Latex hyperbranched anion exchanger

Abstract

A process for preparing a modified latex particle wherein the particle comprises a polycondensate bonded to a functional group on the latex particle and the process for forming a polycondensate comprises reacting an amino group present on the latex particle with (i) at least a first polyfunctional compound, or (ii) at least a first multifunctional compound having at least two functional groups that react with said functional groups of the latex, and at least a first amine compound comprising an amino group selected from the group consisting of ammonia, primary amines and secondary amines, or (ii) at least a second multifunctional compound having at least two functional groups that react with said functional groups of the latex, and at least a second amine compound comprising an amino group selected from the group consisting of ammonia, primary amines and secondary amines, to form a first polycondensate reaction product comprising ion exchange sites and a first unreacted excess of functional groups.

Description

Field of the invention

[0001] The present invention relates to ion exchange packing based on latex particles suitable for use in chromatographic media and a process for their preparation. BACKGROUND

[0002] Ion chromatography is a powerful technique for the determination of various inorganic and organic ions. However, providing anion exchangers with high efficiency and selectivity, as well as stability in highly basic media required for the separation of anions still poses a challenge to achieve separation of anions.

[0003] This is because the separation effect provided by anion exchangers depends on various parameters including the type of matrix, particle size, particle size distribution, hydrophilicity of the stationary phase, water content of the stationary phase and packing process.

[0004] There is therefore a need for a stable ion exchange material providing high efficiency and selectivity.

[0005] Latex agglomerated anion exchangers, as described in EP 0058358 A1, have high performance. However, the capacity of the latex particles is limited by the fixed size and composition of the latex, generally enabling not more than 2 amino groups per latex functional group.

[0006] Hyperbranched anion exchangers consisting of a sulfonated substrate and a bonded hyperbranched condensation polymer, as described in C. Pohl, C. Saini, New developments in the preparation of anion exchange media based on hyperbranched condensation polymers Chromatogr. A 1213 (2008) 37-44, have potential applications and also provide high performance. However, to increase the capacity, a large number of reaction cycles is required, which leads to an excessively high degree of cross-linking, thus affecting the selectivity of the stationary phase.

[0007] The citation or discussion of a document in this specification should not necessarily be construed as an admission that such document is prior art to the present application or that it is fully known or available to the public for the particular use described in this specification.

[0008] Since the chromatographic selectivity is not only influenced by the substrate properties but also depends on the structure of the functional layer, it would be of significant advantage to provide a new type of ion exchange material employing a new type of substrate in combination with a hyperbranched layer to provide additional options for ion separation. SUMMARY

[0009] The present invention seeks to address at least some of the above problems by seeking to combine features from each of the above matrices to provide a new and highly effective ion exchange material.

[0010] Thus, the present application provides a process for preparing modified latex particles, wherein the particles comprise a polycondensate bonded to functional groups, in particular amino and / or hydroxyl functional groups, on the latex particles and the process for forming the polycondensate comprises: (a) reacting functional groups present on the latex particles with: (i) at least a first polyfunctional compound having at least two functional groups reactive with the functional groups, or (ii) at least a first polyfunctional compound having at least two functional groups reactive with the functional groups, and at least a first amine compound comprising an amino group selected from the group consisting of an amine, a primary amine and a secondary amine to form a first polycondensate reaction product (CPRP) comprising ion exchange sites and first unreacted excess functional groups.

[0011] Typically, in the process for preparing modified latex particles, the polycondensate is bonded to functional groups, at least some of which are located on the surface of the latex particles.

[0012] In the process for preparing modified latex particles, where the functional groups are amino groups, the amino groups on the latex particles are preferably primary and / or secondary or tertiary amine groups.

[0013] As used herein, the term "at least some of the functional groups are located on the surface" means that the polycondensate can be bonded to functional groups located throughout the latex particle, but at least some of the functional groups must be bonded to functional groups located on the outer surface of the latex particle. For example, at least 25% of the polycondensate can be bonded to functional groups on the outer surface of the latex particle, for example at least 50% of the polycondensate can be bonded to functional groups on the outer surface of the latex particle, or at least 75% of the polycondensate can be bonded to functional groups on the outer surface of the latex particle.

