WO1999042078A2

WO1999042078A2 - Hardenable dental material

Info

Publication number: WO1999042078A2
Application number: PCT/EP1999/000877
Authority: WO
Inventors: Wolfgang Podszun; Joachim Krüger; Werner Finger; Frank Louwet
Original assignee: Agfa-Gevaert Aktiengesellschaft
Priority date: 1998-02-23
Filing date: 1999-02-10
Publication date: 1999-08-26
Also published as: WO1999042078A3; AU2833199A; DE19807631A1

Abstract

Hardenable dental material, containing bead polymerizate cross-linked through Si-O-Si groups with a mean particle size of 1 to 10 νm and characterized by high wear resistance and a smooth, high-lustrous surface.

Description

Curable dental materials

The invention relates to curable dental compositions containing bead polymers crosslinked via Si-O-Si groups and having an average particle diameter of 1 to

10 μm.

Curable dental materials are widely used in dentistry and dental technology e.g. used as plastic filling materials, tooth varnishes, sealers, fastening materials, veneering materials and for the production of artificial teeth.

Conventional curable dental materials contain (meth) acrylate monomers and fillers as the main constituents. The fillers can be inorganic substances such as silicon dioxide, silicates or glasses. Organic fillers are usually polymers that can be in irregular form or as spheres. Spherical polymers are preferred as organic fillers. EP 2 850 916 describes dental materials which contain crosslinked bead polymers with an average particle diameter of 10 to 100 μm, which are methacrylate polymers which are crosslinked with ethylene glycol dimethacrylate or divinylbenzene.

These dental materials have good processing properties, but show increased wear and the formation of an insufficiently smooth surface when subjected to heavy loads.

It has now been found that curable dental compositions which contain bead polymers crosslinked via Si-O-Si groups and having an average particle size of 1 to 10 μm can be cured to dental materials which have high wear resistance and a smooth, high-gloss surface. The invention relates to curable dental compositions which contain bead polymers crosslinked via Si-O-Si groups and having an average particle size of 1 to 10 μm.

In a preferred embodiment of the present invention, the curable dental compositions contain

a) 5 to 65 parts by weight of bead polymers crosslinked via Si-O-Si groups and having an average particle size of 1 to 10 μm

b) 35 to 70 parts by weight of monomers

c) 0 to 65 parts by weight of inorganic filler

d) 0.1 to 5 parts by weight of starter additives

e) 0 to 10 parts by weight of additives.

The bead polymers (a) crosslinked via Si-O-Si groups contain 50 to 99% by weight of polymerized vinyl monomer units and 1 to 50% by weight of polymerized

Silane monomer units, preferably 75 to 98% by weight of vinyl monomer units and 2 to 25% by weight of silane monomer units, particularly preferably 85 to 98% by weight of vinyl monomer units and 2 to 15% by weight of silane monomer units. The silane monomer units are at least partially crosslinked via Si-O-Si groups, for example at least 50%, up to the total (100%) of the possible ones

Si-O-Si crosslinking.

Crosslinking silane monomer units are those of the formula R '(R ³ ) a

CH, = C— (CO-OR ² ) - Si (X) 3-a (I),

considered in the

R ^{1 represents} hydrogen or methyl,

R ^{2 is} straight-chain or branched C ₂ -C ₁₂ alkylene whose carbon chain can be interrupted by -O-, -NH-, -COO- or -NH-COO-,

R ^{3 represents} straight-chain or branched C] -C ₆ alkyl or phenyl,

X represents a hydrolyzable group,

a takes the value zero, one or two and

b takes the value zero or one.

Straight-chain or branched alkylene with 2 to 12 carbon atoms is, for example, dimethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, octa-methylene, decamethylene or dodecamethylene and 1,2-propylene, 1,2- and

1,3-butylene and similarly known branched structures. If the carbon chain is interrupted by -O-, -NH-, -COO- or -NH-COO-, the range of polyethers, polyamines, oligoesters or oligourethanes is reached in a known manner. In place of C ₂ -C ₂ alkylene, there is preferably a C ₂ -C ₆ alkylene whose carbon chain can be interrupted by -O-.

