DE102014118901A1 - Biodegradable, applicable in medical technology or biology hybrid polymers and starting silanes for this purpose - Google Patents

Abstract

The invention relates to a silane of the formula (1) R 1 aSiR 4 -a (1) where R 1 is an organic substituent bonded to the silicon via oxygen and having a hydrocarbon-containing chain represented by at least two C (O) O groups is interrupted, wherein in the individual, formed by interruptions hydrocarbon units within this chain a maximum of 8 carbon atoms follow each other and each of the silicon atom remote end of the hydrocarbon-containing chain has an organically polymerizable group, R is a hydrolytically condensable group or hydroxy and a 1, 2 , 3 or 4, as well as a silane mixture of different silanes of the formula (1), wherein different silanes of the mixture have the same substituent R1 and different values for the subscript a, the average value for a in the mixture being about 2. Furthermore, the invention relates to an organically modified, optionally organically polymerized silicic acid polycondensate, formed by hydrolytic condensation of a silane or silane mixture as indicated above and optionally polymerized by subsequent organic polymerization of the organically polymerizable groups. The organically modified, optionally organically polymerized silicic acid polycondensates of the invention are biodegradable and are suitable for use in medical engineering and biology, for example for the production of a biologically or medically usable article or an article for cell stabilization or cell culture.

Description

The present invention relates to novel, inorganically condensable silanes and their condensates and / or polymers. These silanes contain one or more oxygen-bonded to the silicon substituents or groups with ester, optionally with ether and / or thioether, as well as organically polymerizable units such as C = C double bonds or ring-opening systems, eg epoxy groups. The silanes can be condensed inorganically and / or polymerized organically via the C =C double bonds. Such organic polymerization can be carried out, for example, by means of 2-photon polymerization (2PP), so that structured, substantially monomer-free materials can be obtained. These are stable against irradiation with γ-rays so that they can be sterilized. By varying the proportion of inorganically crosslinkable units and / or on organically polymerizable units, the mechanical properties of the hybrid polymers produced from the silanes can be adjusted specifically so that they resemble those of natural, soft or hard tissues. They can be colonized by cell types such as endothelial cells and are therefore suitable, for example, as scaffolds for stabilizing and growing cells. The hybrid polymers are decomposed more or less strongly when stored in buffers within a few weeks, resulting in toxic harmless, usually water-soluble, small-scale degradation products such as C ₂ dicarboxylic acids. Also, the oxygen bridge between the substituents containing the ester groups and the silicon atom is cleaved. Thus, the hybrid polymers according to the invention are suitable for the production of biodegradable or resorbable implants or scaffolds with adapted for the particular application mechanical data.

Restoration of diseased or damaged tissue remains one of the major challenges in regenerative medicine. The growth of cells on three-dimensional (3D), mostly porous "scaffolds" (tissue engineering, TE for short) is a promising approach for producing autologous tissue. Scaffolds for TE must be biocompatible and biodegradable, cell attachment and support cell proliferation and adapted to the mechanical requirements of the respective tissue.

For the production of scaffolds there are numerous procedures. The most common of the older conventional methods are solvent casting, particulate leaching, gas foaming, phase separation, freeze drying, electrospinning and self-assembly. However, none of these manufacturing methods allows precise control over pore size, geometry, and spatial distribution of pores. In addition, interconnectivity can not be ensured. Newer methods circumvent these disadvantages. To create highly complex structures, three-dimensional objects can be constructed using a computer-aided design (CAD) of multiple layers. Techniques that take advantage of this technique are referred to as rapid prototyping or solid free-form methods. With these methods, anatomically adapted scaffolds can be generated based on computed tomography (CT) or magnetic resonance tomography (MRI) data. Frequently used is the stereolithography. In this technique, a chemical reaction - photopolymerization - is initiated by electromagnetic radiation. The material to be structured or the material formulation to be structured must therefore fulfill the requirement of being able to react with light. As a result, a phase transition from liquid to solid takes place in the exposed areas. In the subsequent development step thus only the remaining liquid material is dissolved away. With the help of a laser beam, structures can be created layer by layer. Advantages of this method are that highly organized three-dimensional scaffolds with defined porosity, pore size and interconnectivity of the pores can be produced with high reproducibility and this is possible with only a few process steps. Restrictions in polymer choice and upscaling problems, on the other hand, are disadvantageous. A good resolution is provided by a special case of stereolithography, namely two-photon polymerization (2PP). With this technique ultrafine structures can be produced at high resolution. It is based on the simultaneous absorption of two photons (two photon absorption, TPA), which triggers the decomposition of the initiator molecules and thus also the subsequent chemical reaction between the generated radicals and the monomers. Due to the simultaneous absorption of two photons, very high light intensities are necessary for the excitation, which can be achieved by ultrashort laser pulses. The rate of two-photon absorption depends non-linearly on the intensity. As a result, the polymerization takes place only in a spatially narrow range around the laser focus, whereby resolutions of <100 nm can be achieved. If the focus is moved through the material, three-dimensional microstructures are produced in the exposed areas in one process step. This method has the advantage that both the external shape of the scaffold and the intrinsic porosity of the structure can be controlled. The physiological action of extracellular matrix (ECM) is to provide the cells in the body with an opportunity to adhere and to control cell and tissue functions such as differentiation, growth, proliferation, and interactions between cells.

From a chemical point of view, scaffolds made of biopolymers produced by 2PP are well suited to adequately mimic the ECM for tissue engineering. When using degradable scaffold materials, dissecting the scaffold under physiological conditions also provides the opportunity to create room for cell migration and expansion.

For some time, materials that can be used for medical technology have been searched for, which can be structured specifically and which are biodegradable despite the successful polymerization of organic groups, in particular of (methacrylate and other) C =C double bonds. Have so F. Claeyssens et al. in "Three Dimensional Biodegradable Structures Fabricated by Two Photon Polymerization", Langmuir 25, 3219-3223 (2009) Poly (ε-caprolactone-co-trimethylene carbonate) -b-poly (ethylene glycol) -b-poly (ε-caprolactone-co-trimethylene carbonate) having a photoinitiator with the aid of the two-photon catalyst is prepared from the biodegradable triblock copolymer. Polymerization can produce structures that could be suitable as a scaffold. Also biodegradable organic polymerizable hybrid polymers have already been considered for this purpose. This is usually around variations known ORMOCER® ^® s, ie hydrolytically condensed silane compounds bearing organic crosslinkable groups. Some such ORMOCERE have already been described as inherently biocompatible, see R. Narayan et al., In Mater. Res. Soc. Symp. P 2005, 845, 51 and in Acta Biomater. 2006, 2, 267 , Hybrid materials that are at least partially biodegradable under physiological conditions have been used by D. Tian et al. in the Journal of Polymer Science, Part A - Polymer Chemistry, "Biodegradable and Biocompatible Inorganic-Organic Hybrid Materials, I. Synthesis and Characterization", 1997, 35 (11) 2295-2309 described. R. Houbertz et al. showed in Coherence and Ultrashort Pulse Laser Emission, 2010, 583 and in WO 2011/098460 A1 biocompatible 2PP structurable materials. These contain either residues attached via Si-C bonds that carry organically polymerizable groups, or they are generated from a mixture of silanes with Si-C bonded organic-polymerizable groups and organic-polymerizable compounds. Based on examples WO 2011/098460 A1 could be shown that such structured materials in buffers such as PBS suffer a weight loss, that must be biodegradable to a certain extent biologically by hydrolytic means, and can be colonized by cells.