[0014] The functional groups (i.e. amino and / or hydroxyl groups), for example primary, secondary and / or tertiary amino groups, on the latex particles (at least on the outer surface thereof) can already be present on the latex particles (e.g. present after the latex particles have been formed) or can be formed by converting functional groups capable of being converted to amino or hydroxyl groups. Examples of functional groups capable of being converted to amino groups include those groups which can be converted to amino groups, i.e. primary, secondary and / or tertiary amine groups, directly or indirectly by hydrolysis or by reaction with an amine.

[0015] Processes for preparing such latex particles will be well known to those skilled in the art.

[0016] The amino groups can be mono- or polyfunctional, i.e. the amino groups can comprise a single primary, secondary or tertiary amine group, or can comprise more than one primary, secondary or tertiary amine group, such as two or three primary, secondary or tertiary amine groups.

[0017] As used herein, "a functional group capable of conversion to an amino group by hydrolysis" is intended to include groups that provide a primary, secondary, or tertiary amino group upon exposure to an acidic or basic medium. For example, an amido group.

[0018] As used herein, "a functional group capable of conversion to an amino group by reaction with an amine, directly or indirectly" is intended to include groups that form a primary, secondary, or tertiary amino group upon reaction with an amine. For example, by nucleophilic displacement of a haloalkane, epoxide ring opening, or reductive amination.

[0019] At least two functional groups of the at least first polyfunctional compound can comprise at least one functional group selected from the group consisting of epoxide, haloalkane, halobenzyl, tosylate, methyl sulphide, and mixtures thereof. In a preferred aspect, at least two functional groups of the at least first polyfunctional compound can comprise an epoxide functional group.

[0020] Suitable epoxides include diepoxybutane, ethylene glycol diglycidyl ether, butylene glycol diglycidyl ether, diethylene glycol diglycidyl ether, hexylene glycol diglycidyl ether, glycerol triglycidyl ether, and many other compounds that incorporate two or more epoxide groups, including the epoxy resins commonly used in commercial epoxy formulations. Suitable haloalkanes include dichloroethane, dichloropropane, dichlorobutane, dibromoethane, dibromopropane, dibromobutane, and many other haloalkanes. Suitable halobenzyis include α,α-dichlorotoluene and α,α-dibromotoluene, and many other halobenzyis. Suitable tosylates include ethylene glycol tosylate, diethylene glycol tosylate, and tosylates of various other aliphatic or aromatic polyols. Suitable methyl sulphides include 1,3-bis(methylthio)propane and 1,4-bis(methylthio)butane, and many other polydimethylsulfides. The polyfunctional compounds of the present invention preferably include epoxide polyfunctional groups, which are defined to include monoepoxide compounds, diepoxide compounds, and / or polyepoxides in compounds that include polymers.

[0021] The size of the polyfunctional compound can vary over a wide range, from simple non-polymeric compounds with molecular weights less than 87 to small molecular weight polymeric compounds with molecular weights of 234 to 10,000. Preferably, the polyfunctional compound is water soluble and consists of glycidyl ethers of polyols, or contains glycidyl ethers attached to hydrophilic polymers such as polyethylene glycol or polypropylene glycol, or combinations of all three, such as glycerol propoxyl triglycidyl ether.

[0022] Other multifunctional reagents capable of forming polycondensates with multifunctional amines or multifunctional epoxides can also be used in conjunction with or in place of materials suitable for reaction with amines or materials suitable for reaction with epoxides. Alternative multifunctional reagents suitable for reaction with multifunctional amines include 2-methyl-2-nitro-l,3-propanediol, dithiobis(succinimidyl propionate), cyanuric chloride, and multifunctional acid chlorides such as hexamethylene adipimidate dimethyl hydrochloride. Alternative multifunctional reagents suitable for reaction with multifunctional epoxides include compounds such as multifunctional thiols. Preferably, the suitable reagents are also water soluble to facilitate water-based synthesis methods.

[0023] The at least first amine compound includes an amino group selected from the group consisting of ammonia, primary amines, and secondary amines. The at least first amine compound can include additional amino groups and can include both primary and secondary amines as well as tertiary amines.

