Chromatographic material with improved pH stability, methods for its preparation and its uses

Abstract

Chromatographic material including: Substrate having a surface, wherein the substrate has a polymer layer covalently bonded to the surface; wherein the polymer layer comprises polymer molecules covalently attached to the surface of the substrate, wherein each polymer molecule is attached to the surface via multiple siloxane bonds and each polymer molecule is linked to one or more functionalizing compounds, each comprising a functional group, wherein the functional group comprises C14-C22 alkyl.

Description

Referral back to related applications

[0001] This application claims the priority advantage under 35 USC §119(e) of the preliminary US patent application serial no. 62 / 103,869 [Attorney file no. 19697P1 / NAT] by Xiaodong LIU, Xiao CUI, Xuefei SUN for “CHROMATOGRAPHIC MATERIAL WITH IMPROVED pH STABILITY, METHOD FOR ITS MANUFACTURING AND ITS USES” filed on January 15, 2015, the disclosure of which is hereby incorporated in its entirety by reference. Field of invention

[0002] This invention relates to the field of chromatographic sample separation, which includes liquid chromatography and solid-phase extraction, and in particular to the material and the synthesis of the material for use as a stationary phase in chromatographic sample separation. The invention further relates to the uses of the material, especially in the separation of aminoglycoside antibiotics. The invention also relates to chromatography columns and solid-phase extraction columns that contain the material as a stationary phase. background

[0003] Liquid chromatography (LC), such as high-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography (UHPLC), and solid-phase extraction (SPE) are routinely used in both analytical and preparative chromatography applications to determine the quality and quantity of analytes in a wide variety of samples. In these chromatographic techniques, the separation of a sample, which comprises a mixture of components (also called analytes), is achieved by transporting the sample in a liquid mobile phase through a stationary phase in a column. This causes the sample to separate into its components due to the different distributions of each component between the mobile and stationary phases (i.e., the components have different partition coefficients). The stationary phase is typically in the form of a particle bed packed into the column or as a monolithic material contained within the column.

[0004] A bed of non-porous particles has a relatively small sample capacity. Therefore, porous particles containing a network of pores are often used to increase the surface area of ​​the stationary phase and thus improve the separation capacity. The porous particles can be completely porous, with the pores extending over the mass of the particles. As an alternative to completely porous particles, so-called fused-core particles, also known as surface-porous particles, have recently been used. These are particles that have a non-porous core (also called a fused or solid core) and are porous only in an outer layer or region surrounding the non-porous core.

[0005] The selectivity of a stationary phase for analytes is primarily determined by the column chemistry, which is key in LC separation. Column chemistry is routinely controlled by modifying the stationary phase surface, generally by binding ligands to the surface.

[0006] Silicon dioxide particles are frequently used as the stationary phase, either as non-porous, fully porous, or surface-porous particles. Silicon dioxide-based HPLC columns are used for a wide range of applications due to their excellent physical strength, high efficiency, and sophisticated surface compound chemistry.

[0007] However, silicon dioxide-based columns are subject to pH limitations. Under acidic conditions, the bound ligands can be cleaved from the siloxane (Si-O-Si) bond between the silicon dioxide surface and the ligand, leading to a decrease in hydrophobic retention in the case of a C18-bonded column. Under basic conditions, hydroxide ions can erode the silicon dioxide substrate by disrupting the siloxane bonds in the silicon dioxide framework, causing the collapse of the packed bed or the vapor space (empty) in the column.

[0008] Stationary-phase media for HPLC separations are generally prepared by modifying the silicon dioxide surface with silylizers. Monofunctional silylizers are often used to form single-layer surface coatings, while bi- and trifunctional silylizers are used to form polymer coatings on silicon dioxide surfaces, generally resulting in improved chemical stability. However, the use of some silylizers leads to coatings with undesirable properties, including instability towards hydrolysis and insufficient masking of acidic silanols on silicon dioxide surfaces. Consequently, the typical pH working range for C18 silicon dioxide columns prepared using these approaches is between 2 and 8.

[0009] Several attempts have been made to produce pH-stable stationary silicon dioxide phases for HPLC applications.

[0010] In an approach to the production of stable separation media for HPLC applications, Fisk et al. (WO 00 / 45951 A1) disclose a process for the production of porous inorganic / organic hybrid silicon dioxide particles as a solid support for further surface modifications. After reaction with silylating agents, such as dimethyl octadecyl chlorosilane, the resulting materials exhibited reduced silanol activity and improved hydrolysis resistance with an extended pH operating range of 1 to 13. Disadvantages of this approach include lower capacity and reduced column efficiency, primarily due to the limited availability of surface silanols and the slightly polymeric nature of the material.

[0011] In another approach, Glajch et al. (US Patent 4 705 725 A) describe separation media modified by the covalent bonding of a monofunctional silane to the surface, wherein the silane contains two sterically hindering groups and an additional functional group attached to the silicon atom.

[0012] Columns packed with such materials exhibited increased hydrolysis resistance at low pH. The use of such silylating agents is disadvantageous because the bound phases often have a lower surface coverage, leading to reduced phase stability under high pH conditions.

[0013] In another procedure, JJ Kirkland et al. report on the preparation of bidentate silane-based stationary phases for reversed-phase HPLC (JJ Kirkland; JB Adams, Jr.; MA van Straten; HA Claessens, Analytic Chemistry, 70: 4344-4352 (1998)). Such stationary phases are characterized by good hydrolysis resistance at low, medium, and high pH values ​​(1.5–11.5) and satisfactory column efficiency. Similarly, Liu et al. (US Patent 7,074,491 B2) describe polar-embedded bidentate reversed-phase materials that exhibit an extended pH range (pH 1.5–10.5) and unique selectivity.

[0014] MJ Wirth describes the immobilization of a monolayer of silane ligands on a silicon dioxide surface by horizontal polymerization of mixed trifunctional silanes, which exhibit higher hydrolysis resistance compared to conventional monomeric stationary phases (MJ Wirth, HO Fatunmbi, Anal. Chem. 65 (1993) 822). The resulting silicon dioxide stationary phase is reported to be stable for 100 hours after exposure to a solution at pH 1.8 (50°C) and to degrade by less than 5% after 30 hours of treatment with a solution at pH 10. While the horizontal polymer layer helps protect the silicon dioxide surface from attack, the siloxane linkage generated in the polymer chain remains exposed to the environment and will readily hydrolyze under extreme conditions, compromising the long-term stability of the silicon dioxide phase.

[0015] The use of polymer-encapsulated silicon dioxide is another approach to improving stationary-phase stability by combining the high mechanical strength of a silicon dioxide substrate with the high chemical stability of polymers. The polymer layer is formed on the silicon dioxide surface to protect it from aggressive pH conditions. Various hydrophobic polymers, such as polymethyl octadecylsiloxane (MJJ Hetem, JW De Haan, HA Claessens, CA Cramers, A. Deege, G. Schomburg, J. Chromatogr. A 540 (1991) 53) and polybutadiene (M. Hanson, KK Unger, G. Schomburg, J. Chromatogr. A 517 (1990) 269), have been used to encapsulate the silicon dioxide particles. These coating layers are first physically deposited on the silicon dioxide surface and then crosslinked or chemically bonded to the substrate. However, several disadvantages have been reported, such as… B.Non-uniform surface coverage and lower pH stability than desired at pH extremes are drawbacks. Furthermore, stationary phases produced using this approach suffer from the inherent problems of column bleed and manufacturing reproducibility. The polymer layer can also be deposited at multiple points on an inorganic support surface. For example, the silicon dioxide surface can be modified with a styrene-vinylmethyldiethoxysilane copolymer by refluxing the toluene suspension for 5 hours (A. Kurganov, V. Davankov, T. Isajeva, K. Unger, F. Eisenbeiss, J. Chromatogr. A 660 (1994) 97). However, the resulting polymer layer is not sufficiently stable because the immobilization efficiency is low due to steric hindrance of the copolymer chain. The immobilized polymer layer must be crosslinked to improve its hydrolysis resistance in an aggressive environment.

[0016] H. Engelhardt et al. described improved stability of a stationary silicon dioxide phase achieved through the copolymerization of vinyl-modified silicon dioxide with acrylic acid derivatives. In the first step, the silicon dioxide is modified with a silane containing an individual vinyl group in the presence of triethylamine. In the second step, the surface is coated by polymerizing an acrylic acid derivative, incorporating the desired functionality, with the immobilized vinyl groups in solution using α,α'-azoisobutyronitrile (AIBN) as an initiator. Free-radical polymerization was carried out for 2–3 hours at a temperature between 80°C and 120°C. The resulting polymer-encapsulated silicon dioxide phases exhibited a longer lifetime than the conventional brush-type phase under basic conditions.However, they were not sufficiently stable and quickly failed when used at a pH above 9.0 (H. Engelhardt, H. Löw, W. Eberhardt, M. Mauß, Chromatographia, 27 (1989) 535).

[0017] An important application of pH-stable stationary phases is the simultaneous qualitative and quantitative determination of aminoglycosides by HPLC. Aminoglycoside antibiotics are frequently used as clinical and veterinary drugs to treat infections caused by Gram-negative bacteria. However, these antibiotics can cause ototoxicity and nephrotoxicity to varying degrees. Therefore, it is crucial to develop sensitive and reliable analytical methods for determining aminoglycoside content during drug manufacturing and to monitor aminoglycoside residues in different sample matrices. However, HPLC separations of aminoglycosides are challenging due to their structural similarity, extremely high hydrophilicity, and lack of chromophores.Ion-pair reversed-phase liquid chromatography (IP-RPLC), ion chromatography (IC), and hydrophilic interaction liquid chromatography (HILIC) are used to analyze aminoglycosides without any derivatives. Reversed-phase columns (e.g., C18) are the columns of choice when dealing with aminoglycoside antibiotics because they offer the desired selectivity, high efficiency, and excellent mechanical strength. However, the requirement for extremely acidic conditions (e.g., pH ~1) makes most silicon dioxide-based C18 columns unsuitable for this application. Most C18 columns only last 24 to 48 hours before losing more than 20% of their reversed-phase capacity.

[0018] DE 10 2005 031 166 A1 discloses a process for the surface modification of solid support materials, characterized by the following reaction steps: a) providing a solid support material, b) reacting the solid support material with silanes in the presence of an ionic liquid as a solvent, c) separating the support material, d) optionally washing and drying the support material. This document further describes the reaction of a monolithic molded body with vinylsilane and subsequent polymerization with styrene / divinylbenzene.

[0019] US 5,840,388 A discloses a coated microcapillary column for high-performance electrophoresis. A preferred microcapillary comprises a quartz glass capillary column, wherein the inner surface of the column has an interconnected polymer coating of a polyvinyl alcohol-based (PVA) polymer, which is covalently attached to the column wall by Si-O-Si bonds.

[0020] US 2003 / 0219597A1 discloses a silicon dioxide-based material comprising a silicon dioxide-based substrate and a polymerized organic material deposited thereon. The polymerized organic material consists of reactive organic molecular groups bonded to the silicon dioxide-based substrate.

[0021] DE 35 86 838 T2 discloses a modified material comprising (1) a support covalently bonded to a synthetic polymer; (2) wherein the synthetic polymer comprises a copolymer produced by free radical polymerization of (a) a polymerizable compound containing an epoxy group that can directly couple covalently to a hydroxyl group of the support, and a vinyl group that can undergo free radical polymerization; and (b) a polymerizable compound having the formula wherein R is an α, β-ethyleneistically unsaturated polymerizable residue, R1; and R2; represent identical or different C1-C6 alkyl or alkanoyl groups, and R3 is a direct bond or a C2-C3 alkyl group, wherein R1 and R2 together with the nitrogen atom can form a heterocyclic ring, wherein the amount of compound (a) in the synthetic polymer is sufficient to effect covalent coupling of the polymer to the support, but is insufficient to cause a loss of porosity of the modified material, characterized in that the support is silicon oxide.

[0022] US 5,447,617 A discloses coated capillary electrophoresis columns and methods for their use in electrophoretic separations. The coated capillary columns comprise a tube segment with an inner surface having a bonded polymer coating. The bonded polymer coating comprises a hydrophobic polymer functionality covalently bonded to the inner surface and a hydrophilic polymer bonded to the hydrophobic polymer functionality. Summary

[0023] According to one aspect of the invention, the following is provided: Comprehensive chromatographic material: Substrate that has a surface and that has a polymer layer covalently bonded to the surface; wherein the polymer layer comprises polymer molecules covalently attached to the surface of the substrate, each polymer molecule being attached to the surface via multiple siloxane bonds (i.e., Si-O-Si bonds), and each polymer molecule being linked to one or more (preferably several) functionalizing compounds, each comprising a functional group, wherein the functional group comprises C14-C22 alkyl. The functional group particularly and desirablely has chromatographic functionality.

[0024] The material can therefore be considered a polymer-encapsulated material.

[0025] The polymer preferably comprises a siloxane polymer or a polymer containing silyl groups. The silyl groups of this polymer allow the polymer to attach to a silicon dioxide substrate via siloxane bonds.

[0026] The polymer layer is preferably formed by covalently attaching at least one polymer molecule to the surface of the substrate, wherein each polymer molecule is attached to the surface via several siloxane bonds and each polymer molecule contains several first reactive groups (in particular olefinic groups, especially vinyl groups or allyl groups or thiol groups), and reacting the first reactive groups of the attached polymer molecules with at least one functionalizing compound comprising a second reactive group that reacts with the first reactive groups (in particular an olefinic group or -SH (thiol) group), and which further comprises a functional group that in particular has a chromatographic functionality, wherein the functional group comprises C14-C22 alkyl.

[0027] In a particularly preferred embodiment, the invention provides the following: Comprehensive chromatographic material: Silicon dioxide substrate having a surface and a polymer layer covalently bonded to the surface; wherein the polymer layer is formed by covalent attachment of at least one polymer to the surface of the substrate, wherein the polymer is selected from a vinylalkoxysiloxane polymer and a vinyl-functionalized silyl-modified polybutadiene, wherein each polymer molecule is attached to the surface via multiple siloxane bonds (Si-O-Si) and each polymer molecule contains multiple vinyl groups, and wherein the vinyl groups of the attached polymer molecules react with the at least one functionalizing compound comprising a second reactive group that reacts with the vinyl groups of the attached polymer molecules, wherein the second reactive group is selected from a vinyl, allyl or thiol group, and further comprising a C14-C22 alkyl functional group (preferably C18 alkyl), wherein the functional group in particular has a chromatographic functionality, such as a reversed-phase chromatographic functionality.

[0028] The material according to the invention thus comprises a substrate, a polymer layer bonded to the substrate, and a functional compound bonded to the polymer layer. The polymer layer acts in such a way that it bonds the functional compound to the substrate and protects the substrate from hydrolysis. The functional compound enables chromatographic separation of analytes, e.g., by reversed-phase separation.

[0029] According to another aspect of the invention, a method for forming functionalized silicon dioxide for chromatographic purposes is provided, the method comprising: In a first stage, the silicon dioxide reacts with at least one first functionalizing compound under conditions of elevated temperature and reduced pressure; wherein the first functionalizing compound or compounds comprise one or more silyl groups for reacting with the surface of the silicon dioxide and one or more first reactive groups, whereby the first functionalizing compound or compounds are covalently attached to the surface of the silicon dioxide and the first reactive groups are left in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with at least one second functionalizing compound comprising one or more second reactive groups that are reactive with the one or more first reactive groups, and which further comprises a functional group, wherein the functional group comprises C14-C22 alkyl.

