EP1232018B1 - Method for applying a polymer on a carrier - Google Patents

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

The present invention relates to a method in which one or more polymers can be applied in layers to a carrier material. The same applies to The present invention, the polymer network, which by the inventive Method is available, in a preferred embodiment, the polymer Network is made such that its conformation to one or more Template connections is adjusted. Another aspect of the present invention relates to the use of the polymer produced according to the invention Network in processes in which substances are manufactured, separated, detected or in other substances are converted.

In processes in which according to the known prior art polymers on a Polymer solutions are usually applied to the carrier Rotated carrier. This concentration of the polymer solution, however, results in polymer coatings get that generally not satisfactory properties exhibit. For example, the polymer networks produced in this way used for material separation processes, the loadability with a Insufficient values, or the retention time of the substrate is in generally so short that in these separation processes there is insufficient selectivity is achieved. The reproducibility of the characteristics of the polymer is also the same Network and the assigned carrier, for example with regard to its Polymer content, usually insufficient.

Coatings with polymers are described, for example, in Wilfried Plum, dissertation, D 82 (RWTH Aachen), Shaker Verlag, 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, inter alia, in the German patent applications DE-A 198 55 173.8 and DE-A 199 28 236.6.

Accordingly, it was an object of the present invention to provide a method which allows a polymer to be applied to a support in such a way that the above disadvantages are avoided.

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

The stepwise application of the at least one polymer can be carried out in accordance with all suitable procedures are carried out to ensure that at least per step a layer of the polymer is applied so that a layered polymer structure is applied to the carrier material.

(i) eine Lösung des mindestens einen Polymers mit dem Trägermaterial bei Reaktionsbedingungen in Kontakt gebracht wird, bei denen das mindestens eine Polymer auf dem Trägermaterial nicht gebunden wird und anschließend die Reaktionsbedingungen derart variiert werden, daß das mindestens eine Polymer auf dem Trägermaterial gebunden wird, oder

(ii) eine Lösung des mindestens einen Polymers mit dem Trägermaterial bei Reaktionsbedingungen in Kontakt gebracht wird, bei denen die Lösung des mindestens einen Polymers unter Theta-Bedingungen vorliegt.

In a preferred embodiment, the present invention relates to a method 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 is brought into contact with the support material under reaction conditions in which the at least one polymer is not bound to the support material and the reaction conditions are then varied in such a way 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.

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

According to (i), the reaction conditions are chosen so that when they are brought into contact the solution with the carrier material does not bind the at least one Polymer is carried out on the carrier material. These reaction conditions are, for example adjusted by one or more suitable solvents. Prefers In this regard, solvents are used in which the at least one The polymer is so soluble that it does not bind to the carrier material.

In the context of the present invention, the term “means the polymer not bound to the carrier material "that by measuring the distribution coefficient essentially no bond can be found.

These reaction conditions can also be selected by suitable temperature can be achieved in which, for example, the solution with the carrier material at so high temperatures is brought into contact that the binding of the at least a polymer on the carrier material is omitted.

These reaction conditions can also be adjusted by suitable adjustment of the pH the polymer solution can be achieved when the binding of the at least a polymer depends on the pH of the carrier material.

It is also conceivable to use a suitable combination of two or more of these methods the binding of the at least one polymer to the carrier material is prevented.

This specific type of reaction leads to, among other things, that reaction conditions under which the solution contained at least a polymer fails, can be avoided.

As for contacting the solution of the at least one polymer with the As far as at least one carrier material is concerned, all suitable ones are in principle Procedures possible.

For example, it is possible to use a solution containing the at least one polymer comprises to bring into contact with the carrier material. It is also conceivable that Carrier material first in contact with the at least one solvent bring and then in the at least one solvent the at least one polymer contribute. It is also possible to first cover the substrate with at least one a solvent and then a solution that the comprises at least one polymer. Become two or more polymers used, it is conceivable, each separately or together with one or more other polymers in a solvent or solvent mixture to solve and the individual solutions, each of which is at least one polymer comprises, together or separately with the carrier material, which optionally already dissolved or colloidally dissolved or suspended in at least one solvent to contact.

In principle, all carrier materials are suitable within the scope of the present to which the at least one polymer can be applied by bonding can. If two or more different polymers are used, then it is sufficient within the scope of the method 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 for two or more different ones Polymers can be applied to the carrier material by binding.

Become two or more different polymers and two or more different carrier materials are used, among other things conceivable that all polymers applied to all carrier materials can be. It is also conceivable that one or more polymers on one or more carrier materials and one or more different polymers applied to one or more different carrier materials can be.

If two or more different carrier materials are used, can no polymer is applied to one or more of them as long as at least one of the carrier materials polymer is applied. Can also other polymers and compounds, such as those commonly used Aids are applied, the binding of the polymer to the carrier material can also be achieved through other interactions and / or processes can. Furthermore, the polymers present in the solution or / and Connections are not applied to the carrier and for example in the Solution remain. Among other things, it is conceivable that at least one of these Polymers applied in a further step to, for example, a carrier material will, before this further step with the solution that this polymer includes, is brought into contact.

According to (i), the reaction conditions become such after contacting changed that the binding of the at least one polymer to the support material he follows. As described above, it is within the scope of the present invention of course conceivable that in the event that two or more different Polymers or / and two or more different carrier materials used a polymer is bound to a carrier material.

As for the variation of the reaction conditions, all changes are conceivable, which are suitable for binding at least one of the polymers to enable the carrier material.

For example, if the bond is temperature dependent, it is conceivable to either increase or decrease the temperature depending on what change favors the bond. In likewise preferred embodiments is the composition of the solution containing the at least one polymer contains, changed or this solution was slowly concentrated.

(a) die Zusammensetzung der Lösung durch Variation des mindestens einen Lösungsmittels oder durch Zugabe mindestens einer weiteren Verbindung geändert wird, oder

(b) die Lösung derart eingeengt wird, daß die Konzentration des mindestens einen Polymers in der Lösung beim Einengen weitgehend konstant gehalten wird, oder

(c) mindestens eine Methode gemäß (a) und die Methode (b) geeignet kombiniert werden.

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 is changed by varying the at least one solvent or by adding at least one further compound, 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 suitably combined.

As for the change in the composition of the solution that the at least one As far as polymer is concerned, in principle all processes are conceivable that are suitable to enable binding by this change.

In a preferred embodiment, the solution in which the at least a polymer is contained, at least one further solvent is added, the poorer solvent properties with respect to at least one of the polymers having.

In a likewise preferred embodiment, the composition of the Solution changed so that at least one acidic or at least one basic Compound or a mixture of two or more thereof are added, by which the pH of the solution is changed so that the binding at least one of the polymers is enabled. Of course it is also possible to get one or add several buffer solutions, through which the pH value of the solution so is changed so that the binding of at least one of the polymers is made possible.