Biodegradable, purely organic materials which have been prepared via polymerization of C =C double bonds have the disadvantage that they can only contain a relatively small proportion of organically polymerizable groups, so that their degradability is ensured, especially on the breaking up is based on ester and / or ether groups which are preferably present in the molecule several times. Biodegradation or the like produced, biodegradable, purely organic materials (thermoplastics) such as polylactides do not have this disadvantage, but they are not structurable on the polymerization, so that they must be converted via molding processes in their final form. The known ORMOCER ^® -Hybridmaterialien can be both an organic polymerization of C = C double bonds and via inorganic cross-linking reactions (Si-O-Si-bond formation) solidify, wherein the presence of organically polymerizable C = C double bond is a spatial Structuring in the polymerization allows. However, the Si-C bonds present therein are not susceptible to hydrolysis under physiological conditions.

The object of the present invention is to overcome the disadvantages of the prior art and to provide materials which, on the one hand, are accessible to a narrower cross-linking than purely organic materials and can therefore achieve mechanical properties which were not previously adjustable but, on the other hand, below physiological conditions much better (faster and / or more) should be degradable than previously known hybrid materials. In addition, the materials according to the invention should be sterilizable and biocompatible, so that they are suitable for the production of implants or scaffolds.

The object is achieved by the provision of silanes of the formula (1) R ¹ _a SiR _4-a (1) and condensates / polymers produced therefrom or therewith, wherein the silanes according to the invention have at least one, preferably more (on average about two average) substituents R ¹ per silicon atom which is / are usually composed exclusively of organic components and via oxygen the silicon is / are bound. Each of these substituents R ¹ has a hydrocarbon-containing chain of variable length (straight or branched, preferably ring-free) which is interrupted by at least two, preferably at least three -C (O) O groups (ester groups, pointing in any direction). Here follow in the individual, formed by the interruptions Hydrocarbon units within this chain a maximum of 8, preferably not more than 6 and more preferably not more than four carbon atoms on each other. In addition, the end of the hydrocarbon-containing chain remote from the silicon atom or, in the case of branched structures, at least one (preferably each) of these ends has an organically polymerizable group selected from groups containing an organically polymerizable C =C double bond, preferably acrylic or , more preferably, methacrylic groups, especially acrylate or, more preferably, methacrylate groups, and ring-opening systems such as epoxides. The organic polymerization may, but need not, be a polyaddition; it can be inducible photochemically, thermally or chemically (2-component polymerization, anerobic polymerization, redox-induced polymerization). The combination of self-curing with z. B. photoinduced or thermal curing is also possible.

The hydrocarbon chain may be further interrupted by oxygen atoms (ether groups) or sulfur atoms (thioether groups). The hydrocarbon moieties between the ether, thioether and ester groups are preferably alkylene units and may, but are not necessarily, substituted with one or more substituents which are preferably selected from hydroxy, carboxylic, phosphoric, phosphonic, phosphoric and (preferably primary or secondary) amino and amino acid groups. The index a in these silanes is selected from 1, 2, 3 and 4, the silanes of the formula (1) generally being present as mixtures of silanes with different meanings of the subscript a and this index in the mixture frequently having an average value of approx 2 owns. R is a hydrolytically condensable group and preferably selected from groups of the formula R'COO ^- but may also be OR 'or OH, where R' is alkyl and preferably methyl or ethyl.

The invention will be explained in more detail with reference to a schematic representation of a silane of the formula (1) according to the invention. Shown is one of the substituents R ¹ , attached via an oxygen atom to the silicon atom. This oxygen atom is part of a polyethylene glycol group having n ethylene glycol units and thus n alkylene groups each having two carbon atoms. The last of these units is esterified with ethylenedicarboxylic acid, whose second carboxylic acid unit is in turn esterified with (here optionally substituted with any substituent R ", which may be especially CH ₃ , COOH or CH ₂ OH, substituted) ethylene glycol, the second OH group with Methacrylic acid was esterified to give a derivative of 4- [2- (methacryloyloxy) ethoxy] 4-oxo-butanoic acid, MES.) Thus, the group is unbranched (except for the branching possibly caused by R ") and has on its remote from the silicon atom, a methacrylic group which can be organically polymerized via their C = C double bond. It should be understood that the substituent R "in this scheme is given by way of example only, and it will be understood that such substituents may (also) be present at (other) random locations.

The two carboxylic ester groups present in this group are susceptible to hydrolysis and here designated DG I and DG II. The ester bond between the methacrylic acid and the optionally substituted with R "ethylene glycol is hydrolytically cleavable.The cleavage of" DG III ", the Si-O bond, is also carried out under hydrolysis conditions.Thus for the first time a material is provided, which also at the coupling site In addition, polyether groups, such as EM Christenson et al. in Wiley InterScience on June 2, 2004 under DOI: 10.1002 / jbm.a.30067 be addressed in some constellations in vivo oxidatively cleaved.

It can be seen directly from the above explanations that the provision of only short, by oxygen atoms, sulfur atoms or ester groups (-C (O) O-) interrupted hydrocarbon chains in the hydrolytic degradation largely leads to small molecular weight products, which are generally physiologically harmless as such , In the above example, for example, succinic acid and a cross-linked polymethacrylate fragment, which is also toxicologically harmless due to the crosslinking. The latter is likely to be relatively small molecular depending on the crosslinking conditions, since the silane molecules are already aligned relatively rigidly to each other due to the preceding hydrolytic condensation, which is why a higher-level crosslinking of an uninterrupted plurality of methacrylate groups is unlikely. If materials are used, the additional OH or COOH substituents or similar. At the respective hydrocarbon chains may arise molecules that occur in the human body as intermediates such as lactic acid or citric acid, so that they could be introduced into its metabolism. The remaining substantially inorganic residues are believed to be essentially fragments of Si-O-Si linkages that are externally occupied by hydroxy groups.

Hydrolysis and condensation of the above silane (here of formula (1) with R = OAc, ie CH ₃ C (O) O) results in a resin (an organically modified silicic acid polycondensate), hereinafter referred to as "GM resin":

The substitution of silicon with two of the organic substituents R ^{1 in question} is an average value; the starting "silane" for the resin usually consists of a mixture of different silanes in which at least part, one, two, three or four of these organic groups are bonded to a silicon atom, with an average of two of the organic groups per silicon atom available. The number of OAc (acetyl) groups on the silicon is also a statistical value (the acetyl groups come in the example of the starting material, silicon tetraacetate, and remain even under hydrolytic conditions in about the specified proportion). The hydroxy groups formed by hydrolysis of OAc groups are converted to Si-O-Si bridges under the conditions of hydrolytic condensation.

This resin and other resins were polymerized organically and examined in this state for their mechanical properties. It follows that the length of the substituent R ¹ according to the invention has an influence on the tensile strain (Tensile Strength) and the modulus of elasticity (Young's Modulus): the longer the substituent, the softer the material becomes.

This can be seen by comparing the polymerized GM resin (hereinafter referred to as "poly-GM") with the polymerization product of a resin of the invention which differs therefrom only in that six instead of three ethylene glycol units are present in the group :

This resin is referred to as SV I resin, its polymerization product as poly SV I. The mechanical properties can likewise be greatly influenced by the number of organically polymerizable C =C double bonds per substituent R ¹ : If this substituent is branched and the two branch ends each contain an organically polymerisable C =C double bond, these values increase by approx a power of ten. This can be seen from a comparison of the values for poly-GM and poly-SV with the polymerization product of another resin according to the invention of the following composition.