[0030] According to yet another aspect of the invention, a method for the formation of functionalized silicon dioxide for chromatographic purposes is provided, the method comprising: In a first stage, the silicon dioxide reacts with at least one first functionalizing compound under conditions of elevated temperature; wherein the first functionalizing compound or compounds comprise a polymer or polymers having several silyl groups for reacting with the surface of the silicon dioxide and several first reactive groups, whereby the first functionalizing compound or compounds are covalently attached to the surface of the silicon dioxide and the first reactive groups are left in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with at least one second functionalizing compound comprising one or more second reactive groups that are reactive with the one or more first reactive groups, and which further comprises a functional group, wherein the functional group comprises C14-C22 alkyl.

[0031] The invention thus relates to the production of stationary phase material by functionalizing silicon dioxide substrates with polymers at elevated reaction temperatures and preferably reduced pressures. The material has proven to be very pH-stable and useful as a separation medium.

[0032] In the process, which uses an elevated reaction temperature and reduced pressure, the at least one first functionalizing compound is preferably a polymer, as described below in this document, i.e., the polymer for covalent attachment to the substrate surface, or it may be a silane monomer (e.g., a vinylsilane). In particular, the polymer may be of the type of a siloxane polymer (e.g., vinylsiloxane polymer) or a silyl-modified polymer, such as silyl-modified polybutadiene, as described below.

[0033] The second functionalizing compound is preferably a hydrocarbon compound comprising an olefinic group or bond, in particular an alkyl compound, or it is an alkylthiol or arylthiol, as described below.

[0034] The first bonded layer of the polymer layer on the surface, i.e., formed from the first functionalizing compound or polymer, is preferably made from a polymer with specific dimensions (molecular weights) that are neither too small for good stability nor too large to clog pores, thus causing poor chromatography. The second bonded (functionalizing) layer of the polymer layer is preferably formed by copolymerizing the second functionalizing compound (containing functional groups (e.g., alkyl or aryl) and olefinic reactive groups (e.g., vinyl, allyl, styrene, acrylamide, acrylate, etc.)) with the first reactive groups in the first bonded layer (e.g., vinyl and allyl groups).

[0035] The second stage of the process preferably provides the polymer encapsulation of the silicon dioxide phases by means of polymerization of the polymer layer by free radicals.

[0036] The invention uses a polymer (whereby this term encompasses a molecule that may elsewhere be referred to as an oligomer) to form a polymer layer, wherein the polymer layer has several reactive (e.g., vinyl) groups and several silyl groups for attachment to a surface, resulting in better coverage and protection of the surface siloxane bonds than the use of simple small vinyl-functional silane molecules as described in Engelhardt et al. (Chromatographia, 27 (1989) 535). In the latter case, the surface siloxane bonds are more susceptible to attack under acidic or basic conditions. Tests have shown that the use of a polymer in the form described in this document can provide 50 to 100% higher stability at extreme pH values ​​(pH 1 and pH 13) compared to the use of a corresponding monomeric vinylsilane molecule.

[0037] The materials provided according to the invention can exhibit outstanding stability under acidic conditions and significantly improved robustness under basic conditions. A column packed with such material (such as a chromatography or solid-phase extraction column) can be suitable for the separation of aminoglycoside antibiotics with excellent resolution and chemical robustness. A C18-functionalized material according to the invention has shown excellent hydrolysis resistance at extremely low pH conditions and exhibits significantly improved stability under basic conditions. A column packed with such a C18-functionalized material has proven suitable for the separation of aminoglycoside antibiotics with longer lifetime and higher resolution.

[0038] According to a further aspect of the invention, a method for separating aminoglycoside antibiotics is provided, comprising flowing a mobile phase containing a sample with one or more aminoglycoside antibiotics through a column to chromatographically separate the one or more aminoglycoside antibiotics from each other and / or from one or more other components of the sample, wherein the column is packed with the chromatographic material according to the present invention. Preferably, the pH of the mobile phase is approximately 1 or less, which is typical for the separation of aminoglycoside antibiotics. The chromatographic material according to the invention can also be useful in other applications with basic phases, e.g., at a pH of approximately 11.

[0039] In an embodiment for producing the chromatographic material as described above, the process may further include reacting the silicon dioxide during the first and / or second stage at a reduced pressure (in particular below atmospheric pressure and preferably below 500 mbar).

[0040] In one embodiment, a chromatographic material can be produced by a process comprising, in a first step, the reaction of silicon dioxide with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar. The first functionalizing compound or compounds comprise one or more silyl groups for reacting with the surface of the silicon dioxide and one or more first reactive groups. This causes the first functionalizing compound or compounds to be covalently bound to the surface of the silicon dioxide, leaving the first reactive groups in an unreacted state. In a second step, the one or more first reactive groups of the surface-bound first functionalizing compound or compounds are reacted with the at least one second functionalizing compound.The second functionalizing compound comprises one or more second reactive groups that are reactive with the one or more first reactive groups, and a functional group, the functional group comprising C14-C22 alkyl. The retention time of a hydrophobic neutral compound in a chromatographic analysis varies by no more than ±10% while a mobile phase is passed through the chromatographic material for more than 20 hours, with the mobile phase having a pH of approximately 1 or less. The hydrophobic neutral compound may include acetanilide.

[0041] With regard to the chromatographic material described above, it may further include repeating a step of reacting the silicon dioxide with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar during the first stage, but before the second stage. A step of reacting the one or more first reactive groups of the surface-bound first functionalizing compound(s) with the at least one second functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar during the second stage may be repeated.

[0042] With regard to the chromatographic material described above, the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage can be carried out in the absence of a solvent. Similarly, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound(s) with the at least one second functionalizing compound in the second stage can be carried out in the absence of a solvent.

[0043] With regard to the chromatographic material described above, the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage can be carried out in the presence of a catalyst.

[0044] With regard to the chromatographic material described above, the first functionalizing compound may comprise a vinylsiloxane polymer. The vinylsiloxane polymer may have a formula I: where n is an integer from 3 to 100, and R1 and R2 are independently selected from the group consisting of: alkoxy, hydroxyl and halogen.

[0045] With regard to the chromatographic material described above, the first reactive group may comprise a member selected from the group consisting of vinyl groups and allyl groups. The functional group may comprise a member selected from the group consisting of an alkyl and an aryl group. In particular, the functional group may comprise a C4-C30 alkyl group. The second reactive group may comprise a member selected from the group consisting of a vinyl group, an allyl group, and a thiol group. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The accompanying drawings, which are included in and form part of this patent specification, illustrate the currently preferred embodiments of the invention and, together with the general description above and the detailed description below, serve to explain the features of the invention (where the same reference numerals denote the same elements). Fig. Figure 1 (Scheme 1) shows the preparation of vinyl-functionalized silicon dioxide using vinylsilane polymer. Fig. Figure 2 (Scheme 2) shows the preparation of vinyl-functionalized silicon dioxide using vinylsilane copolymer. Fig. Figure 3 (Scheme 3) shows the preparation of vinyl-functionalized silicon dioxide using triethoxysilyl-modified polybutadiene. Fig. Figure 4 (Scheme 4) shows the preparation of vinyl-functionalized silicon dioxide using diethoxymethylsilyl-modified polybutadiene. Fig. Figure 5 (Scheme 5) shows the preparation of vinyl-functionalized silicon dioxide using trimethoxysilane monomer. Fig. Figure 6 (Scheme 6) shows a preparation of polymer-encapsulated silicon dioxide. Fig. Figure 7 (Scheme 7) shows the preparation of C8 with S-bonding silicon dioxide. Fig. Figure 8 illustrates a hydrolysis resistance test at a pH of 1 (0.1M TFA) and 80°C using the newly developed pH-stable C18 phase 42 and the known C18 column (Mark A). Fig. Figure 9 illustrates a hydrolysis resistance test at a pH of 13 (0.1M NaOH) and 30°C using the newly developed pH-stable C18 phase 43 and the known C18 column (Mark A). Fig. Figure 10 shows the performance test of a column packed with the newly developed pH-stable C18 phase 42. Fig.Figure 11 shows the ion-pair reversed-phase LC separation of gentamicin sulfate under the low pH condition (100 mM TFA, pH ~1) using the newly developed pH-stable C18 phase 42. Fig. Figure 12 shows the ion-pair reversed-phase LC separation of spectinomycin sulfate under the low pH condition and in the presence of HFBA using the newly developed pH-stable C18 phase 42. Fig. Figure 13 illustrates the effect of the HFBA concentration in the mobile phase (100 mM TFA) on the retention factors of 8 aminoglycoside antibiotics using the newly developed pH-stable C18 phase 42. Fig. Figure 14 illustrates the robustness test of the column packed with the newly developed pH-stable C18 phase 42 under the low pH condition (100 mM TFA, pH ~1) and 50°C using gentamicin as a test probe. Detailed description

[0047] Various preferred features, embodiments and examples of the invention will now be described in more detail. Definitions:

[0048] In this document, the term "hydrocarbon" and the like (e.g., hydrocarbon unit, hydrocarbon residues, etc.) includes alkyl and aryl groups as defined below in this document.

[0049] In this document, "carbon chain length" or "total carbon chain length" refers to the longest carbon chain length in the molecule. Thus, in the case of straight chains, the chain lengths are simply numbered, for example:

[0050] Chain branches are not included in the chain length count, such as:

[0051] In the case of an aryl group, the number of carbon atoms in the benzene ring counts as 4 in the chain length for a para bond and 3 for a meta bond, for example:

[0052] All heteroatoms are not counted as carbon atoms in the carbon chain length.

[0053] In this document, the term 'alkyl', whether alone or as part of another substituent, unless otherwise specified, means a straight or branched chain or cyclic hydrocarbon residue, or a combination thereof, which may be fully saturated, monounsaturated, or polyunsaturated and may include divalent and polyvalent radicals, where the number of carbon atoms is indicated (i.e., C1-C1). 10(meaning one to ten carbon atoms). Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl (e.g., -CH2-CH2-CH3, -CH2-CH2-CH2-), isopropyl, n-butyl, t-butyl, isobutyl, sec. butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An unsaturated alkyl group is one that has one or more double or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and their higher homologs and isomers. Unless otherwise specified, the term "alkyl" also includes those alkyl derivatives that are defined in more detail below as "heteroalkyl".Alkyl groups restricted to hydrocarbon groups are called "homoalkyl". The term "alkyl" can also mean "alkylene" or "alkyldiyl" as well as alkylidenes in cases where the alkyl group is a divalent radical.

[0054] Typical alkyl groups include, among others: methyl; ethyls such as ethenyl, ethenyl, ethinyl; propyls such as propan-1-yl, propan-2-yl, cyclopropan-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl (allyl), cycloprop-1-en-1-yl; cycloprop-2-en-1-yl, prop-1-yn-1-yl, prop-2-yn-1-yl, etc.; butyls such as... B. Butan-1-yl, Butan-2-yl, 2-Methyl-Propan-1-yl, 2-Methyl-Propan-2-yl, Cyclobutan-1-yl, But-1-en-1-yl, But-1-en-2-yl, 2-Methyl-Prop-1-en-1-yl, But-2-en-1-yl, But-2-en-2-yl, Buta-1,3-dien-1-yl, buta-1,3-dien-2-yl, cyclobut-1-en-1-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-1-yl, but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc. and the like.

[0055] In this document, the term "alkylene" or "alkyldiyl," whether used alone or as part of another substituent, means a divalent radical originating from an alkyl group, as in the example of -CH2CH2CH2-(propylene or propane-1,3-diyl), and further includes those groups described below as "heteroalkylenes." Typically, an alkyl (or alkylene) group has 1 to approximately 30 carbon atoms, preferably 1 to approximately 25 carbon atoms, more preferably 1 to approximately 20 carbon atoms, even more preferably 1 to approximately 15 carbon atoms, and most preferably 1 to approximately 10 carbon atoms. A “low alkyl”, “low alkylene” or “low alkyldiyl” is a shorter-chain alkyl, alkylene or alkyldiyl group that generally has approximately 10 or fewer carbon atoms, approximately 8 or fewer carbon atoms, approximately 6 or fewer carbon atoms or approximately 4 or fewer carbon atoms.

[0056] In this document, the term "alkylidene," whether used alone or as part of another substituent, means a divalent radical originating from an alkyl group, as in the example of CH3CH2CH2= (propylidene). Typically, an alkylidene group has 1 to approximately 30 carbon atoms, preferably 1 to approximately 25 carbon atoms, more preferably 1 to approximately 20 carbon atoms, even more preferably 1 to approximately 15 carbon atoms, and most preferably 1 to approximately 10 carbon atoms. A "low alkyl" or "low alkylidene" is a shorter-chain alkyl or alkylidene group, generally having approximately 10 or fewer carbon atoms, approximately 8 or fewer carbon atoms, approximately 6 or fewer carbon atoms, or approximately 4 or fewer carbon atoms.

[0057] In this document, the terms "alkoxy", "alkylamino" and "alkylthio" (or thioalkoxy) are used in their conventional meaning and refer to those alkyl groups which are attached to the rest of the molecule via an oxygen atom, an amino group or a sulfur atom respectively.

[0058] In this document, the term "heteroalkyl," alone or in combination with another term, unless otherwise specified, means a stable straight or branched chain or a cyclic hydrocarbon radical, or combinations thereof, comprising the specified number of carbon atoms and at least one heteroatom selected from the group consisting of O, N, Si, S, and B, wherein the nitrogen and sulfur atoms may optionally be oxidized and the nitrogen heteroatom may optionally be quaternized. The heteroatom(s) O, N, B, S, and Si may be located at any inner position of the heteroalkyl group or at the position where the alkyl group is attached to the rest of the molecule. Examples include - CH2-CH2-O-CH3, -CH2-CH2-NHCH3, -CH2-CH2-N(CH3)-CH3, -CH2-S-CH2-CH3, -CH2-CH2,-S(O)-CH3, -CH2-CH2-S(O)2-CH3, -CH=CH-O-CH3, -Si(CH3)3, -CH2-CH=N-OCH3 and -CH=CH-N(CH3)-CH3.Up to two heteroatoms can follow one another, as in -CH2-NH-OCH3 and -CH2-O-Si(CH3)3. Similarly, the term "heteroalkylene," whether alone or as part of another substituent, refers to a divalent radical derived from a heteroalkyl group, as in the examples of -CH2-CH2-S-CH2-CH2- and -CH2-S-CH2-CH2-NH-CH2-. In heteroalkylene groups, the heteroatoms can also occupy either one or both ends of the chain (e.g., alkylenoxy, alkylenedioxy, alkyleneamino, alkylenediamino, and the like). Optionally, in alkylene and heteroalkylene bonding groups, the orientation of the bonding group is not implied by the direction in which the bonding group formula is written. For example, the formula -CO2R'- optionally represents both -C(O)OR' and -OC(O)R'.