In an equally preferred embodiment, according to the invention Compounds suitable for the process, such as, for example, salts for example metal cations, or suitable organic compounds added, by adding at least one of the polymers.

In a likewise preferred embodiment, the solution that the least contains a polymer, so concentrated that the concentration of at least a polymer that is to be bound to the support material in the Solution remains largely constant. In a very particularly preferred embodiment this solution is concentrated by a correspondingly slow one Process control by which the polymer concentration is kept largely constant becomes.

It is also possible to in, the solution containing the at least one polymer Presence of a non-specific or non-selective cross-linking reagent to dryness. In this embodiment, the generally is carried out so that the polymer from the solution faster on the support is deposited as it is depleted from solution in particular Deposits avoided when spinning off.

In a further preferred embodiment, the method according to the invention can be carried out such that a solution containing the at least one polymer contains, by a device filled with carrier material, preferably a packed column, passed through, preferably pumped, then a non-specific or non-selective cross-linking reagent by using Carrier filled device is passed through, then again Solution with at least one polymer, the same or different from the first performed polymer can be through the device filled with carrier material is passed through, etc. This embodiment is excellent for the continuous, comparatively time-effective application of polymer layers, especially when the polymer solutions and the crosslinker can be passed one after the other from the respective storage containers.

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

Depending on the reaction conditions chosen, it is within the scope of the invention Process conceivable that one polymer or more, different from each other Polymers are applied to the carrier material. Among other things, it is conceivable to choose the reaction conditions such that two or more of each other different polymers applied simultaneously to the carrier material be, whereby a layer is formed on the carrier material, the two or more different polymers. Become two or more of each other different carrier materials used, it is conceivable that on each Carrier material is a layer of a polymer is applied, which is a polymer or may comprise two or more different polymers.

Of course, it is also possible that two or more layers in one step at least one polymer can be applied to the carrier material, 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 necessary, any further layer of the polymer is bound to the previous layer. Anyone can In principle, a single type of polymer or two or more different from one another Include polymers.

In a further embodiment, a solution of the at least a polymer in contact with the support material under reaction conditions is brought, in which the solution of the at least one polymer under theta conditions is present. With regard to this embodiment, the application takes place of the at least one polymer on the support material is particularly preferred during the contacting of the solution with the carrier material. To the The term "theta condition" is inter alia on M. Yamakawa, Modern Theory of Polymer Solutions, Harper & Row, New York (1971), pp. 72 f. directed.

According to the method described above, preference is given to a first Step a layer of at least one polymer is applied to the carrier material and on this first layer in a second step a second layer and on the second layer, if necessary in a third step a third layer and so on. In terms of the appropriate methods of application are detailed on the above Discussion referred.

Under the term "binding" as used in the context of the present invention is used, all covalently reversible, covalently irreversible and non-covalent interactions understood by which the at least one Polymer with the carrier material and / or with a possibly already on the Carrier material applied or optionally applied to a polymer layer Polymer layer can interact.

• Wasserstoffbrückenbindungen;
• Dipol-Dipol-Wechselwirkungen;
• Van der Waals-Wechselwirkungen;
• Hydrophobe Wechselwirkungen;
• Charge-Transfer-Wechselwirkungen, z.B. π-π-Wechselwirkung;
• Ionische Wechselwirkungen;
• Koordinative Bindung, z.B. an Übergangsmetallen;
• Kombinationen dieser Wechselwirkungen.

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:

• Hydrogen bonds;
• Dipole-dipole interactions;
• Van der Waals interactions;
• Hydrophobic interactions;
• Charge transfer interactions, eg π-π interaction;
• Ionic interactions;
• Coordinative binding, eg to transition metals;
• Combinations of these interactions.

Accordingly, essentially all polymers in the invention Methods are used, for example for the formation of such non-covalent Interactions are able. Here it is among other things conceivable that the at least one functional group via which the polymer at least forms one of these non-covalent interactions in the polymer strand itself or / and in at least one side chain of the polymer strand lies.

The term "functional group" as used in the context of the present invention is accordingly used includes all chemical structures through which non-covalent, but also covalently reversible or covalently irreversible interactions can be done. In particular, hydrocarbon chains also fall and other structural units through which Van der Waals interactions are built can be under the term functional group.

With regard to the covalently reversible interaction, examples are among others binding via disulfide bridges or via labile esters or imines such as, for example Called Schiff bases or enamines.

In principle, all polymers can be used in the process according to the invention who are capable of developing these interactions. there it can be commercially available or also such polymers, which are produced specifically for the method according to the invention. at the latter embodiment, it is conceivable, among other things, a commercially available To derivatize polymer in such a way that it has side groups which are used for Training of the desired interaction are needed. It is the same possible to produce the polymer from suitable monomers in such a way that in the polymer strand or / and such functional ones in the side chains of the polymer There are groups through 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 by all methods known from the prior art respectively. In this regard, DE-A 198 55 173.8 and those cited therein State of the art referenced.

Another possibility to derivatize polymers is the polymer analog Implementation of functional group-containing polymers with derivatization compounds represents.

In a preferred embodiment, in the method according to the invention derivatized polymer can be provided, which is manufactured by it is that a polymer having at least one functional group with at least one activation reagent or a derivative of an activation reagent is implemented, this implementation being homogeneous or heterogeneous, preferred can be done homogeneously.

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

Within the scope of this embodiment of the method according to the invention the polymer having at least one functional group with at least an activated and / or at least one non-activated derivatization reagent and / or an activating reagent at the same time, i.e. in the sense of "One-pot reaction" are implemented.

About this implementation of the activated, having at least one functional group Polymers with a derivatizing reagent can be a desired one Rest are introduced into the polymer.

If a polymer was reacted with different activation reagents, so these activated functional groups can be compared to one or have several reactivating reagents different reactivity. Accordingly, it is conceivable within the scope of the method according to the invention in this way to selectively derivatize functional groups. The term "selective" in this context means that a polymer, for example two or has more functional groups different from one another, for example with two different activation reagents is implemented so that a subsequent reaction with a derivatization reagent for derivatization predominantly to exclusively on the activated functional one or more Groups takes place, which is activated with one of these two activation reagents or are, usually on or with respect to the derivatization reagent more reactive activated functional group (s).

In the method according to the invention it is also possible to use the activation reagent before the implementation with the at least one functional group React polymer with the derivatization reagent, then this Reaction product with at least one functional group Implement polymer.