Straight-chain or branched C _r C ₆ alkyl is, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl and the known C ₅ and C ₆ hydrocarbon radicals. Hydrolysable groups on the Si atom are known to the skilled person and include for example halogen atoms such as fluorine, chlorine or bromine, in particular chlorine, alkoxy groups such as C _j -CG-alkoxy, in particular methoxy or ethoxy, furthermore carboxylate and carbonamido groups such as acetate, propionate, Acetylamino or propionylamino. Preferably, X represents a chlorine atom or C _j -C ₄ alkoxy, particularly preferably methoxy and ethoxy.

a is preferably 0; b preferably 1.

Preferred silane monomer units are those of the formula

R '

CH ₂ = C-CO-OR ¹ - SiX ₃ (II)

wherein

Rl2 is straight-chain or branched C ₂ -Cg alkylene, the carbon chain of which can be interrupted by -O- and

R ¹ and X have the meaning given above.

Examples of suitable silane monomer compounds are:

Vinyl-trimethoxysilane, vinyl-triethoxysilane, vinyl-methyl-dimethoxysilane, vinyl-methyl-diethoxysilane, γ-methacryloyloxypropyl-trimethoxysilane, γ-methacryloyl-oxypropyl-triethoxysilane, γ-methacryloyloxypropyl-methyl-dimethoxysilane diethoxysilane, γ-acryloyloxypropyl-trimethoxysilane, γ-acryloyloxypropyl-triethoxysilane, γ-acryloyloxypropyl-methyl-dimethoxysilane and γ-acryloyloxypropyl-methyl-diethoxysilane. The silane monomer units initially polymerized into the bead polymers according to the invention are converted in the course of the further preparation in such a way that the hydrolyzable groups are at least partially split off by hydrolysis reaction and the Si-OH groups formed are converted to Si-O-Si bridges by a condensation reaction.

Several of the silane monomer compounds can also be used in a mixture.

Vinyl monomers for the crosslinked bead polymers according to the invention are one or more compounds from the group of unsubstituted or substituted straight-chain, branched or cyclic olefins and diolefins, unsaturated carboxylic acids or their derivatives and the vinyl derivatives of carboxylic acids. Examples include: styrene, α-methylstyrene, vinyltoluene, substituted vinyltoluenes, such as vinylbenzylchloride, butadiene, isobutylene, 2-chlorobutadiene, 2-methylbutadiene, vinylpyridine, cyclopentene, cyclopentadiene and others; (Meth) acrylic acid esters such as ethyl methacrylate, butyl methacrylate, butyl acrylate and hydroxymethyl methacrylate, acrylonitrile and others; Vinyl acetate, vinyl propionate and others. One or more vinyl monomers from the group of styrene and the (meth) acrylic acid esters mentioned, in particular one or more, is (are) preferred

(Meth) acrylic acid ester used.

The average particle diameter of the bead polymers is preferably 1 to 10 μm. The particle diameter distribution is preferably narrow, particularly preferably almost monodisperse.

The crosslinked bead polymers with an average particle diameter of 1 to 10 microns and narrow particle diameter distribution are obtained by 50 to 99 wt .-% vinyl monomers and 1 to 50 wt .-% silane monomers of the formula R '(R ³ ) a

CH ₂ = C - (CO-OR) - Si (X) 3-a

in the

R ^{1 represents} hydrogen or methyl,

R ^{2 is} straight-chain or branched C ₂ -C ₂ alkylene, the carbon chain of which can be interrupted by -O-, -NH-, -COO- or -NH-COO-,

R ^{3 represents} straight-chain or branched Ci-Cg-alkyl or phenyl,

X represents a hydrolyzable group,

a takes the value zero, one or two and

takes the value zero or one,

in a polar medium with the aid of a radical generator as an initiator in the presence of a polymer which is soluble in this medium and has a molecular weight M _w of 5-10 ³ to 5-10 ⁵ in an amount of 0.5 to 15% by weight, based on the amount of

Medium, and optionally in the further presence of a low molecular weight surfactant in an amount of 0.2 to 5 wt .-%, based on the amount of the medium, polymerized and, if appropriate, the polymer formed is then aftertreated by the action of aqueous acid or base.