This resin is referred to as SV II resin whose polymerization product as Poly-SV II.

steigen die mechanischen Werte des polymerisierten Materials (bezeichnet als "Poly SV III) auf das ca. Dreifache im Vergleich zum reinen, polymerisierten Poly-GM.An equally significant increase results from an increase in the proportion of inorganic crosslinking groups: If the silane used for the GM resin is not subjected as such to a hydrolytic condensation, but together with another silane with many (eg two to three) hydrolytically condensable radicals and Incidentally, only short organic substituents, for example with a partially hydrolyzed / condensed ethyltriacetoxysilane or a partially hydrolyzed / condensed tetraethoxysilane, where, for example, the below, designated SV III resin material is formed,

The mechanical values of the polymerized material (referred to as "Poly SV III") increase approximately three-fold compared to the pure, polymerized poly-GM.

Moreover, the mechanical properties can still be influenced to some extent by the degree of condensation of the resins: the more the condensation takes place, i. the more Si-O-Si bridges are present, the harder the product becomes.

The values measured for the materials described above are shown in Table 1 below where they are related to the corresponding values of natural tissue. Table 1 Synthesized materials Tensile strength [MPa] Natural tissue Tensile strength [MPa] Poly-GM 4.3 ± 0.2 bladder 0.27 ± 0.14 Poly-SV I 1.8 ± 0.2 blood vessel 1.4 to 11.1 Poly-SV II 30.3 ± 3.1 aorta 1.72 ± 0.89 Poly-SV III 12.5 ± 0.6 cartilage ~ 5 Synthesized materials Modulus of elasticity [MPa] Natural tissue Modulus of elasticity [MPa] Poly-GM 43.5 ± 2.6 Soft tissue 0.4 to 350 Poly-SV I 18.9 ± 1.1 Poly-SV II 615 ± 116 Hard tissue 10-1500 Poly-SV III 109 ± 11.1

It can be seen that with the materials according to the invention a specifically sought adaptation of the mechanical values to certain tissues can be effected. Since both the inorganic and the organic crosslinking density can be adjusted, the skilled person can achieve exactly the desired values by suitable choice within the parameters which the invention describes.

The organically polymerizable groups (for example the C =C double bonds) are optionally polymerizable in the bulk of the resin, but above all also at structurally desired points in a bath of the resin material. Thus, the condensed resin can be presented as a mass (liquid or pasty) and polymerized, for example, with 2-photon polymerization ("TPA processing") in a desired shape or a desired pattern. For this purpose, an exposure is preferably carried out with laser light in a known manner, such as in WO 2011/098460 A1 described. Instead, of course, a structuring with other techniques, for example, by the so-called. Rapid prototyping, in which the desired shape is generated by sequentially exposing a superficial bath layer with subsequent lowering of the solidified layer.

Upon irradiation, essentially all organic C = C double bonds are reacted, irrespective of whether the irradiation is structured or takes place over the entire material. This can be determined by the in 1 (dark graph: the condensed GM resin before polymerization, mixed with 1% photoinitiator.) The two nearly superimposed, light graphene show the irradiated resin, once before and once after an additional irradiation with γ- The abscissa represents the wavenumbers [cm ^-1 ] and the ordinate the intensity in relative units (arbitrary units, "au"). The irradiated resin was therefore examined once before and once after additional irradiation with γ-rays, because gamma-irradiation is the simplest and most widely used technique of sterilization in the medical sector - the fitness also with regard to this aspect is a further advantage of the invention. The high degree of conversion of the organically polymerisable groups contributes to good biocompatibility, because methacrylate monomers, which in turn would be formed when degrading unpolymerized structures, are usually relatively toxic molecules, and it is therefore highly desirable to suppress their formation during degradation.

The unpolymerized material can then be washed away. A three-dimensional structure made in this way is in FIG 6 shown. Because of this structurability, the materials according to the invention for producing filigree objects, such as scaffolds, are well suited. Resistance to gamma radiation also makes the objects sterilizable.

With regard to the use of the materials according to the invention for scaffolds and the associated requirement of biodegradability under physiological conditions, the degradation behavior of inventive, already organically crosslinked materials was investigated. In the body, the pH can vary between 1 and 9, depending on which region is considered. Therefore, a study in different pH ranges makes sense.

The organically polymerized materials were stored in various buffers with pH's between 4.65 (acetate buffer) and 9.6 (carbonate bicarbonate buffer). The 2 to 5 show in the ordinate the weight loss in [%], in the abscissa the storage time in weeks. It was found that the pH of the surrounding medium has a strong influence on the rate of degradation. For the polymers poly-GM, poly-SV I and poly-SV III, the largest mass loss occurred in a carbonate-bicarbonate buffer (about 40-60% after about 16 weeks); After this time it was significantly lower in demineralized water (pH 6.5-7.0 at 20 ° C) (about 10-20%), phosphate buffered saline ("PBS", pH 7.4) and in acetate buffer with one pH of 4.65 at 20 ° C (the latter each about 5-10%). Poly-SV III, on the other hand, degrades relatively slowly, even in the slightly alkaline state, while degradation in acid is comparable to the degradation rates of the other polymers.

From the four examples examined, it can be shown that over the chosen four month period, there was mass loss in all the organically crosslinked hybrid polymers, with the rate of degradation being strongly influenced by the structural differences in the polymers. It can be seen that the degradation is influenced not only by the pH of the medium, but also by variations in the structural composition of the hybrid polymers. The more hydrophilic groups (such as, for example, ethylene glycol units) are contained, the faster the degradation takes place. In contrast, a greater organic (cross) crosslinking or a higher inorganic content and a higher degree of condensation (a higher inorganic crosslinking) slow the hydrolysis rate. These insights can be used to select custom materials for specific applications.

It is also noteworthy that the measured degradation rates were essentially constant over time. Although the values show that the degradation is not fast, it is still significant, because biodegradation usually only takes effect within a relatively long period of time: First, the injuries must have healed or the cells have grown and proliferated before the mechanical support (implant, scaffold) may disappear due to degradation.

The proportion of organically crosslinkable groups can be adjusted in the materials according to the invention in a wide range. If the organic cross-linking is relatively low, it is expected that in the degradation of the hybrid polymers, those structures which can not otherwise decompose, e.g. Polymethacrylatstrukturen relatively low molecular weight, dissolved from the polymer composite and z. B. macrophages can be absorbed and decomposed by digestion.

It has also been shown that upcyte endothelial cells adhere well to organically polymerized poly-GM and other materials of the invention and do not lose their characteristic morphology. Immunostaining (with anti-tubulin β and DAPI) also led to the detection of cell divisions of cells adhering to this material.

Accordingly, the present invention provides a new class of organo-inorganic hybrid polymers which are biodegradable and biocompatible, whose mechanical properties can be adapted to those of certain tissues, and which are determined by two-photon polymerization (2-PP) or by other means the mass or structured organic polymerize and show a high degree of conversion of organic polymerizable groups.

The biodegradability, determined by the mass loss, depends on the pH of the environment. In addition, it can be influenced by modifications of the polymer structure.

The mechanical properties can be adjusted within a certain range and thus adapted to those of native tissues. The adjustment is made significantly by the variation of the content of organic polymerizable groups, the length of the group in question and the inorganic content.

In particular, the 2-PP polymerization can produce three-dimensional, finely structured objects, so that the invention is also suitable for the production of scaffolds.

Light-induced polymerization leads to hybrid polymers with high degree of conversion of the C = C groups and thus degradation products that are substantially free of toxic relevant components. Irradiation with gamma rays can be used for sterilization purposes since such irradiation does not adversely affect the already polymerized material.