Another conceivable embodiment of the present invention exists therein the polymer having at least one functional group with different Products from reactions of activation reagents and derivatization reagents implement. For example, a mixture of compounds be reacted with the polymer, the mixture being reaction products an activation reagent and two or more different derivatization reagents includes. A mixture is also conceivable, the reaction products one derivatization reagent and two or more different ones Activation reagents included. Of course it is also possible, should this be the case be required to use a mixture that consists of reaction products of two or more different activation reagents and two or more different ones Derivatization reagents. Of course it is in the frame the present invention also possible the various reaction products from activation reagent and derivatization reagent not in a mixture, but individually and in the desired order with the at least one to implement functional group-containing polymer.

In principle, all activation reagents known from the literature can be used as activation reagents be used. An overview of a whole series of activation reagents used to activate various functional Groups can be used, for example, the one already cited above Article by P. Mohr, M. Holtzhauer, G. Kaiser, who reference in this regard fully included in the context of the present patent application becomes. Chloroformic acid esters and chloroformic acid esters in particular mentioned with electron-withdrawing residues.

wobei R₁ und R₂ gleich oder unterschiedlich sind und geradkettig, verzweigtkettig oder zu einem Carbozyklus oder einem Heterozyklus verbrückt sein können und so gewählt sind, daß das Aktivierungsreagens oder das Derivat des Aktivierungsreagens mit dem mindestens eine fünktionelle Gruppe aufweisenden Polymer in homogener Phase umgesetzt werden kann.In particular, the present invention describes a method in which the activating reagent is derived from a compound of the following structure (I):

wherein R ₁ 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 activation reagent or the derivative of the activation reagent are reacted with the polymer having at least one functional group in a homogeneous phase can.

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

wobei R₃ bis R₁₀ gleich oder unterschiedlich sein können und Wasserstoff, geradkettige oder verzweigtkettige Alkyl-, Aryl-, Cycloalkyl-, heterocyklische und Aralkyl-Reste mit bis zu 30 C-Atomen darstellen können, oder aber mehrere der R₃ bis R₁₀ wiederum zu einem Carbo- oder Heterozyklus verbrückt sein können und so gewählt sind, daß das Aktivierungsreagens oder das Derivat des Aktivierungsreagens mit dem mindestens eine funktionelle Gruppe aufweisenden Polymer in homogener Phase umgesetzt werden kann.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 '),

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 R ₁₀ can in turn be bridged to form a carbocycle or heterocycle and are selected such that the activating reagent or the derivative of the activating reagent can be reacted with the polymer having at least one functional group in a homogeneous phase.

wobei R₃ bis R₁₀ wie oben definiert sind.The present invention further describes a process 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 activating reagent is derived from a compound of structure (II), as indicated above, where R ₃ to R _{10 are} each hydrogen.

The connections with the structures (I), (I ') and (II) are according to all common, Processes known from the prior art can be produced. Such a process for ONB-Cl is, for example, in P. Henklein et al., Z. Chem. 9 (1986), p. 329 f. specified.

With the activation reagents or derivatives of activation reagents as described above can in principle all polymers that have at least one the activation reagents have reactive functional group, implemented become.

Among others, polymers are preferred in the process according to the invention used which have a group as at least one functional group, which has at least one nucleophilic unit.

Examples of 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 ₁₁ Groups, PO ₃ H ₂ groups, PO ₃ HR ₁₁ groups, COOH groups and mixtures of two or more thereof, R ₁₁ being chosen so that the activation reagent or the derivative of the activation reagent with the at least one functional polymer can be implemented 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.

As the polymer having at least one functional group, both natural and synthetic polymers can be used. any 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 in homogeneous phase is made and from the later use of the derivatized polymer.

In the context of this invention, the term "polymer" naturally goes without saying equally high molecular weight compounds that are used in polymer chemistry as "Oligomers" are referred to.

• Polysaccharide, wie z.B. Cellulose, Amylose und Dextrane;
• Oligosaccharide wie z.B. Cyclodextrine;
• Chitosan;
• Polyvinylalkohol, Poly-Thr, Poly-Ser;
• Polyethylenimin, Polyallylamin, Polyvinylamin, Polyvinylimidazol, Polyanilin, Polypyrrol, Poly-Lys;
• Poly(meth)acrylsäure(ester), Polyitaconsäure, Poly-Asp;
• Poly-Cys;

Without wishing to restrict it to specific polymers, the following may be mentioned as possible polymers having at least one functional group:

• Polysaccharides such as cellulose, amylose and dextrans;
• Oligosaccharides such as 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 are homopolymers, but also copolymers and in particular Block copolymers and statistical copolymers are in principle suitable for use in existing methods to be used. Both copolymers are included non-functionalizable fractions such as co-styrene or co-ethylene or also to name copolymers such as co-pyrrolidone.

• partiell oder vollständig alkylierte oder acylierte Cellulose;
• Polyvinylacetat / Polyvinylalkohol;
• Polyvinylether / Polyvinylalkohol;
• N-Butylpolyvinylamin / Polyvinylamin.

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.

• Poly(acrylsäure)-Co-Vinylacetat;
• Polyvinylalkohol-co-Ethylen;
• Polyoxymethylen-co-Ethylen;
• modifizierte Polystyrole, wie z.B. Copolymere des Styrols mit (Meth)acrylsäure(estern);
• Polyvinylpyrrolidon und dessen Copolymere mit Poly(meth)acrylaten.

Polymer / copolymer mixtures can also be used. All suitable polymer / copolymer mixtures can be used, for example mixtures of the above-mentioned polymers and copolymers, among which is to be mentioned here, among others:

• Poly (acrylic acid) -co-vinyl acetate;
• Polyvinyl alcohol-co-ethylene;
• Polyoxymethylene co-ethylene;
• modified polystyrenes, such as copolymers of styrene with (meth) acrylic acid (esters);
• Polyvinyl pyrrolidone and its copolymers with poly (meth) acrylates.

All of the polymers or / and copolymers described above or their mixtures can of course also in underivatized form in the are used as long as it is ensured that, as described in the context of the present application, for at least one Carrier material and / or to at least one other, in the invention Process used polymers covalent and / or non-covalent interactions can train.

As described above, the at least one functional group Polymer with an activating reagent such as a compound of structure (II), this reaction product can, as also described above can be reacted with a derivatization reagent.

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

For example, derivatization reagents are used which have the general composition HY-R ₁₂ . Y stands for example for O, NH, NR ₁₃ or S, where R ₁₂ and R _{13 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:
Bomeol, (-) - menthol, (-) - ephedrine, α-phenylethylamine, adrenaline, dopamine.

Another possibility is to activate the activated in the inventive method Polymer with a mono- or polyhydric alcohol containing amino groups or Implement thiol. Will that contain at least one functional group If polymer is activated, for example, with ONB-Cl, the one containing amino groups reacts mono- or polyvalent alcohol or the mono- or polyvalent amino group-containing Thiol selective with the amino group. The thus introduced into the polymer OH or SH groups can then be used again in a further step activate with, for example, one of the activation reagents described above, whereby chain extensions and branches, depending on the value of the originally used alcohols or thiols.