The non-aqueous polar medium for the preparation of the bead polymers according to the invention comprises one or more compounds from the group of Cι-C ₈ - alkanols, the open-chain or cyclic C ₄ -C ₈ ether, C _r _C6 nitriles, the C _j - C ₆ acid amides, the C ₃ -C ₆ esters and the C ₃ -C ₆ ketones. Examples are: Methanol, ethanol, propanol, i-propanol, butanol, i-butanol, tert-butanol, hexanol, octanol, diethyl ether, dibutyl ether, dioxane, tetrahydrofuran, acetonitrile, propionitrile, dimethylformamide, methyl acetate, ethyl acetate, ethyl propionate, acetone, methyl ethyl ketone, methyl tert-butyl ketone and other compounds known to the person skilled in the art. The alcohols mentioned or a mixture of them are preferably used, in particular the C 1 -C ₄ -alcohols. For the polarity of the medium, it is sufficient if at least 50% by weight of one or more of the polar compounds mentioned is present in the reaction medium.

The rest, for example 0.01 to 50 wt .-% of the reaction medium can consist of non-polar hydrocarbons or halogenated hydrocarbons such as hexane, heptane, benzene, chlorobenzene and others.

However, water is permissible in amounts, for example up to 40% by weight of the total polar polymerization medium. Ethanol can be used in the form of the technically available azeotrope with water. With regard to the water content, other of the solvents mentioned can also be used in the form which is usually available in chemical engineering.

The polymerization is carried out with the help of a radical generator as a polymerization initiator. Such radical formers are known to the person skilled in the art and include in particular peroxy compounds and azo compounds. If the polar medium contains a proportion of water, sodium or potassium persulfate is a suitable initiator. Azodiisobutyronitrile, for example, is particularly suitable. Such radical formers are used in an amount of 0.05 to 5%, preferably 0.1 to 2%, based on the total amount of the comonomers.

The polymerization is further carried out in the presence of a polymer which in

Polymerization medium is soluble and has a molecular weight M _w of 5-10 ³ to 5-10 ⁵ , preferably 10 ⁴ to 2-10 ⁵ . This soluble polymer is used in an amount of 0.2 to 15, preferably 0.5 to 5,% by weight, based on the amount of the polymer sationsmediums used. This polymer acts as a dispersant and can be of natural or synthetic origin. Examples include: cellulose derivatives such as methyl cellulose, ethyl cellulose and hydroxypropyl cellulose, vinyl acetate polymers such as polyvinyl acetate, ethylene-vinyl acetate copolymers with 50 to 90% by weight vinyl acetate units in the copolymer, other vinyl acetate copolymers and partially saponified

Polyvinyl acetates, for example with a degree of saponification of 5 to 25% of all acetate groups. Other suitable polymers are poly-N-vinylpyrrolidone (PVP) substituted PVP, poly-N-vinylcaprolactam and its substituted derivatives, copolymers of PVP and vinylcaprolactam and other polymers which meet the requirements according to the molecular weight and those given above

Meet solubility. The sodium and potassium salts of maleic anhydride copolymers are also particularly suitable, in particular the monosodium salt of the copolymer of 50 mol% styrene and 50 mol% maleic anhydride.

Suitable surfactants can be nonionic or ionic surfactants, which are known in principle to the person skilled in the art. Among the many surfactants, the anionic surfactants include, for example, the sodium salts of sulfosuccinic acid esters and the cationic surfactants N-alkylammonium salts, such as methyl tricaprylammonium chloride, among others. Examples of non-ionic surfactants are the ethoxylation products of nonylphenol.

The polymerization temperature is in the range from 50 to 140 ° C. The polymerization temperature and the decomposition temperature of the radical generator are coordinated. The pressure is fundamentally not critical for the polymerization; it is therefore preferred to work at normal pressure. A pressure higher than normal can be useful if polymerization is to be carried out in a low-boiling solvent at a higher temperature. For temperature control, it is further preferred to work at the boiling point of the polar polymerization medium. When using higher-boiling reaction media, it can therefore be advantageous to work under a somewhat reduced pressure (evaporative cooling). The polymerization time is a few hours, in many cases 2 to 12 hours, and is known, inter alia, depending on the size of the reaction mixture.

The particle diameter of the bead polymers according to the invention can be controlled by the combination of the polymerization parameters mentioned and can be determined by simple preliminary tests. An essential polymerization parameter is the polarity of the polarization medium. It was found that the more polar the solvent, the finer the particles; for example, the particle diameter decreases in the series of n-propanol, ethanol and methanol as the polymerization medium used. By mixing various of the above

Connections for the polar reaction medium can now be infinitely adjusted to the desired particle diameter.