However, the use of the materials according to the invention extends not only to the abovementioned uses. They can generally be used for a variety of purposes, for example in the form of bulk materials, fibers, composites, cements, adhesives, potting compounds, coating materials, for use in the (reaction) extruder and in the field of multiphoton polymerization. Particularly important is a use for medical applications (eg as an implant, bone substitute material, bone cement).

The following examples illustrate the preparation of the individual materials listed above. Synthesis of 4- [2- (methacryloyloxy) ethoxy] -4-oxobutanoyl chloride (MES-Cl)

The synthesis of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid chloride (MES-Cl) was detected in minor modification (reverse order of addition and lower excess of thionyl chloride) TE Kristensen et al., Org. Lett. 2009, 11, 2968 69.83 g (303.3 mmol, 1.0 equiv) of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid (MES) were added under nitrogen, stirring and refluxing with 72.62 g (m.p. 610.4 mmol, 2.0 equiv.) Of thionyl chloride. The clear colorless solution was stirred for 30 min at 30 ° C and 1 h at 50 ° C. Subsequently, the excess thionyl chloride and the volatile constituents were removed under reduced pressure or in an oil pump vacuum.
Yield: 75.88 g (305.2 mmol, 100%).
M _ber. (C ₁₀ H ₁₃ ClO ₅ ) = 248.66 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 3 H, C H _3), 2.70 to 2.73 (t, 2 H, C H ₂ CH ₂ C (O) Cl, ³ J _HH = 6.52 Hz), 3.22 to 3.25 (t, 2 H, CH ₂ C H ₂ C (O) Cl, ³ J _HH = 6.53 Hz), 4.35-4.40 (m, 4 H, OC H ₂ C H ₂ O), 5.61-5.62 (m, 1 H, H ₂ C =, cis), 6.13 (s, 1 H, H ₂ C =, trans).
¹³ C-NMR (100.6 MHz, _CDCl3):
δ [ppm] = 18.26 ( C H ₃ ), 29.24 ( C H ₂ CH ₂ C (O) Cl), 41.69 (CH ₂ C H ₂ C (O) Cl), 62.19 u , 62.85 (O C H ₂ C H ₂ O), 126.23 (H ₂ C =), 135.84 (= C (CH ₃ ) C (O) OR), 167.09 (= C (CH ₃ ) C (O) OR), 170.67 ( C (O) OR) u. 172.96 ( C (O) Cl).
FT-IR: v ~ [cm ^-1 ] = 2961 (m, v (CH)), 1794 (vs, RCOCl v (C = O)), 1721 (vs, v (C = O)), 1637 (m , v (C = C)), 712 (m, v (C-Cl)).
μ-Raman: v ~ [cm ^-1 ] = 2955 u. 2928 (vs, v (CH)), 1793 (w, RCOCl v C = O)), 1714 (s, v (C = O)), 1639 (s, v C = C)), 707 (m, v (C-Cl)), 434 (s, v C-Cl)). Synthesis of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid triethylene glycol ester (MES-TEG)

As a guide for the synthesis of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid triethylene glycol ester (MES-TEG) was a provision of Wiseman et al., J. Am. Chem. Soc. 2005, 127, 5540 Under a nitrogen atmosphere, 47.99 g (319.6 mmol, 3.2 equiv.) Of triethylene glycol (TEG) were dissolved in 100 ml of dichloromethane, and 9.17 g (115.6 mmol, 1.1 equiv.) Of pyridine were added. To the ice-cold colorless solution was added 24.81 g (99.8 mmol, 1.0 equiv.) Of MES-Cl with stirring. The mixture was stirred for 24 h at 30 ° C and then treated with 800 ml of cold ethyl acetate, whereupon pyridine hydrochloride precipitated as a white precipitate, which was removed in the subsequent extraction. The organic phase was washed by washing three times with 200 ml of cold water and dried over sodium sulfate. The solvent was removed by distillation, the product was freed from volatile components for 3 hours in an oil pump vacuum, and 0.2% by weight hydroquinone methyl ether (HQME) was added for stabilization. Insolubles were removed by filtration through a 5 μm pore size syringe filter. The product was stored with stirring in a PE bottle until further use.
Raw yield: 37.34 g

In the raw yield, the proportion of disubstituted triethylene glycol (MES ₂ TEG), which is formed as a by-product in the synthesis, when both OH groups are esterified, not yet considered. This proportion was determined by means of the ¹ H-NMR spectrum. For this purpose, the signal at ≈3,60 ppm corresponding to the CH ₂ group directly adjacent to the Alkohlfunktionalität in MES-TEG and is generated solely by the major product was defined as a reference. The proportion of MES ₂ TEG can be calculated from the ratio of the integral for this signal to those of the other signals resulting from the superposition of main and by-product. It is ≈15 mol%. Since the by-product is not a disadvantage in the further reaction, the mixture was not further separated.

If the proportion of MES ₂ TEG is subtracted by calculation, the yield is 29.18 g (80.5 mmol, 81%).
M _ber. (MES-TEG, C ₁₆ H ₂₆ O ₉ ) = 362.37 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 3 H, C H _3), 2.67 (m, 4H, CC H ₂ C H ₂ C), 3.60-3.62 (m, 2 H, (OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OH), 3.65-3.73 (m, 8 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OH) 4.25- 4.28 (m, 2 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₂ OH), 4.35 (s, 4 H, OC H ₂ C H ₂ O), 5.60-5.61 ( m, 1 H, H ₂ C =, cis), 6.13 (s, 1 H, H ₂ C =, trans).
¹³ C-NMR (100.6 MHz, _CDCl3):
δ [ppm] = 18.28 ( C H ₃ ), 28.92 (C C H ₂ C H ₂ C), 61.75, 62.34, 62.40, 63.74, 69.04, 70, 33, 70, 58 u. 72.48 (4x O C H ₂ C H ₂ O), 126.13 (H ₂ C =), 135.89 (H ₂ C = C (CH ₃ ) C (O) OR), 167.13 (= C (CH ₃ ) C (O) OR), 172.09 u. 172.23 (O C (O) CH ₂ CH ₂ C (O) O).
FT-IR: v ~ [cm ^-1 ] = 3463 (m, v (OH)), 2955 u. 2876 (m, v (CH)), 1737 (vs, v (C = O)), 1637 (m, v (C = C)).
μ-Raman: v ~ [cm ^-1 ] = 2955 u. 2928 (vs, v (CH)), 1714 (s, v (C = O)), 1634 (s, v (C = C)). Synthesis of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid hexaethylene glycol ester (MES-HEG)

The synthesis of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid hexaethylene glycol ester (MES-HEG) was carried out analogously to the reaction to give MES-TEG: Under a nitrogen atmosphere, 85.90 g (304.3 mmol, 3, 2 eq.) Of hexaethylene glycol (HEG) and 8.71 g (110.1 mmol, 1.1 equiv.) Of pyridine in 100 ml of dichloromethane. Under ice-cooling and stirring, 23.68 g (95.2 mmol, 1.0 equiv.) Of MES-Cl was added. The mixture was stirred at 30 ° C for 24 h and the product isolated, purified and stabilized as described previously for MES-TEG.
Crude yield: 32.74 g

In the crude yield, the proportion of disubstituted hexaethylene glycol (MES ₂ HEG), which is formed as a by-product in the synthesis, has not yet been considered. This fraction was determined by means of the ¹ H-NMR spectrum and is ≈5 mol%. Since the by-product is not a disadvantage in the further reaction, the mixture was not further purified.