[0059] In this document, the terms "cycloalkyl" and "heterocycloalkyl," alone or in combination with other terms, refer, unless otherwise specified, to cyclic versions of "alkyl" and "heteroalkyl," respectively. Additionally, in heterocycloalkyl, a heteroatom may occupy the position where the heterocycle is attached to the rest of the molecule. Examples of cycloalkyl include cyclopentyl, cyclohexyl, 1-cyclohexenyl, 3-cyclohexenyl, cycloheptyl, and the like. Examples of cycloalkyl include 1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl, 3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl, 1-piperazinyl, 2-piperazinyl and the like.

[0060] In this document, the term "halo" or "halogen," alone or in combination with another term, unless otherwise specified, means a fluorine, chlorine, bromine, or iodine atom. Additionally, terms such as "haloalkyl" mean that monohaloalkyl and polyhaloalkyl compounds are included. For example, the term "halo(C1-C4)alkyl" is to be understood as including, but not limited to, trifluoromethyl, 2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the like.

[0061] In this document, unless otherwise specified, the term "aryl" means a polyunsaturated aromatic substituent, which may be a single ring or multiple rings (preferably between one and three rings) fused or covalently linked together. The term "heteroaryl" refers to aryl groups (or rings) containing between one and four heteroatoms selected from N, O, S, Si, and B, the nitrogen and sulfur atoms optionally being oxidized and the nitrogen atom(s) optionally being quaternized. A heteroaryl group may be attached to the rest of the molecule via a heteroatom.Non-limiting examples of aryl and heteroaryl groups include phenyl, 1-naphthyl, 2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl, 2-Phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-Pyridyl, 2-Pyrimidyl, 4-Pyrimidyl, 5-Benzothiazolyl, Purinyl, 2-Benzimidazolyl, 5-Indolyl, 1-Isoquinolyl, 5-Isoquinolyl, 2-Quinoxalinyl, 5-Quinoxalinyl, 3-Quinolyl, and 6-Quinolyl. Substituents for each of the aryl and heteroaryl ring systems listed above are selected from the group of acceptable substituents described below.

[0062] For reasons of space, in this document the term "aryl," when used in combination with other terms (e.g., aryloxy, arylthioxy, arylalkyl), encompasses both aryl and heteroaryl rings as defined above. Thus, the term "arylalkyl" is to be understood as including those radicals in which an aryl group is attached to an alkyl group (e.g., benzyl, phenethyl, pyridylmethyl, and the like), including those alkyl groups in which a carbon atom (e.g., a methylene group) has been replaced by, for example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl, 3-(1-naphthyloxy)propyl, and the like).

[0063] Each of the preceding terms (e.g., "alkyl," "heteroalkyl," "aryl," and "heteroaryl") is to be understood as encompassing both substituted and unsubstituted forms of the specified radical. Preferred substituents for each type of radical are listed below.

[0064] Substituents for the alkyl and heteroalkyl radicals (including those groups often referred to as alkylene, alkenyl, heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) are generally called "alkyl group substituents" and can be one or a variety of groups, selected from, among others, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, -OR', =O, =NR', =N-OR', -NR'R", -SR', -halogen, -SiR'R"R"', -OC(O)R', -C(O)R', -CO2R', -CONR'R", -OC(O)NR'R", -NR"C(O)R', -NR'-C(O)NR"R"', -NR"C(O)2R', -NR-C(NR'R”R'”)=NR””, -NR-C(NR'R”)=NR'”, -S(O)R', -S(O)2R', -OS(O)2R', -S(O)2NR'R”, -NRSO2R', -CN and -NO2 in a number in the range from zero to (2m'+1), where m' is the total number of carbon atoms in such a radical.R', R", R"' and R"" each preferably refer independently to hydrogen, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, e.g., aryl substituted with 1-3 halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy groups, or arylalkyl groups. If a compound according to the invention comprises more than one R group, for example, each of the R groups is selected independently, as are all R', R", R'" and R"" groups if more than one of these groups is present. If R' and R" are attached to the same nitrogen atom, they can combine with the nitrogen atom to form a 5-, 6- or 7-membered ring. For example, -NR'R" is to be understood as comprising, among others, 1-pyrrolidinyl and 4-morpholinyl.From the foregoing discussion of substituents, a person skilled in the art will understand that the term ‘alkyl’ is to be understood as including groups including carbon atoms bonded to groups other than hydrogen groups, such as haloalkyl (e.g., -CF3 and -CH2CF3) and acyl (e.g., -C(O)CH3, -C(O)CF3, -C(O)CH2OCH3 and the like).

[0065] Analogous to the substituents described for the alkyl radical, substituents for the aryl and heteroaryl groups are generally referred to as "aryl group substituents".The substituents are selected from, for example, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, -OR', =O, =NR', =N-OR', -NR'R", -SR', -halogen, -SiR'R"R"', -OC(O)R', -C(O)R', -CO2R', -CONR'R", -OC(O)NR'R", -NR"C(O)R', -NR'-C(O)NR"R"', -NR"C(O)2R', -NR-C(NR'R"R'")=NR"", -NR-C(NR'R")=NR'", -S(O)R', -S(O)2R', -S(O)2NR'R", -NRSO2R', -CN and -NO2, -R', -N3, -CH(Ph)2, Fluorine(C1-C4)alkoxy and Fluorine(C1-C4)alkyl, in a number ranging from zero to the total number of open valences on the aromatic ring system, and wherein R', R", R"' and R"" are preferably selected independently from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl.If a compound according to the invention comprises more than one R group, for example, each of the R groups is selected independently, as are all R', R", R'" and R"" groups if more than one of these groups is present.

[0066] The substrate can be particulate or monolithic, preferably particulate. The substrate material can be a metal oxide (where this term includes a metal oxide such as silicon dioxide, and an inorganic-organic hybrid material (in particular a metal oxide-organic hybrid material), as described, for example, in WO 00 / 45951). The substrate can, in particular, be a silicon dioxide (SiO2) substrate (where this term includes a silicon dioxide / organic hybrid), an aluminum oxide (Al2O3) substrate, a titanium dioxide (TiO2) substrate, or a zirconium dioxide (ZrO2) substrate. A silicon dioxide substrate (where this term includes a silicon dioxide / organic hybrid) is most preferred. The surface of the silicon dioxide may have silanol (hydroxyl) groups prior to the covalent attachment of the polymer at the end, for example.so that the silyl groups of the polymer described in this document react with the aforementioned surface silanol groups.

[0067] The polymer layer is covalently bonded to the substrate surface. The polymer layer is formed by the covalent attachment of at least one polymer (the term also includes oligomers) to the substrate surface. Each polymer molecule is attached to the surface via multiple siloxane bonds (Si-O-Si). Each polymer molecule comprises several reactive groups (especially olefinic groups, particularly vinyl or allyl groups, or thiol groups), and these reactive groups of the attached polymer molecules react with the at least one functionalizing compound.

[0068] In detail, the polymer layer is preferably formed by covalently attaching at least one polymer (where the term also includes oligomers) to the surface of the substrate, wherein each polymer molecule is attached to the surface via several siloxane bonds (Si-O-Si) and each polymer molecule contains several first reactive groups (in particular olefinic groups, especially vinyl groups or allyl groups or thiol groups), and reacting the first reactive groups of the attached polymer molecules with at least one functionalizing compound comprising a second reactive group (i.e., at least one second reactive group) that reacts with the first reactive group (where the second reactive group is in particular an olefinic group (where the term olefinic in this document includes reactive groups having double bonds, e.g.,The functional group comprises a vinyl, allyl, styrene, acrylamidyl, acrylate) or thiol group (-SH) and further comprises a functional group. The functional group preferably has chromatographic functionality. In particular, the functional group comprises alkyl or aryl, preferably C4-C30 alkyl or aryl.

[0069] The polymer molecules are not formed at the surface from surface-bound monomers; the polymer molecules are already polymer molecules before they are attached to the surface. In this way, the polymer (which has several first reactive groups and several silyl groups) is bound to the silicon dioxide surface, resulting in better coverage and protection of the surface siloxane bonds than the use of small vinyl-functional silane molecules as described above in Engelhardt et al., which leave the surface siloxane bonds more susceptible to attack under acidic or basic conditions.

[0070] The polymer preferably comprises and utilizes a silyl group or groups for attaching the polymer to the substrate (especially a silicon dioxide substrate). Accordingly, the silyl group is preferably an activated silyl group, i.e., one possessing groups (leaving groups) that can react with a substrate surface (especially silicon dioxide) and enable the polymer to attach to the substrate surface. The silyl groups thus covalently bind the polymer to the silicon dioxide substrate via siloxane bonds (Si-O-Si). A first silicon atom in the siloxane bond originates from the silyl group. A second silicon atom in the siloxane bond originates from the silicon dioxide, i.e., the silicon dioxide surface.

[0071] The silyl group or groups of the polymer molecules preferably have a formula: where at least one of R 1 , R 2 , R 3 a departure group. Preferably R1 , R 2 , R 3 independently consisting of an oxygen atom (e.g., which bonds with a substrate (silicon) atom in the substrate or bonds with another silicon atom of the polymer), a hydroxyl group, a halogen group, an alkoxy group (i.e., methoxy, ethoxy, etc.), a dialkylamino group, an acyl group, an alkyl group (optionally a heteroalkyl group or a heterocycloalkyl group), an aryl group (optionally a heteroyaryl group) or selected a reactive group (i.e., the first reactive group described in this document, for example, an olefinic group such as vinyl, allyl, etc.).

[0072] The groups R 1 , R 2 and R 3 They can be the same or all different. Preferably, at least one, optionally two of the R is / are the same. 1 , R 2 , R 3-groups, a departure group. Even more preferred is at least one of the R 1 , R 2 , R 3 -groups an alkoxy group (preferably methoxy, ethoxy or propoxy, especially methoxy), a dialkylamino group or a halogen atom.

[0073] In the case of vinylsiloxane polymers, the silyl group typically has a leaving group (terminal silyl groups can have two leaving groups), a reactive group, and two bonds (terminal silyl groups can have one such bond) to corresponding oxygen atoms, which are linked to adjacent silicon atoms of the polymer. The leaving groups enable the polymer to form siloxane bonds with the substrate silicon dioxide surface.

[0074] The polymer comprises several reactive groups, referred to in this document as the first reactive groups. The first reactive groups are preferably reactive olefinic groups or reactive thiol groups, particularly olefinic groups. The reactive olefinic groups of the polymer are preferably vinyl or allyl groups. The several reactive groups are preferably all of the same type, e.g., all vinyl.

[0075] The polymer preferably exhibits a “fixed” distance between adjacent first reactive groups (e.g., between adjacent vinyl groups), i.e., the distance between adjacent first reactive groups is essentially uniform for all reactive groups in the polymer molecule. For example, homopolymer 1 of Fig. 1 a repeating 3-atom interval between the first reactive groups (e.g. vinyl groups).

[0076] In one embodiment, the at least one polymer preferably comprises at least one siloxane polymer having reactive groups. In particular, in this embodiment, the at least one polymer preferably comprises at least one vinylsiloxane polymer (i.e., a siloxane polymer having reactive vinyl groups). The size (i.e., number-average molecular weight MW) n The hardness of the (optionally vinyl) siloxane polymer is preferably between 500 and 10,000 Daltons (Da). The vinyl siloxane polymer is preferably a vinyl alkoxy siloxane polymer.

[0077] In a preferred embodiment, the vinylsiloxane polymer can have a formula I: where n is an integer from 3 to 100, and R1 and R2 are independently selected from alkoxy, particularly methoxy and ethoxy, hydroxyl, and halogen (particularly Cl). R1 ​​and R2 are preferably independently selected from alkoxy, particularly methoxy and ethoxy, and hydroxyl. R1 and R2 are more preferably independently selected from alkoxy, particularly methoxy and ethoxy. R1 and R2 are particularly preferably identical, preferably both being either methoxy or ethoxy.

[0078] In a preferred embodiment, the vinylsiloxane polymer can have a formula II:

[0079] Alternatively, a polymer having ethoxy groups or hydroxyl groups instead of the methoxy groups in formula II is also a preferred embodiment.

[0080] A surface-bound polymer layer formed from a polymer of formula I or II (with methoxy or ethoxy groups) has a general structure as follows, where vinyl-reactive groups are present:

[0081] In formula I or II, a number of the vinyl groups can be replaced by alkyl groups, e.g. C1-C4 alkyl, especially C1-C3 alkyl.

[0082] The vinylsiloxane polymer can be a copolymer, i.e., it contains a mixture of vinylsiloxane units and alkylsiloxane units (especially C1-C4 alkyl). The copolymer can, for example, have a nominal formula III: where R1 and R2 are defined as above for formulas I and II, and where n is an integer from 3 to 100 and m is an integer from 1 to 70 (preferably 1 and 20), or Formula IV, for example.

[0083] The vinylsiloxane units and the alkylsiloxane units in the preceding formulas may be present in the polymer as blocks, randomly distributed, or in varying positions. Alternatively, a polymer having methoxy groups or hydroxyl groups instead of the ethoxy groups in Formula IV is also a preferred embodiment.

[0084] In another embodiment, the at least one polymer preferably comprises at least one silyl group containing polymer (i.e., at least one polymer containing several silyl groups), preferably with a MW n from 500 to 10,000 Daltons. In particular, such a polymer can be modified polybutadiene, especially silyl-modified polybutadiene, preferably with a MW nfrom 500 to 10,000 Daltons. The polymer containing at least one silyl group comprises trialkoxysilyl groups as the silyl groups (e.g., trimethoxysilyl or triethoxysilyl). The at least one silyl-modified polybutadiene preferably comprises a trialkoxysilyl-modified polybutadiene (the size of the trialkoxysilyl-modified polybutadiene polymer (i.e., molecular weight MW)). n ) preferably is 500 - 10,000 Daltons). For example, the polybutadiene can be a trimethoxysilyl-modified polybutadiene or a triethoxysilyl-modified polybutadiene.

[0085] The silyl-modified polybutadiene can have a nominal repeating unit of formula V: where R 1 , R 2 and R 3 independently selected from alkoxy, especially methoxy and ethoxy, hydroxyl, halogen (especially Cl) and alkyl (especially C1-C3 alkyl, most especially methyl), provided that at least one of R 1 , R 2 and R3 a leaving group (especially methoxy and ethoxy). R 1 , R 2 and R 3 are preferably selected independently from alkoxy, especially methoxy and ethoxy, and hydroxyl. R 1 , R 2 and R 3 are preferably selected independently from alkoxy compounds, especially methoxy and ethoxy. R 1 , R 2 and R 3 are particularly preferably the same, preferably either methoxy or ethoxy.

[0086] In a preferred embodiment, the silyl-modified polybutadiene can be an alkoxysilyl-modified polybutadiene having a nominal repeating unit of formula VI: where each R 1 regardless of whether it is methoxy or ethoxy. Preferably all R 1 the same group.

[0087] For example:

[0088] Alternatively, a polymer having methoxy groups or hydroxyl groups instead of the ethoxy groups in formula VII is also a preferred embodiment.

[0089] In another preferred embodiment, the silyl-modified polybutadiene can be an alkylalkoxysilyl-modified polybutadiene. For example, the alkylalkoxysilyl-modified polybutadiene can have a nominal repeating unit of formula VIII:

[0090] Alternatively, a polymer having methoxy groups or hydroxyl groups instead of the ethoxy groups in formula VIII is also a preferred embodiment.