[0024] Suitable primary amine-type amino groups include methylamine, ethylamine, propylamine, isopropylamine, butylamine, isobutylamine, sec-butylamine, t-butylamine, amylamine, t-amylamine, hexylamine, heptylamine, octylamine, benzylamine, phenethylamine, ethanolamine, 3-amino-l-propanol, l-amino-2-propanol, 2-amino-l-propanol, 2-amino-l,3-propanediol, 4-amino-l-butanol, and many other primary amines with or without additional polar and / or hydrophilic substituents.

[0025] Suitable secondary amine-type amino groups include dimethylamine, diethylamine, dipropylamine, diisopropylamine, dibutylamine, diisobutylamine, di-sec-butylamine, di-t-butylamine, di-t-amylamine, diamylamine, dihexylamine, diethanolamine, methyl ethanolamine, ethyl ethanolamine, morpholine, and many other secondary amines with or without additional polar and / or hydrophilic substituents.

[0026] Suitable amine compounds include aliphatic diamines such as ethylenediamine, 1,3-diaminopropane, 1,2-diaminopropane, 1,4-diaminobutane, 1,5-diaminopentane, 1,6-diaminohexane, 1,7-diaminoheptane, 1,8-diaminooctane, 1,9-diaminononane, 1,10-diaminodecane, 1,12-diaminododecane, 1,2-diaminocyclohexane, 1,4-diaminocyclohexane; aromatic benzyl diamines such as m-xylylenediamine, p-xylylenediamine; aliphatic polyamines such as diethylenetriamine, triethylenetetramine, and higher polymeric analogs; and various other structures that combine multiple primary, secondary, and / or tertiary amine groups in a single compound.

[0027] Both primary and secondary amines have multifunctional properties, i.e., each amine group contains at least two functional groups that can react with the multifunctional to form a CPRP, as will be described below. The size of the amine compound can vary over a wide range, from simple non-polymeric compounds with molecular weights ranging from 17, for example, to small molecular weight polymeric compounds with molecular weights of 200 to 10,000. Preferably, each amino group in the amine compound should have at least three atoms connecting between each amino group in order to achieve good reactivity for each amino group, but polymeric species such as polyethyleneimine and polyamines derived from hydrolytic cleavage of N-vinylformamide polymers can also be used in the present invention.

[0028] In step (a) of the method of making modified latex particles, the functional groups (i.e., amino and / or hydroxyl groups) on the latex particles are reacted with (i) at least a first multifunctional compound having at least two functional groups that react with the functional groups or (ii) at least a first multifunctional compound having at least two functional groups that can react with the functional groups and at least a first amine compound comprising an amino group selected from the group consisting of ammonia, primary amines, and secondary amines to form a first condensate reaction product comprising ion exchange sites and first unreacted excess functional groups.

[0029] The reaction in step (a) is carried out to provide excess unreacted (and thus reactive) functional groups. These functional groups can be unreacted functional groups on the multifunctional compound or unreacted functional groups on the amine compound in the first CPRP. By "unreacted" is meant that one or more functional groups have not reacted, e.g., have not participated in a condensation reaction and are thus still reactive.

[0030] The reaction in step (a) also provides ion exchange sites, at least on the outer surface of the latex. The term "ion exchange sites" means functional groups present on the condensate that have a positive or negative charge depending on the desired use. For example, quaternary ammonium sites on the condensate at least on the outer surface of the latex.

[0031] In step (a), a large excess of at least the first multifunctional compound or at least the first multifunctional compound and at least the first amine compound can be used.

[0032] The compounds used in step (a) can include the first amine compound as the only amine compound and the first multifunctional compound as the only multifunctional compound. Alternatively, it can include a mixture of the first amine compound with one or more additional amine compounds. Further, it can include the first multifunctional compound alone along with the first amine compound or additional amine compounds or it can include a mixture of the first multifunctional compound with one or more additional multifunctional compounds. In this way, each condensate reaction product can be tailored to include the desired functionality.

[0033] Further, the amino groups in each amine compound and the two functional groups in the polyfunctional compound can be the same as or different from each other. For example, the first amine compound can include at least only primary amine groups, only secondary amine groups, one or more primary and / or secondary amine groups, etc. Similarly, the first polyfunctional compound can include at least two functional groups that react with the same type or different types of amino groups, and can additionally include more than two functional groups.