If the proportion of MES ₂ HEG is subtracted by calculation, the yield is 30.45 g (61.6 mmol, 65%).
M _ber. (MES-HEG, C ₁₆ H ₂₆ O ₉ ) = 494.53 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 3 H, C H _3), 2.67 (m, 4H, CC H ₂ C H ₂ C), 3.60-3.62 (m, 2 H, (OCH ₂ CH ₂ ) ₅ CH ₂ C H ₂ OH), 3.65-3.73 (m, 20 H, OC H ₂ CH ₂ (OC H ₂ C H ₂ ) ₄ C H ₂ CH ₂ OH), 4.23-4.26 (m, 2 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₅ OH), 4.35 (s, 4 H, OC H ₂ C H ₂ O), 5.60 g 5.61 (m, 1 H, H ₂ C =, cis), 6.13 (s, 1 H, H ₂ C =, trans).
¹³ C-NMR (100.6 MHz, _CDCl3):
δ [ppm] = 18.27 ( C H ₃ ), 28.92 (C C H ₂ C H ₂ C), 61.70, 62.34, 62.38, 63.89, 69.03, 70, 33, 70, 56, 70, 60 u. 72.52 (7x O C H ₂ C H ₂ O), 126.12 (H ₂ C =), 135.88 (= C (CH ₃ ) C (O) OR), 167.09 (= C (CH ₃ ) C (O) OR), 172.04 u. 172.19 (O C (O) CH ₂ CH ₂ C (O) O).
FT-IR: v ~ [cm ^-1 ] = 3466 (m, v (OH)), 2873 (s, v (CH)), 1737 (vs, v (C = O)), 1637 (m, v ( C = C)).
μ-Raman: v ~ [cm ^-1 ] = 2935 u. 2888 (vs, v (CH)), 1722 (m, v (C = O)), 1643 (m, v (C = C)). Synthesis of 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxo-butanoic acid (GDM-SA)

The synthesis of 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxo-butanoic acid (GDM-SA) was carried out in accordance with a protocol of JH Liu, DS Wu, KY Tseng, Macromol. Chem. Physic. 2004, 205, 2205 , To a solution of 32.10 g (320.8 mmol, 1.0 equiv.) Of succinic anhydride (SA) and 665.3 mg (5.5 mmol, 0; 02 equiv) 4-dimethylaminopyridine (DMAP) as catalyst in 300 ml of 1,4-dioxane was added another solution of 73.21 g (320.8 mmol, 1.0 equiv.) Of 1,3-glycerol dimethacrylate (GDM) and 109.5 mg (0.2% by weight) of 4-hydroxyanisole (HQME) as a stabilizer in 120 ml of 1,4-dioxane. The mixture was refluxed for 40 h at 80 ° C and then cooled to room temperature for 1 h. Thereafter, it was diluted with 460 ml of cold dichloromethane, washed twice with 330 ml of cold water and dried over sodium sulfate. The solvent was removed under reduced pressure and volatiles separated in an oil pump vacuum.
Yield: 96.97 g (295.4 mmol, 92%).
M _ber. (GDM-SA, C ₁₅ H ₂₀ O ₈ ) = 328.31 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.94 (s, 6 H, C H _3), 2.67 (m, 4H, CC H ₂ C H ₂ C), 4.19 to 4.45 (m, 4 H, OC H ₂ CHORC H ₂ O), 5.36-5.45 (m, 1 H, C H ) 5.61-5.62 (m, 2 H, H ₂ C =, cis), 6.13 ( s, 2H, H ₂ C =, trans).
¹³ C-NMR (100.6 MHz, _CDCl3):
δ [ppm] = 18.23 ( C H ₃ ), 28.73 u. 28.78 (C C H ₂ C H ₂ C), 62.48 u. 67.05 (O C H ₂ CHOR C H ₂ O), 69.51 ( C H), 126.51 (H ₂ C =), 135.61 (= C (CH ₃ ) C (O) OR), 166.82 (= C (CH ₃₎ C (O) OR), 171.20 (C (O) OR), 177.71 (C (O) OH).
FT-IR: v ~ [cm ^-1 ] = 3265 (m, v (OH)), 2961 u. 2930 (m, v (CH)), 1724 (vs, v (C = O)), 1638 (m, v (C = C)).
μ-Raman: v ~ [cm ^-1 ] = 2965 u. 2932 (vs, v CH)), 1722 (s, v C = O)), 1639 (s, v C = C)). Synthesis of 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxobutanoic Acid Chloride (GDM-SA-Cl)

The synthesis of 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxo-butanoic acid (GDM-SA-Cl) was carried out analogously to the synthesis of MES-Cl: 90.30 g (275.0 mmol, 1.0 equiv.) Of GDM-SA were added under nitrogen atmosphere and with stirring to 65.27 g (551.4 mmol, 2.0 equiv.) Of thionyl chloride for 30 min at 30 ° C and 1 h stirred at 50 ° C. The excess thionyl chloride and volatiles were then removed under reduced pressure or oil pump vacuum.
Yield: 92.64 g (267.2 mmol, 97%).
M _ber. (GDM-SA-Cl, C ₁₅ H ₁₉ ClO ₇ ) = 346.76 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 6 H, C H _3), 2.70 to 2.73 (t, 2 H, C H ₂ CH ₂ C (O) Cl, ³ J _HH = 6.9 Hz), 3.21-3.24 (t, 2 H, CH ₂ C H ₂ C (O) Cl, ³ J _HH = 6.8 Hz), 4.25-4.44 (m, 4 H, OC H ₂ CHORC H ₂ O), 5.34-5.46 (m, 1 H, C H ), 5.60-5.63 (m, 2 H, H ₂ C =, cis), 6.13 (m, 2H, H ₂ C =, trans).
¹³ C-NMR (100.6 MHz, _CDCl3):
δ [ppm] = 18.25 ( C H ₃ ), 29.32 ( C H ₂ CH ₂ C (O) Cl), 41.69 (CH ₂ C H ₂ C (O) Cl), 62.38 ( O C H ₂ CHOR C H ₂ O), 70.05 ( C H), 126.57 (H ₂ C =), 135.58 (= C (CH ₃ ) C (O) OR), 166.77 ( = C (CH ₃ ) C (O) OR), 170.04 ( C (O) OR) u. 172.81 ( C (O) Cl).
FT-IR: v ~ [cm ^-1 ] = 2961 u. 2930 (m, v (CH)), 1794 (vs, RCOCl v C = O)), 1724 (vs, v C = O)), 1638 (m, v C = C)), 712 (m, v C Cl)).
μ-Raman: v ~ [cm ^-1 ] = 2965 u. 2932 (vs, v CH)), 1797 (w, RCOCl v C = O)), 1722 (s, v C = O)), 1639 (s, v C = C)), 712 (w, v c- Cl)), 439 (s, v C-Cl)). Synthesis of 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxo-butanoic acid triethylene glycol ester (GDM-SA-TEG)

The further conversion of GDM-SA into 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxo-butanoic acid triethylene glycol ester (GDM-SA-TEG) was carried out in a manner analogous to the synthesis of MES reagents. TEG: 48.88 g (325.5 mmol, 3.4 equiv.) Of TEG and 9.32 g (117.8 mmol, 1.2 equiv.) Of pyridine were dissolved in 100 ml of dichloromethane under a nitrogen atmosphere. 33.37 g (96.2 mmol, 1.0 equiv.) Of GDM-SA-Cl were added with ice-cooling and stirring. The mixture was stirred at 30 ° C for 24 h and then the product was isolated, purified and stabilized as described previously for MES-TEG.
Crude yield: 37.20 g

In the raw yield, the proportion of disubstituted alcohol (GDMSA ₂ TEG), which is formed as a by-product in the synthesis, has not yet been considered. This proportion was determined as previously described for MES-TEG using the ¹ H-NMR spectrum and is ≈20 mol%. Since the by-product is not a disadvantage in the further reaction, the mixture was not further purified.

