JP2003534393A - Method of 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

Detailed Description of the Invention

The present invention relates to a method of applying one or more polymers in layers to a support material. The present invention also relates to a polymer network obtained by the method according to the invention, which polymer network is preferred such that its conformation is compatible with one or more template compounds. Manufactured in an embodiment. A further aspect of the invention relates to the use of the polymer network produced according to the invention in a method in which a substance is produced, separated, detected or converted into another substance.

The methods applied to the support in a known state of the art usually involve a polymer solution applied to the support in a rotary evaporator. However, this concentration of polymer solution does not in principle lead to polymer coatings with satisfactory properties. When the polymer network produced by this method is used, for example, for a substance separation method, the loadability of the substrate is insufficient, or the retention time of the substrate is in principle very short, The selectivity in these separation methods is insufficient. Similarly, the reproducibility of the polymer network and the characteristic data of the coated support, for example with respect to the polymer content, is generally poor.

Polymer coatings are described, for example, by Wilfried Plum, thesis, D 82 (RWTH Aachen
), Verlag Shaker, Aachen 1995, G.I. Schomburg et al. ， Chromatographia
, 18 (1984) 265 and A.S. Kurganov et at. , Journal of Chromatogra
phy A, 660 (1994) 97-111.

Suitable polymers are, in particular, German patent application DE-A 198 55 173.8.
And DE-A 199 28 236.6. Thus, one object of the present invention was to provide a method by which a polymer can be applied to a support in a way that avoids the abovementioned disadvantages.

The invention thus provides that in at least one step at least one layer of at least one polymer is bonded to a support material and in at least one further step at least one of at least one polymer. Two other layers,
A method of applying at least two layers of at least one polymer to a support material, characterized in that it is applied to at least one polymer layer bonded to the support material.

In this respect, the at least one polymer can be applied stepwise by any suitable method which ensures that at least one layer of the polymer is applied per step, so that the layer morphology is The polymer structure is applied to the support material.

In a preferred embodiment, the invention provides: (i) contacting a solution of at least one polymer with a support material under reaction conditions under which at least one polymer is not bound to the support material, Is changed such that at least one polymer is bound to the support material, or (ii) at least one polymer under reaction conditions in which a solution of at least one polymer is present under theta conditions. At least in one step, comprising contacting a solution of a polymer with the support material, bonding at least one layer of at least one polymer to the support material.

In this regard, according to (i), the solution contacted with the support material may comprise one or more suitable solutions, wherein at least one polymer is
It can be dissolved or colloidally dissolved in the solvent or solvent mixture or suspended, for example in the form of a nanosuspension.

According to (i), the reaction conditions are selected such that the solution is in contact with the support material in the absence of at least one polymer bond to the support material. These reaction conditions are set, for example, by one or more suitable solvents. Solvents preferably used in this respect are those in which at least one polymer is very soluble such that there is no bond to the support material.

For the purposes of the present invention, "polymer is not bound to the support material" means that the binding is substantially undetectable by measuring the partition coefficient. Similarly, these reaction conditions are achieved by choosing a suitable temperature, for example by contacting the solution with a support material at a temperature so high that there is no binding of at least one polymer to the support material. You can Furthermore, if the binding of at least one polymer to the support material is pH dependent,
These reaction conditions can also be achieved by appropriately adjusting the pH of the polymer solution.

It is likewise conceivable to suppress the binding of at least one polymer to the support material by suitable combination of two or more of these methods. Certain methods of managing the reaction particularly avoid reaction conditions in which at least one polymer present in the solution precipitates.

As regards the contact of the solution of at least one polymer with the at least one support material, in principle all suitable process controls are conceivable. Thus, for example, a solution containing at least one polymer can be contacted with the support material. Similarly, the support material is first contacted with at least one solvent,
Then it is also conceivable to put at least one polymer in at least one solvent. It is also possible to first contact the support material with at least one solvent and then add a solution containing at least one polymer. If two or more polymers are used, it is also conceivable to dissolve each one polymer in each case in one solvent or solvent mixture, separately or together with one or more other polymers,
It is also possible to contact these individual solutions. Each of the individual solutions, together with or separately from the support material, comprises at least one polymer, which polymer, if appropriate, has already been dissolved in at least one solvent,
Alternatively, it is present as a colloid, which is dissolved or suspended.

All support materials which can be applied by attaching at least one polymer onto them are suitable in principle for the present invention. If two or more different polymers are used, it is sufficient for the method according to the invention if one of the said polymers can be applied bound to a support material. Of course, it is also conceivable that two or more different polymers can be applied by binding to the support material.

When using two or more different polymers and two or more different support materials,
In particular, it is believed that all polymers can be applied to all support materials.
Similarly, it is contemplated that one or more polymers can be applied to one support material and one or more different polymers can be applied to one or more different support materials.

When using two or more different support materials, it is not possible to apply the polymer to one or more of the support materials, as long as the polymer is applied to at least one of the support materials. Furthermore, it is also possible to apply further polymers and compounds, for example the customary auxiliaries, in which case the binding of the polymers to the support material can also be achieved by other interactions or / and methods. it can. A further possibility is that the polymer or / and the compound present in the solution is not applied to the support but is, for example, still present in the solution. It is particularly envisaged to apply at least one of these polymers in a further step, for example to a support material which has been contacted with a solution containing this polymer before this further step.

According to (i), the reaction conditions are changed such that after contacting, at least one polymer is bound to the support material. As mentioned above, of course, where two or more different polymers or / and two or more different support materials are used, one polymer may be attached to one support material for the purposes of the present invention. Conceivable.

With respect to the changes in the reaction conditions, all changes are conceivable which are suitable for allowing the support material to bind at least one of the polymers. If the binding is temperature dependent, it is conceivable, for example, to raise or lower the temperature in order to favor the binding. In a likewise preferred embodiment, the composition of the solution containing at least one polymer is varied or the solution is slowly concentrated.

Thus, the present invention provides that the reaction conditions according to (i) are: (a) changing the composition of the solution by changing at least one solvent or by adding at least one other compound. Or (b) concentrating the solution so as to keep the concentration of at least one polymer in the solution substantially constant during the concentration, or (c) at least one method according to (a), and a method ( It also relates to the above method, characterized in that b) is varied by a suitable combination.

As regards changing the composition of the solution containing at least one polymer, in principle all suitable methods are conceivable for enabling the binding by this change.

In a preferred embodiment, at least one other solvent having poorer solvent properties for at least one of the polymers is added to the solution containing the at least one polymer.

In a likewise preferred embodiment, the composition of the solution is varied, ie at least one acidic compound or at least one basic compound or a mixture of two or more thereof is added, whereby at least one of the polymers is Change the pH of the solution to allow binding. Of course, adding one or more buffer solutions to
H can also be varied so that at least one of the polymers is capable of binding.

In a likewise preferred embodiment, in the process according to the invention, by adding a suitable compound, eg a salt, including for example a metal cation or a suitable organic compound,
At least one bond of the polymer occurs.

In a likewise preferred embodiment, the solution containing at least one polymer is concentrated,
The concentration of at least one polymer bound to the support material remains substantially constant in solution. In a very particularly preferred embodiment, the solution is concentrated by controlling the process appropriately and slowly to keep the polymer concentration substantially constant.

In addition, the solution containing at least one polymer can be concentrated to dryness in the presence of a non-specific or non-selective cross-linking reagent. This embodiment, which is generally done so that the polymer is deposited on the support from the solution faster than the polymer concentration in the solution is reduced, particularly prevents precipitation during rotary evaporation.