In another, already described embodiment of the inventive The method has at least one functional group Polymer reacted with an activated derivatization reagent, the latter from the reaction of an activation reagent with the derivatization reagent is obtained.

Activated derivatives of Amines, alcohols, thiols, carboxylic acids, sulfonic acids, sulfates, phosphates or phosphonic acids with at least one functional group Polymer implemented, wherein, again in a preferred embodiment, the Connections with ONB-Cl are activated.

wobei R₃ bis R₁₀ wie oben definiert sind und R₁₄ bis R₂₁ im allgemeinen keinen Beschränkungen unterliegen, beispielsweise auch Chiralität aufweisen können, und im erfindungsgemäßen Verfahren so gewählt werden, daß die Umsetzung mit dem mindestens eine funktionelle Gruppe aufweisenden Polymer in homogener Phase durchgeführt werden kann. Dabei werden die Substituenten R₁₄ bis R₂₁ in der Regel in Abhängigkeit von der gewünschten Wechselwirkung mit dem Substrat gewählt. Dabei können R₁₄ bis R₂₁ gleich oder verschieden sein und Wasserstoff, einen geradkettigen oder verzweigtkettigen Alkyl-, Aryl- oder Aralkylrest mit bis zu 30 C-Atomen oder entsprechende Heteroatome aufweisende Reste darstellen.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 (III) to (IX):

wherein R ₃ to R _{10 are} as defined above and R ₁₄ to R ₂₁ are generally not subject to any restrictions, for example may also have chirality, and are chosen in the process according to the invention in such a way that the reaction with the polymer having at least one functional group in a 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.

Polyvalent amines, alcohols, thiols, carboxylic acids, sulfonic acids, Sulfates, phosphates or phosphonic acids reacted with an activating reagent and this reaction product with the at least one functional Group-containing polymer are implemented, in particular here Polyols should be mentioned.

Of course, it is also conceivable to activate derivatization reagents and to react with the polymer having at least one functional group, the two or more different types of the above functional Have groups. Examples include amino alcohols to call.

Such multivalent derivatization reagents can be used in the present Invention selectively partially or completely with an activation reagent activated and with the at least one functional group Polymer are implemented.

Both the implementation of the at least one functional group Polymers with an activated derivatization reagent as well as the implementation of the polymer having at least one functional group with an activating reagent and then reacting the product with a derivatization reagent according to the inventive method, polymer derivatives to produce that have a wide variety of spatial arrangements.

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

• Aminosäuren mit aliphatischen Resten wie z.B. Glycin, Alanin, Valin, Leucin, Isoleucin;
• Aminosäuren mit einer aliphatischen Seitenkette, die eine oder mehrere Hydroxylgruppen umfaßt, wie z.B. Serin, Threonin;
• Aminosäuren, die eine aromatische Seitenkette aufweisen, wie z.B. Phenylalanin, Tyrosin, Tryptophan;
• Aminosäuren, die basische Seitenketten umfassen, wie z.B. Lysin, Arginin, Histidin;
• Aminosäuren, die saure Seitenketten aufweisen, wie z.B. Asparaginsäure, Glutaminsäure;
• Aminosäuren, die Amidseitenketten aufweisen, wie z.B. Asparagin, Glutamin;
• Aminosäuren, die schwefelhaltige Seitenketten aufweisen, wie z.B. Cystein, Methionin;
• Modifizierte Aminosäuren, wie z.B. Hydroxyprolin, γ-Carboxylglutamat, O-Phosphoserin;
• Derivate der genannten oder von gegebenenfalls weiteren Aminosäuren, beispielsweise an der oder gegebenfalls den Carboxylgruppen mit beispielsweise Alkyl- oder Arylresten, die gegebenenfalls geeignet substituiert sein können, veresterte Aminosäuren.

Such a derivative, which is tailor-made for biological substrates, then has corresponding receptor groups which, for example, can also have structures occurring in nature or parts of such structures responsible for binding, 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 others, preferred in the context of the present invention is a derivative of a polymer having at least three functional groups, as described above, in which at least one receptor 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 glycine, alanine, valine, leucine, isoleucine;
• Amino acids with an aliphatic side chain which comprises one or more hydroxyl groups, such as, for example, serine, threonine;
• Amino acids that have an aromatic side chain, such as phenylalanine, tyrosine, tryptophan;
• Amino acids comprising basic side chains, such as lysine, arginine, histidine;
• Amino acids that have acidic side chains, such as aspartic acid, glutamic acid;
• Amino acids that have amide side chains, such as asparagine, glutamine;
• Amino acids that have sulfur-containing side chains, such as cysteine, methionine;
• Modified amino acids, such as, for example, 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 there is also the use of one or more di- or oligopeptides conceivable, in particular homopeptides that only consist of the same amino acids are constructed, are to be mentioned. An example of a dipeptide is, for example To call hippuric acid. Furthermore, beta, gamma or other structurally isomeric amino acids and peptides derived from them, e.g. depsipeptides be used.

eingesetzt werde, die dadurch gekennzeichnet sind, daß R₀ für ein Halogenatom oder einen Rest (X')

steht und R₁', R₂'; R₁" und R₂" gleich oder unterschiedlich sind und Wasserstoff, geradkettige oder verzweigtkettige Alkyl-, Aryl-, Cycloalkyl-, heterocyclische oder Aralkylreste mit bis zu 30 C-Atomen darstellen oder entweder R₁' und R₂' oder R₁" und R₂" oder sowohl R₁' und R₂' als auch R₁" und R₂" zu mindestens einem Carbocyclus oder zu mindestens einem Heterocyclus oder zu mindestens einem Carbocyclus und zu mindestens einem Heterocyclus verknüpft sind. Insbesondere sind hierbei beispielhaft Verbindungen,die die folgenden Strukturen (X₁) bis (X₃₉) umfassen, zu nennen:

wobei R''' für Wasserstoff oder für einen geradkettigen oder verzweigtkettigen, gegebenenfalls substituierten Alkyl-, Aryl- oder Aralkylrest mit bis zu 30 C-Atomen steht In general, compounds of the general structure (X)

are used, which are characterized in that R _{0 is} a halogen atom or a radical (X ')

stands and R ₁ ', R ₂ '; R ₁ "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 ₁ 'and R ₂ ' or R ₁ " and R ₂ "or both R ₁ 'and R ₂ ' as well as R ₁ " 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 (X ₁ ) 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 already at the derivatization the derivatization reagent with regard to its chemical Condition among other things with regard to the later binding of the polymer to the carrier material and / or to a further polymer and / or another To design polymer layer. In particular, the derivatization reagent Contain groups that are responsible for covalent and / or non-covalent interaction are selective or specific.