If the proportion of GDMSA ₂ TEG is subtracted by calculation, the yield is 26.23 g (57.0 mmol, 59%).
M _ber. (GDM-SA-TEG, C ₂₁ H ₃₂ O ₁₁ ) = 460.47 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.94 (s, 6 H, C H _3), 2.67 (s, 4H, CC H ₂ C H ₂ C), 3.60-3.62 (m, 2 H, (OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OH), 3.65-3.74 (m, 8 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OH), 4.25 -4.45 (m, 6 H, OC H ₂ CHORC H ₂ O and OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₂ OH), 5.36-5.43 (m, 1 H, C H ) , 5.61 (m, 2H, H ₂ C =, cis), 6, 12-6, 13 (m, 2H, H ₂ C =, trans).
¹³ C-NMR (100.6 MHz, _CDCl3):
δ [ppm] = 18.26 ( C H ₃ ), 28.89 u. 29.02 (C C H ₂ C H ₂ C), 61.74, 62.47, 63.75, 69.03, 70.33, 70.57, and the like. 72.47 (3x O C H ₂ C H ₂ O and O C H ₂ CHOR C H ₂ O), 69.37 ( C H), 126.46 (H ₂ C =), 135.64 (= C (CH ₃ ) C (O) OR), 166.78 (= C (CH ₃ ) C (O) OR), 171.40 u. 172.06 (O C (O) CH ₂ CH ₂ C (O) O).
FT-IR: v ~ [cm ^-1 ] = 3473 (m, v (OH)), 2957, 2929 u. 2877 (m, v CH)), 1725 (vs, v C = O)), 1638 (m, v C = C)).
μ-Raman: v ~ [cm ^-1 ] = 2962 u. 2932 (vs, v CH)), 1722 (s, v C = O)), 1639 (s, v (C = C)).

Reaction of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid triethylene glycol ester (MES-TEG) with silicon tetraacetate and hydrolysis / condensation of the product to prepare the base material resin (GM resin)

10.37 g (39.2 mmol, 1.0 equiv) of silicon tetraacetate were mixed with 36.40 g of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid triethylene glycol ester (MES-TEG), which was approximately 15 mole% disubstituted by-product (MES ₂ TEG) were added. This corresponds to an MES-TEG content of 28.44 g (78.5 mmol, 2.0 equiv.). This mixture was first stirred for 1 min at room temperature and then heated to 50 ° C for 3 h at 15 mbar. The product was devolatilized for 8 h in an oil pump vacuum and filtered with the aid of compressed air through a filter having a pore size of 30 μm.
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 6H, C H ₃ ), 2.09-2.16 (m, residue C H ₃ COOSi), 2.67 (s, 8 H, CC H ₂ C H ₂ C), 3.60-3.71 (m, 16 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OSi), 3.92-4.09 (m, 4 H, ( OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OSi), 4.24-4.25 (m, 4 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₂ OSi), 4.35 (m, 8 H OC H ₂ C H ₂ O), 5.60-5.61 (m, 2 H, H ₂ C =, cis), 6.14 (m, 2 H, H ₂ C =, trans).

The mixture was then hydrolyzed in several steps at 30 ° C. For this purpose, it was in each case mixed with 100 .mu.l of water, stirred for 5 min, freed from volatile components for 5 h in an oil pump vacuum and stirred further until the next interval. The degree of hydrolysis of the Si-OAc and Si-OAlk groups was checked by ¹ H-NMR. The addition of water was repeated until the residual acetate content and the alcohol hydrolysis were as low as possible.
Crude yield: 33.96 g

In the raw yield, the proportion of disubstituted alcohol (MES ₂ TEG), which is included in MES-TEG, but is not reacted in the synthesis, not yet considered. If this proportion is deducted by calculation, the yield is 26.00 g (32.4 mmol, 83%).
M (GM) _ber. = ≈802 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 6H, C H ₃ ), 2.08-2.11 (m, residue C H ₃ COOSi), 2.66 (s, 8 H, CC H ₂ C H ₂ C), 3.58-3.71 (m, 16 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OSi), 3.92-4.02 (m, 4 H, ( OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OSi), 4.23-4.26 (m, 4 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) OSi), 4.35 (m, 8 H, OC H ₂ C H ₂ O), 5.60 (m, 2 H, H ₂ C =, cis), 6.13 (m, 2 H, H ₂ C =, trans).
²⁹ Si NMR (75.5 MHz, acetone-d ⁶ ):
δ [ppm] = -82.76 (Q ^0, ≈11%), -86.97 to -89.99 (Q ^1, ≈35%), -94.00 to -96.99 (Q ^2, ≈ 38%), -101.47 to -103.22 (Q ^3, ≈16%).

Reaction of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid hexaethylene glycol ester (MES-HEG) with silicon tetraacetate and hydrolysis / condensation of the product to prepare the resin for structural variant I (SV I resin)

14.09 g (53.3 mmol, 1.0 equiv.) Of silicon tetraacetate were mixed with 56.82 g of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid hexaethylene glycol ester (MES-HEG), which was ca. 5 mole% disubstituted by-product, added (proportion of MES-HEG: 52.76 g (106.7 mmol, 2.0 equiv.)) And reacted as described previously in the synthesis of GM resin, devolatilized and pressure filtered.
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 6H, C H ₃ ), 2.08-2.16 (m, balance C H ₃ COOSi), 2.67 (s, 8 H, CC H ₂ C H ₂ C), 3.57-3.71 (m, 40 H, OCH ₂ C H ₂ (OC H ₂ C H ₂ ) ₄ OC H ₂ CH ₂ OSi), 3.91-4.08 (m, 4 H, (OCH ₂ CH ₂ ) ₅ OCH ₂ C H ₂ OSi), 4.23-4.26 (m, 4 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₅ OSi), 4.35 (m , 8 H OC H ₂ C H ₂ O), 5.60 (m, 2 H, H ₂ C =, cis), 6.13 (m, 2 H, H ₂ C =, trans).

The subsequent hydrolysis / condensation was carried out stepwise at 30 ° C. as explained above in the synthesis of GM resin and was monitored by ¹ H-NMR.
Raw yield: 54.48 g

In the crude yield, the proportion of disubstituted alcohol (MES ₂ HEG), which is contained in MES-HEG, but is not reacted in the synthesis, not yet considered. If this proportion is deducted by calculation, the yield is 50.42 g (47.0 mmol, 88%).
M (SV I) calc _. = ≈1073 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.95 (s, 6H, C H ₃ ), 2.06-2.11 (m, balance C H ₃ COOSi), 2.67 (s, 8 H, CC H ₂ C H ₂ C), 3.57-3.71 (m, 40 H, OCH ₂ C H ₂ (OC H ₂ C H ₂ ) ₄ OC H ₂ CH ₂ OSi), 3.91-4.01 (m, 4 H, (OCH ₂ CH ₂ ) ₅ OCH ₂ C H ₂ OSi), 4.23-4.26 (m, 4 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₅ OSi), 4.35 (m , 8 H OC H ₂ C H ₂ O), 5.60-5.61 (m, 2 H, H ₂ C =, cis), 6.13 (m, 2 H, H ₂ C =, trans).
²⁹ Si NMR (75.5 MHz, acetone-d ⁶ ):
δ [ppm] = -82.79 u. -83.47 (Q ^0, 7%), -86.02 to -90.09 (Q ^1, 30%), -93.63 to -97.40 (Q ^2, 44%), -100.60 to -104.96 (Q ^3, 19%).