In a further preferred embodiment, the method according to the invention comprises passing a solution containing at least one polymer through a device loaded with a support material, preferably in a packed column, preferably by pumping. , Followed by passing a non-specific or non-selective cross-linking agent through the device loaded with the support material and then once again at least one polymer which may be the same as or different from the first passed polymer. The solution having can be carried out by passing it through a device loaded with a support material or the like. This embodiment is particularly suitable for continuous and relatively rapid application of polymer layers, especially when sequentially passing the polymer solution and crosslinker from each storage vessel.

In a further preferred embodiment of the method according to the invention, two or more of the above methods can be combined, which comprises changing the temperature in a suitable manner. Thus, for example, both changing the composition of the solution as described above and, in a suitable manner, supplementing the solution slowly and / or changing the temperature are conceivable.

It is envisaged for the method according to the invention to apply one polymer or a plurality of different polymers to the support material according to the selected reaction conditions. It is specifically contemplated that the reaction conditions are selected such that two or more different polymers are simultaneously applied to the support material to produce a layer comprising the two or more different polymers on the support material. If two or more different support materials are used, it is conceivable to apply to each support material a polymer layer which may contain one polymer or two or more different polymers.

Of course, it is also possible to apply to the support material two or more layers of at least one polymer in one step, in which case the first layer of polymer is bound to the support material and the polymer A second layer of the polymer is bonded to the first layer and, where appropriate, a further layer of polymer in each case is bonded to the previous layer. Furthermore, each layer can in principle also contain one type of polymer or two or more different polymers.

In a further aspect, according to (ii), the solution of at least one polymer is contacted with the support material under reaction conditions under which the solution of at least one polymer is present under theta conditions. In this embodiment, the application of the at least one polymer to the support material is very particularly preferably carried out while the solution is in contact with the support material. Regarding the "theta condition", M. Yamakawa, Modern T
heory of Polymer Solutions, Harper & Row, New York (1971), pp. 72 See below.

In the above method, it is preferred that in the first step a layer of at least one polymer is applied to the support material and in the second step this second layer is applied to the first layer,
Also, if appropriate, it is preferable to apply the third layer to the second layer in the third step, and so on. See the detailed discussion above for suitable application methods.

The term “binding” as used for the present invention is at least 1
One polymer interacts with the support material and / or with the polymer layer already applied to the support material, if appropriate, or with the polymer layer applied to the polymer layer, if appropriate. All reversible covalent interactions, which can
It refers to irreversible covalent and non-covalent interactions.

The non-covalent interactions that can occur with the first polymer with respect to the support material and / or with the second polymer, which may be the same as or different from the first polymer, are in particular: hydrogen bonds; Child interaction; -van der Waals interaction; -hydrophobic interaction; -charge transfer interaction, such as pi-pi interaction; -ionic interaction; -coordination bond to transition metal, for example-of these interactions It is a combination.

Thus, in the method according to the invention, it is possible to use, for example, virtually all polymers which are capable of producing said non-covalent interactions. In this regard, the functional groups, through which the polymer gives rise to at least one of these non-covalent interactions via at least one functional group, are present in the polymer strand itself or / and on at least one side of the polymer strand. It is especially considered to be present in the chain.

Thus, the term “functional group” as used for the present invention refers not only to non-covalent interactions, but to all reversible covalent interactions or non-reversible covalent interactions that can occur. Contains chemical structure. The term functional group comprises in particular hydrocarbon chains and other structural units in which van der Waals interactions can occur.

Reversible covalent interactions include, for example, inter alia, bonds via disulfide bridges or bonds via labile esters or imines, such as via Schiff bases or enamines, among others.

In principle, any polymer capable of producing these interactions can be used in the method according to the invention. They can be commercially available polymers or other polymers specially prepared for the method according to the invention. In the latter embodiment, it is specifically contemplated to derivatize a commercially available polymer with the necessary side groups to generate the desired interaction. Polymers can also be prepared from suitable monomers such that the polymer strands, and / or the side chains of the polymers, contain those functional groups that can initiate the desired interactions.

In the method according to the invention, when one or more polymers are first derivatized and then used in the method according to the invention, the derivatization can be carried out by all methods known in the art. . In this regard, DE-A 198 55.
See 173.8. Prior art is cited therein.

Another possibility for derivatizing polymers is the polymer-like reaction of functionalized polymers with derivatized compounds. In a preferred aspect, there is provided in a method according to the invention a derivatized polymer prepared by reacting a polymer having at least one functional group with at least one activating reagent or derivative of an activating reagent. Is possible. The reaction can be a homogeneous reaction or a heterogeneous reaction, preferably a homogeneous reaction.

In this case, usually the activating reagent is such that at least one functional group of the polymer reacts with the activating reagent during the reaction, so that the reactivity of the polymer is enhanced in the subsequent reaction with the derivatizing reagent. Selected to be done.

Within this aspect of the method according to the invention, a polymer having at least one functional group is provided with at least one activated and / or at least one non-activated derivatizing reagent and / or Or at the same time with the activation reagent, ie
The reaction can be performed by the method of "one-pot reaction".

This reaction of an activated polymer having at least one functional group with a derivatizing reagent allows the desired group to be introduced into the polymer. If this reaction involved the reaction of the polymer with a different activating reagent, these activated functional groups may have different reactivities for one or more derivatizing reagents. Thus, it is conceivable within the scope of the method according to the invention to selectively derivatize the functional groups in this way. In this respect, the term "selective" refers to those activating functional groups whose reaction with a derivatizing reagent for subsequent derivatization is activated by one of these two activating reagents. Polymers having, for example, two or more different functional groups, as occurs in principle exclusively on the activated functional group (s) and on the activated functional group (s) that are more reactive with the derivatizing reagent. Is reacted with, for example, two different activating reagents.

Further, in the method according to the present invention, the activating reagent is reacted with the derivatizing reagent before reacting with the polymer having at least one functional group, and then the reaction product is reacted with at least one functional group. It can also be reacted with a polymer having groups.

Another possible embodiment of the invention consists of reacting a polymer bearing at least one functional group with various products resulting from the reaction of an activating reagent with a derivatizing reagent. Thus, for example, a mixture of compounds can be reacted with a polymer. The mixture comprises the reaction product of an activating reagent and two or more different derivatizing reagents. Mixtures containing the reaction products of derivatizing reagents and two or more different activating reagents are also contemplated. Of course, if desired, a mixture containing the reaction products of two or more different activating reagents and two or more different derivatizing reagents can be used. It is, of course, also within the scope of the present invention to react the various reaction products of the activating reagent and the derivatizing reagent with the polymer having at least one functional group alone in the desired order, not as a mixture. You can also

All activating reagents known from the literature can be used as activating reagents. A summary of the entire series of activating reagents that can be used to activate various functional groups is provided, for example, in P. Mohr, M, cited above, which is fully incorporated by reference in the context of this patent application. . Holtzhauer, G. Kaiser. In this regard, particular mention may be made of chloroformates and chloroformates having electron withdrawing groups.

[0045]   In particular, the invention provides an activating reagent with the following structure (I):

[0046]

[Chemical 1]

Wherein R ₁ and R ₂ are the same or different and can be straight chains, branched chains, or can be bridged to form carbocycles or heterocycles, Also, the activating reagent or the derivative of the activating reagent is selected from the compounds of (which are selected such that they can react in a homogeneous phase with a polymer having at least one functional group).

In this respect, R ₁ and R ₂ can be, for example, cycloalkyl groups, cycloalkenyl groups, alkyl groups, aryl groups or aralkyl groups having up to 30 carbon atoms.

[0049]   In a preferred embodiment, the present invention provides an activating reagent with the following structure (I ′)

[0050]

[Chemical 2]

Wherein R ₃ to R ₁₀ can be the same or different and are hydrogen, a linear or branched alkyl group having 30 or less carbon atoms, an aryl group, a cycloalkyl Groups, heterocyclic groups and aralkyl groups, or other plural R ₃ ~
R ₁₀ can in turn be bridged to form carbocycles or heterocycles and is chosen such that the activating reagent or derivative of the activating reagent can react in the homogeneous phase with a polymer having at least one functional group. It is a method of deriving from the compound.