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

For the production of a suitable polymer which is used for binding to the carrier material or the functional bond required to a polymer layer In principle, any method that has this polymer is suitable for groups leads.

wie oben definiert, aktiviert wurdeAmong 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, the may be the same as or different from the first low molecular weight compound, to obtain 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) before the reaction

as defined above

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

In a further preferred embodiment of the method according to the invention are the individual polymer layers, which in turn are preferred in individual steps applied 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 by non-covalent Interaction of the at least one polymer with the carrier material takes place and the application of the at least one further layer of the at least one Polymers done by covalent crosslinking.

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

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

With regard to the covalent interaction, in principle, among others Ester, amide, carbonate, hydrazide, urethane or urea bonds or thio-analogous or nitrogen-homologous bonds are formed.

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

In a further preferred embodiment of the present invention it is conceivable, the binding of the first polymer layer to the support material and / or Binding of other polymer layers, one polymer layer on each already applied polymer layer is bound using at least one Carry out crosslinking reagent. Under the term "cross-linking reagent" all compounds are understood in the context of the present invention, which have at least two functional groups through which this connection non-covalently and / or covalently reversible or / and covalently irreversible with either the carrier material and at least one polymer or with at least two polymers, the same or different from each other can be interacts.

In principle, all suitable cross-linking reagents come from the state compounds known in the art. Accordingly, networking can for example in a covalently reversible manner, in a covalently irreversible manner or in a non-covalent manner, with crosslinking in a non-covalent manner For example, cross-links via ionic interaction or via charge-transfer interaction. Such cross-linking procedures or reagents include in Han, K.K., et al., Int. J. Biochem., 16: 129 (1984), Ji, T.H., et al., Meth. Enzymol., 91, 580 (1983) and Means, G. and Feeney, R.E., Bioconj. Chem., 1, 2 (1990). As a possible non-covalent In this context, interactions also affect everyone Non-covalent interactions already described in detail above. The same applies to covalently reversible interactions, as well have already been described as examples above. As there are also regarding the cross-linking reagents all suitable non-covalent interactions conceivable.

Likewise, the formation of a non-covalent crosslinking can, for example take place if in the event that two basic groups of, for example, polyallylamine are crosslinked with each other, a dibasic acid such as Glutaric acid is added, or in the event that two acidic groups of, for example Polyacrylic acid to be cross-linked, a divalent Base such as ethylenediamine is added. Can also be exemplary a non-covalent cross-linking through complex-forming metal ions or through Metal complexes are formed with free coordination points. Generally can do all possible with regard to non-covalent crosslinking Interactions are referred to, which 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 Schiff base. Crosslinking via ionic interaction can occur, for example, via two residues, one of which as a structural unit is a quaternary ammonium ion and the other as a structural unit, for example ―COO ^- or ―SO ₃ ^- having. Crosslinking via hydrogen bonds can, for example, be formed between two complementary base pairs, for example via the following structure:

In general, non-covalently crosslinkable polymers can be used in terms of Networking points are designed to be complementary, with mutually complementary Structural units are, for example, acid / triamine or uracil / melamine. The crosslinking reagent can also be used for non-covalent crosslinking be complementary to the crosslinking sites on the polymer strand. As an an example this would include an amine group on the polymer strand and a dicarboxylic acid to name as crosslinking reagent.

Is it necessary within the scope of the method according to the invention that a crosslinking step at least one of the functional groups that are attached to the Networking are involved, so this is essentially after all Methods that are known from the prior art are conceivable. In particular a functional group can be activated according to a method, as described above in the activation and derivatization of polymers is described in detail.

As cross-linking reagents that can lead to covalently irreversible cross-linking, are among other things two or more functional connections such as To name diols, diamines or dicarboxylic acids. For example implemented divalent crosslinker with the activated polymer derivative or the at least divalent activated crosslinking reagent with the non-activated polymer derivative.

wie oben definiert, aktiviert wurdeIf in the process according to the invention the 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 two functional Group-containing second low molecular weight compound, which may be the same as or different from the first low molecular weight compound, is prepared to give a condensation compound, the method being characterized in that at least one of the functional groups involved in this reaction is reacted with before the reaction a connection structure (X)

as defined above

Compounds of the following structures (XI ₁ ) to (XI ₁₇ ) 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:

The following reaction routes (A) and (B), in which the remainder 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:

Accordingly, all materials are suitable as carrier materials, which like covalent and / or non-covalent interactions described above which can form at least one polymer.

In particular, it is conceivable for the carrier material to be dissolved or colloidally dissolved or suspended. In this context, in particular, it is conceivable that the carrier material is a polymer or a polymer network, as described under other manufactured in the method according to the invention, as described below becomes.

If the carrier material is a solid, its surface can even, such as plates made of glass or metal, or curved or embedded in porous bodies, for example tubular or sponge-like, such as for example zeolites, silica gel or cellulose beads. They can continue Carrier materials of natural origin or synthetic nature. As an example may include gelatin, collagen or agarose.

In a preferred embodiment of the present invention, the first Polymer layer, which is applied to the carrier material, via non-covalent Interaction without using a cross-linking reagent on the carrier material bound, and the polymer layers with each other by covalent crosslinking cross-linked using at least one cross-linking reagent.

With regard to the cross-linking reagents, it is within the scope of the present invention conceivable that either non-selective / non-specific or / and selective / specific cross-linking reagents are used. Under the term "selective "specific crosslinking reagent" is used in the context of the present Invention understood a crosslinking reagent, the two or more different has functional groups, of which at least one group in comparison to at least one different group under given reaction conditions with a functional group of another polymer or the carrier material prefers to respond. The term also includes such crosslinking reagents, which have two or more identical functional groups, their chemical However, the environment differs and / or the sterically different are arranged and therefore at least one of them under given reaction conditions with a functional group of another polymer or the Carrier material reacts preferentially. This term also includes such cross-linking reagents, the same or different functional groups have that differ in selectivity / specificity because a Part of the functional groups according to a method as described above an activation reagent is activated. Of course, with the connections, which have two or more different functional groups, one or more of the functional groups with possibly different ones reactive groups must be activated so that the reactivity of a Part of the optionally activated groups on the reactivity of the other Part of the possibly activated groups differs. Combinations of two or more of the influences described that affect specificity / selectivity impact are of course also conceivable.

Accordingly, the present invention also relates to a method as described above, characterized in that the covalent crosslinking by at least a non-specific or non-selective cross-linking reagent or at least a specific or selective crosslinking reagent or by a mixture from two or more of them.

As for the use of these cross-linking reagents, they are all Processes conceivable, at least for the application according to the invention a layer of at least one polymer on the carrier material which, as described, is preferably carried out gradually.

