg, 83 μmol) and triethylamine (36 mg, 0.35 mmol ) in dichloromethane (60 mL) and the suspension was concentrated to dryness in vacuo (85 mbar, water bath 0 ° C). The coated silica gel was washed with tetrahydrofuran (60 ° C, 4 x 25 mL), suction filtered and washed with dichloromethane (50 mL).

For the second coating, poly (benzyl-N-allyl carbamate) with a degree of derivatization of 14% (1.60 g) was dissolved in boiling glacial acetic acid (100 mL, approx. 117 ° C), after cooling with dichloromethane (100 mL, 1, 18 mol) and mixed with 100 mL pyridine (100 mL, 1.26 mol) to deteriorate the solubility of the polymer. Then dimethylaminopyridine (DMAP, 80 mg, 0.65 mmol) and again pyridine (12 mL, 0.15 mol) were added. Subsequently, the cloudiness was removed with a few drops of glacial acetic acid. After encore of the silica gel reacted and coated with the crosslinker as described above, the mixture was agitated on a shaker for 30 minutes and, after suction extraction, washed with dichloromethane (4 × 50 mL) over a glass frit.

The coated silica gel was crosslinked again as described above and then, according to the second method, covered with a third polymer layer.

The mixture was swollen in a frit in dimethylformamide (30 min). The remaining activated crosslinker groups were deactivated by slowly passing a solution of diethylamine (2 mL, 1.42 g, 19.41 mmol) in DMF (40 mL). To completely deactivate the mixture, it was rinsed four more times with the filtrate solution. The mixture was then washed with tetrahydrofuran (60 ° C., HPLC grade, 4 x 50 mL) and with dichloromethane (4 x 50 mL) and sucked dry.

The coated silica gel was mixed with glacial acetic acid (100 mL), the suspension heated to boiling, suction filtered, washed with dichloromethane (5 x 50 mL), dried (110 ° C, 16 h) and sieved through a 45 μm sieve.

The weight was 9.4 g.

Example 2

Gradual coating of silica gel SP 300-15 / 30 with poly (benzyl-N-carbamate) with a degree of derivatization of 14% and cross-linking of the polymer with dodecanedioic acid bis (N-hydroxy-5-norbornene-2,3-dicarboximide) ester ( alternative variant) Poly (benzyl-N-allyl carbamate) with a degree of derivatization of 14% (1.60 g) was dissolved in 100 ml of glacial acetic acid at 50 ° C. within 30 minutes. Silica gel 300 Å, 20 μm (Daisogel SP 300-15 / 30) (10.00 g) was added to the polymer solution and the suspension was agitated for 3 hours on a shaker. After suction through a glass frit, the residue was washed with the following solutions: dichloromethane (4 x 30 mL), pyridine (0.7 mL) in dichloromethane (30 mL), dichloromethane (4 x 30 mL). The mixture was then dried at 50 ° C. in vacuo.

For crosslinking, the coated silica gel obtained was converted into a solution of bis-dodecanoic acid (N-hydroxy-5-norbomen-2,3-dicarboximide) ester (100 mg, 0.18 mmol) and triethylamine (54 mg, 0.54 mmol) added to dichloromethane (80 mL) and the suspension was evaporated to dryness in vacuo (100 mbar, water bath 0 ° C). The coated silica gel was boiled up in THF (40 mL), suction filtered and washed with hot THF (3 x 40 mL) and dichloromethane (2 x 30 mL).

For the further coating, poly (benzyl-N-allylcarbamate) with a degree of derivatization of 14% (1.66 g) was dissolved in 100 ml glacial acetic acid at 50 ° C within 30 minutes, after cooling with dichloromethane (100 mL) and diluted with pyridine ( 100 mL) added to deteriorate the solubility of the polymer. Then dimethylaminopyridine (DMAP, 22 mg, 0.15 mmol) and 13 mL pyridine were added. The resulting turbidity was removed by adding 3 mL glacial acetic acid. The coated silica gel obtained above and reacted with the crosslinker was added to this solution and the mixture was agitated on a shaking machine for 30 minutes. After suction filtration over a glass frit, the residue was washed with the following solutions: THF (60 ° C, 4 x 40 mL), pyridine (0.6 mL) in dichloromethane (30 mL), dichloromethane (3 x 30 mL). The mixture was then dried at 50 ° C. in vacuo.

In an analogous manner, the process of crosslinking and the further coating with polymer was repeated once in each case. The coated silica gel was suspended in a frit in THF (10 mL). The remaining activated crosslinker groups were quenched by slowly leaching a solution of diethylamine (0.27 g, 3.7 mmol) in THF (10 mL) four times. The residue was then washed with THF (60 ° C., 4 × 20 mL) and dichloromethane (2 × 10 mL) and sucked dry.

The coated silica gel was mixed with glacial acetic acid (40 mL), the suspension was heated to boiling, suction filtered and washed with dichloromethane (4 x 20 mL). The mixture was then washed with a solution of 0.25 ml of pyridine in 15 ml of dichloromethane and THF (4 × 20 ml) and dried.