[0052]   Furthermore, the present invention provides that the activation reagent has the following structure (II):

[0053]

[Chemical 3]

(Wherein R ₃ to R ₁₀ are as defined above). In a likewise preferred embodiment, the present invention is (wherein, R ₃ ~ R _{1 0} is hydrogen) The above structure (II) is a method of inducing the activation reagent from a compound represented by the.

The compounds having structures (I), (I ′) and (II) can be prepared by all conventional methods known in the art. Examples of said methods for ONB-Cl are given, for example, in P. Henklein et al., Z. Chem. 9 (1986), pp. 329 et seq.

In principle, the activating reagent or a derivative of the activating reagent described above can react with any polymer having at least one functional group which reacts with the activating reagent.

The polymers which are particularly preferably used in the process according to the invention have, as at least one functional group, a group having at least one nucleophilic unit. Particularly preferred and to be mentioned are functional groups of polymers having at least one functional group, in particular OH groups, optionally substituted amino groups, SH groups, OSO ₃ H groups, SO ₃ H groups, OPO ₃ H ₂ Group, OPO ₃ HR ₁₁ group, PO ₃ H ₂ group, PO ₃ HR ₁₁ group,
COOH groups, and mixtures thereof or two or more thereof, wherein R ₁₁ is the activating reagent or the derivative of the activating reagent in the homogeneous phase and / or the heterogeneous phase, respectively.
It is selected so that it can react with a polymer having at least one functional group. The polymer having at least one functional group can also include other polar groups such as, for example, -CN.

Both natural and artificial polymers can be used as polymers having at least one functional group. A possible limitation with respect to the choice of polymer arises only due to the fact that for the purposes of the invention the reaction of the polymer takes place in homogeneous phase, for which derivatized polymers are used.

For the purposes of the present invention, the term “polymer” likewise comprises, of course, the relatively high molecular weight compounds which are referred to in polymer chemistry as “oligomers”. Possible polymers with at least one functional group are in particular: -polysaccharides such as cellulose, amylose and dextran; -oligosaccharides such as cyclodextrins; -chitosan; -polyvinyl alcohol, polythreonine, polyserine; -Polyethyleneimine, polyallylamine, polyvinylamine, polyvinylimidazole, polyaniline, polypyrrole, poly-lysine; -poly (female) acrylic acid (ester), polyitaconic acid, poly-aspartic acid; -poly-cysteine, but specific It is not limited to these polymers.

Not only homopolymers, but also copolymers, in particular block and random copolymers, are likewise suitable in principle for use in the process according to the invention. In this regard, said 2 having an unfunctionalizable portion
One must mention a class of copolymers such as co-styrene or co-ethylene, or other copolymers such as co-pyrrolidone.

When derivatizing a polymer in the homogeneous liquid phase by the method according to the invention, use mixed functional polymers or other prederivatized polymers to obtain optimum solubility Is preferred.

[0062]   Examples of them are:   -Partially or fully alkylated or acrylated cellulose;   -Polyvinyl acetate / polyvinyl alcohol;   -Polyvinyl ether / polyvinyl alcohol;   -N-butylpolyvinylamine / polyvinylamine Is mentioned.

It is also possible to use polymer / copolymer mixtures. In this respect, all suitable polymer / copolymer mixtures can be used, for example the mixtures of polymers and copolymers already mentioned above, in particular: -poly (acrylic acid) -co-vinyl acetate; -polyvinyl alcohol-co- Ethylene; -polyoxymethylene-co-ethylene; -modified polystyrene, such as copolymers of styrene and (meth) acrylic acid (ester);-copolymers of polyvinylpyrrolidone and poly (meth) acrylate.

Of course, all of the above-mentioned polymers or / and copolymers or mixtures thereof may be used, as described within the scope of this application, with at least one support material used in the process according to the invention, or / And non-derivatized form in the process according to the invention, as long as it is ensured that covalent or / and non-covalent interactions with at least one other polymer can occur. it can.

As described above, the polymer having at least one functional group is treated with an activating reagent,
For example, when reacting with a compound of structure (II), the reaction product can be reacted with a derivatizing reagent, also as described above.

All reagents which can react with the activated polymer and lead directly or indirectly to the desired derivatized polymer can in principle be used for this purpose. Particularly in the method according to the present invention, the compound used as the derivatizing reagent is a compound having at least one nucleophilic group.

The derivatizing reagent used has, for example, the general composition HY-R ₁₂ . In the above formula, Y is, for example, O, NH, NR ₁₃ or S, and R ₁₂ and R ₁₃ can generally be selected without limitation. They are, for example, optionally appropriately substituted alkyl or aryl groups.

Additionally, the activated polymer can be reacted with a nucleophilic chiral compound. Examples of the chiral nucleophilic compound include: borneol, (−)-menthol, (−)-ephedrine, α-phenylethylamine, adrenaline, and dopamine.

Another possibility is to react the activated polymer with a monofunctional or multifunctional alcohol or thiol containing amino groups in the process according to the invention. Polymers containing at least one functional group, such as ONB-
When activated with Cl, monoalcohols or polyalcohols containing amino groups or monothiols or polythiols containing amino groups react selectively with amino groups. The OH or SH groups thus introduced into the polymer are then reactivated in a separate step, for example with one of the activating reagents described above, to functionalize the alcohol or thiol used first. Depending on valency, chains can be extended and branched.

In another aspect of the method according to the invention already described above, a polymer having at least one functional group is reacted with an activated derivatizing reagent. The activated derivatization reagent is obtained by reacting the activation reagent with the derivatization reagent.

Activated derivatives of amines, alcohols, thiols, carboxylic acids, sulphonic acids, sulphates, phosphates or phosphonic acids are preferably reacted with polymers having at least one functional group in the process according to the invention. .
In a preferred embodiment, the resulting compound is reactivated with ONB-Cl.

Thus, these activated derivatizing reagents, which can be reacted with polymers having at least one functional group, are especially of the general formulas (III) to (IX):

[0073]

[Chemical 4]

[0074]

[Chemical 5]

[0075]

[Chemical 6]

[0076]

[Chemical 7]

[0077]

[Chemical 8]

[0078]

[Chemical 9]

[0079]

[Chemical 10]

With In the above formula, R ₃ to R ₁₀ are as defined above, and R _{14 to} R ₂₁ are generally not limited, and may, for example, show chirality,
It is selected in the process according to the invention such that the reaction with the polymer having at least one functional group can take place in homogeneous phase. In this regard, the substituent R ₁₄ ~ R ₂₁ is usually selected according to the desired interaction with the substrate. Furthermore, R ₁₄ ~ R ₂₁ can be the same or different and can be hydrogen, a straight or branched chain alkyl, aryl or aralkyl group having up to 30 carbon atoms, or a hetero group. It can be a corresponding group having atoms.

Similarly, polyfunctional amines, alcohols, thiols, carboxylic acids, sulfonic acids, sulphates, phosphates or phosphonic acids are reacted with activating reagents, the product of the reaction having at least one functional group. It can also be reacted with a polymer. In particular, polyol is mentioned.

Of course, it is also conceivable to activate derivatizing reagents having two or more different types of the abovementioned functional groups and to react them with polymers having at least one functional group. In this regard, examples include amino alcohols in particular.

The polyfunctional derivatizing reagents described above can be partially or completely activated with activating reagents selectively for the purposes of the invention and reacted with polymers having at least one functional group.

Reacting a polymer having at least one functional group with an activated derivatizing reagent and reacting a polymer having at least one functional group with an activating reagent according to the method according to the present invention; Both, by reacting the product with a derivatizing reagent, polymer derivatives with a wide variety of spatial arrangements can be prepared.