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 onto a polymer layer polymer layer applied using a selective / specific Crosslinking reagent applied, so in a preferred embodiment proceeded in such a way that the starting material to which the polymer layer was applied with a solution containing the at least one cross-linking reagent and the at least one polymer, which are applied as a polymer layer should be brought into contact. Here reaction conditions are chosen among which the crosslinking reagent, preferably with the educt or with the one to be applied Polymer reacts. By varying the reaction conditions in a next step, the crosslinking takes place, for example by the reaction product from the polymer to be applied and crosslinking reagent over at least a functional group of the crosslinking reagent reacts with the starting material or, for example, the reaction product of starting material and crosslinking reagent the polymer to be applied reacts.

Selective / specific cross-linking reagents are used in the invention The method is preferably used when the carrier material and polymer or Polymer and polymer are cross-linked with each other via functional groups that have the same or similar reactivity. Examples of selective / specific Activation reagents include, for example, polyvalent carboxylic acids, Diamines or diols activated with different reactive groups are or of which only a part of the functional groups is activated. Further Examples include connections that are at least two different have functional groups, such as, inter alia, amino acids, Hydroxy acids or amino alcohols, the different functional Groups have different reactivity under given reaction conditions. Of course, the connections can have two or more have different functional groups, one or more of the functional groups with possibly different reactive groups be activated so that the reactivity of some of the activated, if necessary Groups of the reactivity of the other part of the optionally activated Groups differ, as already described above.

Are non-selective / non-specific cross-linking reagents in the method according to the invention used, including two preferred procedures to call. Just as with the procedure described above, in which intramolecular cross-linking is avoided and one Polymer layer applied to the support material or another polymer layer is, these preferred procedures are carried out so that the intramolecular networking or / and the intermolecular networking within a polymer layer is largely avoided and a polymer layer is applied becomes. Small cross-links within a polymer layer can contribute to an additional stabilization of the polymer network.

(aa) das mindestens eine Vernetzungsreagenz in einem ersten Schritt mit der zuletzt aufgebrachten Lage des mindestens einen Polymers reagiert und das Reaktionsprodukt in einem weiteren Schritt mit einer Lösung, umfassend das mindestens eine Polymer, in Kontakt gebracht wird und durch Reaktion des mindestens einen, in der Lösung enthaltenen Polymers mit dem Reaktionsprodukt mindestens eine weitere Lage des mindestens einen Polymers auf das Reaktionsprodukt aufgebracht wird, oder

(bb) eine Lösung, umfassend das mindestens eine Vernetzungsreagenz und das mindestens eine Polymer, mit der zuletzt aufgebrachten Lage des mindestens einen Polymers bei Reaktionsbedingungen in Kontakt gebracht wird, bei denen die Reaktion des mindestens einen Vernetzungsreagenzes sowohl mit der zuletzt aufgebrachten Lage des mindestens einen Polymers als auch mit dem mindestens einen, in der Lösung enthaltenen Polymer erfolgt, oder

(cc) die Methoden gemäß (aa) und (bb) in geeigneter Weise kombiniert werden.

Accordingly, the present invention also relates to a method as described above, using at least one non-specific or one non-selective crosslinking reagent, characterized in that the crosslinking is carried out 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 in a further step the reaction product is brought into contact with a solution comprising the at least one polymer and by reaction of the at least one the solution containing polymer 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 like this performed that the cross-linking reagent at temperatures with the last applied Polymer layer is brought into contact, in which the cross-linking reagent statistically even over the existing polymer layer distributed and in which a reaction of the cross-linking reagent with that already existing polymer layer largely The temperatures at which this are usually in the range of 0 to -70 ° C.

Also when choosing the other reaction conditions such as pH, type of Solvent, concentration of crosslinking reagent in the solvent care is taken in this preferred embodiment of the method that the reaction of the cross-linking reagent with the existing polymer layer largely is omitted until the crosslinking reagent is statistically uniform over the already existing polymer layer is distributed.

By appropriate variation of the reaction conditions in a next Step the statistically evenly distributed cross-linking reagent with the already existing polymer layer reacted such that the crosslinking reagent predominantly reacted via one or more functional groups and at least a functional group of the cross-linking reagent through which the cross-linking to the next polymer layer, not with the existing one Polymer layer reacts. This usually takes place again at low temperatures, these are usually in the range of 0 to -10 ° C. Is favored this further through the use of short-chain cross-linking reagents or / and Immobilization of the polymer layer. Ways of Networking Like This other can be induced, for example, use of ultrasound or photochemical cross-linking.

Of course, it is also possible with appropriate crosslinking reagents or / and with a corresponding, already existing polymer layer, the above described reaction control by varying the pH value and / or variation to control the solvent or / and by adding modifiers, where combinations of some or all of the methods are of course also conceivable are.

In this context, reference can also be made to the specific methods that can be applied as described above to start the To prevent binding of a polymer and to stimulate it in a further step.

According to method (aa), the next step is to find a solution that at least comprises a polymer which is to be applied as the next polymer layer, with the reaction product from cross-linking reagent and already existing polymer layer brought into contact. The reaction conditions will then be like this changed that the reaction is particularly preferred between the unreacted functional groups of the bound to the existing polymer layer Crosslinking reagent and the polymer to be applied as the next polymer layer he follows. Among other things, it is also conceivable that the reaction conditions by adding the solution comprising the at least one polymer which to be applied as the next polymer layer, are influenced in such a way that a further change in the reaction conditions no longer has to take place.

Also with regard to this step of applying the next polymer layer among other things, the specific methods referred to above described can first be applied to the binding of a polymer prevent and stimulate in a further step.

The method is also used in a particularly preferred embodiment carried out according to (bb) such that the solution comprising the at least one Cross-linking reagent and the at least one polymer with which was applied last Location of the at least one polymer under reaction conditions Is brought into contact, in which no reaction takes place initially, but both Cross-linking reagent and polymer to be applied are statistically Distribute evenly over the existing polymer layer.

As already described in connection with method (aa), this is done Contacting in a preferred embodiment at low temperatures, usually in the range from 0 to -70 ° C.

Also when choosing the other reaction conditions such as pH, type of Solvent, concentration of crosslinking reagent in the solvent or concentration of the polymer to be applied in the solvent is given in This preferred embodiment of the method ensured that the reaction the cross-linking reagent with the existing polymer layer and the reaction of the polymer to be applied with the crosslinking reagent is largely avoided and the crosslinking reagent and the polymer to be applied randomly evenly distributed over the existing polymer layer.

