Polyoxovanadate as a photoinitiator in the polymerization of monomers or oligomers

Abstract

Use of a polyoxovanadate as a photoinitiator in the polymerization of monomers, wherein the polyoxovanadate has at least two organic ligands with the structure -(CH2) x -R carries, with x = 0 to 7 and R = OH, N3, NH2, Br or COOH, and wherein the monomer is an acrylate-functionalized oligomer selected from acrylate-difunctionalized siloxanes and acrylate-difunctionalized ethylene glycols.

Description

[0001] The invention relates to the use of polyoxovanadates as a photoinitiator for polymerization.

[0002] Currently, a large number of photoinitiators exist for the photopolymerization of monomers, each focusing on use in specific environments. For example, α-hydroxyketone derivatives are used for application in aqueous environments and in biological and medical contexts, one particularly relevant example being 2-hydroxy-1-[4-(2-hydroxyethoxy)phenyl]-2-methyl-1-propanone (structure according to formula I).

[0003] Another relevant group in this field is that of the phosphine derivatives, the most prominent of which is LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate, structure according to formula II). This molecule is characterized by high water solubility (47 g / L) and absorption up to 380 nm with low cytotoxicity. These photoinitiators are referred to as type I photoinitiators. While type I photoinitiators undergo direct homolytic cleavage upon irradiation with light, thus generating a radical, type II photoinitiators typically abstract a proton from a neighboring donor species (often amines). Water-soluble examples include eosin-γ and riboflavin. A disadvantage of type II photoinitiators is the need to add donor molecules.

[0004] Polyoxometalates have also been discussed as potential photoinitiators.

[0005] In Liang, Zhije et al. (2022) polymerization using catechol-modified polyoxovanadates is described.

[0006] Yin, Panchao et al. (2011) reveal a fluorescent surfactant with a hexavanadate cluster as the head group.

[0007] Chen, Qin et al. (1992) describe polyoxovanadate coordination compounds with a hexametalate core.

[0008] Furthermore, a Keggin-type polyoxomolybdate H3PMo 12 O 40 It was described as a photoinitiator for the radical polymerization of trimethylolpropane triacrylate (Xiao, Pu et al. (2013)). Various other additives or monomers were used there, such as the following:

[0009] It is described there that in a mixture of molybdophosphoric acid (phosphomolybdic acid, H3PMo 12 O 40) with an iodine species and (TMS)3Si-H as well as the monomer EPOX, which polymerizes cationically, the resulting silylium cation (R3Si + ) initiates cationic polymerization. Molybdophosphoric acid generates the silylium cations in this process. This mixture can also initiate the radical polymerization of acrylates.

[0010] Currently, the selection of known water-soluble photoinitiators is also severely limited in their applications due to a number of properties of the molecules used. The known photoinitiator according to formula I is cytotoxic at higher concentrations and has an extinction coefficient of 4 M at 365 nm. -1 cm -1It has relatively low water solubility and therefore must be used in organic solvents or mixtures, which limits its range of applications. The photoinitiator according to formula III cannot absorb light above 350 nm, and although LAP (according to formula II) is characterized by high water solubility and low cytotoxicity, the photoinitiator is unable to absorb at higher wavelengths of the visible light range. This limitation makes its use in a medical / biological context impossible, as UV light is damaging to cells.

[0011] Purely inorganic polyoxometalates are not suitable for use in a biological context due to the high cytotoxicity of this class of substances.

[0012] In general, many type II photoinitiators are limited in their applications by the type of donor molecules that must be added to the mixture (such as triethylamine and ethyl 4-(dimethylamino)benzoate, two toxic or mutagenic substances) to ensure successful polymerization.

[0013] There is still a great need for new photoinitiators.

[0014] The object of the invention is to provide suitable photoinitiators for the polymerization of monomers. The initiation should occur as quickly as possible to enable application in 3D printing. The photoinitiators should be so well-suited (e.g., due to favorable extinction coefficients) that they do not require additives such as iodine or silyl compounds, triethylamine, or benzoates. They should be able to effectively initiate the polymerization with as few additives as possible (except for the solvent containing the monomer).

[0015] The problem is solved by the features of the independent claims. Preferred embodiments are described in the dependent claims.

[0016] The invention relates to the use of a polyoxovanadate as a photoinitiator in the polymerization of monomers or oligomers (here photopolymerization), for example in the polymerization of acrylates or epoxides, in particular also of acrylate-functionalized oligomers (these oligomers are also referred to in the context of the invention as the monomers to be polymerized).