[0091] A covalent attachment of the polymer of formula V, VI or VII to silicon dioxide can result in a surface-bound polymer layer as follows, in which vinyl-reactive groups are present:

[0092] A covalent attachment of the polymer of formula VIII to silicon dioxide can yield a surface-bound polymer layer as follows, in which vinyl-reactive groups are present:

[0093] The use of the polymers described in this document offers numerous advantages, for example: enabling multiple attachments to the substrate for stability while maintaining controllability compared to polymers with very high molecular weight, which can tend to clog the pores in the substrate; enabling subsequent surface modification with copolymerization of allyl or vinyl functional compounds, whereby a “fixed” distance between adjacent reactive (e.g., vinyl) groups promotes the formation of a more uniform protective layer on the substrate surface; and enabling flexibility in the stationary phase or column chemistry due to a selection of functional groups for polymer attachment.

[0094] After the substrate has reacted with the polymer in the first reaction step to form the layer covalently bonded to the substrate surface (e.g., a layer with vinyl functionality), the substrate is preferably subsequently reacted (further functionalized) with a silane (silane monomer, not polymer) that also possesses the first reactive group, such as a vinyl group. For example, a vinylsilane with alkyl and / or alkoxy groups, such as vinyldimethylethoxysilane, can be used. This facilitates better coverage of the silicon dioxide surface with reactive groups (vinyl groups) because the smaller monomers can fill gaps between polymer molecules. The surface can then be functionalized in the second step.

[0095] The functionalizing compound for the second-stage functionalization (i.e., functionalization of the first bonded layer) can be a polymeric or non-polymeric molecule, preferably a non-polymeric molecule. The functionalizing compound preferably comprises a group that reacts with the reactive groups of the polymer (i.e., the first reactive groups). The reactive group of the functionalizing compound is referred to in this document as the second reactive group. In particular, a reactive olefinic group, or thiol, of the functionalizing compound reacts with an olefinic group of the polymer. The second reactive group of the functionalizing compound is preferably a vinyl group, an allyl group, or a thiol group.In this document, groups containing double bonds, including vinyl, allyl, styrenes, acrylamides and acrylates, are included within the scope of the term olefinic group.

[0096] The functionalizing compound comprises a functional group. The functional group advantageously provides chromatic functionality, e.g., reversed-phase functionality. The functional group comprises C14–C22 alkyl, e.g., C18 alkyl. The alkyl can be substituted or unsubstituted. Each of these groups can optionally include a heteroatom in the form of a sulfur (S) and / or oxygen (O) linker, and / or can optionally include a (primary, secondary, tertiary, or quaternary) amino group, sulfonamide group, amide group, carbamate group, phosphonate group, sulfonate group, and / or carboxylate group.

[0097] In one embodiment, the functionalizing compound is preferably a hydrocarbon compound comprising an olefinic group or bond, particularly an alkyl compound, preferably a straight-chain alkyl, wherein the total carbon chain length is C14-C22, e.g., C14, C16, or C18; or e.g., C15 or C17. The hydrocarbon can be alkyl or aryl, substituted or unsubstituted. The alkyl compound is preferably an alkyl compound having a terminal olefinic group (e.g., an alkene) and a total chain length as described above. Particularly preferred functionalizing compounds for the second-stage functionalization are thus C14, C16, or C18 alkenes; most preferably, C18 alkenes. The double bond (olefinic group) of the alkene is preferably located at a terminal position of the carbon chain, e.g., 1-octadecene.

[0098] In another embodiment, the functionalizing compound is preferably an arylthiol or arylthiol, wherein the total carbon chain length is, for example, C14, C16 or C18; or, for example, C15 or C17.

[0099] The invention also provides for the production of stationary phase material by functionalizing silicon dioxide substrates with polymers under elevated temperature, preferably at reduced pressures, to form pH-stable separation media. At least one first reaction step, i.e., the reaction of the silicon dioxide with at least one first functionalizing compound, is carried out at elevated temperature and reduced pressures. Preferably, a catalyst is also used, and the reaction is carried out in the absence of solvents (solvent-free conditions).

[0100] In particular, the invention provides a method for forming functionalized silicon dioxide for chromatographic purposes comprising: Reacting the silicon dioxide with at least one first functionalizing compound under conditions of an elevated reaction temperature (especially above room temperature and preferably above 100°C) and reduced pressure (especially below atmospheric pressure and preferably below 500 mbar), preferably in the absence of solvent; wherein the first functionalizing compound or compounds comprise one or more silyl groups for reacting with the surface of the silicon dioxide and one or more first reactive groups (in particular one or more vinyl groups, allyl groups and / or one or more thiol groups), whereby the first functionalizing compound or compounds are covalently attached to the surface of the silicon dioxide and the first reactive groups are left in an unreacted state; and

[0101] Reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with at least one second functionalizing compound comprising one or more second reactive groups that react with the one or more first reactive groups (in particular, one or more second reactive groups containing an olefinic bond and / or -SH (thiol) group), and further comprising a functional group that in particular has chromatographic functionality, especially alkyl or aryl, e.g., C18-alkyl. The at least one first functionalizing compound is preferably the polymer as described in this document, i.e., the polymer for covalent attachment to the surface of the substrate, or, in another embodiment, it may be a silane monomer (e.g., a vinylsilane). The polymer may in particular be of the type of a siloxane polymer (e.g.,vinylsiloxane polymer) or silyl-modified polymers, such as silyl-modified polybutadiene, as described in this document.

[0102] The second functionalizing compound is preferably the functionalizing compound described in this document, i.e., a hydrocarbon compound comprising an olefinic group or bond, in particular an alkyl compound, or it is an alkylthiol or arylthiol, as described in this document.

[0103] The reaction conditions provided by the invention (increased temperature, reduced pressure; optionally with catalyst, optionally with predeposition) offer numerous advantages, for example: the formation of a stable bond to the bound polymer layer; better control over the thickness of the bound polymer layer; and less pore clogging, which is better for chromatography.

[0104] The second reaction stage, i.e., the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound, does not have to take place under reduced pressure, while an increased temperature is desirable.

[0105] The elevated temperature of the first reaction stage is preferably in the range of: at least approximately 100°C, or at least approximately 110°C, or at least approximately 120°C, or at least approximately 140°C, or at least approximately 160°C, or at least approximately 180°C, or at least approximately 200°C, particularly at least approximately 160°C, or at least approximately 180°C, or at least approximately 200°C; particularly the aforementioned ranges up to approximately 200°C, or up to approximately 220°C, or up to approximately 240°C, or up to approximately 260°C, or up to approximately 280°C, or up to approximately 300°C. Preferably, the elevated temperature for the first reaction stage is in the range of approximately 200 °C to approximately 300 °C, or approximately 210 °C to approximately 290 °C, or approximately 220 °C to approximately 280 °C, or approximately 230 °C to approximately 270 °C, or approximately 250 °C.

[0106] The reduced pressure for the first reaction stage is preferably in the range of: less than 500 mbar, more preferably less than 400 mbar, even more preferably less than 300 mbar, and even more preferably less than 200 mbar, and most preferably less than 100 mbar. The pressure is preferably at least 0.01 mbar, more preferably at least 0.1 mbar or at least 1 mbar.

[0107] The reduced pressure and the increased temperature for the first reaction stage are preferably applied simultaneously for at least a certain period (first reaction period). This period can be at least 1 hour, or at least 2 hours, or at least 4 hours, or at least 8 hours, or at least 12 hours. The period can be up to 20 hours, or up to 30 hours. The increased temperature is preferably applied for at least this period. The reduced pressure is preferably applied for essentially the same period as the increased temperature.

[0108] The reaction is preferably catalyzed. The reaction medium therefore preferably comprises a catalyst in contact with the reactant species. A suitable known polymerization catalyst can be used. Particularly preferred catalysts are organic amines, for example tetramethylethylenediamine.

[0109] The second stage of the process preferably involves polymer encapsulation of the silicon dioxide phases by polymerization of the polymer layer through free radicals. This polymerization is preferably carried out in the presence of an initiator.

[0110] For the second stage of the process (encapsulated polymer layer formed by copolymerization in the presence of an initiator), an elevated temperature is again used. The pressure in the second stage can be at or above atmospheric pressure, e.g., in the range of 1 to 2 atmospheres.

[0111] The elevated temperature for the second reaction stage is preferably in the range of: at least approximately 100°C, or at least approximately 110°C, or at least approximately 120°C, or at least approximately 140°C; particularly in the aforementioned ranges up to approximately 300°C, or up to approximately 200°C, or up to approximately 190°C, or up to approximately 180°C, or up to approximately 160°C. More preferably, the elevated temperature for the second reaction stage is in the range of approximately 100°C to approximately 300°C, or approximately 100°C to approximately 200°C, or approximately 110°C to approximately 190°C, or approximately 120°C to approximately 180°C, or approximately 130°C to approximately 170°C.

[0112] The reduced pressure for the second reaction stage is preferably applied for a certain period (second reaction period). This period can be at least 1 hour, or at least 2 hours, or at least 4 hours, or at least 8 hours, or at least 12 hours. The period can be up to 20 hours, or up to 30 hours.

[0113] Both the first and second reaction stages are preferably carried out in an inert atmosphere, i.e., in an inert gas (e.g., nitrogen or argon). The reactants are preferably purged with inert gas before the elevated temperature is applied and, in the case of the first reaction stage, before the pressure is reduced. The inert atmosphere is then preferably maintained during the period of elevated temperature and, in the case of the first reaction stage, reduced pressure. In another embodiment, where the reaction pressure is reduced to below 50 mbar, the reaction can be carried out without purging with an inert gas.

[0114] Preferably, the first reaction step is carried out in the absence of an organic solvent. Preferably, the second reaction step is carried out in the absence of an organic solvent. Any solvents that may be used in any part of the process are preferably removed before applying the elevated reaction temperature. Advantages of a solvent-free process, especially for polymerization to functionalization, include: improved control over surface modification; and improved control over column chemistry. It should be noted that the absence of a solvent can refer to the absence of a liquid solvent or a liquid organic solvent.

[0115] Various reaction schemes can be used to implement the process of the invention. Numerous processing steps, including various optional steps, can be incorporated into the reaction schemes. The figure below refers to silicon dioxide, but it can also be used with other substrates.

[0116] The process can include a pretreatment step for the silicon dioxide. The crude silicon dioxide was acid-treated in 0.1M HNO3 at 90°C for 4 hours and then thoroughly rinsed with deionized water until the filtrate was nearly neutral. The acid-treated silicon dioxide was dried under vacuum at 150°C for at least 12 hours and then stored in a desiccator.

[0117] The silicon dioxide is preferably dried before undergoing a first reaction stage.

[0118] The silicon dioxide is preferably placed in a reaction vessel.

[0119] The process preferably comprises a first reaction stage in which the substrate is functionalized with first reactive groups, preferably olefinic groups, particularly vinyl groups. For the first stage, a first functionalizing compound is preferably added to the silicon dioxide, wherein the first functionalizing compound is preferably the polymer described in this document, i.e., the polymer for covalent attachment to the surface of the silicon dioxide. A vinylalkoxysiloxane polymer is most preferred. The first functionalizing compound may be contained in an organic solvent (e.g., methanol) at the time of its addition, which can be subsequently removed.

[0120] A catalyst (e.g., an organic amine) for the first reaction step is preferably mixed with the silicon dioxide and the first functionalizing compound. Alternatively, a volatile catalyst can be used, which does not require mixing but is instead placed in the same reaction vessel as the silicon dioxide.

[0121] Preferably, all volatile components, such as all organic solvents, can be removed, for example, under reduced pressure. This can be done either before or after the addition of a catalyst, but preferably before the addition of a catalyst to prevent a reaction from being initiated. In this way, the first reaction stage is preferably carried out under solvent-free conditions.

[0122] After the addition of the first functionalizing compound and optionally the catalyst, they can be mixed with the silicon dioxide.

[0123] The components of silicon dioxide, the first functionalizing compound and the catalyst are preferably rinsed with an inert gas (e.g. nitrogen or argon) in a reaction vessel before the reaction and preferably remain in the inert gas atmosphere during the reaction.

[0124] The first reaction stage is carried out by heating the components in the reaction vessel (silicon dioxide, first functionalizing compound, and catalyst) to an elevated temperature for a first reaction period, as described in this document. In a preferred embodiment, the first reaction stage is carried out under reduced pressure, preferably less than 100 mbar (e.g., by evacuating the reaction vessel to the desired pressure).

[0125] The silicon dioxide functionalized with the first reactive groups can then be filtered, washed and optionally dried.

[0126] The silicon dioxide functionalized with the first reactive groups can optionally be further reacted (i.e., further functionalized) with a silane (not polymer) containing a first reactive group (e.g., vinyl), such as a vinylsilane of formula A, where the R groups are independently alkoxy, hydroxyl, halogen, or alkyl:

[0127] The silicon dioxide, which is further functionalized with the first reactive groups, can then be filtered, washed and optionally dried.

[0128] The process preferably includes a second reaction stage in which the silicon dioxide functionalized with the first reactive groups (vinyl groups) is reacted with a second functionalizing compound comprising a second reactive group (e.g., allyl group) and a functional group (e.g., alkyl group).

[0129] For the second stage, a second functionalizing compound is added to the silicon dioxide, which is already functionalized with the first reactive groups (vinyl groups). This second functionalizing compound is the C14-C22 alkene compound as described in this document. A C18 alkene is most preferred, optionally mixed. The second functionalizing compound can be mixed with the silicon dioxide in an organic solvent (e.g., dichloromethane), which can be removed later.

[0130] An initiator (e.g., dicumyl peroxide) may be included in the mixture of the second functionalizing compound and silicon dioxide, e.g., to initiate polymerization by free radicals.

[0131] Preferably, all volatile components, such as all organic solvents, can be removed, for example, under reduced pressure. In this way, the second reaction stage is preferably carried out under solvent-free conditions.

[0132] The components of the first functionalized silicon dioxide, the second functionalizing compound and the initiator are preferably purged with an inert gas (e.g. nitrogen or argon) in a reaction vessel before the reaction and preferably remain in the inert gas atmosphere during the reaction.

[0133] The second reaction step is carried out by heating the components in the reaction vessel (first functionalized silicon dioxide, second functionalizing compound, and initiator) to an elevated temperature (e.g., 50–300°C) for a second reaction period, as described in this document. A functionalized, polymer-encapsulated silicon dioxide is obtained. The silicon dioxide can optionally be filtered and washed before use in a chromatographic column.

[0134] The substrate (preferably a silicon dioxide substrate) can be completely porous, surface porous or non-porous, and it can be particulate or monolithic.

[0135] The substrate according to the invention is preferably a chromatographic material or has chromatographic properties, for use, for example, in LC or SPE applications.

[0136] The substrate is preferably particulate, wherein the particles of the substrate are typically or preferably substantially spherical, but in some embodiments may have an irregular shape. The particles preferably have a narrow size distribution.

[0137] In some examples, the particles are essentially “monodisperse” or essentially “homodisperse”, indicating that the particle size of the majority of the particles (e.g., 80, 90, or 95% of the particles) is not significantly (e.g., not more than 10%) below or above the mean particle size (D). 50 ). In an exemplary monodisperse particle population, 90% of the particles have an average particle size of approximately 0.9 x D. 50 and approximately 1.1 x D 50This is advantageous for chromatographic applications. While monodisperse particles are preferred, particles with a broader particle size distribution can be beneficial in many applications.