[0034] A successive CPRP can be formed after step (a) by reacting the unreacted excess functional groups of the first CPRP with other polyfunctional compounds and / or amine compounds. The compounds used to form the successive CPRP will depend on the non-reacted functional groups present on the previous CPRP. For example, if the first CPRP is formed by step (a)(i), a successive CPRP can be formed using an excess of amine compounds or an excess of polyfunctional compounds and amine compounds. Alternatively, if the first CPRP is formed by step (a)(ii), a successive CPRP can be formed using an excess of polyfunctional compounds or an excess of polyfunctional compounds and amine compounds.

[0035] Accordingly, the method defined above can further comprise step (b)(i) or (b)(ii), wherein in step (b)(i) the unreacted excess functional groups on the CPRP of step (a)(i) can be reacted with at least a second amine compound or both at least a second polyfunctional compound and at least a second amine compound to form a second CPRP comprising ion exchange sites and second unreacted excess functional groups; and in step (b)(ii) the unreacted excess functional groups on the CPRP of step (a)(ii) can be reacted with at least a second polyfunctional compound or both at least a second polyfunctional compound and at least a second amine compound to form a second CPRP comprising ion exchange sites and second unreacted excess functional groups.

[0036] In this way, the polyfunctional compounds and amine compounds can be added sequentially or all at once to form successive CPRPs.

[0037] The process can be repeated any number of times to achieve the desired properties of the final product.

[0038] Accordingly, the method can further comprise reacting a further amine compound and / or polyfunctional compound with the unreacted excess amine compound portion or polyfunctional compound portion from the first or second polycondensate reaction product of step (a) or (b).

[0039] Referring to step (b)(i) or (ii) and any subsequent repetition (if present), at least the second amine compound or the second polyfunctional compound can be characterized in a similar manner to the first amine compound and the first polyfunctional compound. Thus, the second amine compound can be mixed with one or more additional amine compounds, and can include one or more primary and / or secondary amine groups in the second amine compound.

[0040] It should be noted that the terms "second amine compound" and "second polyfunctional compound" in step (b)(i) or (ii) are used to indicate that step (b)(i) or (ii) occurs after step (a). However, the meaning of the term "second amine compound" includes an amine compound that is the same as or different from the first amine compound. Similarly, the term "second polyfunctional compound" includes a second polyfunctional compound that is the same as or different from the first polyfunctional compound.

[0041] As noted above, at any point in the above process, the outer layer of the condensation reaction product on the latex particles has cationic functionality, such as amine groups, that are ion exchange sites. This reaction product can be used directly in this form without further modification. In this case, the reaction product will have both strong basic anion exchange sites and weak basic anion exchange sites, which can be advantageous for certain separation processes.

[0042] However, strong base anion exchange sites can be introduced into the outer layer of the condensation polymer by a capping reaction with a capping compound that includes a tertiary amine group. In this way, the reaction is capped or terminated, and the number of quaternary amines in the ion exchange coating is greatly increased, which is particularly important when the substrate is used as an anion exchange packing for chromatographic columns and the like.

[0043] The condensate on the latex particles can be converted for use as a cation exchange substrate by reacting the excess amine reactive functional groups on the outer surface of the coated substrate with a cationic amine-containing functional compound. Suitable cationic amine-containing functional groups include sulfonic acids, phosphonic acids, and carboxylic acids or combinations thereof. Preferably, a suitable cationic amine-containing functional compound contains two or more cationic functional groups such that the total number of cationic functional groups exceeds the number of previously formed anion exchange sites. Suitable compounds include: Y-carboxyglutamic acid, nitrilotriacetic acid, 3,3',3"-nitrilotripropionic acid, N-(2-carboxyethyl)iminodiacetic acid, N-(phosphonomethyl)glycine, 2-amino-3-phosphonopropionic acid, iminobis(methylphosphonic acid), 2-aminoethylphosphonic acid, piperazine-1,4-bis(2-ethanesulfonic acid), homocysteic acid, and 2-amino-3-sulfopropionic acid, as well as many other cationic amine-containing functional compounds. Other suitable cationic functional groups include sulfonic acids, phosphonic acids, and carboxylic acids. Other suitable cationic functional compounds include: chloroacetic acid, bromoacetic acid, chloropropionic acid, bromopropionic acid, 2-chloroethanesulfonic acid sodium salt, 2-bromoethanesulfonic acid sodium salt, or 1,4-butanesultone. Phosphonic acid cationic functional groups can be introduced using suitable reagents such as phosphorus pentachloride or phosphorus oxybromide followed by hydrolysis.