In a likewise preferred embodiment, the invention is a derivative of the type discussed herein, which has at least one receptor group with a binding unit that determines the binding of a biological substrate. is there.

In that case, said derivative prepared to be compatible with the biological substrate is, for example:
It has suitable receptor groups that can participate in binding and can also have naturally occurring structures or parts of said structures that can then interact with biological substrates. In this regard, groups of enzymes, amino groups, peptides, sugars, amino sugars, sugar acids and oligosaccharides and their derivatives are mentioned in particular. Regarding the above-mentioned receptor groups, the naturally occurring principle relating to the binding between the receptor and the substrate
) Is retained, and as a result, this aspect may lead to, for example, synthases, binding domains of antibodies or other physiological epitopes. In this respect, as mentioned above, derivatives of polymers having at least three functional groups are particularly preferred for the present invention, in which case at least one receptor group is an amino acid residue or an amino acid derivative residue. . Possible amino acids are, for example: -amino acids with aliphatic groups, such as glycine, alanine, valine, leucine, isoleucine; -amino acids with aliphatic side chains containing one or more hydroxyl groups, such as serine, threonine; Amino acids having aromatic side chains, such as phenylalanine, tyrosine, tryptophan; Amino acids containing basic side chains, such as lysine, arginine, histidine; Amino acids having acidic side chains, such as aspartic acid, glutamic acid; Having amino acids. For example asparagine, glutamine; amino acids with sulfur-containing side chains, for example cysteine, methionine; modified amino acids, for example hydroxyproline, γ-carboxy-glutamine,
O-phosphoserine; -derivatives of the above amino acids, or optionally other amino acids, for example by one alkyl group or aryl group, which may optionally be suitably substituted, such as with respect to one carboxyl group, or where appropriate. It is an amino acid esterified with multiple carboxyl groups.

Instead of amino acids, it is also conceivable to use one or more dipeptides or oligopeptides, in particular homopeptides composed exclusively of the same amino acid. Examples of the dipeptide include hippuric acid. In addition, beta, gamma or other structural isomer amino acids, and peptides derived therefrom, such as depsipeptides, can also be used.

The activating reagents which can be very commonly used in the method according to the invention have the general structure (X)

[0089]

[Chemical 11]

[Wherein R ₀ is a halogen atom, or

[0091]

[Chemical 12]

A group (X ′) represented by and R ₁ ′, R ₂ ′; R ₁ ″ and R ₂ ″ are the same or different and have hydrogen, 30 or less carbon atoms. A straight-chain or branched-chain alkyl group, aryl group, cycloalkyl group, heterocyclic group or aralkyl group, or any of R ₁ ′ and R ₂ ′ or R ₁ ″ and R ₂ ″, or R _{Both 1} ′ and R ₂ ′ and R ₁ ″ and R ₂ ″ combine to form at least one carbocycle or at least one heterocycle, or at least one carbocycle and at least one heterocycle] Is a compound represented by. In this connection, the compounds which must be mentioned in particular by way of example are the structures (X1) to (X39) below:

[0093]

[Chemical 13]

[0094]

[Chemical 14]

[0095]

[Chemical 15]

[0096]

[Chemical 16]

[0097]

[Chemical 17]

[0098]

[Chemical 18]

[0099]

[Chemical 19]

[0100]

[Chemical 20]

[0101]

[Chemical 21]

[0102]

[Chemical formula 22]

[0103]

[Chemical formula 23]

[0104]

[Chemical formula 24]

[0105]

[Chemical 25]

[0106]

[Chemical formula 26]

[0107]

[Chemical 27]

[0108]

[Chemical 28]

[0109]

[Chemical 29]

[0110]

[Chemical 30]

[0111]

[Chemical 31]

[0112]

[Chemical 32]

[0113]

[Chemical 33]

[0114]

[Chemical 34]

[0115]

[Chemical 35]

[0116]

[Chemical 36]

[0117]

[Chemical 37]

[0118]

[Chemical 38]

[0119]

[Chemical Formula 39]

[0120]

[Chemical 40]

[0121]

[Chemical 41]

[0122]

[Chemical 42]

[0123]

[Chemical 43]

[0124]

[Chemical 44]

[0125]

[Chemical formula 45]

[0126]

[Chemical formula 46]

[0127]

[Chemical 47]

[0128]

[Chemical 48]

[0129]

[Chemical 49]

[0130]

[Chemical 50]

[0131]

[Chemical 51]

Embedded image wherein R ″ is hydrogen or a linear or branched optionally substituted alkyl, aryl or aralkyl group having up to 30 carbon atoms. It is a compound.

Within the scope of the present invention, in particular during derivatization, the derivative in relation to its chemical properties, in particular for the purpose of subsequent attachment of the polymer to a support material or / and another polymer or / and another polymer layer. A chemical reagent can be added. In particular, the derivatizing reagent can include groups that are selective or specific for covalent and / or non-covalent interactions.

In a further embodiment of the method according to the invention, it is also possible to prepare the polymer from suitable monomers by suitable methods, which polymer is then, if appropriate, derivatized according to the method described above. can do.

Suitable polymers having the necessary functional groups for attachment to the support material or attachment to the polymer layer are in principle prepared appropriately by any method which leads to this polymer.

Particularly preferably, at least one functional group of the first low molecular weight compound having at least two functional groups has at least two functional groups which may be the same as or different from the first low molecular weight compound. The polymer is prepared by using the method of preparing a condensation compound by reacting with at least one functional group of one other second low molecular weight compound to obtain the condensation compound. The method is such that at least one of the functional groups contained in this reaction is reacted with the structure (X
)

[0137]

[Chemical 52]

It is characterized by being activated by reacting with a compound represented by: In a particularly preferred embodiment, the first layer applied to the at least one support material is bonded such that non-covalent interactions of the type described above occur between the polymer layer and the support material. .

In another preferred embodiment of the method according to the invention, each polymer layer, which in turn is preferably used in one step, is linked together by covalent crosslinks. Thus, the present invention provides for non-covalent interaction of at least one polymer with a support material to bond at least one layer of at least one polymer to the support material and then covalently crosslink. By this, at least one further layer of at least one polymer is applied.

With regard to the covalent crosslinks which are particularly preferably formed between the respective polymer layers, as mentioned above, possible interactions are all suitable reversible covalent interactions and / or irreversible covalent interactions. Is.

With regard to reversible covalent interactions, mention may in particular be made, for example, by disulphide bridge bonds or bonds via labile esters or imines, such as via Schiff bases or enamines. When at least one basic group and at least one acidic group interact with each other, the occurrence of non-covalent interactions by changing pH can be mentioned as an example.

Regarding covalent interactions, in particular, in principle ester bonds, amide bonds, carbonate bonds, hydrazide bonds, urethane bonds or urea bonds or thio analogue bonds or nitrogen-homologous linkages are formed in principle. Is possible.

The functional groups present in the polymer strands of the at least one polymer used or / and in at least one side chain of the at least one polymer are such that at least one functional group of the support material or another polymer (the The functional groups, in turn, are present in the polymer strand or / and in at least one side chain of this polymer) so as to interact with the support material and the first polymer layer or with each polymer layer. In between, covalent or / and non-covalent interactions may occur.

In a further preferred embodiment of the invention, at least one cross-linking reagent is used to attach the first polymer layer to the support material and / or to attach the further polymer layer (each polymer layer). Are bonded to the previously applied polymer layer). For the purposes of the present invention, a "crosslinking reagent
The term "gent)" refers to a support material and at least one polymer, or to at least two polymers which may be the same or different from each other, non-covalently and / or reversibly covalently or / and All compounds having at least two functional groups which interact irreversibly covalently are meant.