Reaction of 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxo-butanoic acid triethylene glycol ester (GDM-SA-TEG) with silicon tetraacetate and hydrolysis / condensation of the product to prepare the resin for Structure variant II (SV II resin)

The transesterification of silicon tetraacetate by GDM-SA-TEG was carried out as follows: 7.91 g (29.9 mmol, 1.0 equiv) of silicon tetraacetate were mixed with 40.13 g of 4- {1,3-bis [(methacryloyl) oxy] propan-2-yloxy} -4-oxo- Butansäure-triethylene glycol ester (GDM-SA-TEG) containing about 20 mol% disubstituted by-product (proportion of GDM-SA-TEG: 28.29 g (61.4 mmol, 2.0 equiv.)) Reacted. The product was then devolatilized and pressure filtered.
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.94 (s, 12 H, C H ₃ ), 2.09-2.16 (m, balance C H ₃ COOSi), 2.66 (s, 8 H, CC H ₂ C H ₂ C), 3.58-3.69 (m, 16 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OSi), 3.92-4.09 (m, 4 H, ( OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OSi), 4,23-4,45 (m, 12 H, OC H ₂ CHORC H ₂ O, and OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₂ OSi) , 5.33 to 5.47 (m, 2 H, C H), 5.61 (m, 4 H, H ₂ C =, cis), 6.12 (m, 4 H, H ₂ C =, trans ).

The hydrolysis / condensation was carried out stepwise at 30 ° C as previously described in the synthesis of GM resin and was monitored by ¹ H-NMR.
Crude yield: 32.01 g

In the raw yield, the proportion of disubstituted alcohol (GDMSA ₂ TEG), which is contained in GDM-SA-TEG, but is not reacted in the synthesis, not yet considered. If this proportion is deducted by calculation, the yield is 20.17 g (20.6 mmol, 69%).
M (SV II) calc _. = ≈980 g / mol
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 1.94 (s, 12 H, C H ₃ ), 2.07 (m, residue C H ₃ COOSi), 2.66 (s, 8 H, CC H ₂ C H ₂ C), 3.58-3.75 (m, 16 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OSi), 3.92-3.95 (m, 4 H, (OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OSi), 4.23-4.45 (m, 12 H, OC H ₂ CHOC H ₂ O, and OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₂ OSi), 5.37 -5.46 (m, 2 H, C H), 5.61 (m, 4 H, H ₂ C =, cis), 6.12 (m, 4 H, H ₂ C =, trans).
²⁹ Si NMR (75.5 MHz, acetone-d ⁶ ):
δ [ppm] = -82.80 (Q ^0, ≈30%), -89.4 to -89.51 (Q ^1, ≈38%), -96.51 to -96.78 (Q ^2, ≈ 24%), -98.77 to -110.12 (Q ^3, ≈8%).

Partial Hydrolysis and Condensation of Ethyltriacetoxysilane (pHK-EtSi (OAc) ₃ )

5.00 g (21.4 mmol, 1.0 equiv.) Of ethyltriacetoxysilane were dissolved in 3.72 g (64.0 mmol, 3.0 equiv.) Of acetone-d ⁶ and stirred at 30 ° C with 285 μl (15.8 mmol, 0.7 equiv.) Of water in the form of a 10 ^-2 molar hydrochloric acid solution (pHK-EtSi (OAc) ₃ -V1). The mixture was stirred for 24 h at room temperature and not worked up further, so as not to affect the equilibrium.

The synthesis was carried out analogously with 10 ^-1 and 1 molar hydrochloric acid solution (pHK-EtSi (OAc) ₃ -V2 and -V3). The evaluation of the corresponding ¹ H-NMR spectra for pHK-EtSi (OAc) ₃ -V1 to -V3 is summarized in Table A5 below. Tab. A5: Integrals of the CH ₃ groups in the ¹ H-NMR spectra of the mixtures pHK-EtSi (OAc) ₃ -V1 to -V3 for the partial hydrolysis and condensation of ethyltriacetoxysilane in acetone-d ⁶ after 24 h. mixture c (HCl) [mol / l] Proportion of C H ₃ COOSi 2.06-2.10 ppm [%] Proportion of C H ₃ COOH 2.01 ppm [%] pHK-EtSi (OAc) ₃ -V1 10 ^-2 51 49 pHK-EtSi (OAc) ₃ -V2 10 ^-1 51 49 pHK-EtSi (OAc) ₃ -V3 1 54 46

ermittelt. Für die partielle Hydrolyse und Kondensation von Ethyltriacetoxysilan sind lediglich T-Gruppen zu beachten. Tab. A6: Verteilung der T-Gruppen in den ²⁹Si-NMR-Spektren der Mischungen pHK-EtSi(OAc)₃-V1 bis -V3 für die partielle Hydrolyse von Ethyltriacetoxysilan nach 6 h. Mischung c(HCl) [mol/l] Anteil an T⁰ –43,91 ppm [%] Anteil an T¹ –49,12 bis –52,82 ppm [%] Anteil an T² –55,99 bis –60,47 ppm [%] Anteil an T³ –66,04 bis –67,20 ppm [%] K [%] pHK-EtSi(OAc)₃-V1 –210 < 1 69 15 16 49 pHK-EtSi(OAc)₃-V2 –110 2 66 16 16 49 pHK-EtSi(OAc)₃-V3 1 7 59 18 16 48 The results of the ²⁹ Si NMR measurements for pHK-EtSi (OAc) ₃ -V1 to -V3 to determine the degree of condensation of the mixtures are summarized in Table A6. The degree of condensation was according to the formula below

determined. For the partial hydrolysis and condensation of ethyltriacetoxysilane only T groups are to be considered. Tab. A6: Distribution of the T groups in the ²⁹ Si NMR spectra of the mixtures pHK-EtSi (OAc) ₃ -V1 to -V3 for the partial hydrolysis of ethyltriacetoxysilane after 6 h. mixture c (HCl) [mol / l] Proportion of T ⁰ -43.91 ppm [%] Proportion of T ¹ -49.12 to -52.82 ppm [%] Proportion of T ² -55.99 to -60.47 ppm [%] Proportion of T ³ -66.04 to -67.20 ppm [%] K [%] pHK-EtSi (OAc) ₃ -V1 -210 <1 69 15 16 49 pHK-EtSi (OAc) ₃ -V2 -110 2 66 16 16 49 pHK-EtSi (OAc) ₃ -V3 1 7 59 18 16 48

Cocondensation of the product of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid triethylene glycol ester and silicon tetraacetate ((MES-TEG) ₂ -Si (OAc) ₂ ) with partially hydrolyzed ethyltriacetoxysilane (pHK-EtSi (OAc) ₃ - V3) for the representation of the resin for structural variant III (SV III resin)

In a further synthesis, the addition product of MES-TEG and silicon tetraacetate ((MES-TEG) ₂ Si (OAc) ₂ ) was reacted with partially condensed ethyltriacetoxysilane (pHK-EtSi (OAc) ₃ -V3).