[0044] One or more of the condensate functional groups can be branched and / or crosslinked. For example, the second, third, or higher CPRP can be branched and crosslinked by appropriate selection of reagents and by selection of reagents and by adjustment of reagent ratios and excesses of one or the other of the amine compound and the polyfunctional compound as described below.

[0045] For example, the "second CPRP" of step (b)(i) or (ii) can be prepared using a mixture of a multifunctional amine and a multifunctional epoxide. The composition of this layer can be adjusted so that the mixture will not gel under the conditions under which the "second CPRP" is applied. For example, methylamine (a trifunctional amine capable of reacting with a total of three epoxy groups to form a quaternary amine ion exchange site) is preferably combined with a water soluble diepoxy (a difunctional epoxide), in a preferred embodiment with butanediol diglycidyl ether. If these two components are combined in a two to three molar ratio of methylamine to butanediol diglycidyl ether, they tend to form a cross-linked gel because they are combined together in a stoichiometry of complementary functionality. This reaction mixture in the slurry mode or in the flow-through "packed column" mode can be undesirable because in the former case, gelation will result in the suspension of matrix particles in a stable gel that is not suitable for use in liquid chromatography, and in the latter case, will result in the formation of extremely high pressures, thereby precluding the use of pumping as a means of transporting reagents, making the material unsuitable for use in liquid chromatography. Instead, the ratio of the two reagents is adjusted so that no gel is formed (preferably using a composition that is close to, but not a composition that is capable of gelling), so that the solution can be passed through the "packed column" without experiencing the high pressures characteristic of gelation. Furthermore, as this solution is passed through the column, the coating thickness will continue to increase.

[0046] A useful "CPRP coating", such as a first and / or second and / or subsequent CPRP coating, can be achieved by using a 1 : 1 molar ratio of the preferred reagents, while allowing these reagents to react in the presence of the product of step (a) or (b) at 65°C for one hour. If a subsequent CPRP is being formed, the use of this composition allows the formation of a substantially linear CPRP on the product of step (a) or the product of step (b)(i) or (b)(ii).

[0047] The polycondensate formed with this composition contains a significant number of ion exchange sites (i.e., reactive amine sites) because under these conditions, the amine reactant is in excess with respect to the functionality of the reagents.

[0048] For example, when methylamine (a tri-functional reagent) and butanediol diglycidyl ether (a di-functional reagent) are combined in a 1 : 1 ratio, a polymer will be formed in which, on average, two moles of butanediol diglycidyl ether reagent are attached to each mole of methylamine reagent, forming a substantially linear polymer, and the resulting polymer is primarily an alternating polymer in which amine groups and butanediol diglycidyl ether groups alternate in the polymer chain. A majority of all the amine groups thus formed are tertiary amines at the completion of the "CPRP" preparation step, although some amine groups will be quaternary amines and some amine groups will be secondary amines at this time. These tertiary amine groups (as well as the secondary amine groups) are still available for further reaction, forming quaternary ammonium sites at each reaction site. Thus, the "CPRP", such as the "first CPRP" or the "second CPRP", can be used in subsequent treatment with a multi-functional epoxide.

[0049] In one aspect of the method of making modified latex particles, the latex can be reacted with a large excess (e.g., 50 to 200%) of a multi-functional epoxide (multi-functional compound), preferably butanediol diglycidyl ether. By utilizing a large excess of multi-functional epoxide, the latex is now decorated with pendant unreacted epoxide groups. After treatment with a large excess (e.g., 50% to 200%) of a multi-functional epoxide, the substrate can then be treated with a large excess of a multi-functional amine (amine compound), preferably methylamine. This results in the surface being modified with pendant groups containing amine functionality having two residual reactive sites.