After the end of the polymerization, the polymer obtained can be treated with acidic or alkaline water in order to bring about or complete the crosslinking in the manner described above via Si-OH groups and their condensation to form Si-O-Si groups. To this end, acidic or alkaline water can be added to the polymerization batch and, after crosslinking, the bead polymer can be obtained by filtration and washed if necessary. Since the polymer in the course of the polymerization from the polar, non-aqueous

If the polymerization medium fails, it can also be obtained in another process variant first by filtration, it being possible to recycle the polymerization medium, whereupon in a separate second step the polymer which has been filtered off is treated with acidic or alkaline water for crosslinking.

Acidic or alkaline water are aqueous acids or alkalis, for example aqueous hydrochloric acid or sulfuric acid or aqueous sodium hydroxide solution or potassium hydroxide solution. The acidic or alkaline water is added to the polymerization batch or to the filtered polymer in such an amount that the polymerization batch or slurry of the filtered polymer is contained therein Water has a pH from -1 to 3, preferably from 0 to 2, or from 11 to 14, preferably from 12 to 13. Acidic hydrolysis and crosslinking are preferably carried out. The amount of acidic or alkaline water is not critical except for the adjustment of the pH mentioned, especially since the small amount required for at least partial hydrolysis and crosslinking

There is always enough water. In the variant of adding acidic or alkaline water to the polymerization batch, a ratio of approximately 10% by weight of acidic or alkaline water, based on the polymerization batch, has proven useful. The hydrolysis and crosslinking can take place at a temperature of 0 to 50 ° C., preferably at room temperature; the reaction time, mainly depending on the batch size, is 15 minutes to a few hours.

When using a water-containing polar medium and persulfate as the initiator, the crosslinking reaction takes place in situ, so that a separate crosslinking step is not necessary.

The crosslinking reaction and the degree of crosslinking ultimately obtained can be monitored or controlled analytically in a simple manner by determining the solubility in a good solvent, for example in tetrahydrofuran / ethyl acetate or dimethylformamide. The bead polymers have a gel content, measured in tetrahydrofuran at 25 ° C of 90% and more. The shape, size and particle diameter distribution of the bead polymer are not changed in the crosslinking reaction.

Monomers (b) suitable according to the invention are in particular methacrylates and acrylates. Esters of (meth) acrylic acid with 1- to 5-valent alcohols with 2 to 30 carbon atoms are preferred. So-called epoxy acrylates, such as the bis-GMA of the formula, are also very suitable Monomer 1

Urethane acrylates which can be prepared by reacting diisocyanates and hydroxyalkyl (meth) acrylates may also be mentioned. Examples of particularly suitable urethane acrylates are:

Monomer 5

Monomer 6

Monomer 7

Monomer 8

In addition, reaction products from polyols, diisocyanates and hydroxyalkyl (meth) acrylates (DE-A 3 703 120, DE-A 3 703 080 and DE-A 3 703 130) are listed.

The monomers or monomer mixtures used should have a viscosity of 50 to 5000 mPa.s, preferably 100 to 2000 mPa.s (in each case at 20 ° C.). Highly viscous monomers can be mixed with low-viscosity monomers, so-called reactive diluents. Suitable reactive diluents are, for example, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, hexanediol dimethacrylate, neopentyl glycol dimethacrylate and trimethylolpropane triacrylate. Conventional mixtures of methyl methacrylate and ethylene glycol dimethacrylate can also be used as monomers (b) to produce artificial teeth.

The inorganic fillers (c) can consist, for example, of spherical, approximately spherical or by grinding or directly by the production (for example, produced in flame hydrolytic processes), regularly or irregularly shaped particles. The inorganic fillers can be used with a monodal, bimodal or polymodal particle size distribution. The fillers generally have a maximum in the distribution curve in the range from 0.005 to 5 μm. Suitable inorganic fillers are, for example, glasses in the form of spheres or in the form of irregularly shaped particles obtained by grinding and having average particle sizes in the range from 0.5 to 5 μm. Also suitable are flame-hydrolytically obtained oxides of silicon and aluminum with particle sizes in the range from 5 to 500 nm. The BET surface area of the inorganic fillers is 20 to 600 m ² / g, preferably 50 to 300 m ² / g. The inorganic fillers are used in the form treated with adhesion promoters.