In a next step, the reaction conditions are then changed in such a way that the crosslinking reagent with both the existing polymer layer as also reacts with the polymer that is applied as the next layer. in this connection it is conceivable, inter alia, that the crosslinking reagent initially already with the existing polymer layer and then with the polymer to be applied reacted to form the new polymer layer. It is also conceivable that the cross-linking reagent simultaneously with the already existing polymer layer and the polymer to be applied reacts to form the new polymer layer. It is also possible for the crosslinking reagent to be statistically uniformly distributed first reacted with the statistically evenly distributed polymer and then the reaction product with the existing polymer layer Formation of the new polymer layer reacts. The reactions of the cross-linking reagent take place with the existing polymer layer on the one hand and the polymer to be applied, on the other hand, not at the same time, so it is possible to Varying the reaction conditions first one of the reactions, by further Varying the reaction conditions to perform the other reaction.

As for the change in the reaction conditions, here are all options and combinations already described above. In particular, the next step can also be applied with regard to this step Polymer layer can be referred to, among other things, the specific methods that as described above can be used to first bind a To prevent polymers and to stimulate them in a further step. Possibilities, Examples of how this crosslinking can be induced include also use of ultrasound or photochemical cross-linking.

The use of ultrasound or photochemical crosslinking are a matter of course Methods that are very general for each crosslinking step, as described in Within the scope of the present invention is used in principle can be.

Examples of non-selective / non-specific cross-linking reagents are below other, for example, divalent epoxides, isocyanates, chlorotriazines, amidines or aldehydes. Succinimide are also activated. particularly preferred ONBund N-hydroxy-phthalimide-activated compounds. Amongst other things they also refer to the cross-linking reagents explicitly listed above directed. In a preferred embodiment of the method according to the invention are symmetrical, usually bivalent cross-linking reagents and activated dicarboxylic acids are very particularly preferably used.

The chain length of the cross-linking reagents used in any of the embodiments of the method according to the invention is generally arbitrary and adaptable to the requirements of the respective process. The chain itself can be aliphatic or aromatic or araliphatic. The can continue Chain one or more functional groups used to form covalent or are capable of non-covalent interactions.

The chain length is preferably in the case of crosslinking reagents which have a carbon chain have, in the range of 2 to 24 carbon atoms, particularly preferably in the range from 4 to 24 carbon atoms and particularly preferably in the range from 8 to 12 carbon atoms.

The polymers used in the process according to the invention are subject to essentially only the limitation that they are in at least one location Formation of the interactions as described above on a carrier material can be applied. Polymers are particularly preferably used, which have a molecular weight in the range of 2,000 to 100,000 g / mol. The molecular weights are determined by GPC.

Accordingly, the present invention also relates to a method as described above, characterized in that the at least one polymer has a molecular weight in the range of 2,000 to 100,000 g / mol.

Here are three preferred embodiments of the method according to the invention to call.

In a first embodiment, the at least one polymer is applied in such a way that that it has a largely uncoiled structure, but as close as possible above of the theta point with carrier material and / or already applied polymer layer is brought into contact. In this embodiment, the solution in which this at least one polymer dissolved and with carrier material and / or polymer layer is contacted, a solvent or solvent mixture chosen in which the polymer is largely uncoiled, of course also by the specific choice of other reaction conditions such as for example, 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 largest possible distribution coefficient of Polymer. Are particularly preferred for this preferred embodiment Polymers used that have a molecular weight less than about 30,000 have g / mol. With this embodiment, the application of is largely monomolecular polymer layers favored.

In a second embodiment, solvents or solvent mixtures or other reaction conditions chosen such that the at least one Polymer in the solution is near above the theta point. Through this special embodiment, which is particularly preferred by polymers favored with a molecular weight in the range of more than about 30,000 g / mol it is possible to apply the polymer in loose polymer balls to favor.

In a third embodiment, solvents or solvent mixtures or other reaction conditions chosen such that the at least one Polymer in the solution is near below the theta point. Here it is possible, inter alia, to form at least one polymer To apply nanoparticles.

The individual crosslinking steps carried out in the process according to the invention can be done so that an essentially any degree of crosslinking the polymer layers are reached with each other. The method is preferred however, so that the degree of crosslinking of a polymer chain with two other polymers is cross-linked, is in the range of 0.5 to 25%. This Degree of crosslinking is based on the monomer units of a polymer chain that was cross-linked with two neighboring polymer chains. Is particularly preferred this degree of crosslinking in the range of 2 to 10%.

Accordingly, the present invention also relates to a method as described above, characterized in that the degree of crosslinking in the range of 0.5 up to 25%, based on the monomer units of one with two adjacent polymer chains cross-linked polymer chain.

In the described method according to the invention, it is possible to use a carrier material to apply a polymer network, for example, by the covalent cross-linking of the polymer layers with one another has a structure that consists of two- or three-dimensional cells. Such a cell of the polymer Network is usually by at least one cross-linking reagent, the two polymer layers cross-linked and part of at least one polymer, from which the polymer layers are formed. Whichever chemical structure the at least one cross-linking reagent or the at least one have a polymer used, it is conceivable, among other things, that the cells are constructed such that the cell interacts with at least one Template connection is possible. Therefore, the present invention also describes a method as described above in which a polymeric network is applied at least one polymer layer is formed on at least one carrier material the polymeric network comprising one or more interaction cells, via which the polymer network with at least one template compound in can interact covalently or / and non-covalently.

In a preferred embodiment, the method according to the invention can do so be performed that the polymeric structure by the application at least of a polymer built up in at least one layer on at least one carrier material with respect to the interaction cells to at least one template connection is adjusted.

In addition to the previously described embodiments, the present invention describes therefore also a method as described above, characterized in that that the conformation of the polymeric structure by interaction and crosslinking results, during or after application at least one of the layers of the at least one polymer on the carrier material is adapted to at least one template connection.

The present invention also describes a method in which the polymer Structure that has been applied and produced on the carrier material, is detached from the carrier material and then used in applications such as for example, are described below.

The present invention also encompasses the polymeric network itself, the is obtainable according to a method as described above.

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

The polymer network that can be produced by the method according to the invention is distinguished in a particularly preferred embodiment from the fact that it is insoluble, but nevertheless has swellability.

Accordingly, the present invention also relates to the use of a method as described above, or a polymeric network, obtainable by a method as described above for producing an at least one Template connection adapted polymeric network.

The polymeric networks produced according to the invention can because of their Structure comprising interaction cells, as described above, in a preferred one Embodiment can be used in processes in which, for example Fabrics manufactured, converted into other fabrics or from other fabrics be separated. It is also conceivable that the manufactured according to the invention polymeric networks for the detection of optical, electrical or mechanical Signals are used. The polymer networks are very special suitable for these processes if, as described above, at least a template connection is adapted.