[0050] Repeating the cycle of using a large excess of multi-functional epoxide, followed by a large excess of multi-functional amine, will result in branching points at each amine, with quaternary ammonium sites at the branching points. Theoretically, using butanediol diglycidyl ether and methylamine, and alternating reactions, will result in a doubling of the number of branches per layer. By utilizing this approach, very high capacities can be achieved by repeating the cycle a suitable number of times (e.g., at least 3, 4, 5, 6, 7, 8, or more). The reality is much more complex, as the likelihood of the branches cross-linking together also increases as the branching increases. Thus, materials made using the preferred embodiments will tend to have an increasing amount of cross-linking as the number of cycles increases (assuming at least one of the reagents used has a functionality > 2). However, if the layers are modified with both di-functional amines and di-functional epoxides, alternating, the chain growth will be primarily linear and the cross-linking side reactions will be greatly reduced.

[0051] Another complicating factor that can arise in the chemistry of this reaction is that epoxides tend to undergo base-catalyzed polymerization. Since the polycondensates using this synthetic strategy will be in the hydroxide form, they can induce polymerization of the multifunctional epoxide monomers under some conditions in the absence of any amine. The final polycondensate can incorporate some polyepoxide formed via this polymerization side reaction, which also modifies the surface. The presence of these additional reaction pathways does not limit the utility of the current method per se, as shown by the coating examples in the appendix. Useful components can be made by varying the different combinations, including varying the nature of the amine or epoxide in each layer, or both, or using combinations of amine and epoxide in each layer.

[0052] Epoxide monomers can be used to make hydroxide-selective materials. Hydroxide selectivity requires that hydroxyl functional groups be located near the quaternary amine center of each anion exchange site.

[0053] Epoxide monomers provide such hydroxyl groups as a byproduct of the reaction of epoxide with amine. Thus, such polycondensates are particularly useful for making hydroxide-selective anion exchange phases. However, this does not limit the utility of the present invention to epoxide monomers and amines. In fact, similar polycondensates can also be made using multifunctional halocarbons in combination with multifunctional amines. Such polycondensates will not be hydroxide-selective, but will still be useful for making anion exchange phases.

[0054] While, as noted above, conditions leading to gel formation should generally be avoided, especially in the case of slurry grafting, useful synthesis methods include the use of combinations that ultimately lead to gel formation by simply reducing the exposure time of the substrate to the reaction mixture, so that the exposure time is less than the gelation time of the reaction mixture.

[0055] Thus, the method defined above can include forming the first, second, or subsequent polycondensate in a flow-through chamber by sequentially flowing (i) the at least first multifunctional compound, or (ii) the at least first multifunctional compound and at least first amine compound, through the latex particles or the first, second, or subsequent polycondensate reaction product.

[0056] This can make it possible to pack a large number of latex particles in a bed and coat and take out a large supply as smaller packed analytical columns in a large flow-through column.

[0057] While the method of the present invention can utilize methylamine, as shown above, a variety of alternative multifunctional amines are also suitable for use in the present invention, including simple diamines, triamines, and higher polyamines. The growth requirement of the polymerization step is that the amine contain at least two available reaction sites. Termination of the polymerization can be achieved with a final reaction step with a tertiary amine compound, or the reaction can end without such a terminating reaction.

[0058] The advantage of the present application is that when the polycondensate is applied to a column coated with the latex or product of step (a), the coating process can be interrupted for column evaluation and then the process can be resumed. However, because epoxides are susceptible to hydrolysis under basic conditions, it is generally preferred to interrupt the reaction after reaction with the polyfunctional amine-containing reagent rather than immediately after reaction with the polyfunctional epoxide-containing reagent. Also, although the preferred polyfunctional epoxide is butanediol diglycidyl ether, a variety of polyfunctional epoxides can be used in the present application. Ideally, the polyfunctional epoxide should be water soluble to facilitate the formation of the polycondensate under aqueous conditions, but any of a number of available polyfunctional epoxides can be used for this purpose. In addition, a variety of types of polyglycidyl reagents that are not readily available can be readily synthesized using standard synthetic methods. Although in situ column preparation of the polycondensate is a convenient way to rapidly evaluate different formulations, in situ column preparation is generally less efficient than batch synthesis. However, by using slurry grafting techniques or, preferably, a packed bed reactor, the optimal coating chemistry can be readily transferred to a larger scale batch process.