Examples of suitable adhesion promoters are silane and titanate compounds, such as trimethylchlorosilane, hexamethyldisiloxane, 3-aminopropyltrimethoxysilane, butyl titanate and isopropyl titanate. Adhesion promoters with polymerizable groups, such as vinyltrimethylsiloxane, allyltrimethoxysilane and γ-methacryloyloxypropyltrimethoxysilane, are particularly suitable.

The aftertreatment of the fillers is known per se. The treatment with silane compounds is advantageously carried out in a non-aqueous solvent such as toluene, methylcyclohexane, acetone, THF or methyl ethyl ketone, the reaction being catalyzed with acids or amines. The suitable amount of adhesion promoter depends on the size of the surface of the inorganic filler. In general, an amount of 0.5 to 5% by weight is well suited.

Known per se as starter additives (d) for initiating the polymerization

Starter systems are used. These are systems which supply free radicals, anions or cations and which can trigger free-radical, anionic or cationic polymerization. In the case of a radical-supplying system, peroxides or aliphatic azo compounds are particularly suitable, for example benzoyl peroxide, lauryl peroxide or azoisobutyronitrile; the systems are usually used in amounts of 0.1 to 5% by weight. While curing at elevated temperature can be carried out solely by peroxides or other radical initiators, it is generally advisable to add accelerators, preferably aromatic amines, for curing at room temperature. Suitable accelerators are e.g. N, N-substituted toluidines and xylidines, such as N, N-dimethyl-p-toluidine or N, N-bis (2-hydroxyethyl) xylidine. Hardening can generally be achieved by adding 0.5 to 3% by weight of the amines mentioned.

However, it is also possible to produce dental materials that polymerize under the action of light, for example UV light, visible light or laser light. In these cases, photo polymerization initiators and accelerators are used.

Photopolymerization initiators are known per se.

These are preferably carbonyl compounds such as benzoin and its derivatives, in particular benzoin methyl ether, benzoyl and benzyl derivatives, for example 4,4-oxidibenzyl and other dicarbonyl compounds such as thiacetyl, 2,3-pentadione or metal carbonyls such as pentacarbonylmanganese, quinones such as 9,10-phenanthrenequinone and camphorquinone or their derivatives. The proportion of such photopolymerization initiators is preferably about 0.01 to about 5% by weight of the total composition.

The light-curable photopolymerizable compositions preferably also contain substances which accelerate the polymerization reaction in the presence of photopolymerization initiators. Known accelerators are, for example, aromatic amines such as p-toluidine and dimethyl-p-toluidine, trialkylamines such as trihexylamine, polyamines such as N, N, N ', N'-tetraalkylalkylenediamine, barbituric acid and dialkyl barbituric acid and sulfimides.

The accelerators are generally used in an amount of from 0.01 to about 5% by weight of the total mixture.

Suitable additives (e) include, for example, stabilizers, light stabilizers, UV protective agents, pigments, dyes, fluorescent agents or plasticizers.

A particularly suitable UV stabilizer is 2-hydroxy-4-methoxybenzophenone. Another preferred material is 2- (2'-hydroxy-5-methylphenyl) benzotriazole. For example, hydroquinone, p-benzoquinone and p-butylhydroxytoluene may also be mentioned.

To set a color that is as true to nature as possible, the dental materials according to the invention can also contain pigments and dyes known per se.

example 1

Preparation of a bead polymer crosslinked via Si-O-Si groups

56 g of polyvinylpyrrolidone, 8 g of methyltricaprylammonium chloride and 0.64 g were placed in a reaction flask with a reflux condenser, stirrer and thermometer

Azodiisobutyronitrile dissolved in 1600 ml of methanol. A mixture of 97.5 g of methyl methacrylate and 2.5 g of gamma-methacryloxypropyltrimethoxysilane was added to the solution. The mixture was heated with stirring for 5 hours and then cooled to 25 ° C. Then 100 ml of 1N HCl were added dropwise. The mixture was stirred for a further hour at 25 ° C, then the bead polymer was

Centrifuge isolated, washed with methanol and dried at 50 ° C. 70 g of a monodisperse bead polymer were obtained. The average particle size was 3.8 μm.