[0138] The particles are typically microparticles, preferably 0.1 µm or larger in mean particle diameter, preferably up to 1000 µm in mean particle diameter. More preferred are particles with a diameter of 1 to 1000 µm, or 0.1 to 500 µm or 1 to 500 µm, or even more preferably 0.1 to 100 µm or 1 to 100 µm, or even more preferably 0.1 to 50 µm, in particular 0.1 to 10 µm or 0.2 to 10 µm or 1 to 10 µm, and most preferably 1.5 to 5 µm in diameter.

[0139] The particles can be porous (including partially porous, fully porous, or surface-porous) or non-porous. They can be useful for the production of solid-core chromatographic materials.

[0140] When porous particles are formed, the pores of the particles can have any size. The nominal pore size is typically given in angstroms (10 -10 m, Å). A pore size distribution (PSD) is calculated from the adsorption data using the BJH (Barrett Joyner-Halenda) method, and the mean pore size (W) is determined. BJH) is defined as the maximum value of the PSD. In one example, the mean size or mean diameter of the pores lies between approximately 1 and approximately 5000 Å, in particular between approximately 50 and approximately 5000 Å. In another example, the volume-averaged diameter of the pores lies between approximately 10 and 5000 Å, between approximately 10 and 4000 Å, between approximately 10 and 3000 Å, between approximately 10 and 2000 Å, between approximately 10 and 1000 Å, between approximately 10 and 800 Å, between approximately 10 and 600 Å, between approximately 10 and 500 Å, between approximately 10 and 400 Å, between approximately 10 and 300 Å, between approximately 10 and 200 Å, between approximately 10 and 100 Å, between approximately 20 and 2000 Å, between approximately... 20 and approx. 1000 Å, between approx. 20 and approx. 500 Å, between approx. 20 and approx. 300 Å, between approx. 20 and approx. 200 Å, between approx. 20 and approx. 100 Å, between approx. 30 and approx. 2000 Å, between approx. 30 and approx. 1000 Å, between approx. 30 and approx. 500 Å, between approx. 30 and approx. 300 Å, between approx. 30 and approx.200 Å, between approx. 30 and approx. 100 Å, between approx. 40 and approx. 2000 Å, between approx. 40 and approx. 1000 Å, between approx. 40 and approx. 500 Å, between approx. 40 and approx. 300 Å, between approx. 40 and approx. 200 Å, between approx. 40 and approx. 100 Å, between approx. 50 and approx. 2000 Å, between approx. 50 and approx. 1000 Å, between approx. 50 and approx. 500 Å, between approx. 50 and approx. 300 Å, between approx. 50 and approx. 200 Å, between approx. 50 and approx. 100 Å, between approx. 60 and approx. 2000 Å, between approx. 60 and approx. 1000 Å, between approx. 60 and approx. 500 Å, between approx. 60 and approx. 300 Å, between approx. 60 and approx. 200 Å, between approx. 60 and approx. 100 Å, between approx. 70 and approx. 2000 Å, between approx. 70 and approx. 1000 Å, between approx. 70 and approx. 500 Å, between approx. 70 and approx. 300 Å, between approx. 70 and approx. 200 Å, between approx. 70 and approx. 100 Å, between approx. 80 and approx. 2000 Å, between approx. 80 and approx. 1000 Å, between approx. 80 and approx. 500 Å, between approx. 80 and approx. 300 Å, between approx. 80 and approx. 200 Å, between approx. 100 and approx. 200 Å, between approx.100 and approximately 300 Å, between approximately 100 and approximately 400 Å, between approximately 100 and approximately 500 Å, between approximately 200 and approximately 500 Å, or between approximately 200 and approximately 600 Å. Preferably, the mean pore size is between approximately 30 and approximately 2000 Å, more preferably between approximately 80 and approximately 1000 Å. Most preferably, the mean pore size is between approximately 80 and approximately 300 Å.

[0141] The specific surface area (BET) of the particulate substrate material typically ranges between approximately 0.1 and approximately 2,000 m². 2 / g, most typically between approximately 0.1 and approximately 1,000 m 2 / g. For example, the specific surface area of ​​the particle-like material lies between approximately 1 and approximately 1,000 m². 2 / g, between approximately 1 and approximately 800 m 2 / g, between approximately 1 and approximately 600 m 2 / g, between approximately 1 and approximately 500 m 2 / g, between approximately 1 and approximately 400 m 2 / g, between approximately 1 and approximately 200 m 2 / g or between approximately 1 and approximately 100 m 2 / g. In another example, the specific surface area of ​​the material lies between approximately 10 and approximately 1,000 m². 2 / g, between approximately 10 and approximately 800 m 2 / g, between approximately 10 and approximately 600 m 2 / g, between approximately 10 and approximately 500 m 2 / g, between approximately 10 and approximately 400 m 2 / g, between approximately 10 and approximately 200 m 2 / g or between approximately 10 and approximately 100 m 2 / g. In another example, the specific surface area of ​​the material lies between approximately 50 and approximately 1,000 m². 2 / g, between approximately 50 and approximately 800 m 2 / g, between approximately 50 and approximately 600 m 2 / g, between approximately 50 and approximately 500 m 2 / g, between approximately 50 and approximately 400 m 2 / g, between approximately 50 and approximately 200 m 2 / g or between approximately 50 and approximately 100 m 2 / g. Preferably, the specific surface area of ​​the particulate material lies between approximately 1 and approximately 500 m². 2 / g, or between approximately 10 and approximately 500 m 2 / g (especially between approx. 50 and approx. 500 m) 2 / g). In another example, the specific surface area is preferably between approximately 10 and approximately 100 m². 2 / G.

[0142] For non-porous particles, the specific surface area is preferably between approximately 0.5 and 10 m². 2 / g. For non-porous particles, the mean particle diameter is preferably from 0.1 to 5 µm.

[0143] In view of the above detailed description, numerous preferred material types can be implemented, as shown in Table 1 below:

[0144] The material according to the invention can be used in nano-LC, analytical LC, or scaled-up preparative LC or SPE. In various embodiments, the material is arranged as a packed bed or monolith in a column. For example, a plastic or metal column is packed with the material.

[0145] The chromatographic material of the present invention can be used in a method for separating analytes, comprising flowing a mobile phase containing a sample of analytes through a column to chromatographically separate the analytes from one another, the column being packed with the chromatographic material according to the present invention. Preferably, the pH of the mobile phase is approximately 11 or less, and advantageously, the pH of the mobile phase can be approximately 1 or less, which is typical for the separation of aminoglycoside antibiotics.Accordingly, the material can be used in a process for separating one or more aminoglycoside antibiotics from each other and / or from other components of a sample, wherein the process comprises flowing a mobile phase containing a sample with one or more aminoglycoside antibiotics and optionally one or more other components through a column to chromatographically separate the one or more aminoglycoside antibiotics from each other and / or from one or more other components of the sample, the column being packed with the chromatographic material according to the present invention. The pH of the mobile phase in such a process is preferably 1 or less. The process is preferably a process for separating a plurality of aminoglycoside antibiotics from each other from a sample containing a plurality of aminoglycoside antibiotics.

[0146] These materials offer a wide range of high-performance characteristics. They exhibit outstanding stability under acidic conditions and significantly improved robustness under basic conditions. A column packed with such material is suitable for the separation of aminoglycoside antibiotics with excellent resolution and chemical robustness. Examples

[0147] To enable a more detailed understanding of the invention, numerous exemplary and / or preferred embodiments of the invention are now described with reference to the accompanying drawings, but without limiting the scope of the invention. Example 1: Vinyl alkoxysiloxane polymers (Fig. 1)

[0148] The vinylalkoxysiloxane polymers used in the examples below were used in the condition supplied by Gelest, unless otherwise stated. Fig.Figure 1 illustrates vinyl methoxysiloxane homopolymer 1: (gel, Cat# VMM-005) and vinyl methoxysiloxane homopolymer 2: (gel, Cat# VEE-005). Fig. 2 illustrates vinylethoxysiloxane-propylethoxysiloxane copolymer 3: (Gel, Cat# VPE-005). Example 2: Preparation of vinyl-functionalized silicon dioxide. Preparation of a vinylalkoxysiloxane polymer-modified phase in solution (Fig. 1, Scheme 1)

[0149] Phase 10: 20 g dried porous spherical silicon dioxide particles (d p , 3 µm; surface area, 225 m 2 / g; pore size, 175 Å) were transferred to a 250 mL round-bottom flask, followed by the addition of a mixture of 5 g vinylethoxysiloxane homopolymer 2 and 0.5 g tetramethylethylenediamine (e.g., Aldrich) in toluene (60 mL). After careful dispersion of the above slurry, the reaction mixture was placed under stable reflux and stirred for 72 hours. The silicon dioxide particles were filtered and thoroughly washed with toluene and acetone. Subsequently, the bound silicon dioxide was dispersed in a mixture of 100 mL of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved again in 60 ml of toluene, followed by the addition of 5 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.5 g of tetramethylethylenediamine (e.g., Aldrich).The resulting mixture was refluxed for 24 hours. The functionalized silicon dioxide particles were filtered and thoroughly washed with toluene and acetone to yield phase 10.

[0150] Phase 11: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 300 m 2 / g; pore size, 120 Å) were transferred to a 250 mL round-bottom flask, followed by the addition of a mixture of 7 g vinylethoxysiloxane homopolymer 2 and 0.5 g tetramethylethylenediamine (e.g., Aldrich) in toluene (60 mL). After careful dispersion of the above slurry, the reaction mixture was placed under stable reflux and stirred for 72 hours. The silicon dioxide particles were filtered and thoroughly washed with toluene and acetone. Subsequently, the bound silicon dioxide was dispersed in a mixture of 100 mL of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved again in 60 ml of toluene, followed by the addition of 7 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.5 g of tetramethylethylenediamine (e.g., Aldrich).The resulting mixture was refluxed for 24 hours. The functionalized silicon dioxide particles were filtered and thoroughly washed with toluene and acetone to yield phase 11.

[0151] Phase 12: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 225 m 2 / g; pore size, 175 Å) were transferred to a 250 mL round-bottom flask, followed by the addition of a mixture of 5 g vinylethoxysiloxane homopolymer 2 and 0.5 g tetramethylethylenediamine (e.g., Aldrich) in toluene (60 mL). After careful dispersion of the above slurry, the reaction mixture was placed under stable reflux and stirred for 72 hours. The silicon dioxide particles were filtered and thoroughly washed with toluene and acetone. Subsequently, the bound silicon dioxide was dispersed in a mixture of 100 mL of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved again in 60 ml of toluene, followed by the addition of 5 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.5 g of tetramethylethylenediamine (e.g., Aldrich).The resulting mixture was refluxed for 24 hours. The functionalized silicon dioxide particles were filtered and thoroughly washed with toluene and acetone to yield phase 12.

[0152] Phase 13: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 200 m 2 / g; pore size, 200 Å) were transferred to a 250 mL round-bottom flask, followed by the addition of a mixture of 5 g vinylethoxysiloxane homopolymer 2 and 0.5 g tetramethylethylenediamine (e.g., Aldrich) in toluene (60 mL). After careful dispersion of the above slurry, the reaction mixture was placed under stable reflux and stirred for 72 hours. The silicon dioxide particles were filtered and thoroughly washed with toluene and acetone. Subsequently, the bound silicon dioxide was dispersed in a mixture of 100 mL of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved again in 60 ml of toluene, followed by the addition of 5 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.5 g of tetramethylethylenediamine (e.g., Aldrich).The resulting mixture was refluxed for 24 hours. The functionalized silicon dioxide particles were filtered and thoroughly washed with toluene and acetone to yield phase 13.

[0153] Phase 14: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 30 m 2 / g; pore size, 1000 Å) were transferred to a 250 mL round-bottom flask, followed by the addition of a mixture of 1.2 g vinylethoxysiloxane homopolymer 2 and 0.1 g tetramethylethylenediamine (e.g., Aldrich) in toluene (60 mL). After careful dispersion of the above slurry, the reaction mixture was placed under stable reflux and stirred for 72 hours. The silicon dioxide particles were filtered and thoroughly washed with toluene and acetone. Subsequently, the bound silicon dioxide was dispersed in a mixture of 100 mL of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved again in 60 ml of toluene, followed by the addition of 1.2 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.1 g of tetramethylethylenediamine (e.g., Aldrich).The resulting mixture was refluxed for 24 hours. The functionalized silicon dioxide particles were filtered and thoroughly washed with toluene and acetone to yield phase 14. Example 3: Preparation of vinyl-functionalized silicon dioxide. Preparation of a vinylalkoxysiloxane polymer-modified phase, originally reacted under solvent-free conditions at elevated temperature at 1 atmosphere (atm, Fig. 1, Scheme 1)

[0154] Phase 15: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 300 m 2 / g; pore size, 120 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 7 g vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently all volatile components were removed under reduced pressure. After the addition of a catalyst (e.g., 0.5 g tetramethylethylenediamine) to the flask, the reaction mixture was placed on a rotary evaporator (i.e., Rotavap) at 20 rpm and evaporated at 160°C for 16 hours. 0The silicon dioxide was held at 1 atm and 1°C. The resulting silicon dioxide was dispersed in toluene (100 ml) and treated in an ultrasonic bath for 15 min, then filtered and thoroughly washed with toluene and acetone. Alternatively, the silicon dioxide was dispersed in a mixture of 100 ml of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved in 60 ml of toluene, followed by the addition of 7 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.5 g of tetramethylethylenediamine (e.g., Aldrich). The resulting mixture was refluxed for 24 hours. After cooling, the silicon dioxide particles were filtered and the cake was washed with toluene and acetone to yield phase 15.

[0155] Phase 16: 20 g dried porous spherical silicon dioxide particles (d p, 5 µm; surface area, 225 m 2 / g; pore size, 175 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 5 g vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were removed under reduced pressure. After adding a catalyst (e.g., 0.5 g tetramethylethylenediamine) to the flask, the reaction mixture was placed on a rotary evaporator at 20 rpm and evaporated at 160°C for 16 hours. 0The silicon dioxide was held at 1 atm and 1°C. The resulting silicon dioxide was dispersed in toluene (100 ml) and treated in an ultrasonic bath for 15 min, then filtered and thoroughly washed with toluene and acetone. Alternatively, the silicon dioxide was dispersed in a mixture of 100 ml of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved in 60 ml of toluene, followed by the addition of 5 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.5 g of tetramethylethylenediamine (e.g., Aldrich). The resulting mixture was refluxed for 24 hours. After cooling, the silicon dioxide particles were filtered and the cake was washed with toluene and acetone to yield phase 16.

[0156] Phase 17: 20 g dried porous spherical silicon dioxide particles (d p, 5 µm; surface area, 200 m 2 / g; pore size, 200 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 5 g vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were removed under reduced pressure. After adding a catalyst (e.g., 0.5 g tetramethylethylenediamine) to the flask, the reaction mixture was placed on a rotary evaporator at 20 rpm and evaporated at 160°C for 16 hours. 0The silicon dioxide was held at 1 atm and 1°C. The resulting silicon dioxide was dispersed in toluene (100 ml) and treated in an ultrasonic bath for 15 min, then filtered and thoroughly washed with toluene and acetone. Alternatively, the silicon dioxide was dispersed in a mixture of 100 ml of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved in 60 ml of toluene, followed by the addition of 5 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.5 g of tetramethylethylenediamine (e.g., Aldrich). The resulting mixture was refluxed for 24 hours. After cooling, the silicon dioxide particles were filtered and the cake was washed with toluene and acetone to yield phase 17.