The cross-linking reagents considered are in principle the appropriate compounds in the chair known in the art. Thus, cross-linking can occur, for example, reversibly covalently, irreversibly covalently, or non-covalently. In the case of cross-linking by non-covalent bond, for example, cross-linking by ionic interaction or cross-linking by charge transfer interaction can be mentioned. These types of cross-linking methods and reagents are described 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). Possible non-covalent interactions which may be mentioned in this connection are all non-covalent interactions already detailed above. The same applies to the reversible covalent interactions described above by way of example as well. Even then, all suitable non-covalent interactions are also conceivable for the cross-linking reagents.

Similarly, where, for example, two basic groups of polyallylamine are cross-linked together, a dibasic acid, such as glutaric acid, is added, or two acidic groups of, for example, polyacrylic acid are cross-linked together. In some cases, non-covalent cross-linking can occur if a diacid base such as ethylenediamine is added. Similarly, by way of example, non-covalent cross-links can be formed by complexing metal ions or by metal complexes having free coordination sites. With respect to non-covalent cross-linking, very generally one can mention all the possible interactions already explained above.

Reversible covalent crosslinks can be formed, for example, by forming a sulfur-sulfur bond to provide a disulfide bridge between two groups attached to one or more polymer strands, or by adding a Schiff base. It can be achieved by forming. Crosslinking by ionic interaction can be formed, for example, by two groups, one of the two groups having a quaternary ammonium ion as a structural unit and the other having a quaternary ammonium ion as a structural unit, for example: It has COO ⁻ or —SO ₃ ⁻ .

Cross-linking by hydrogen bonding is, for example, between two complementary base pairs, for example the following structure:

[0149]

[Chemical 53]

It can be formed by. Non-covalently cross-linked polymers can very commonly have complementary structures with respect to the cross-linking sites, examples of complementary structural units are acids / triamines or uracils / melamines. In the case of non-covalent cross-linking, the cross-linking reagent can also be complementary to the cross-linking sites on the polymer strand. Examples are amino groups on polymer strands and dicarboxylic acids as cross-linking reagents.

If activation of at least one of the functional groups involved in the crosslinking is necessary for the method according to the invention in connection with the crosslinking step, activation by all methods in the prior art is essential. It is possible to think. In particular, the functional groups can be activated by the methods detailed above for polymer activation and derivatization.

Crosslinking reagents which are capable of producing irreversible covalent crosslinks to be mentioned are, in particular, difunctional or polyfunctional compounds such as diols, diamines or dicarboxylic acids. These require, for example, the reaction of a bifunctional cross-linking agent with an activated polymer derivative, or the reaction of at least a bi-functional activated cross-linking reagent with a non-activated polymer derivative. And

If the cross-linking in the method according to the invention takes place by using at least one cross-linking reagent, this cross-linking reagent may in particular comprise at least one functional group of the first low molecular weight compound having at least two functional groups. , At least one other second low molecular weight compound having at least two functional groups (the second low molecular weight compound may be the same as or different from the first low molecular weight compound), It can be a condensation compound prepared by reacting to give a condensation compound, characterized in that at least one of the functional groups involved in the reaction is, prior to the reaction, a structure (defined above). X)

[0154]

[Chemical 54]

It is a point activated by reacting with the compound represented by. As examples of (activated) cross-linking reagents, the following structures (XI ₁ ) to (XI ₁₇ ):

[0156]

[Chemical 55]

[0157]

[Chemical 56]

[0158]

[Chemical 57]

[0159]

[Chemical 58]

[0160]

[Chemical 59]

[0161]

[Chemical 60]

[0162]

[Chemical formula 61]

[0163]

[Chemical formula 62]

[0164]

[Chemical formula 63]

[0165]

[Chemical 64]

[0166]

[Chemical 65]

[0167]

[Chemical formula 66]

[0168]

[Chemical formula 67]

[0169]

[Chemical 68]

[0170]

[Chemical 69]

[0171]

[Chemical 70]

[0172]

[Chemical 71]

Examples thereof include compounds represented by: Examples of crosslinking reagents used according to the invention are dimeric crosslinking agents prepared from phenylalanine and leucine by the method described above, as follows:

[0174]

[Chemical 72]

Examples of the preparation of the condensation compound used as the crosslinking reagent in the method according to the present invention include the following reaction pathways (A) and (B), in which case:
The BNO group has the following structural unit (XII):

[0176]

[Chemical formula 73]

[0177] Is.   Reaction pathway (A):

[0178]

[Chemical 74]

[0179]   Reaction route (B):

[0180]

[Chemical 75]

Thus, suitable support materials are all materials which are capable of undergoing the above-mentioned covalent or / and non-covalent interactions with at least one polymer.

In particular, the support material is considered to be in the form of a solution or colloidal solution or suspension. In this respect, the support material is specially prepared by the method according to the invention,
It is also considered to be the polymer or polymer network described below.

If the support material is a solid, its surface can be flat, for example a plate of glass or metal, or it can be curved or embedded in a porous body. It can be tubular or sponge-like, for example zeolites, silica gel or cellulose beads. Furthermore, the support material can be a natural or synthetic material. Examples include in particular gelatin, collagen or agarose.

In a preferred embodiment of the invention, the first polymer layer applied to the support material is
It is bound to the support material via non-covalent interactions without a cross-linking agent, and then the polymer layers are cross-linked together by covalent cross-linking with at least one cross-linking reagent.

With respect to cross-linking reagents, the use of non-selective / non-specific or / and selective / specific cross-linking reagents is contemplated for the present invention. For the purposes of the present invention, the term "selective / specific cross-linking reagent" has two or more different functional groups, of which at least one group is different from the other under certain reaction conditions. At least 1
It is meant to react preferentially with further polymer functional groups or support materials as compared to one group. Also, the term is a functional group having two or more identical functional groups, but different functional groups in a chemical environment and / or stereochemically different configurations, and thus at least one functional group of them. The group also encloses a cross-linking reagent that reacts preferentially with further polymer functional groups or support materials under the given reaction conditions. Furthermore, the term also refers to activation groups having functional groups that are the same or different from each other, and thus differ in selectivity / specificity because some of the functional groups are activated with activating reagents by the method described above. Also includes reagents. Of course, in compounds having two or more different functional groups, one functional group or other functional groups can be activated with different reactive groups, where appropriate, and as a result The reactivity of some of the functional groups activated in any case differs from the reactivity of other functional groups activated in appropriate cases. Of course, as well, combinations or two or more of the above effects which act on the selectivity / specificity are likewise conceivable.

Thus, the present invention is directed to or by at least one non-specific or non-selective cross-linking reagent or at least one specific or selective cross-linking reagent.
It also relates to the above method, characterized in that a mixture of one or more causes covalent cross-linking.

With regard to the use of these cross-linking reagents, it is conceivable to manage the process in any suitable manner for applying at least one layer of at least one polymer to a support material according to the invention. The application is preferably carried out stepwise, as explained.

In the method according to the invention, a polymeric layer is applied to a support material, or a support material, or a polymer layer applied to a polymer layer, using a selective / specific cross-linking reagent. If there is a step of applying to the layer, in a procedure for this in a preferred embodiment the starting material on which the polymeric layer is applied is at least one crosslinking reagent and at least one applied as polymeric layer.
And a solution containing two polymers. The reaction conditions selected in this case are those under which the crosslinking reagent selectively reacts with the starting materials or with the polymer to be applied. By changing the reaction conditions, for example by reacting the reaction product of the polymer to be applied with the cross-linking reagent, via at least one functional group of the cross-linking reagent, with the starting material, or, for example, the starting material Cross-linking occurs in the next step by reacting the reaction product of the and the cross-linking reagent with the polymer to be applied.