To this was added 9.56 g (36.2 mmol, 1.0 equiv) as described previously with 33.55 g (85.1 mmol) of 4- [2- (methacryloyloxy) ethoxy] -4-oxo-butanoic acid triethylene glycol ester containing about 15 mol% disubstituted by-product, reacted (proportion of MES-TEG: 26.21 g (72.3 mmol, 2.0 equiv.), reacted and the reaction product devolatilized. Dissolve 49 g (36.2 mmol, 1.0 equiv) of ethyltriacetoxysilane in 6.32 g (108.8 mmol, 3.0 equiv.) Of acetone, add 480 μl of water (26.6 mmol, 0.74 equiv. ) in the form of a 10 ^-2 molar hydrochloric acid solution and stirred for 24 h at 30 ° C. Then both mixtures were added together, the solvent was removed under reduced pressure or in an oil pump vacuum.
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 0.71-1.05 (m, 5H, C H ₃ C H ₂ Si), 1.95 (s, 6H, C H ₃ ), 2.08-2.16 (m, Residue C H ₃ COOSi), 2.67 (s, 8 H, CC H ₂ C H ₂ C), 3.58-3.71 (m, 16 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OSi), 3.92-4.09 (m, 4 H, (OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OSi), 4.23-4.27 (m, 4 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₂ OSi), 4.35 (m, 8 H OC H ₂ C H ₂ O), 5.60-5.61 (m, 2 H, H ₂ C =, cis) , 6.13 (m, 2H, H ₂ C =, trans).

The two compounds were then hydrolyzed stepwise at 30 ° C and co-condensed as explained in more detail in the synthesis of GM resin. The reaction was monitored by ¹ H-NMR.
¹ H-NMR (400.1 MHz, CDCl ₃ ):
δ [ppm] = 0.64-1.00 (m, 5H, C H ₃ C H ₂ Si), 1.95 (s, 6H, C H ₃ ), 2.06-2.08 (m, Residue C H ₃ COOSi), 2.66 (s, 8 H, CC H ₂ C H ₂ C), 3.59-3.72 (m, 16 H, OCH ₂ C H ₂ OC H ₂ C H ₂ OC H ₂ CH ₂ OSi), 3.92-3.95 (m, 4 H, (OCH ₂ CH ₂ ) ₂ OCH ₂ C H ₂ OSi), 4.23-4.26 (m, 4 H, OC H ₂ CH ₂ (OCH ₂ CH ₂ ) ₂ OSi), 4.35 (m, 8 H OC H ₂ C H ₂ O), 5.60 (m, 2 H, H ₂ C =, cis), 6.13 (m, 2H, H ₂ C =, trans).
²⁹ Si NMR (75.5 MHz, acetone-d ⁶ ):
δ [ppm] = -50.12 to -61.44 (T ¹ , ≈20%), -58.06 to -61.44 (T ² , ≈28%), -66.87 to -67.26 (T ³ , ≈5%), -82,81 (Q ⁰ , ≈3%), -86,10 to -89,42 (Q ¹ , ≈9%), -93,70 to -96,25 ( Q ² , ≈22%), -100.74 to -103.34 (Q ³ , ≈ 12%), -109.67 (Q ⁴ , <1%).
Crude yield: 33.21 g

In the raw yield, the proportion of disubstituted alcohol (MES ₂ TEG), which is included in MES-TEG, but is not reacted in the synthesis, not yet considered. If this proportion is deducted by calculation, the yield is 25.87 g (60.2 mmol, 83%).
M (SV III) calc _. = ≈860 g / mol

Each of the resin systems to be investigated was admixed with 1% by weight of the photoinitiator Lucirin-TPO and stirred at 30 ° C. or 40 ° C. until the initiator had dissolved (about 24-48 h).

For the tensile strength measurements, test specimens with a total length of 54 mm and a cross section of 2 mm × 4 mm were produced on the basis of DIN 53504. The ends were irradiated for 30 s and the bridge for a total of 100 s per side with a blue light lamp from VOCO in the wavelength range 380-520 nm.

For the degradation and biocompatibility tests, specimens in disc shape (diameter about 10 mm, height about 2 mm) with a weight of about 200 mg each were prepared by irradiating the resin systems with the above light source. Each side of the pane was exposed for 100 s, the edge for another 30 s.

Alternatively, the resin systems can also with 1 wt .-% of a thermal initiator, such. B. dibenzoyl peroxide are added and stirred at 40 ° C until it has dissolved (about 24 h). Thereafter, samples may be prepared by curing the formulation at 100 ° C for 4 hours.

QUOTES INCLUDE IN THE DESCRIPTION

This list of the documents listed by the applicant has been generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Cited patent literature

• WO 2011/098460 A1 [0005, 0005, 0023]

Cited non-patent literature

• F. Claeyssens et al. in "Three Dimensional Biodegradable Structures Fabricated by Two Photon Polymerization", Langmuir 25, 3219-3223 (2009) [0005]
• R. Narayan et al., In Mater. Res. Soc. Symp. P 2005, 845, 51 and in Acta Biomater. 2006, 2, 267 [0005]
• D. Tian et al. in the Journal of Polymer Science, Part A - Polymer Chemistry, "Biodegradable and Biocompatible Inorganic-Organic Hybrid Materials, I. Synthesis and Characterization", 1997, 35 (11) 2295-2309 [0005]
• R. Houbertz et al. showed in Coherence and Ultrashort Pulse Laser Emission, 2010, 583 [0005]
• EM Christenson et al. in Wiley InterScience on June 2, 2004 under DOI: 10.1002 / jbm.a.30067 [0011]
• TE Kristensen et al., Org. Lett. 2009, 11, 2968 [0039]
• Wiseman et al., J. Am. Chem. Soc. 2005, 127, 5540 [0040]
• JH Liu, DS Wu, KY Tseng, Macromol. Chem. Physic. 2004, 205, 2205 [0046]

Claims (11)

Silane of the formula (1) R ¹ _a SiR _4-a (1) wherein R ^{1 is} an organic substituent attached to the silicon via oxygen and having a hydrocarbon-containing chain interrupted by at least two -C (O) O groups, wherein in the individual hydrocarbon units formed therein by interruptions Chain is at most 8, preferably not more than 6, and more preferably not more than four carbon atoms follow each other and each of the hydrocarbon atom-remote end of the hydrocarbon-containing chain has an organically polymerizable group, R is a hydrolytically condensable group or hydroxy and a 1, 2, 3 or 4 is. A silane according to claim 1, wherein the organic polymerizable group has at least one organically polymerizable C = C double bond or an epoxy ring. A silane according to claim 2, wherein the polymerizable C = C double bond is part of an acrylate or methacrylate group. A silane according to any one of claims 1 to 3, wherein the hydrocarbon chain of the organic substituent R ^{1 is} further interrupted by oxygen atoms and / or sulfur atoms. A silane according to any one of the preceding claims wherein the hydrocarbon chain of the organic substituent R ^{1 has} alkylene units optionally substituted with one or more groups selected from hydroxy, carboxylic, phosphate, phosphonic, phosphoric ester, amino and amino groups. A silane according to any one of the preceding claims wherein the organic substituent R ^{1 is} straight chain or branched chain. A silane according to any one of the preceding claims wherein the hydrolytically condensable group is selected from acyl, alkyl and alkoxy. Silane mixture of different silanes according to any one of the preceding claims, wherein different silanes of the mixture have the same substituent R ¹ and different values for the subscript a, wherein the average value for a in the mixture is about 2. Organically modified silicic acid polycondensate, formed by hydrolytic condensation of a silane of claims 1 to 7 or of a silane mixture according to claim 8.  Organically modified, polymerized silicic acid polycondensate, formed by hydrolytic condensation of a silane of claims 1 to 7 or a silane mixture according to claim 8 and subsequent organic polymerization of the organically polymerizable groups. Use of an organically modified, polymerized silicic acid polycondensate according to claim 9 or claim 10 for the preparation of a biologically or medically usable article or an article for cell stabilization or cell culture.

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