[0017] According to the invention, the polyoxovanadate carries at least two organic ligands with the structure -(CH2) x -R, with x = 0 to 7 and R=OH, N3, NH2, Br or COOH, and the monomer is an acrylate-functionalized oligomer selected from acrylate-difunctionalized siloxanes and acrylate-difunctionalized ethylene glycols.

[0018] “Polyoxovanadates” within the meaning of the invention are anionic metal oxo cluster compounds consisting of vanadate, i.e., (VO4 3- )-units are constructed and bridged via oxygen atoms. A polyoxovanadate is a polyoxometalate. In the context of the invention, it can, for example, have the structure [V v 60 13 {(OCH2)3CCH2N3}2] 2- Wear. A polyoxovanadate of the Lindqvist type is advantageous.

[0019] Examples of countercations include alkali metal cations or NH4. + and others are being considered.

[0020] The photoinitiator according to the invention allows the polymerization of a desired polymer.

[0021] The photoinitiator according to the invention absorbs incident light and thereby generates a free electron that can be transferred to neighboring molecules. This initiates a radical polymerization. The photoinitiator can also be used as a starting point for subsequent modifications of the finished polymer to be produced.

[0022] The invention further relates to a process for the photopolymerization of monomers, comprising the steps of: a) Providing the monomer, wherein the monomer is an acrylate-functionalized oligomer selected from acrylate-difunctionalized siloxanes and acrylate-difunctionalized ethylene glycols, b) Addition of a polyoxovanadate as a photoinitiator (as a powder or solution; in particular the polyoxovanadate used according to the invention), wherein the polyoxovanadate carries at least two organic ligands having the structure (CH2)xR, with x = 0 to 7 and R = OH, N3, NH2, Br or COOH, and c) Irradiation with light. The order of steps a) and b) is interchangeable.

[0023] The subject matter therefore also includes the use of polyoxovanadate in the process according to the invention.

[0024] This means that all statements regarding the use of polyoxovanadate according to the invention also apply to the polyoxovanadate used in the process according to the invention.

[0025] It should be explicitly included that the monomers provided may also be mixtures of different monomers or types of monomers, resulting in copolymers. Advantages

[0026] It has surprisingly been shown that polyoxovanadates are suitable as photoinitiators in the polymerization of monomers, for example acrylates.

[0027] The polyoxovanadates used do not require any previously necessary additives – additives such as iodine compounds, silyl compounds like (TMS)3Si-H, triethylamine, or ethyl 4-(dimethylamino)benzoate. These can be omitted.

[0028] Furthermore, 3D printing enables the radiation-based design of new surfaces for cell growth in the form of hydrogels or freely configurable three-dimensional structures, specifically in medical / biological contexts, because absorption occurs even at longer wavelengths of the visible light spectrum, for example at 400 or even up to 500 nm. UV light would be damaging to cells.

[0029] However, with the polyoxovanadata according to the invention, it is equally possible to photoinitiate in the range of very lower wavelengths (0.2-200 nm).

[0030] Polyoxovanadates are thermostable up to temperatures above 200°C.

[0031] The extinction coefficient of polyoxovanadate (ε = 2596 M) -1 cm -1 For the exemplary connection from embodiment 1), the value is an order of magnitude higher than that of LAP (ε = 218 M). -1 cm -1 and three above that of Irgacure 2959 (ε = 4 M -1 cm -1 ) (Fairbanks et al. (2009)) at a wavelength of 365 nm and thus provides a significantly more efficient absorption of the incident light than comparable industry standards. Preferred embodiments

[0032] In a preferred embodiment of the invention, the polyoxovanadate comprises at least two organic ligands, each comprising an alkyl group (linear or branched) with 1-7 carbon atoms (preferably 1-3, particularly preferably 1). That is to say, the polyoxovanadate carries these two ligands. The two ligands can be different. Preferably, however, they are the same. The length of the alkyl groups is, as has been found, not essential, but relatively variable.

[0033] “Organic ligand” within the meaning of the invention means a substituent of the polyoxovananadate, preferably at the end of the -(OCH2)3C- structural moiety of the polyoxovananadate. The polyoxovananadate (without this ligand moiety) is fully oxidized, as for example in V v 60 13 {(OCH2)3C-}.

[0034] The advantage of this embodiment is that this organic structural unit offers improved biocompatibility and reduces cytotoxicity. Unlike other polyoxometalates, the polyoxovanadate is non-toxic. This means that with the photoinitiator in this embodiment, medical or biological materials can be printed (by polymerization), and the polyoxovanadate subsequently remaining within them does not inhibit cell growth.