When cross-linking a support material and a polymer, or a polymer and a polymer together via functional groups having the same or similar reactivity, a selective / specific cross-linking reagent, preferably a method according to the invention, is used. Used in. Selective / specific activation reagents include:
Activated with different reactive groups or only some of its functional groups are activated, for example polybasic carboxylic acids, diamines or diols, among others. Further examples include, in particular, compounds having at least two different functional groups, such as in particular amino acids, hydroxy acids or amino alcohols, where the different functional groups differ in their reactivity under the given reaction conditions. Of course, in compounds having two or more different functional groups, one functional group or several other functional groups can be activated with different reactive groups, where appropriate, so that As explained, the reactivity of some of the functional groups activated when appropriate differs from the reactivity of other functional groups activated when appropriate.

When using a non-selective / non-specific cross-linking reagent in the method according to the invention,
Special mention should be made of the two preferred ways of managing the method. Similar to the above method controls of preventing intramolecular cross-linking and applying the polymer layer to the support material or to another polymer layer, these preferred ways of controlling the method are intramolecular within the polymer layer. Cross-linking or / and inter-molecular cross-linking is substantially prevented and is done in such a way that the polymer layer is applied. A small degree of cross-linking within the polymer layer can contribute to further stabilization of the polymer network.

The invention thus provides: (aa) in a first step, reacting at least one cross-linking reagent with the most recently applied layer consisting of at least one polymer layer, and then in a further step At least one of the reaction products by contacting the reaction products with a solution containing at least one polymer and then reacting at least one polymer present in the solution with the reaction products. Applying at least one further layer of one polymer, or (bb) the most recently applied layer of at least one crosslinking reagent of at least one polymer and at least one polymer present in solution. At least one solution containing at least one cross-linking reagent and at least one polymer under reaction conditions that react with both At least 1 characterized in that the cross-linking is carried out by contacting with the most recently applied layer of polymer of (1) or (cc) in a suitable manner by combining the methods according to (aa) and (bb). It also relates to the above method using two non-specific or non-selective cross-linking reagents.

In a very particularly preferred embodiment, the method (aa) is such that the cross-linking reagent is evenly and randomly distributed over the polymer layer already present and the reaction of the cross-linking reagent with the polymer layer already present is substantially. It is carried out in such a way that the crosslinking reagent is brought into contact with the most recently applied polymer layer at a temperature which does not occur normally. The temperature used for this is usually 0 ° C to -70 ° C.

In this preferred embodiment of the invention, the reaction of the cross-linking reagent with the existing polymer layer is substantially effected until the cross-linking reagent is evenly and randomly distributed over the already existing polymer layer. Care should be taken in selecting other reaction conditions, such as pH, solvent properties, concentration of cross-linking reagent in the solvent, so as not to occur.

By appropriately changing the reaction conditions, in the next step, the cross-linking reagent mainly contains 1
A method of reacting through one or more functional groups and at least one functional group of the cross-linking reagent (through which cross-linking with the next polymer layer occurs) does not react with an already existing polymer layer. At this point, the randomly and evenly distributed cross-linking reagent is reacted with the already existing polymer layer. This reaction usually takes place once again at a low temperature of 0-10 ° C in principle. This reaction is further advantageously carried out by the use of short-chain cross-linking reagents and / or immobilisation of the polymer layer. In particular, possible methods of inducing this crosslinking are, for example, the use of ultrasonic crosslinking or photochemical crosslinking.

Also, of course, with respect to a suitable crosslinking reagent, or / and with respect to a suitable polymer layer already present, by changing the pH or / and the solvent or / and by adding a modifier (of course It is also conceivable to combine some or all of the methods), and control of the reaction can be controlled.

In this respect, it is possible to refer to particular methods which can be used as already explained above in order to first inhibit the polymer binding and then to induce it in a further step.

According to method (aa), in a first step, a solution containing at least one polymer to be applied as the next polymer layer is contacted with a reaction product of a crosslinking reagent and a polymer layer already present. Let The reaction conditions are then such that the reaction between the unreacted functional groups of the crosslinking reagent bound to the already existing polymer layer and the polymer applied as the next polymer layer is particularly favorable. Change. In this regard, it is also possible to influence the reaction conditions by adding a solution containing at least one polymer which is applied as the next polymer layer, so that no further modification of the reaction conditions is required.

Also for this step of applying the next polymer layer, it can be used as already explained above in order to first inhibit the polymer binding and then to induce it in a further step. It is also possible to refer to a specific method.

Also in a particularly preferred embodiment, there is no initial reaction, but under reaction conditions in which both the cross-linking reagent and the applied polymer are uniformly and randomly distributed over the already existing polymer layer, The method according to (bb) is carried out by contacting the most recently applied layer of at least one polymer with a solution containing at least one crosslinking reagent and at least one polymer.

As already mentioned in connection with method (aa), this contact is carried out at a low temperature, in principle at a temperature of 0 to −70 ° C., in a preferred embodiment. In this preferred embodiment of the method, the reaction of the cross-linking reagent with the existing polymer layer and the reaction of the applied polymer layer with the cross-linking reagent does not substantially occur, and the polymer applied with the cross-linking reagent is Other choices of reaction conditions such as pH, nature of the solvent, concentration of the cross-linking reagent in the solvent, or polymer applied in the solvent, so that it is evenly and randomly distributed over the already existing polymer layer. Also pay attention to the selection of concentration.

In the next step, the reaction conditions are changed such that the crosslinking reagent reacts with both the polymer layer already present and the polymer applied as the next layer. In this respect, in particular, it is conceivable that the crosslinking reagent reacts first with the already existing polymer layer and subsequently with the applied polymer to form a new polymer layer. It is likewise conceivable that the cross-linking reagent reacts simultaneously with the already existing polymer layer and the applied polymer to form a new polymer layer. A further possibility is that first the randomly evenly distributed cross-linking reagent reacts with the randomly evenly distributed polymer, and subsequently the reaction product reacts with the polymer layer already present. Then, a new polymer layer is formed. On the one hand, if the reaction between the cross-linking reagent and the already existing polymer layer, on the other hand, does not occur simultaneously with the polymer to be applied, by changing the reaction conditions, one of the reactions is first carried out, Also, other reactions can be performed by further changing the reaction conditions.

Regarding the modification of the reaction conditions, all the possibilities and combinations already described above are
Reference may be made in this connection. In particular, also with respect to this step of applying the next polymer layer, a particular method which can be used first as described above to inhibit the binding of the polymer and then in a further step to induce binding, Can be referenced. Possible ways in which cross-linking can be particularly induced are, for example, the application of ultrasonic cross-linking or photochemical cross-linking.

Application of ultrasonic crosslinking or photochemical crosslinking is, of course, in principle a method which can be used very generally for each crosslinking step carried out for the present invention. Non-selective / non-specific cross-linking reagents include, for example, difunctional epoxides, isocyanates, chlorotriazines, amidines or aldehydes. Likewise, mention should be made of succinimide-activated, particularly preferably ONB-activated and N-hydroxyphthalimide-activated compounds. In this regard, reference may be made in particular to the crosslinking reagents specifically mentioned above. In a preferred embodiment of the process according to the invention, symmetrical and in principle divalent crosslinking reagents are used, very particularly preferably activated dicarboxylic acids.

The chain length of the cross-linking reagent used in any of the method embodiments according to the present invention is generally the desired length and can be adapted to the requirements of the particular method. The chain itself can be aliphatic or aromatic or araliphatic. The chain can further include one or more functional groups that can generate covalent or non-covalent interactions.

In the case of cross-linking reagents having carbon chains, the chain length is preferably from 2 to 2 carbon atoms.
4, particularly preferably 4 to 24 carbon atoms, particularly preferably 8 carbon atoms
~ 12 pieces.

The polymer used in the method according to the invention has at least 1 part relative to the support material.
It is applied as one layer and is essentially subject only to the limitation that it is possible to generate the interactions as described above. Particularly preferably used polymer is 200
It has a molecular mass of 0 to 100,000 g / mol. In this case, the molecular mass is measured by GPC.