[0157] Phase 18: 20 g dried porous spherical silicon dioxide particles (d p, 5 µm; surface area, 30 m 2 / g; pore size, 1000 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 1.2 g vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were removed under reduced pressure. After adding a catalyst (e.g., 0.1 g tetramethylethylenediamine) to the flask, the reaction mixture was placed on a rotary evaporator at 20 rpm and evaporated at 160°C for 16 hours. 0The silicon dioxide was held at 1 atm and 1°C. The resulting silicon dioxide was dispersed in toluene (100 ml) and treated in an ultrasonic bath for 15 min, then filtered and thoroughly washed with toluene and acetone. Alternatively, the silicon dioxide was dispersed in a mixture of 100 ml of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and treated in an ultrasonic bath for 2 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried overnight under vacuum at 105°C. The dried silicon dioxide was dissolved in 60 ml of toluene, followed by the addition of 1.2 g of vinyldimethylethoxysilane (e.g., Gelest) and 0.1 g of tetramethylethylenediamine (e.g., Aldrich). The resulting mixture was refluxed for 24 hours. After cooling, the silicon dioxide particles were filtered, and the cake was washed with toluene and acetone to yield phase 18. Example 4: Production of vinyl-functionalized silicon dioxide. Production of a vinylalkoxysiloxane polymer-modified phase under solvent-free conditions at elevated temperature and reduced pressure (Fig. 1, Scheme 1)

[0158] Phase 19: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 300 m 2 / g; pore size, 120 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 7 g vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific pressure (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100°C) and maintained at that temperature for 16 hours.After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor, which was equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 7 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was evacuated to a desired value (e.g. below 100 mbar) using a vacuum pump.The reactor was brought to a desired temperature (> 100). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 19.

[0159] Phase 20: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 225 m 2 / g; pore size, 175 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 5 g of vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 20.

[0160] Phase 21: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 200 m 2 / g; pore size, 200 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 5 g of vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 21.

[0161] Phase 22: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 30 m 2 / g; pore size, 1000 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 1.2 g of vinylethoxysiloxane homopolymer 2 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g tetramethylethylenediamine) and 1.2 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 22. Example 5: Production of vinyl-functionalized silicon dioxide. Production of a vinylalkoxysiloxane copolymer 3-modified phase under solvent-free conditions at elevated temperature and reduced pressure (Fig. 2, Scheme 2)

[0162] Phase 23: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 300 m 2 / g; pore size, 120 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 7 g vinylethoxysiloxane-propylethoxysiloxane copolymer 3 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 7 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 23.

[0163] Phase 24: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 225 m 2 / g; pore size, 175 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 5 g vinylethoxysiloxane-propylethoxysiloxane copolymer 3 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After the placement of a catalyst (e.g., 0.5 g tetramethylethylenediamine), the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 24.

[0164] Phase 25: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 200 m 2 / g; pore size, 200 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 5 g vinylethoxysiloxane-propylethoxysiloxane copolymer 3 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 25.

[0165] Phase 26: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 30 m 2 / g; pore size, 1000 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 1.2 g vinylethoxysiloxane-propylethoxysiloxane copolymer 3 in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g tetramethylethylenediamine) and 1.2 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 26. Example 6: Production of vinyl-functionalized silicon dioxide. Production of a polybutadiene-modified phase under solvent-free conditions at elevated temperature and reduced pressure (Figs. 3 and 4, Schemes 3 and 4)

[0166] Phase 27: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 300 m 2 / g; pore size, 120 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 13.5 g of triethoxysilyl-modified poly-1,2-butadiene 4 (gel, Cat# SSP-055) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 7 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 27.

[0167] Phase 28: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 225 m 2 / g; pore size, 175 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 9.6 g of triethoxysilyl-modified poly-1,2-butadiene 4 (gel, Cat# SSP-055) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 28.

[0168] Phase 29: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 200 m 2 / g; pore size, 200 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 9.6 g of triethoxysilyl-modified poly-1,2-butadiene 4 (gel, Cat# SSP-055) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 29.

[0169] Phase 30: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 30 m 2 / g; pore size, 1000 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 2.4 g of triethoxysilyl-modified poly-1,2-butadiene 4 (gel, Cat# SSP-055) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g tetramethylethylenediamine) and 1.2 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 30.

[0170] Phase 31: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 300 m 2 / g; pore size, 120 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 13.5 g of diethoxymethylsilyl-modified poly-1,2-butadiene 5 (gel, Cat# SSP-058) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 7 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 31.

[0171] Phase 32: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 225 m 2 / g; pore size, 175 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 9.6 g of diethoxymethylsilyl-modified poly-1,2-butadiene 5 (gel, Cat# SSP-058) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 32.

[0172] Phase 33: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 200 m 2 / g; pore size, 200 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 9.6 g of diethoxymethylsilyl-modified poly-1,2-butadiene 5 (gel, Cat# SSP-058) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 33.

[0173] Phase 34: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 30 m 2 / g; pore size, 1000 Å) were transferred to a 250 ml round-bottom flask, followed by the addition of a solution of 2.4 g of diethoxymethylsilyl-modified poly-1,2-butadiene 5 (gel, Cat# SSP-058) in a suitable solvent (e.g., methanol). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and subsequently, all volatile components were completely removed under reduced pressure. The dried mixture was placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g of tetramethylethylenediamine) in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a specific value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering and washing with acetone, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.1 g tetramethylethylenediamine) and 1.2 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was brought to a desired value (e.g., temperature) using a vacuum pump.The reactor was evacuated (below 100 mbar). The reactor was brought to a desired temperature (> 100 mbar). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 34. Example 7: Production of vinyl-functionalized silicon dioxide. Production of a vinylalkoxysiloxane-monomer-modified phase under solvent-free conditions at elevated temperature and reduced pressure (Fig. 5, Scheme 5)

[0174] Phase 35: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 300 m 2 / g; pore size, 120 Å) were placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 7 g vinyltrimethoxysilane in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a desired value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 7 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was evacuated to a desired value (e.g. below 100 mbar) using a vacuum pump.The reactor was brought to a desired temperature (> 100). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 35.

[0175] Phase 36: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 225 m 2 / g; pore size, 175Å) were placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyltrimethoxysilane in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a desired value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was evacuated to a desired value (e.g. below 100 mbar) using a vacuum pump.The reactor was brought to a desired temperature (> 100). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 36.

[0176] Phase 37: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 200 m 2 / g; pore size, 200 Å) were placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyltrimethoxysilane in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a desired value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.5 g tetramethylethylenediamine) and 5 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was evacuated to a desired value (e.g. below 100 mbar) using a vacuum pump.The reactor was brought to a desired temperature (> 100). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 37.

[0177] Phase 38: 20 g dried porous spherical silicon dioxide particles (d p , 5 µm; surface area, 30 m 2 / g; pore size, 1000Å) were placed in a reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.15 g tetramethylethylenediamine) and 1 g vinyltrimethoxysilane in the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. The reactor was then evacuated to a desired value (e.g., below 100 mbar) using a vacuum pump. The reactor was heated to a desired temperature (> 100 0C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone. The resulting silicon dioxide was dispersed in a mixture of 5% acetic acid solution (CH3CN:H2O = 1:1, v / v) and allowed to stand for 12 hours. After filtering, the resulting silicon dioxide was dried under vacuum at 105°C for 12 hours. The dried silicon dioxide was placed back into the reactor equipped with heating and vacuum capabilities. After placing a catalyst (e.g., 0.15 g tetramethylethylenediamine) and 1 g vinyldimethylethoxyisilane into the reactor, the reactor was sealed, followed by purging with an inert gas (e.g., nitrogen or argon) for 30 minutes. Afterwards, the reactor was evacuated to a desired value (e.g. below 100 mbar) using a vacuum pump.The reactor was brought to a desired temperature (> 100). 0 C) was heated and held at the same temperature for 16 hours. After cooling, the silicon dioxide particles were dispersed in toluene (100 ml) and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was washed with toluene and acetone to yield phase 38. Example 8: Production of polymer-encapsulated silicon dioxide phases by polymerization with free radicals (Schemes 6, 7)

[0178] Phase 41: 15 ml of a solvent (e.g., dichloromethane) were mixed with 5 g of vinyl-functionalized silicon dioxide (Phase 19), 3 g of 1-octadecene 6 (e.g., Aldrich), and 0.8 g of dicumyl peroxide (e.g., Aldrich). The resulting mixture was treated in an ultrasonic bath until homogeneity was achieved, and then all volatile components were removed under reduced pressure using a rotary evaporator. The resulting mixture was then transferred to a 100 ml screw-top glass bottle equipped with both a gas inlet and outlet. After purging the bottle with an inert gas (e.g., nitrogen or argon) for 15 minutes, it was sealed (at 1 atm pressure) and heated to a desired temperature (50–300 °C). 0C) heated. After being held at the same temperature for 16 hours, the reaction was cooled, and the reaction mixture was dispersed in toluene and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was thoroughly washed with toluene and acetone to give phase 41.

[0179] Phase 42: 15 ml of a solvent (e.g., dichloromethane) were mixed with 5 g of vinyl-functionalized silicon dioxide (Phase 20), 2.5 g of 1-octadecene 6 (e.g., Aldrich), and 0.5 g of dicumyl peroxide (e.g., Aldrich). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were removed under reduced pressure using a rotary evaporator. The resulting mixture was then transferred to a 100 ml screw-top glass bottle equipped with both a gas inlet and outlet. After purging the bottle with an inert gas (e.g., nitrogen or argon) for 15 minutes, it was sealed and heated to a desired temperature (50–300 °C). 0C) heated. After being held at the same temperature for 16 hours, the reaction was cooled, and the reaction mixture was dispersed in toluene and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was thoroughly washed with toluene and acetone to give phase 42.

[0180] Phase 43: 15 ml of a solvent (e.g., dichloromethane) were mixed with 5 g of vinyl-functionalized silicon dioxide (Phase 21), 2.5 g of 1-octadecene 6 (e.g., Aldrich), and 0.5 g of dicumyl peroxide (e.g., Aldrich). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were removed under reduced pressure using a rotary evaporator. The resulting mixture was then transferred to a 100 ml screw-top glass bottle equipped with both a gas inlet and outlet. After purging the bottle with an inert gas (e.g., nitrogen or argon) for 15 minutes, it was sealed and heated to a desired temperature (50–300 °C). 0C) heated. After being held at the same temperature for 16 hours, the reaction was cooled, and the reaction mixture was dispersed in toluene and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was thoroughly washed with toluene and acetone to give phase 43.

[0181] Phase 44: 15 ml of a solvent (e.g., dichloromethane) were mixed with 5 g of vinyl-functionalized silicon dioxide (Phase 22), 1 g of 1-octadecene 6 (e.g., Aldrich), and 0.35 g of dicumyl peroxide (e.g., Aldrich). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were removed under reduced pressure using a rotary evaporator. The resulting mixture was then transferred to a 100 ml screw-top glass bottle equipped with both a gas inlet and outlet. After purging the bottle with an inert gas (e.g., nitrogen or argon) for 15 minutes, it was sealed and heated to a desired temperature (50–300 °C). 0C) heated. After being held at the same temperature for 16 hours, the reaction was cooled, and the reaction mixture was dispersed in toluene and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was thoroughly washed with toluene and acetone to give phase 44.

[0182] Phase 45 (comparative example): 15 ml of a solvent (e.g., dichloromethane) was mixed with 5 g of vinyl-functionalized silicon dioxide (Phase 22), 0.3 g of 1-Oktene 7 (e.g., Aldrich), and 0.35 g of dicumyl peroxide (e.g., Aldrich). The resulting mixture was treated in an ultrasonic bath until homogeneity was achieved, and then all volatile components were removed under reduced pressure using a rotary evaporator. The resulting mixture was then transferred to a 100 ml glass bottle with a screw cap, equipped with both a gas inlet and outlet. After purging the bottle with an inert gas (e.g., nitrogen or argon) for 15 minutes, the bottle was sealed and heated to a desired temperature (50–300 °C). 0C) heated. After being held at the same temperature for 16 hours, the reaction was cooled, and the reaction mixture was dispersed in toluene and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was thoroughly washed with toluene and acetone to give phase 45.

[0183] Phase 46 (comparative example): 15 ml of a solvent (e.g., dichloromethane) were mixed with 5 g of vinyl-functionalized silicon dioxide (Phase 22), 0.56 g of allylbenzene 8 (e.g., Aldrich), and 0.35 g of dicumyl peroxide (e.g., Aldrich). The resulting mixture was treated in an ultrasonic bath until homogeneity was achieved, and then all volatile components were removed under reduced pressure using a rotary evaporator. The resulting mixture was then transferred to a 100 ml glass bottle with a screw cap, equipped with both a gas inlet and outlet. After purging the bottle with an inert gas (e.g., nitrogen or argon) for 15 minutes, the bottle was sealed and heated to a desired temperature (50–300 °C). 0C) heated. After being held at the same temperature for 16 hours, the reaction was cooled, and the reaction mixture was dispersed in toluene and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was thoroughly washed with toluene and acetone to give phase 46. Production of C8 silicon dioxide phase with S-bond:

[0184] Phase 47 (comparative example): 15 ml of a solvent (e.g., dichloromethane) were mixed with 5 g of vinyl-functionalized silicon dioxide (Phase 22), 0.53 g of 1-octanethiol 9 (e.g., Aldrich), and 0.35 g of dicumyl peroxide (e.g., Aldrich). The resulting mixture was treated in an ultrasonic bath until uniformity was achieved, and then all volatile components were removed under reduced pressure using a rotary evaporator. The resulting mixture was then transferred to a 100 ml screw-top glass bottle equipped with both a gas inlet and outlet. After purging the bottle with an inert gas (e.g., nitrogen or argon) for 15 minutes, it was sealed and heated to a desired temperature (50–300 °C). 0C) heated. After being held at the same temperature for 16 hours, the reaction was cooled, and the reaction mixture was dispersed in toluene and treated in an ultrasonic bath for 30 minutes. After filtering, the cake was thoroughly washed with toluene and acetone to give phase 47.