[0035] The invention also makes it possible to insert molecules into the polyoxovanadate according to the invention, for example by coupling via click chemistry to the end of one of these ligands of the polyoxovanadate. The biocompatibility of the photoinitiator can be controlled by attaching, for example, DNA.

[0036] According to the invention, the polyoxovanadate carries at least two organic ligands with the structure -(CH2) x -R with x=0 to 7 (especially preferred 1 to 7, or also 1 to 3, or even 1) and R= -OH, -N3, -NH2, -Br or -COOH.

[0037] The -(CH2) x The -group clearly corresponds to the oa alkyl group, in a linear form.

[0038] R=N3 or OH is particularly preferred.

[0039] The advantage of a version with x = 1 to 7 is also that the organic group -(CH2) x This enables suitability for biological and medical applications. The cytotoxicity of the polyoxovanadate is reduced. Printing of cells or tissues via photopolymerization of monomers is thus possible. The high cytotoxicity of the polyoxometalate class is thereby reduced.

[0040] However, it is also possible that the organic group carries further alkyl substituents, so that the polyoxovanadate has at least two ligands with the exemplary structure -(CH(CH3)) x-R would include (with the same definition for x and R, as stated above), or even -(C(CH3)2) x -R.

[0041] In a particularly preferred embodiment of these two last-mentioned configurations with at least two organic ligands, exactly two ligands are involved. They are most preferably present in the trans position (at opposite positions) on the polyoxovanadate, which is advantageous for synthetic reasons.

[0042] For example, a DNA molecule could then be attached to these ligands (e.g., using click chemistry), as already mentioned earlier.

[0043] In another preferred embodiment with the organic ligand oa, x = 0 and R = NH2.

[0044] In a further preferred embodiment of the invention, polymerization takes place in an aqueous medium (i.e., the predominant part of the solvent of the mixture to be irradiated is water; in particular, >65% can be water). The polyoxovanadate comprises countercations selected from alkali metals, and (if it bears at least two organic ligands, each comprising an alkyl group with 0-7 carbon atoms) all ligands each bear an OH substituent. Advantageously, all available countercations are such alkali metal cations. Na is particularly preferred. + .

[0045] In the embodiment according to the invention (in which the polyoxovanadate has at least two organic ligands with the structure -(CH2) x-R carries with x=0 to 7 (preferably 1 to 7, or also 1 to 3, or even 1) and R=OH, N3, NH2, Br or COOH) this corresponds to a variant in which the countercations are alkali metals such as sodium and the R is OH for all ligands.

[0046] It has surprisingly turned out to be advantageous that this class of compounds has high water solubility, so that this photoinitiator can be used in aqueous media (either in an aqueous monomer solution or by presenting the photoinitiator already dissolved in water).

[0047] In a particularly preferred variant of this latter version, x=1 to 3, or even 1, is the case for all ligands.

[0048] The use of polyoxovanadate (as a photoinitiator in the photopolymerization of monomers) in 3D printing is also preferred. For use in 3D printers, the material is usually dispensed from a syringe in a monomer solution and then cured with a UV lamp. The monomer solution with photoinitiator is typically injected into a hollow mold, possibly also created using 3D printing (injection molding), to obtain the desired three-dimensional structure after the curing process.

[0049] Acrylate-functionalized oligomers are typically used as monomers in 3D printing. The observed high effectiveness of the photoinitiator according to the invention makes it suitable for 3D printing, as rapid photoinitiation at the start of irradiation is crucial.

[0050] According to the invention, the monomer is an acrylate-functionalized oligomer, namely an acrylate-difunctionalized siloxane, or it is an acrylate-difunctionalized ethylene glycol. Oligomer means a number of repeating units of known 10-30. The acrylate-difunctionalized siloxane is sensibly linear, for example, it is one according to the following structural formula: preferably with n=13±4.

[0051] For example, acrylate-difunctionalized ethylene glycol has one of the following structural formulas: preferably with n=13±10%.

[0052] The preferred use according to the invention (when the polyoxovanadate carries at least two organic ligands, as specified above) is in the production of biological and / or medical tissues by polymerization of monomers. This is because, as already explained above, the organic component, for example the -(CH2) x -, the cytotoxicity is noticeable in the ligand.

[0053] In another preferred embodiment of the invention, the polyoxovanadate has the structural formula M2[V6O 13 {(OCH2)3C-CH2-R}2], where M is the counter cation and -CH2-R is the organic ligand. Preferably, M is selected from NBu4 + and alkali + , such as Na + .

[0054] In a preferred embodiment of the method according to the invention, in step c) the wavelength is 365 nm ± 40 nm (or even 390–405 nm) and / or the distance between the light source and the polyoxovanadate from step b) is 30 mm ± 20 mm. The light source preferably emits with a power of 16 watts ± 6 watts, more preferably 14–18 watts. This has proven to be particularly suitable for the polyoxovanadates according to the invention.