According to elemental analysis, the carbon content of the coated silica gel was 7.2%; this corresponds to 111 mg of polymer per gram of silica gel.

Example 3

Coating of silica gel SP 300-15 / 30 with poly (benzyl-N-carbamate) with a degree of derivatization of 14% and cross-linking of the polymer with dodecanedioic acid bis- (N-hydroxy-5-norbornene-2,3-dicarboximide) ester in the flow process in the packed HPLC column

A glass column with a diameter of 2.5 cm was packed with silica gel 300 Å, 20 μm (Daisogel SP 300-15 / 30) (5.00 g). Poly (benzyl-N-allyl carbamate) with a degree of derivatization of 14% (3.20 g) was dissolved in 200 ml of water and with the addition of 1-2 ml of glacial acetic acid within 2 hours. This polymer solution was pumped in a circle for 24 hours through the glass column with silica gel. The column was washed first with air, then with acetone / water 50:50 vol% (30 ml) and acetone (150 ml) rinsed. According to elemental analysis, the carbon content of the silica gel covered was on average 2.7%.

After the column was rinsed with dichloromethane (50 mL), 14.4 mL of a solution of terephthalic acid bis (N-hydroxy-5-norbornene-2,3-dicarboximide) ester (0.48 g, 0.97 mmol) were used for crosslinking. in 50 mL dichloromethane was pumped into the column and the wait was 20 hours. The amount of crosslinker that was pumped into the column corresponds to a crosslinking of 10% based on the amino groups of the polymer. The column was then rinsed with dichloromethane (300 mL).

For the further coating, poly (benzyl-N-allyl carbamate) with a degree of derivatization of 14% (3.20 g) was dissolved in 200 ml water and with the addition of 1-2 ml glacial acetic acid within 2 hours. This polymer solution was pumped in a circle for 24 hours through the glass column with the coated silica gel. The column is rinsed first with air and then with acetone / water 50:50 vol% (120 ml).

Glazed acetic acid (50 mL) was added to the silica gel, the suspension was heated to boiling, suction filtered and pyridine (20 mL) added. The mixture was then filtered off, washed with THF (60 ° C, 3 x 50 mL) and dried.

According to elemental analysis, the carbon content of the silica gel covered was on average 5.0%.

Claims

claims

1. A method for applying at least two layers of at least one polymer to a support material, characterized in that in at least one step at least one layer of the at least one polymer is bonded to the support material and in at least one further step at least one further layer of the at least one polymer onto which at least one polymer layer bonded to the carrier material is applied.

2. The method according to claim 1, characterized in that in the at least one step in which the at least one layer of the at least one polymer is bonded to the support material, (i) a solution of the at least one polymer is brought into contact with the support material under reaction conditions is, in which the at least one polymer is not bound to the support material and the reaction conditions are then varied such that the at least one polymer is bonded to the support material, or

(ii) a solution of the at least one polymer is brought into contact with the carrier material under reaction conditions in which the solution of the at least one polymer is present under theta conditions.

3. The method according to claim 2, characterized in that the reaction conditions according to (i) are varied in that (a) the composition of the solution is changed by varying the at least one solvent or by adding at least one further compound, or

(c) at least one method according to (a) and method (b) are combined.

4. The method according to any one of claims 1 to 3, characterized in that the binding of the at least one layer of the at least one polymer to the carrier material takes place by non-covalent interaction of the at least one polymer with the carrier material and the application of the at least one further layer of at least one polymer is carried out by covalent crosslinking.

5. The method according to claim 4, characterized in that the covalent crosslinking is carried out by at least one non-specific or non-selective crosslinking reagent or at least one specific or selective crosslinking reagent or by a mixture of two or more thereof.

6. The method according to claim 5, wherein at least one non-specific or a non-selective crosslinking reagent is used, characterized in that the crosslinking is carried out in such a way that (aa) the at least one crosslinking reagent in a first step with the last applied layer of the at least reacts a polymer and in a further step the reaction product is brought into contact with a solution comprising the at least one polymer and by reacting the at least one polymer contained in the solution with the reaction product at least one further

Layer of the at least one polymer is applied to the reaction product, or (bb) a solution comprising the at least one crosslinking reagent and the at least one polymer, with the last layer of the at least one polymer is brought into contact at reaction conditions in which the reaction of the at least one crosslinking reagent takes place both with the last applied layer of the at least one polymer and with the at least one polymer contained in the solution, or

(cc) the methods according to (aa) and (bb) are combined in a suitable manner.

7. The method according to any one of claims 1 to 6, characterized in that the at least one polymer has a molecular weight in the range from 2,000 to

100,000 g / mol.

8. The method according to any one of claims 3 to 7, characterized in that the degree of crosslinking is in the range of 0.5 to 25%, based on the monomer units of a polymer chain crosslinked with two adjacent polymer chains.

9. Polymer network, producible by a method according to one of claims 1 to 8.

10. Use of a method according to one of claims 1 to 8 or a polymeric network according to claim 9 for producing a polymeric network adapted to at least one template compound.