Thus, the present invention provides that at least one polymer comprises from 2000 g / mol to 10
It also relates to the above method, characterized in that it has a molecular mass of 0000 g / mol. In this regard, three preferred embodiments of the method according to the invention will be mentioned.

In a first aspect, at least one of the substantially unrolled structures, but with at least one contact point with the support material or / and the already applied polymer layer, at a distance as short as possible above the theta point. Apply one polymer. In this aspect, the solvent or solvent mixture in which the polymer is present in substantially unrolled form due to the solution in which the at least one polymer is dissolved and in contact with the support material or / and the polymer layer. Select. Of course, other reaction conditions such as temperature, pressure or pH
The unrolled morphology of the polymer can also be aided by a particular choice of. In this case, it is preferably optimized between the evolution of the polymer and the maximization of the partition coefficient of the polymer. The polymers used very particularly preferably for this preferred embodiment have a molecular mass of less than about 30,000 g / mol. This embodiment favors the application of a substantially monomolecular polymer layer.

In a second aspect, the solvent or solvent mixture or other reaction conditions are chosen such that at least one polymer is present in the solution just above the theta point. This particular embodiment, which is very particularly preferred and favored by polymers having a molecular mass of more than about 30,000 g / mol, can favor the application of the polymers in loose polymer coils.

In the third aspect, the solvent or solvent mixture or other reaction conditions are selected such that at least one polymer is present in the solution just below the theta point. In this case, it is especially possible to apply nanoparticles formed from at least one polymer.

The individual cross-linking steps carried out in the method according to the invention can be carried out such that essentially any desired degree of cross-linking of the polymer layer with the further polymer layer is achieved. However, the method is preferably controlled such that the degree of cross-linking of the polymer chains cross-linked with the two other polymers is 0.5% to 25%.
The degree of crosslinking is based on the monomer units of the crosslinked polymer chains with respect to two adjacent polymer chains. The degree of crosslinking is particularly preferably 2% to 10%.

The invention thus also relates to a method as described above, characterized in that the degree of crosslinking is between 0.5% and 25%, based on the monomer units of the polymer chains crosslinked with respect to two adjacent polymer chains. Concerned.

In the above method according to the invention, the support material is provided with a polymer network having a structure consisting of two-dimensional or three-dimensional cells, for example because the polymer layers are covalently crosslinked to one another. It can be applied. The cells of the polymer network are usually formed by at least one cross-linking reagent that cross-links the two polymer layers together and also a portion of the at least one polymer forming the polymer layer. Chemical structure of at least one cross-linking reagent or at least one used
It is specifically contemplated that, according to the chemical structure of one polymer, the cell has a structure that allows the interaction of the cell with at least one templating compound. Thus, the invention also describes the above method, wherein a polymer network is formed by applying at least one polymer layer to at least one support material. In that case, the polymer network comprises one or more interaction cells in which the polymer network is capable of interacting with the at least one templating compound in a covalent or / and non-covalent manner.

At least one polymer present in at least one layer is at least 1
In a preferred embodiment, the method according to the invention is provided in such a way that the polymer network produced by application to one support material is associated with an interaction cell and adapted to at least one templating compound. Can be managed.

The invention thus provides, in addition to the aspects already described, the conformation of the polymer network resulting from the interaction and the cross-linking of at least one of the layers of at least one polymer to the support material. It also relates to the above method, characterized in that it is adapted to at least one templating compound during or after application.

The present invention also provides a method wherein a polymer structure applied to and produced on a support material is peeled from the support material and then used in an application as described in the examples below. explain.

The present invention likewise comprises the polymer network itself obtained by the above method. Thus, the invention also relates to the polymer network that can be produced by the above method.

The polymer networks which can be produced by the process according to the invention are distinguished in a particularly preferred embodiment, in particular by the fact that they are soluble but have the ability to swell.

The invention therefore also relates to the use of the process or the polymer network obtainable by the process for producing a polymer network adapted to at least one templating compound.

The polymer networks produced according to the present invention are, for example, due to their structure comprising interaction cells as described above, for example, substances are produced, converted into or converted from other substances. It can be used in a preferred embodiment in the method of separation. It is likewise conceivable to use the polymer network produced according to the invention for detecting optical, electrical or mechanical signals. If the polymer network is adapted to at least one templating compound as described above, the polymer network is very particularly suitable for these methods.

Hereinafter, the present invention will be described in more detail with reference to Examples. Example 1 Coating of silica gel SP300-15 / 30 with poly (benzyl N-allyl carbamate) with a degree of derivatization of 14%, followed by bis (N-hydroxy-5-norbornene-2,3-dicarboximide dodecanedioate). ) Crosslinking of the polymer with 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, about 117 ° C.), cooled, then diluted with dichloromethane (100 mL, 1.18 mol) and pyridine (112 mL, 1.4).
2 mol) to reduce the solubility of the polymer. Next, a few drops of glacial acetic acid were added to remove turbidity. Silica gel 300Å, 20 μm (Daisogel SP 300-15 /
30) (10.02 g) was added and the mixture was stirred on a shaker for 30 minutes,
After suction filtration using a glass frit, it was washed with dichloromethane (4 × 50 mL).

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

For the second coating, poly (benzyl N-) with a degree of derivatization of 14% (1.60 g)
Allyl carbamate) in boiling glacial acetic acid (100 mL, about 117 ° C.),
After cooling, it was diluted with dichloromethane (100 mL, 1.18 mol) and mixed with pyridine (100 mL, 1.26 mol) to reduce the solubility of the polymer. Then dimethylaminopyridine (DMAP, 80 mg, 0.65 mmol) and additional pyridine (12 mL, 0.15 mmol) were added. A few drops of glacial acetic acid were added to remove turbidity. After adding silica gel coated as described above and reacted with a crosslinker, the mixture was stirred for 30 minutes on a shaker, suction filtered through a glass frit and washed with dichloromethane (4 × 50 mL).

The coated silica gel was further crosslinked as described above and then coated with a third polymer layer according to the second method. Swell the batch in dimethylformamide in a frit (30 minutes)
. The remaining activated crosslinker groups were quenched by slow passage through a solution of diethylamine (2 mL, 1.42 g, 19.41 mmol) in DMF (40 mL). The batch was washed four more times with the filtrate solution in order to completely quench it. Next, tetrahydrofuran (60 ° C., HPLC grade, 4 × 50 mL)
And washed with dichloromethane (4 x 50 mL) and sucked dry.

The coated silica gel is mixed with glacial acetic acid (100 mL), the resulting suspension is heated to boiling, suction filtered and washed with dichloromethane (5 × 50 mL),
It was dried (110 ° C., 16 hours) and screened with a 45 μm screen.

The final weight was 9.4 g. Example 2 Silica gel SP300-15 / 30 stepwise coated with poly (benzyl N-allyl carbamate) with a degree of derivatization of 14%, followed by bis (N-dodecanedioate).
Crosslinking of the Polymer with Hydroxy-5-norbornene-2,3-dicarboximide) (Alternative Variant) Poly (benzyl N-allyl carbamate) with a Derivatization Degree of 14% (1.60 g)
Was dissolved in 100 mL of glacial acetic acid at 50 ° C. for 30 minutes. For the polymer solution, silica gel 300Å, 20 μm (Daisogel SP 300-15 / 3
0) (10.00 g) was added and the suspension was stirred on a shaker for 3 hours. After filtration with suction through a glass frit, the residue is the following solution: dichloromethane (4 x 30 mL), pyridine (0.7 mL) in dichloromethane (30 mL).
Washed with dichloromethane (4 x 30 mL). Then it was dried in vacuum at 50 ° C.