[0055] The photoinitiator is preferably added as a solution (step b) of the process); most preferably as an aqueous solution.

[0056] Unless otherwise specified, it is advisable to combine the different embodiments.

[0057] The invention will now be explained in more detail with reference to several preferred embodiments. These embodiments are not intended to limit the invention. Fig. Figure 1 shows a formulation of the polyoxovanadate (of the cation, there without counterion) with two organic ligands and a residue R (for example OH, N3, NH2, Br). Fig. Figure 2 shows the extinction behavior as a function of the concentration of the polyoxovanadate in a preferred embodiment with organic ligand with-(CH2) x -R with x=1 and R=N3 at 375nm. Fig. Figure 3 shows the corresponding behavior of the compound at 400nm. Fig. Figure 4 shows the extinction behavior of the compound as a function of wavelength. Examples of implementation

[0058] The developed photoinitiator, either in powder form or as a solution, is mixed with the monomer or an oligomer and then irradiated with a light source. Irradiation with wavelengths in the vacuum-UV range (0.2–200 nm) up to the visible wavelength range (405 nm) creates a strongly oxidizing state by exciting an electron in the photoinitiator. This state abstracts an electron from neighboring molecules and thus exists as a radical. This state is energetically unstable and, over time, donates its unpaired electron to neighboring molecules, such as monomers or oligomers. This process initiates a classic radical polymerization. After this process is complete, the photoinitiator returns to its initial state and can be used for further applications or recycled.

[0059] The photoinitiator used in the exemplary embodiments is based on a modified Lindqvist-type polyoxovanadate with fully oxidized vanadium centers, which is described by the molecular formula M n [V v 60 13 {(OCH2)3C-Alkyl-R}2] is described, where M is the countercation (such as n-tetrabutylammonium, lithium, or sodium) and alkyl can be a (linear or branched) alkyl group with 0-7 carbon atoms. R is selected from OH, N3, NH2, Br, or COOH. However, if R = NH2, there is no alkyl group present; therefore, in the other formulas mentioned above, x would then be 0.

[0060] The polyoxovanadate used without the R residue is abbreviated as V6O. 19 .

[0061] In all experiments marked as exemplary embodiments, successful polymerization of the monomer was observed, visually in a Petri dish by means of turbidity. Examples of embodiments using the monomer polyethylene glycol diacrylate (PEGDA): Example 1: R=N3 and (NBu4) + Monomer PEGDA

[0062] The compound is used as polyoxovanadate according to Fig. 1, wherein the counter cation is a tetraalkylamonium cation ([NBu4] + ) is and R=N3. The compound is soluble in acetonitrile, acetone, and dimethylformamide (DMF) and is abbreviated as V6O. 19 -N3 TBA + The two organic ligands have the structure -(CH2) x -N3, where x=1.

[0063] The acrylate was polyethylene glycol diacrylate (PEGDA) with an average molecular weight of 700 g / mol and 13 repeating units. The experimental details are as follows: • 3.0 g H2O • 1.5 g PEGDA stock solution (this is a solution of 50% wt. PEGDA in water) • 500 mg V6O 19 -N3 TBA + Solution in MeCN 10mg / ml • 90s irradiation at 50% power

[0064] The extinction behavior is described in the Fig. Shown 2 to 4.

[0065] The extinction coefficient of polyoxovanadate (ε = 2596 M) -1 cm -1 ) is an order of magnitude greater than that of LAP (ε = 218 M -1 cm -1 and three above that of Irgacure 2959 (ε = 4 M -1 cm -1 The value refers to a 10 vol% solution of MeCN in water with the compound (TBA2[V6O). 13 {(OCH2)3CCH2N3}2]]2. The value was determined via a dilution series using linear regression at a wavelength of 400 nm. For 375 nm, the value would be 5786 M⁻¹ cm⁻¹. -1 . Example 2: R=OH and Na + Monomer PEGDA

[0066] The compound is used as polyoxovanadate according to Fig. 1, where the countercation is a sodium cation and R=OH. The compound is water-soluble and suitable for water-based formulations.