[0185] The summary of the phases produced and reaction conditions is shown in Tables 2 and 3: Table 2: Preparation of a variety of vinyl silicon dioxide phases with different polymer / monomer starting materials (reaction schemes 1 - 5): Vinyl functionalized phase Binding condition silicon dioxide substrate (d p / Pore size / Surface area) Polymer / Monomer Phase 10 Toluene / Reflux 3µm / 175Å / 225 m 2 / g 1 or 2 Phase 11 Toluene / Reflux 5µm / 120Å / 300 m 2 / g 1 or 2 Phase 12 Toluene / Reflux 5µm / 175Å / 225 m 2 / g 1 or 2 Phase 13 Toluene / Reflux 5µm / 200Å / 200 m 2 / g 1 or 2 Phase 14 Toluene / Reflux 5µm / 1000Å / 30 m 2 / g 1 or 2 Phase 15 160°C, solvent-free, 1 atm 5µm / 120Å / 300 m 2 / g 1 or 2 Phase 16 160°C, solvent-free, 1 atm 5µm / 175Å / 225 m 2 / g 1 or 2 Phase 17 160°C, solvent-free, 1 atm 5µm / 200Å / 200 m 2 / g 1 or 2 Phase 18 160°C, solvent-free, 1 atm 5µm / 1000Å / 30 m 2 / g 1 or 2 Phase 19 >150°C, solvent-free, reduced pressure 5µm / 120Å / 300 m 2 / g 1 or 2 Phase 20 >150°C, solvent-free, reduced pressure 5µm / 175Å / 225 m 2 / g 1 or 2 Phase 21 >150°C, solvent-free, reduced pressure 5µm / 200Å / 200 m 2 / g 1 or 2 Phase 22 >150°C, solvent-free, reduced pressure 5µm / 1000Å / 30 m 2 / g 1 or 2 Phase 23 >150°C, solvent-free, reduced pressure 5µm / 120Å / 300 m 2 / g 3 Phase 24 >150°C, solvent-free, reduced pressure 5µm / 175Å / 225 m 2 / g 3 Phase 25 >150°C, solvent-free, reduced pressure 5µm / 200Å / 200 m 2 / g 3 Phase 26 >150°C, solvent-free, reduced pressure 5µm / 1000Å / 30 m 2 / g 3 Phase 27 >150°C, solvent-free, reduced pressure 5µm / 120Å / 300 m 2 / g 4 Phase 28 >150°C, solvent-free, reduced pressure 5µm / 175Å / 225 m 2 / g 4 Phase 29 >150°C, solvent-free, reduced pressure 5µm / 200Å / 200 m 2 / g 4 Phase 30 >150°C, solvent-free, reduced pressure 5µm / 1000Å / 30 m 2 / g 4 Phase 31 >150°C, solvent-free, reduced pressure 5µm / 120Å / 300 m 2 / g 5 Phase 32 >150°C, solvent-free, reduced pressure 5µm / 175Å / 225 m 2 / g 5 Phase 33 >150°C, solvent-free, reduced pressure 5µm / 200Å / 200 m 2 / g 5 Phase 34 >150°C, solvent-free, reduced pressure 5µm / 1000Å / 30 m 2 / g 5 Phase 35 >150°C, solvent-free, reduced pressure 5µm / 120Å / 300 m 2 / g Vinyltrimethoxysilane Phase 36 >150°C, solvent-free, reduced pressure 5µm / 175Å / 225 m 2 / g Vinyltrimethoxysilane Phase 37 >150°C, solvent-free, reduced pressure 5µm / 200Å / 200 m 2 / g Vinyltrimethoxysilane Phase 38 >150°C, solvent-free, reduced pressure 5µm / 1000Å / 30 m 2 / g Vinyltrimethoxysilane Table 3: Preparation of polymer-encapsulated silicon dioxide (PES) phases (reaction schemes 6-7). PES phase (CH 2 =CH)R f Polymerization condition Vinyl-functionalized phase Phase 41 CH2=CHC 16 H 33 6 Dicumyl peroxide, > 120°C Phase 19 Phase 42 CH2=CHC 16 H 33 6 Dicumyl peroxide, > 120°C Phase 20 Phase 43 CH2=CHC 16 H 33 6 Dicumyl peroxide, > 120°C Phase 21 Phase 44 CH2=CHC 16 H 33 6 Dicumyl peroxide, > 120°C Phase 22 Phase 45 CH2=CHC6 H 13 7 Dicumyl peroxide, > 120°C Phase 22 Phase 46 CH2=CHCH2Ph 8 Dicumyl peroxide, > 120°C Phase 22 Phase 47 C8 H 17 SH 9 Dicumyl peroxide, > 120°C Phase 22 Example 9: Low pH stability

[0186] The test consisted of repeated cycles of acid stress conditions and a column test.

[0187] Performance test conditions: stationary phase, Phase 42 and a commercially available C18, column dimensions: 3 x 150 mm; mobile phase: 10% acetonitrile / 90% 10 mM ammonium acetate (pH= 5.2); flow rate, 0.425 ml / min; injection volume, 2 µl; temperature, 30°C; detection, UV at 220 nm; test probes, uracil (0.15 mg / ml), acetanilide (2 mg / ml).

[0188] Acid stress conditions: mobile phase, 0.1 M TFA; flow rate, 0.425 ml / min; temperature, 80°C; duration, 3 h.

[0189] Fig.Figure 8 illustrates the hydrolysis resistance test of Phase 42 (open circles) compared to a commercially available C18 phase (filled circles) produced using conventional C18 silane chemistry (e.g., non-polymeric silane chemistry) under low pH conditions (0.1 M TFA, pH -1). During the 100-hour test period, the retention time of the acetanilide peak changed by -4% for Phase 42. For the conventional C18 phase, it decreased by more than 50% after an 80-hour acid treatment. Phase 42 exhibits higher hydrolysis resistance under low pH conditions. Example 10: High pH stability

[0190] The test consisted of repeated cycles of base stress conditions and a column test. The performance test conditions were: column, pack Phase 43, dimensions, 3 × 150 mm; mobile phase, 10% acetonitrile / 90% 10 mM ammonium acetate (pH = 5.2); flow rate, 0.425 ml / min; injection volume, 2 µl; temperature, 30°C; detection, UV at 220 nm; test probes, uracil (0.15 mg / ml), procainamide (0.15 mg / ml), sodium tosylate (0.15 mg / ml), acetanilide (2 mg / ml).

[0191] The base stress conditions were: mobile phase, 0.1 M NaOH in 10% methanol; temperature, 30 0 C; Duration, 1 h.

[0192] Fig.Figure 9 illustrates the hydrolysis resistance test of Phase 43 (open circles) compared to C18 Phase A (filled circles) under high pH conditions (0.1 M NaOH, pH 13). The efficiency of the actanilide peak began to decrease dramatically for Phase 43 after a 12-hour base treatment. However, this occurred for C18 Phase A after a 5-hour treatment. Phase 43 exhibits better stability at high pH values ​​than C18 Phase A. Example 11: Performance test

[0193] To test the performance of the column packed with Phase 42, a mixture containing uracil, dimethyl phthalate and phenanthrene was used for chromatic separation.

[0194] The test conditions were: column, packing phase 42, particle size 5 µm, column dimensions: 3 × 150 mm; mobile phase: acetonitrile / DI water (70 / 30, v / v); flow rate: 0.425 ml / min; injection volume: 2 µl; temperature: 30°C; detection: UV at 220 nm; and test probes: uracil (peak 1, 0.15 mg / ml), dimethyl phthalate (peak 2, 0.75 mg / ml), and phenanthrene (peak 3, 0.15 mg / ml).

[0195] Fig. Figure 10 illustrates the chromatographic performance of the Phase 42 packed column, including hydrophobic retention, peak asymmetry, and efficiency. Example 12: Aminoglycoside separations

[0196] A range of aminoglycoside antibiotics (e.g., gentamicin, spectinomycin, kanamycin, ribostamycin, streptomycin, apramycin, paromomycin, dihydrostreptomycin, neomycin, netilmycin, tobramycin, amikacin, arbekacin) were analyzed using reversed-phase liquid chromatography (RPLC) through a Phase 42-packed column, as they are highly hydrophilic and difficult to retain on a conventional reversed-phase column. Trifluoroacetic acid (TFA) and heptafluorobutyric acid (HFBA) were used as ion-pair reagents to retain the aminoglycosides. 100 mM TFA in DI water at a pH of approximately 1 was primarily used as the mobile phase. Small amounts of HFBA were added to the mobile phase to enhance retention and adjust selectivity.

[0197] Fig. Figure 11 illustrates the HPLC separation of gentamicin sulfate. Four main components of gentamicin (C1, C2) 1a , C2 and C 2aThe samples were completely separated. More than 15 substances and impurities related to gentamicin were observed as the smaller peaks. The test conditions were: column, packing phase 42, particle size 5 µm, column dimensions: 3 × 150 mm; mobile phase: 100 mM TFA; flow rate: 0.425 ml / min; injection volume: 2 µl; temperature: 30°C; detection: corona aerosol detector; and test sample: gentamicin sulfate (1 mg / ml).

[0198] Fig. Figure 12 illustrates the HPLC separation of spectinomycin sulfate (shown as Peak 1). HFBA was used to achieve optimal separation. The test conditions were: column, packing phase 42, particle size 5 µm, column dimensions: 3 × 150 mm; mobile phase: 100 mM TFA / 100 mM HFBA (93 / 7, v / v); flow rate: 0.425 ml / min; injection volume: 5 µl; temperature: 30°C; detection: corona aerosol detector; and test sample: spectinomycin sulfate (1 mg / ml).

[0199] Fig.Figure 13 illustrates the change in the retention factor (k) for various aminoglycosides upon addition of HFBA in a 100 mM TFA mobile phase. With increasing HFBA concentrations, the retention factors of all aminoglycosides increased because HFBA is a much stronger ion-pairing reagent. However, the increase varied for the different aminoglycosides. In general, the k values ​​for aminoglycosides containing more amino groups increased more with increasing HFBA concentration in the mobile phase than for aminoglycosides containing relatively few amino groups. For example, neomycin contains six primary amino groups, and its k value increased ninefold after the addition of 4 mM HFBA. Spectinomycin has two secondary amino groups, and its k value increased only twice as much under the same conditions. Therefore, the selectivity for aminoglycoside antibiotics can be adjusted by adding HFBA to the mobile phase (100 mM TFA).The test conditions were: column, pack phase 42, particle size 5 µm, column dimensions: 3 × 150 mm; mobile phase: various concentrations of HFBA (0, 0.5 mM, 1 mM, 2 mM, 3 mM and 4 mM in 100 mM TFA); flow rate: 0.425 ml / min; injection volume: 2 µl; temperature: 30°C; detection: corona aerosol detector; and test samples: kanamycin sulfate (1 mg / ml), ribostamycin sulfate (1 mg / ml), streptomycin sulfate (1 mg / ml), apramycin sulfate (1 mg / ml), paromomycin sulfate (1 mg / ml), dihydrostreptomycin sulfate (1 mg / ml), neomycin sulfate (1 mg / ml), and spectinomycin sulfate (1 mg / ml). Example 13: Robustness for aminoglycosides

[0200] To assess robustness for the challenging chromatographic conditions required for aminoglycoside antibiotics, a column packed with Phase 42 was subjected to more than 500 consecutive runs of gentamicin separation at 50°C using 100 mM TFA (approximately pH 1) as the mobile phase. Fig.Figure 14 illustrates the superposition of separations during the process. Overall, Phase 42 exhibited outstanding chemical and chromatographic stability during the investigation – less than 4% retention loss was observed compared to the more than 50% retention loss for a commercially available C18 phase prepared using conventional silane chemistry.

[0201] The test conditions were: column, pack phase 42, particle size 5 µm, column dimensions: 3 × 150 mm; mobile phase: 100 mM TFA; flow rate: 0.425 ml / min; injection volume: 2 µl; temperature: 50°C; detection: corona aerosol detector (CAD, commercially available from Thermo Fisher Scientific); and test sample: gentamicin sulfate (1 mg / ml).