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

example 1 Coating of silica gel SP 300-15 / 30 with poly (benzyl-N-allyl carbamate) des Degree of derivatization 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), after cooling with Dichloromethane (100 mL, 1.18 mol) diluted and with pyridine (112 mL, 1.42 mol) added to deteriorate the solubility of the polymer. After that was the cloudiness is eliminated with a few drops of glacial acetic acid. After encore the batch was made of silica gel 300 Å, 20 µm (Daisogel SP 300-15 / 30) (10.02 g) Moved for 30 minutes on a shaker and after suction over a Glass frit washed with dichloromethane (4 × 50 mL).

For the crosslinking, the coated silica gel became 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 in vacuo (85 mbar, water bath 0 ° C) evaporated to dryness. The coated silica gel was washed with tetrahydrofuran (60 ° C, 4 × 25 mL), suction filtered and washed with dichloromethane (50 mL).

For the second assignment, poly (benzyl-N-allyl carbamate) was used with a degree of derivatization of 14% (1.60 g) dissolved in boiling glacial acetic acid (100 mL, approx. 117 ° C), after cooling, diluted with dichloromethane (100 mL, 1.18 mol) and with 100 mL Pyridine (100 mL, 1.26 mol) was added to deteriorate the solubility of the polymer. Dimethylaminopyridine (DMAP, 80 mg, 0.65 mmol) and again pyridine (12 mL, 0.15 mol) was added. After that was the cloudiness is eliminated 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 then Aspirate through a glass frit, washed with dichloromethane (4 × 50 mL).

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

The mixture was swollen in a frit in dimethylformamide (30 min). By slowly passing a solution of diethylamine (2 mL, 1.42 g, 19.41 mmol) the remaining activated crosslinker groups were deactivated in DMF (40 mL). For complete deactivation, the approach was repeated four more times with the Filtrate solution rinsed. The mixture was then treated with tetrahydrofuran (60 ° C., HPLC grade, 4 × 50 mL) and washed with dichloromethane (4 × 50 mL) and sucked dry.

The coated silica gel was treated with glacial acetic acid (100 mL), the suspension to Boiled, suction filtered, washed with dichloromethane (5 × 50 mL), dried (110 ° C, 16 h) and sieved over 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) 14% degree of derivatization and crosslinking 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 glacial acetic acid at 50 ° C within 30 minutes. To the polymer solution silica gel 300 Å, 20 µm (Daisogel SP 300-15 / 30) (10.00 g) was added and agitated the suspension for 3 hours on a shaker. After suction The residue was washed with the following solutions via a glass frit: 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 the crosslinking, the coated silica gel obtained was converted into a solution of bis-dodecanedioic acid (N-hydroxy-5-norbomen-2,3-dicarboximide) ester (100 mg, 0.18 mmol) and triethylamine (54 mg, 0.54 mmol) in dichloromethane (80 mL) and the suspension in vacuo (100 mbar, water bath 0 ° C) to dryness concentrated. The coated silica gel was boiled in THF (40 mL) and suction filtered and washed with hot THF (3 x 40 mL) and dichloromethane (2 x 30 mL).

For further occupancy, poly (benzyl-N-allyl carbamate) was used with a degree of derivatization of 14% (1.66 g) in 100 ml glacial acetic acid at 50 ° C within 30 Dissolved 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 added. The resulting turbidity was reduced by adding 3 mL Glacial acetic acid removed. To this solution was obtained the crosslinker obtained above reacted, coated silica gel and the batch 30 minutes on a Shaking machine moves. After suction through a glass frit, the residue 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). Then was dried in vacuo at 50 ° C.

The process of networking and further assignment was analogous repeated once with polymer.

The coated silica gel was suspended in a frit in THF (10 mL). By a slow leakage of a solution of diethylamine (0.27 g, 3.7 mmol) in THF (10 mL) were the remaining activated crosslinker groups quenched. The residue was then treated with THF (60 ° C, 4 x 20 mL) and Washed dichloromethane (2 x 10 mL) and sucked dry.

The coated silica gel was treated with glacial acetic acid (40 mL), the suspension to Boiled, suction filtered and washed with dichloromethane (4 x 20 mL). Subsequently, a solution of 0.25 ml of pyridine in 15 ml Washed dichloromethane and THF (4 x 20 mL) and dried.

According to elemental analysis, the carbon content of the silica gel covered 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) of the degree of derivatization 14% and crosslinking 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 2.5 cm diameter glass column was covered with 300 Å, 20 µm silica gel (Daisogel SP 300-15 / 30) (5.00 g) packed. Poly (benzyl-N-allyl carbamate) with one Degree of derivatization of 14% (3.20 g) was in 200 ml of water and with addition 1-2 ml of glacial acetic acid dissolved within 2 hours. This polymer solution was made for Pumped in a circle through the glass column with silica gel for 24 hours. The pillar was 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 documented was Silica gel on average 2.7%.

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

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

The coated silica gel was treated with glacial acetic acid (50 mL), the suspension to Boil heated, suction filtered and pyridine (20 mL) added. Then was suction filtered, washed with THF (60 ° C, 3 x 50 mL) and dried.

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

Claims (10)

1. 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 bound to the support material and in at least one further step at least one further layer of the at least one polymer is applied to the at least one polymer layer bound to the support material.
2. 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 bound to the support material,

   (i) a solution of the at least one polymer is brought into contact with the support material under reaction conditions at which the at least one polymer is not bound to the support material and then the reaction conditions are varied in such a manner 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 at which the solution of the at least one polymer is present under theta conditions.
3. Method according to Claim 2, characterized in that the reaction conditions according to (i) are varied in such a manner 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

   (b) the solution is concentrated in such a manner that the concentration of the at least one polymer in the solution is kept substantially constant during the concentration, or

   (c) at least one method according to (a) and the method (b) are combined.
4. Method according to one of Claims 1 to 3, characterized in that the at least one layer of the at least one polymer is bound to the support material by non-covalent interaction of the at least one polymer with the support material, and the at least one further layer of the at least one polymer is applied by covalent crosslinking.
5. Method according to Claim 4, characterized in that the covalent crosslinking is performed 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. Method according to Claim 5, at least one non-specific or one non-selective crosslinking reagent being used, characterized in that the crosslinking is performed in such a manner 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, is brought into contact with a solution comprising the at least one polymer and by reaction of the at least one polymer, which is present 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 at which the reaction of the at least one crosslinking reagent proceeds not only with the last-applied layer of the at least one polymer but also with the at least one polymer present in the solution, or

   (cc) the methods according to (aa) and (bb) are combined in a suitable manner.
7. Method according to one of Claims 1 to 6, characterized in that the at least one polymer has a molar mass in the range from 2000 to 100,000 g/mol.
8. Method according to one of Claims 3 to 7, 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.
9. Polymer network which can be prepared 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 of a polymer network according to Claim 9 for preparing a polymer network matched to at least one template compound.