Example 2

Preparation of a bead polymer crosslinked via Si-O-Si groups

8.2 g of polyvinylpyrrolidone, 32.8 g of nonylphenol polyglycol (with 6 ethylene oxide units) were dissolved in a mixture of 4260 g of methanol and 2050 g of deionized water in a reaction flask with a reflux condenser, stirrer and thermometer. 1520 g of methyl methacrylate were added to the solution. The mixture was heated to 65 ° C with stirring. 80 g of gamma-methacryloxypropyltrimethoxysilane and 8.2 g of sodium peroxydisulfate, dissolved in 33 g of deionized water, were then added and the mixture was stirred at 65 ° C. for 24 hours. The reaction mixture was cooled to 25 ° C. From a subset of the dispersion obtained

Bead polymer isolated by centrifugation, washed with methanol and dried at 50 ° C. A monodisperse bead polymer with an average particle size of 4.0 μm was obtained. Example 3

Light-curing dental materials

In a kneader, the following ingredients were mixed intensively to form a paste:

TEGDMA = triethylene glycol dimethacrylate

DASA = p-dimethylaminobenzenesulfonic acid-N, N-diallylamide

In each case 500 mg of the pastes 3A to 3D were cured in a layer thickness of 2 mm between glass plates in a Kulzer Dentacolor XL light oven within 90 s. Test specimens with high transparency, high hardness and high wear resistance were obtained. Scanning electronic investigations on fracture surfaces prove that the hardened material is completely homogeneous and that there is no separation between filler and hardened monomer under mechanical stress. Example 4

Cold curing dental compound

4A peroxide paste 60.0 g of bead polymer from Example 2, 40.0 g of monomer 3 and 0.4 g of dibenzoyl peroxide were mixed in a kneader to form a homogeneous paste.

4B amine paste

60.0 g of bead polymer from Example 2, 40.0 g of monomer 3 and 0.6 g of N, N-dihydroxyethyl-p-toluidine were mixed in a kneader to form a homogeneous paste.

500 mg of peroxide paste and 500 mg of amine paste were mixed intensively with a spatula for 15 s. The mixture was filled into an open hollow mold and the curing was checked mechanically with the aid of a probe. The mass was completely cured after 180 s (from the start of mixing).

Example 5

Thermosetting dental material for the production of acrylic teeth

60.0 g of bead polymer from Example 2, 40.0 g of monomer 3 and 0.2 g of dibenzoyl peroxide were mixed in a kneader to form a homogeneous paste. The mixture was filled into tooth molds and cured at 140 ° C. within 10 minutes. The plastic teeth obtained showed high hardness and high wear resistance.

Claims

claims

1. Curable dental compositions containing bead polymers crosslinked via Si-O-Si groups and having an average particle size of 1 to 10 μm.

2. Curable dental compositions according to claim 1

b) 35 to 70 parts by weight of monomers

c) 0 to 65 parts by weight of inorganic filler

d) 0.1 to 5 parts by weight of starter additives

e) 0 to 10 parts by weight of additives.

3. Curable dental compositions according to claim 1, characterized in that the bead polymers crosslinked via Si-O-Si groups polymerize 50 to 99% by weight of polymerized vinyl monomer units and 1 to 50% by weight

Contain silane monomer units and the silane monomer units are at least 50% cross-linked via the Si-O-Si groups.

4. Curable dental compositions according to claim 3, characterized in that the

Silane monomer units of the formula

R '(R °

CH, = C— - (CO-OR) - Si (X), correspond to what

R ^{1 represents} hydrogen or methyl,

R ^{3 represents} straight-chain or branched Cj-C ₆ alkyl or phenyl,

X represents a hydrolyzable group,

a takes the value zero, one or two and

b takes the value zero or one.

5. Curable dental compositions according to claim 3, characterized in that the silane monomer units of the formula

R '

12th

CH ₂ = C-CO-OR SiX,

correspond to what

R ^! Hydrogen or methyl,

R ^{12 is} straight-chain or branched C ₂ -C ₈ alkylene, the carbon chain of which can be interrupted by -O- and

X represents a hydrolyzable group.