[0202] In light of the foregoing, the invention can be made available according to each of the numbered paragraphs below: (1) Chromatographic material comprising: Substrate having a surface, wherein the substrate has a polymer layer covalently bonded to the surface; wherein the polymer layer comprises polymer molecules covalently attached to the surface of the substrate, wherein each polymer molecule is attached to the surface via multiple siloxane bonds and each polymer molecule is linked to one or more functionalizing compounds, each comprising a functional group, wherein the functional group comprises C14-C22 alkyl. (2) Chromatographic material according to paragraph 1, wherein the polymer layer is formed by covalent attachment of polymer molecules to the surface of the substrate via several siloxane bonds, each polymer molecule containing several first reactive groups, and reaction of the first reactive groups of the attached polymer molecules with at least one functionalizing compound comprising a second reactive group that is reactive with the first reactive groups and further comprising a functional group. (3) Chromatographic material according to any of the preceding paragraphs, wherein the functional group has chromatographic functionality. (4) Chromatographic material according to any of the preceding paragraphs, wherein the first reactive groups comprise olefinic groups. (5) Chromatographic material according to any of the preceding paragraphs, wherein the first reactive groups comprise a member selected from the group consisting of vinyl groups and allyl groups. (6) Chromatographic material according to any of the preceding paragraphs, wherein all of the first reactive groups are vinyl groups. (7) Chromatographic material according to any of the preceding paragraphs, wherein there is a substantially uniform distance between adjacent first reactive groups of the polymer. (8) Chromatographic material according to any of the preceding paragraphs, wherein the second reactive group comprises a member selected from the group consisting of an olefinic group and a thiol group. (9) Chromatographic material according to any of the preceding paragraphs, wherein the second reactive group comprises a member selected from the group consisting of a vinyl group and an allyl group. (10) Chromatographic material according to any of the preceding paragraphs, wherein the polymer molecule is based on a vinylsiloxane. (11) Chromatographic material according to any of the preceding paragraphs, wherein the vinylsiloxane polymer has formula I: where n is an integer from 3 to 100, and R1 and R2 are independently selected from the group consisting of: alkoxy, hydroxyl and halogen. (12) Chromatographic material according to paragraph 11, wherein R1 and R2 are selected independently from the group consisting of: methoxy, ethoxy and hydroxyl. (13) Chromatographic material according to paragraph 10, wherein the vinylsiloxane polymer is a copolymer. (14) Chromatographic material according to paragraph 10 or 13, wherein the vinylsiloxane copolymer has a formula III: where R1 and R2 are independently selected from the group consisting of: alkoxy, hydroxyl and halogen; and where n is an integer from 3 to 100 and m is an integer from 1 to 70. (15) Chromatographic material according to any of the preceding paragraphs, wherein the polymer molecule is a silyl-modified polybutadiene. (16) Chromatographic material according to paragraph 15, wherein the silyl-modified polybutadiene is an alkoxysilyl-modified polybutadiene having a repeating unit of formula VI: where each R 1 selected independently from the group consisting of: Methoxy and Ethoxy. (17) Chromatographic material according to paragraph 15 or 16, wherein the silyl-modified polybutadiene is an alkylalkoxysilyl-modified polybutadiene. (18) Method for producing functionalized silicon dioxide for chromatographic purposes, the method comprising: In a first stage, the silicon dioxide is reacted with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar, wherein the first functionalizing compound or compounds comprise the following: one or more silyl groups to react with the surface of the silicon dioxide and one or more first reactive groups, whereby the first functionalizing compound(s) are covalently attached to the surface of the silicon dioxide, leaving the first reactive groups in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound, wherein the second functionalizing compound comprises: one or more second reactive groups that are reactive with the one or more first reactive groups; and a functional group, wherein the functional group comprises C14-C22 alkyl. (19) Method according to paragraph 18, wherein the first functionalizing compound is a polymer. (20) Method according to one of paragraphs 18 to 19, wherein the polymer is selected from the group consisting of: siloxane polymer, vinylsiloxane polymer, vinylalkoxysiloxane, silyl-modified polybutadiene and alkoxysilyl-modified polybutadiene. (21) Method according to one of paragraphs 18 to 20, wherein the first reactive groups are selected from the group consisting of vinyl and allyl groups. (22) Method according to any one of paragraphs 18 to 21, wherein the second functionalizing compound is a C14-C22 alkene. (23) Method according to any one of paragraphs 18 to 22, wherein one or more second reactive groups are selected from the group consisting of olefinic groups and thiol groups. (24) A method according to any one of paragraphs 18 to 23, wherein the temperature in the first stage when reacting the silicon dioxide with at least one first functionalizing compound is at least approximately 200°C. (25) A method according to any one of paragraphs 18 to 24, wherein the temperature in the first stage of reacting the silicon dioxide with at least one first functionalizing compound is in the range of approximately 200 to approximately 300°C. (26) A method according to any one of paragraphs 18 to 25, wherein the pressure in the first stage when reacting the silicon dioxide with at least one first functionalizing compound is less than 100 mbar. (27) Method according to any one of paragraphs 18 to 26, wherein the pressure in the first stage when reacting the silicon dioxide with at least one first functionalizing compound is between 0.1 mbar and approximately 100 mbar. (28) A method according to any one of paragraphs 18 to 27, wherein the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage is carried out in the absence of a solvent. (29) A method according to any one of paragraphs 18 to 28, wherein the reaction of the silicon dioxide with at least one first functionalizing compound is carried out in the first stage in the presence of a catalyst. (30) Method according to any one of paragraphs 18 to 29, wherein the temperature in the second stage when reacting the one or more first reactive groups with the second functionalizing compound is at least approximately 100°C. (31) Method according to any of paragraphs 18 to 30, wherein the temperature in the second stage when reacting the one or more first reactive groups with the second functionalizing compound is in the range of approximately 100 to approximately 200°C. (32) Method according to any one of paragraphs 18 to 31, wherein the pressure in the second stage when reacting the one or more first reactive groups with the second functionalizing compound is at least atmospheric pressure. (33) Method according to any one of paragraphs 18 to 32, wherein the pressure in the second stage when reacting the one or more first reactive groups with the second functionalizing compound is less than 500 mbar. (34) Method for producing functionalized silicon dioxide for chromatographic purposes, the method comprising: In a first stage, the silicon dioxide is reacted with at least one first functionalizing compound under conditions of at least approximately 100°C, wherein the first functionalizing compound or compounds comprise the following: a polymer or polymers having several silyl groups to react with the surface of silicon dioxide and several first reactive groups, whereby the first functionalizing compound(s) are covalently attached to the surface of the silicon dioxide, leaving the first reactive groups in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with at least one second functionalizing compound, wherein the second functionalizing compound comprises: one or more second reactive groups that are reactive with the one or more first reactive groups; and a functional group, wherein the functional group comprises C14-C22 alkyl. (35) Method for separating aminoglycoside antibiotics comprising flowing a mobile phase containing a sample with one or more aminoglycoside antibiotics through a column to chromatographically separate the one or more aminoglycoside antibiotics from each other, wherein the column is packed with the chromatographic material according to any one of paragraphs 1 to 17. (36) The method according to paragraph 35, wherein the pH of the mobile phase is 1.0 or less or 13.0 or more. (37) Chromatographic material produced by a process comprising: In a first stage, the silicon dioxide is reacted with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar, wherein the first functionalizing compound or compounds comprise the following: one or more silyl groups to react with the surface of the silicon dioxide and one or more first reactive groups, whereby the first functionalizing compound(s) are covalently attached to the surface of the silicon dioxide, leaving the first reactive groups in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound, wherein the second functionalizing compound comprises: one or more second reactive groups that are reactive with the one or more first reactive groups; and a functional group, wherein the functional group comprises C14-C22 alkyl; where the retention time of a chromatographic analysis of a hydrophobic neutral compound varies by no more than + / -10%, while a mobile phase is passed through the chromatographic material for more than 20 hours, with the mobile phase having a pH of approximately 1 or less. (38) Chromatographic material according to paragraph 37, the process further comprising: Repeating a step of reacting the silicon dioxide with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar during the first stage, but before the second stage; and Repeating a step of reacting the one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar during the second stage. (39) Chromatographic material according to paragraph 37 or 38, wherein the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage is carried out in the absence of a solvent. (40) Chromatographic material according to any one of paragraphs 37 to 39, wherein the reaction of the one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound is carried out in the second stage in the absence of a solvent. (41) Chromatographic material according to paragraphs 37 to 40, wherein the reaction of the silicon dioxide with at least one first functionalizing compound is carried out in the first stage in the presence of a catalyst. (42) Chromatographic material according to any one of paragraphs 37 to 41, wherein the first functionalizing compound comprises a vinylsiloxane polymer. (43) Chromatographic material according to paragraphs 37 to 42, wherein the vinylsiloxane polymer has formula I: where n is an integer from 3 to 100, and R1 and R2 are independently selected from the group consisting of: alkoxy, hydroxyl and halogen. (44) Chromatographic material according to any one of paragraphs 37 to 43, wherein the first reactive group comprises a member selected from the group consisting of vinyl groups and allyl groups. (45) Chromatographic material according to any one of paragraphs 37 to 44, wherein the second reactive group comprises a member selected from the group consisting of a vinyl group, an allyl group and a thiol group. (46) Chromatographic material according to any one of paragraphs 37 to 45, comprising the hydrophobic neutral compound acetanilide.

[0203] For the purposes of their use in this document, including the claims, singular forms of terms in this document are to be interpreted as including the plural form and vice versa, unless the context suggests otherwise. For example, unless the context suggests otherwise, a singular reference such as "a" or "an" means "one or more".

[0204] Throughout the description and claims of this specification, the words "comprise", "include", "include" and "contain" and variants of the words, for example "comprehensive" and "encompasses", etc., mean "including, but not limited to", and are not intended to exclude (and do not exclude) other components.

[0205] It is understood that modifications may be made to the foregoing embodiments of the invention, which, however, still fall within the scope of the invention. Unless otherwise stated, each feature disclosed in the specification may be replaced by alternative features serving the same, equivalent, or similar purpose. Thus, unless otherwise stated, each disclosed feature represents an example of a generic set of equivalent or similar features.

[0206] The use of one or more of the examples provided herein, or of exemplary language (“for example,” “such as,” “for instance,” “e.g.”, and the like), is intended solely to better illustrate the invention and does not constitute a limitation with respect to the scope of the invention unless otherwise claimed. No linguistic formulation in the specification shall be construed as indicating any unclaimed element as essential to the practice of the invention.

[0207] All steps described in this specification can be performed in any order or simultaneously, unless otherwise specified or the context requires otherwise.

[0208] All features disclosed in this specification may be combined in any combination, except for combinations in which at least some of these features and / or steps are mutually exclusive. In particular, the preferred features of the invention apply to all aspects of the invention and may be used in any combination. Likewise, features described in non-essential combinations may be used separately (not combined with each other).

Claims

[1] Chromatographic material including: Substrate having a surface, wherein the substrate has a polymer layer covalently bonded to the surface; wherein the polymer layer comprises polymer molecules covalently attached to the surface of the substrate, wherein each polymer molecule is attached to the surface via multiple siloxane bonds and each polymer molecule is linked to one or more functionalizing compounds, each comprising a functional group, wherein the functional group comprises C14-C22 alkyl. [2] Chromatographic material according to claim 1, wherein the polymer layer is formed by covalent attachment of polymer molecules to the surface of the substrate via multiple siloxane bonds, each polymer molecule containing multiple first reactive groups, and reacting the first reactive groups of the attached polymer molecules with at least one functionalizing compound comprising a second reactive group that is reactive with the first reactive groups, and further comprising a functional group. [3] Chromatographic material according to claim 1, wherein the functional group has chromatographic functionality. [4] Chromatographic material according to claim 2, wherein the first reactive groups comprise olefinic groups. [5] Chromatographic material according to claim 4, wherein the first reactive groups comprise a member selected from the group consisting of vinyl groups and allyl groups. [6] Chromatographic material according to claim 5, wherein all of the first reactive groups are vinyl groups. [7] Chromatographic material according to claim 2, wherein there is a substantially uniform distance between adjacent first reactive groups of the polymer. [8] Chromatographic material according to claim 2, wherein the second reactive group comprises a member selected from the group consisting of an olefinic group and a thiol group. [9] Chromatographic material according to claim 2, wherein the second reactive group comprises a member selected from the group consisting of a vinyl group and an allyl group. [10] Chromatographic material according to claim 2, wherein the polymer molecule is based on a vinylsiloxane. [11] Chromatographic material according to claim 10, wherein the vinylsiloxane polymer has a formula I: where n is an integer from 3 to 100, and R1 and R2 are independently selected from the group consisting of: alkoxy, hydroxyl and halogen. [12] Chromatographic material according to claim 11, wherein R1 and R2 are independently selected from the group consisting of: methoxy, ethoxy and hydroxyl. [13] Chromatographic material according to claim 10, wherein the vinylsiloxane polymer is a copolymer. [14] Chromatographic material according to claim 10, wherein the vinylsiloxane polymer has formula III: wherein R1 and R2 are independently selected from the group consisting of: alkoxy, hydroxyl and halogen; and wherein n is an integer from 3 to 100 and m is an integer from 1 to 70. [15] Chromatographic material according to claim 2, wherein the polymer molecule is a silyl-modified polybutadiene. [16] Chromatographic material according to claim 15, wherein the silyl-modified polybutadiene is an alkoxysilyl-modified polybutadiene having a repeating unit of formula VI: wherein each R 1 selected independently from the group consisting of: Methoxy and Ethoxy. [17] Chromatographic material according to claim 15, wherein the silyl-modified polybutadiene is an alkylalkoxysilyl-modified polybutadiene. [18] Method for forming functionalized silicon dioxide for chromatographic purposes, the method comprising: In a first stage, the silicon dioxide is reacted with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar, wherein the first functionalizing compound or compounds comprise the following: one or more silyl groups to react with the surface of the silicon dioxide and one or more first reactive groups, whereby the first functionalizing compound(s) are covalently attached to the surface of the silicon dioxide, leaving the first reactive groups in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound, wherein the second functionalizing compound comprises: one or more second reactive groups that are reactive with the one or more first reactive groups; and a functional group, wherein the functional group comprises C14-C22 alkyl. [19] Method according to claim 18, wherein the first functionalizing compound is a polymer. [20] Method according to claim 19, wherein the polymer is selected from the group consisting of: siloxane polymer, vinylsiloxane polymer, vinylalkoxysiloxane, silyl-modified polybutadiene and alkoxysyl-modified polybutadiene. [21] Method according to claim 19, wherein the first reactive groups are selected from the group consisting of vinyl and allyl groups. [22] Method according to claim 19, wherein the second functionalizing compound is a C14-C22 alkene. [23] Method according to claim 19, wherein the one or more second reactive groups are selected from the group consisting of olefinic groups and thiol groups. [24] Method according to claim 23, wherein the temperature in the first stage when reacting the silicon dioxide with at least one first functionalizing compound is at least approximately 200°C. [25] Method according to claim 24, wherein the temperature in the first stage when reacting the silicon dioxide with at least one first functionalizing compound is in the range of approximately 200 to approximately 300°C. [26] Method according to claim 18, wherein the pressure in the first stage when reacting the silicon dioxide with at least one first functionalizing compound is less than 100 mbar. [27] Method according to claim 18, wherein the pressure in the first stage when reacting the silicon dioxide with at least one first functionalizing compound is between 0.1 mbar and approximately 100 mbar. [28] Method according to claim 18, wherein the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage is carried out in the absence of a solvent. [29] Method according to claim 18, wherein the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage is carried out in the presence of a catalyst. [30] Method according to claim 18, wherein the temperature in the second stage when reacting the one or more first reactive groups with the second functionalizing compound is at least approximately 100°C. [31] Method according to claim 30, wherein the temperature in the second stage when reacting the one or more first reactive groups with the second functionalizing compound is in the range of approximately 100 to approximately 200°C. [32] Method according to claim 30, wherein the pressure in the second stage during the reaction of the one or more first reactive groups with the second functionalizing compound is at least atmospheric pressure. [33] Method according to claim 32, wherein the pressure in the second stage during the reaction of the one or more first reactive groups with the second functionalizing compound is less than 500 mbar. [34] Method for forming functionalized silicon dioxide for chromatographic purposes, the method comprising: In a first stage, the silicon dioxide is reacted with at least one first functionalizing compound under conditions of at least approximately 100°C, wherein the first functionalizing compound or compounds comprise the following: a polymer or polymers having several silyl groups to react with the surface of silicon dioxide and several first reactive groups, whereby the first functionalizing compound(s) are covalently attached to the surface of the silicon dioxide, leaving the first reactive groups in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with at least one second functionalizing compound, wherein the second functionalizing compound comprises: one or more second reactive groups that are reactive with the one or more first reactive groups; and a functional group, wherein the functional group comprises C14-C22 alkyl. [35] A method for separating aminoglycoside antibiotics, comprising flowing a mobile phase containing a sample with one or more aminoglycoside antibiotics through a column to chromatographically separate the one or more aminoglycoside antibiotics from each other, wherein the column is packed with the chromatographic material according to claim 1. [36] Method according to claim 35, wherein the pH of the mobile phase is 1.0 or less or 13.0 or more. [37] Chromatographic material produced by a process comprising: In a first stage, the silicon dioxide is reacted with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar, wherein the first functionalizing compound or compounds comprise the following: one or more silyl groups to react with the surface of the silicon dioxide and one or more first reactive groups, whereby the first functionalizing compound(s) are covalently attached to the surface of the silicon dioxide, leaving the first reactive groups in an unreacted state; and In a second stage, the reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound, wherein the second functionalizing compound comprises: one or more second reactive groups that are reactive with the one or more first reactive groups; and a functional group, wherein the functional group comprises C14-C22 alkyl; where the retention time of a chromatographic analysis of a hydrophobic neutral compound varies by no more than + / -10%, while a mobile phase is passed through the chromatographic material for more than 20 hours, with the mobile phase having a pH of approximately 1 or less. [38] Chromatographic material according to claim 37, wherein the process further comprises: Repeating a step of reacting the silicon dioxide with at least one first functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar during the first stage, but before the second stage; and Reaction of one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound under conditions of at least approximately 100°C and less than 500 mbar during the second stage. [39] Chromatographic material according to claim 37, wherein the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage is carried out in the absence of a solvent. [40] Chromatographic material according to claim 39, wherein the reaction of the one or more first reactive groups of the surface-bound first functionalizing compound or compounds with the at least one second functionalizing compound is carried out in the second stage in the absence of a solvent. [41] Chromatographic material according to claim 37, wherein the reaction of the silicon dioxide with at least one first functionalizing compound in the first stage is carried out in the presence of a catalyst. [42] Chromatographic material according to claim 37, wherein the first functionalizing compound comprises a vinylsiloxane polymer. [43] Chromatographic material according to claim 42, wherein the vinylsiloxane polymer has a formula I: where n is an integer from 3 to 100, and R1 and R2 are independently selected from the group consisting of: alkoxy, hydroxyl and halogen. [44] Chromatographic material according to claim 37, wherein the first reactive groups comprise a member selected from the group consisting of vinyl groups and allyl groups. [45] Chromatographic material according to claim 37, wherein the second reactive group comprises a member selected from the group consisting of a vinyl group, an allyl group and a thiol group. [46] Chromatographic material according to claim 37, wherein the hydrophobic neutral compound comprises acetanilide.

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