For crosslinking, the resulting coated silica gel was treated with dodecanedioic acid bis (N-hydroxy-5-norbornene-2,3-dicarboximide) ester (100 mg, 0.18 mmol) in dichloromethane (80 mL). Triethylamine (54m
g, 0.54 mol) and the resulting suspension was evaporated to dryness in a vacuum (100 mbar, water bath 0 ° C.). The coated silica gel was
Boiled in F (40 mL), suction filtered, filtered off, washed with hot THF (3 x 40 mL) and dichloromethane (2 x 30 mL).

For further coating, poly (benzyl N-allyl carbamate) with a degree of derivatization of 14% (1.66 g) was dissolved in 100 mL of glacial acetic acid at 50 ° C. for 30 minutes and after cooling, dichloromethane ( Dilute with pyridine (100 m)
L) to reduce the solubility of the polymer. Next, dimethylaminopyridine (DMAP, 22 mg, 0.15 mmol) and 13 mL of pyridine were added. The resulting turbidity was removed by adding 3 mL of glacial acetic acid. To this solution was added the coated silica gel reacted with the crosslinker obtained above and the batch was shaken on a shaker.
Stir for 0 minutes. After suction filtration using a glass frit, the residue was taken as the following solution: THF (60 ° C., 4 × 40 mL) in dichloromethane (30 mL).
It was washed with pyridine (0.6 mL) and dichloromethane (3 x 30 mL). next,
Dried in vacuum at 50 ° C.

The procedure for cross-linking and further coating on the polymer is carried out once in each case,
Repeated in a similar fashion. At the frit, the coated silica gel was suspended in THF (10 mL). The remaining activated crosslinker groups were quenched by slowly permeating a solution of diethylamine (0.27 g, 3.7 mmol) in THF (10 mL) for 4 times. The residue was then washed with THF (60 ° C, 4x20mL) and dichloromethane (2x10mL), 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 × 20 mL). Then a solution of 0.25 mL of dichloromethane (in 15 mL) pyridine and THF (4 x 20 mL).
Washed with and dried.

By elemental analysis, the carbon content of the coated silica gel was 7.2%; this value is
This corresponds to 111 mg of polymer per 1 g of silica gel. Example 3 Coating of silica gel SP300-15 / 30 with poly (benzyl N-allyl carbamate) with a degree of derivatization of 14%, and bis (N-hydroxy-5-norbornene-2, dodecanedioate by flow method in a packed HPLC column. Cross-linking of polymer with 3-dicarboximide) ester A glass column with a diameter of 2.5 cm was loaded with silica gel 300Å, 20 μm (Daisogel).
SP 300-15 / 30) (5.00 g). Poly (benzyl N-allyl carbamate) (3.20 g) having a derivatization degree of 14% was dissolved in 200 mL of water, and 1 to 2 mL of glacial acetic acid was added thereto over 2 hours. The polymer solution was pumped through a glass column with silica gel for 24 hours. First, flush the column with air and then acetone /
Flushed with 50: 50% by volume of water (30 mL) and acetone (150 mL). According to elemental analysis, the average carbon content of the coated silica gel was 2.7%.

After washing the column with dichloromethane (50 mL), for crosslinking, bis (N-hydroxy-5-norbornene-2, terephthalate, in 50 mL dichloromethane was added.
3-Dicarboximido) ester (0.48 g, 0.97 mmol) solution 14
． 4 mL was pumped into the column for 20 hours. The amount of crosslinking agent pumped into the column is an amount corresponding to 10% crosslinking, based on the amino groups of the polymer. Then the column was washed with dichloromethane (300 mL).

For further coating, poly (benzyl N-allyl carbamate) with a degree of derivatization of 14% (3.20 g) was dissolved in 200 mL of water, whereupon glacial acetic acid 1- 2 mL was added. The polymer solution was pumped through a glass column with coated silica gel for 24 hours. The column was then flushed with air and then with acetone / water 50: 50% by volume (120 mL).

The coated silica gel was mixed with glacial acetic acid (50 mL), the suspension was heated to boiling, then suction filtered and pyridine (20 mL) was added. Filter it with suction,
It was washed with HF (60 ° C., 3 × 50 mL) and dried.

[0235]   By elemental analysis, the average carbon content of the coated silica gel was 5.0%.

─────────────────────────────────────────────────── ─── Continued front page    (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, I T, LU, MC, NL, PT, SE, TR), OA (BF , BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, G M, KE, LS, MW, MZ, SD, SL, SZ, TZ , UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, B Z, CA, CH, CN, CR, CU, CZ, DE, DK , DM, DZ, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, J P, KE, KG, KP, KR, KZ, LC, LK, LR , LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, R O, RU, SD, SE, SG, SI, SK, SL, TJ , TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW F term (reference) 4G072 AA41 CC10 GG03 HH19 JJ47                       QQ06                 4J002 AB01W AB01Y AB02X AB04W                       AB05W AD01Y AD03Y BE02W                       BE02X BE04X BG01W BG04W                       BG05W BH02W BJ00W BJ00X                       CE00W CL02W CM01W CM05W                       DJ008 DJ018 DL008 EU016                       EU017 EU026 EU027 FD147                       FD206

Claims (10)

[Claims] 1. In at least one step at least one layer of at least one polymer is bound to a support material, and in at least one further step at least one other layer of said at least one polymer. Is applied to the at least one polymer layer bonded to the support material, a method of applying at least two layers of the at least one polymer to the support material. 2. (i) contacting a solution of the at least one polymer with the support material under reaction conditions under which the at least one polymer is not bound to the support material; At least one polymer is modified so that it is bound to the support material, or (ii) under reaction conditions where a solution of the at least one polymer is present under theta conditions, The method of claim 1, wherein in at least one step comprising contacting a solution with the support material, the at least one layer of the at least one polymer is attached to the support material. . 3. The reaction conditions according to (i) are varied by: (a) changing at least one solvent, or by adding at least one other compound, to change the composition of the solution; or b) concentrating the solution so as to keep the concentration of the at least one polymer in the solution substantially constant during concentration, or (c) at least one method according to (a), and a method ( Method according to claim 2, characterized in that b) is varied by a suitable combination. 4. The binding of the at least one layer of the at least one polymer to the support material occurs by non-covalent interactions between the at least one polymer and the support material, and 4. The method according to claim 1, wherein the application of the at least one further layer of at least one polymer is carried out by covalent crosslinking. 5. The covalent cross-linking is caused by at least one non-specific or non-selective cross-linking reagent or at least one specific or selective cross-linking reagent, or a mixture of two or more thereof. The method described. 6. (aa) In a first step, the at least one cross-linking reagent is reacted with the most recently applied layer of the at least one polymer, and then:
In a further step, contacting the reaction product with a solution containing the at least one polymer, and then reacting the at least one polymer present in the solution with the reaction product, Applying to the reaction product at least one further layer of said at least one polymer, or (bb) the most recently applied layer of said at least one polymer of said at least one crosslinking reagent. And a solution comprising the at least one cross-linking reagent and the at least one polymer under reaction conditions that reacts with both the at least one polymer present in the solution and a solution comprising the at least one polymer in the immediate vicinity. Contacting with a layer applied to, or (cc) combining the methods according to (aa) and (bb) in a suitable manner. Therefore and performing crosslinking, at least one non-specific or method of claim 5, wherein the use of non-selective crosslinking reagent. 7. The at least one polymer is from 2000 to 100,000.
The method according to claim 1, having a molecular mass of g / mol. 8. The method according to claim 3, wherein the degree of crosslinking is 0.5% to 25% based on the monomer units of the polymer chains crosslinked with respect to two adjacent polymer chains. The method described in. 9. A polymer network that can be produced by the method according to any one of claims 1-8. 10. Use of the process according to any one of claims 1 to 8 or use of the polymer network according to claim 9 for producing a polymer network adapted to at least one templating compound. .