[0067] The acrylate was polyethylene glycol diacrylate (PEGDA) with an average molecular weight of 700 g / mol and 13 repeating units. The experimental details are as follows: • 3.0 g H2O • 1.5 g PEGDA stock solution (50% wt. in water) • 500 mg V6O 19 -OH Na + Solution in H2O 10 mg / ml • 60s irradiation at 30% power • 180s irradiation at 50% Comparative example with LAP and without polyoxovanadate. Monomer PEGDA:

[0068] LAP is a commercially available, conventional photoinitiator. The experimental details are as follows: • 3.35 g H2O • 1.5 g PEGDA stock solution (50% wt. in water) • 150 mg LAP solution (10% wt.) • 60s irradiation at 30% power Examples of embodiments using the monomer acrylate-functionalized polydimethylsiloxane

[0069] The following compound, abbreviated as RC 715, is used as the monomer. Example 3: R=OH and Na + Monomer RC 715

[0070] The compound is used as polyoxovanadate according to Fig. 1, where the counter cation is a sodium cation (Na + ) is and R=OH. The compound is water-soluble.

[0071] The experimental details are as follows: • 200 µl RC 715 • 100 µl V6Q 19 -OH Na + in H2O (2 mg / ml) • 60s irradiation at 30% power -> 5s pause • 90s irradiation at 50% power Comparison example with LAP and without polyoxovanadate. Monomer RC 715:

[0072] LAP is a commercially available, conventional photoinitiator. The experimental details are as follows: • 200 µl RC 715 • 100 µl 10% wt. Lithium phenyl 2,4,6,-trimethylbenzoate (LPA) • 60s irradiation at 30% power • Positive control experiment Non-patented literature

[0073] Chen, Qin et al. (1992): „Coordination Compounds of Polyoxovanadates with a Hexametalate Core. Chemical and Structural Characterization of [...]“, J. Am. Chem. Soc. 1992, Vol. 114, S. 4667 - 4681.

[0074] Fairbanks, Benjamin D. et al. (2009), „Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility“, Biomaterials 2009, Vol. 30, No. 35, S. 6702-6707.

[0075] Yin, Panchao et al. (2011): „A Double-Tailed Fluorescent Surfactant with a Hexavanadate Cluster as the Head Group“, Angew. Chem. Int. Ed. 2011, Vol. 50, S. 2521 - 2525.

[0076] Xiao, Pu et al. (2013), „Keggin-Type Polyoxometalate ([PMo 12 O 40 ] 3- ) in Radical Initiating Systems: Application to Radical and Cationic Photopolymerization Reactions“, Macromol. Chem. Phys. 2013, Vol. 214, S. 1749-1755.

[0077] In Liang, Zhije et al. (2022), „Polymerization of Catechol Employing Polyoxovanadate as Biomimetic Models Catalyze for Textile Dyeing“, Fibers and polymers 2022, Vol. 23, No. 12, S. 3380-3385.

Claims

[1] Use of a polyoxovanadate as a photoinitiator in the polymerization of monomers, wherein the polyoxovanadate has at least two organic ligands having the structure -(CH2) x -R carries, with x = 0 to 7 and R = OH, N3, NH2, Br or COOH, and wherein the monomer is an acrylate-functionalized oligomer selected from acrylate-difunctionalized siloxanes and acrylate-difunctionalized ethylene glycols. [2] Use according to claim 1, wherein x = 1 to 7. [3] Use according to claim 2, wherein R=OH or R=N3. [4] Use according to claim 1, wherein x = 0 and R = NH2. [5] Use according to one of claims 1 or 2 or 3, in the polymerization in aqueous medium, wherein the polyoxovanadate comprises countercations selected from alkali metals, and R=OH for all ligands. [6] Use according to claim 5, wherein x=1 to 3 for all ligands. [7] Use according to any one of claims 1 to 6 wherein the polyoxovanadate carries exactly two of the organic ligands and these are in the trans position. [8] Use according to any one of claims 1 to 7, in 3D printing. [9] Use according to any one of claims 1 to 8, in the production of biological and / or medical tissues by polymerization of monomers. [10] Use according to any one of claims 1 to 9, wherein the polyoxovanadate has the structural formula M2[V V 60 13 {(OCH2)3C-CH2-R}2], where M is the counter cation and -CH2-R is the ligand. [11] Method for the photopolymerization of monomers, comprising the steps: a) Providing the monomer, wherein the monomer is an acrylate-functionalized oligomer selected from acrylate-difunctionalized siloxanes and acrylate-difunctionalized ethylene glycols, b) Addition of a polyoxovanadate as a photoinitiator, wherein the polyoxovanadate contains at least two organic ligands having the structure -(CH2) x -R carries, with x = 0 to 7 and R = OH, N3, NH2, Br or COOH, c) Irradiation with light. [12] Method according to claim 11, wherein in step c) the wavelength is 365nm ±40nm and the distance between the light source and the polyoxovanadate from step b) is 30mm ±20mm.

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