[0059] In general, the epoxide and amine react as shown below.

[0060] In the previously defined method, the latex particles can have an average diameter of from about 0.01 to about 0.5 microns.

[0061] In general, the latex particles can comprise styrenic monomers and / or methacrylate-based monomers. For example, the latex particles can comprise polyvinylbenzyl chloride crosslinked with divinylbenzene or ethylenediamine.

[0062] As previously mentioned, the functional groups on the latex particles can already be present on the latex particles, or can be formed by converting functional groups capable of being converted to amino or hydroxyl groups. For example, the latex particles can comprise epoxy functional groups on at least the outer surface of the latex, which can be converted (e.g., by reaction with methylamine) to amino functional groups.

[0063] The modified latex particles described above can be used to provide ion exchange chromatography packing. Thus, a method for preparing an ion exchange chromatography packing is also defined, wherein the method for producing the packing comprises latex particles obtained as defined in the present application, wherein the latex particles: (i) are ionically bound to a carrier resin having ion exchange sites on at least its available surface (hereinafter "available sites") prior to step (a); or (ii) are ionically bound to a carrier resin having ion exchange sites on at least its available surface (hereinafter "available sites") after formation of the first, second or subsequent polycondensation reaction product.

[0064] In the above method of preparing the ion exchange chromatography packing, the carrier resin can be a synthetic ion exchange resin.

[0065] A wide variety of gel polymers and polyaddition polymers having ion exchange sites (i.e., anion or cation exchange) are known. These synthetic resins and methods for their preparation are described in detail in Chapter 6, Ion Exchange, by Wheaton and Hatch, Vol. 2, J. Marinsky Ed. (New York 1969). For example, synthetic ion exchange resins such as polyphenol-formaldehyde resins, polyacrylic acid resins or polymethacrylic acid resins or nitrile resins, amine-epichlorohydrin resins, graft polymers of styrene onto polyethylene or polypropylene, poly(2-chloromethyl-l,3-butadiene) resins, and especially poly(vinyl aromatic) resins such as those derived from styrene, alpha-methylstyrene, chlorostyrene, chloromethylstyrene, vinyltoluene, vinyl naphthalene, or vinyl pyridine, all of which resins have been suitably crosslinked to render them insoluble in the solvent medium to which they will be exposed and which bear the desired ion exchange sites, are suitable synthetic resins from which the carrier resins can be formed. The synthetic resins employed can be macroporous resins or gel resins as are well known in the art.

[0066] As used herein, the term "available surface" means the surface of the carrier resin that will be in contact with the latex particles (as defined herein) when the carrier resin is contacted with the latex particles (e.g., as a suspension of latex particles).

[0067] For example, when the carrier resin is prepared from gel resin beads, the available surface will be substantially the outer surface of the beads. When the carrier resin is from a macroporous resin, the available surface will be the outer surface of the resin and the inner surface of the small channels that penetrate the structure of the resin and which have a pore size greater than the particle size of the latex particles.

[0068] In a preferred embodiment of the present application, the carrier resin can comprise crosslinked poly(vinyl aromatic) resin beads of about 4 to 10 microns, most preferably a styrene-divinylbenzene copolymer containing from about 25% to about 55% by weight of divinylbenzene monomer, having anion exchange sites or cation exchange sites on the available surface thereof.

[0069] The ion exchange sites on the carrier resin generally comprise a negatively charged functional group, preferably a sulfo functional group, a carboxyl functional group, and / or a phosphonic acid functional group. For example, the ion exchange sites on the available surface of the carrier resin can be sulfo groups.

[0070] The ion exchange sites on the available surface of the carrier resin can then be used to form (irreversible) ionic bonds between the ion exchange sites on at least the outer surface of the latex particles and the oppositely charged sites on the available surface of the carrier resin.

[0071] For example, where the ion exchange sites on at least the outer surface of the latex particles are cationic, the ion exchange sites on the support resin will be anionic, for example quaternary ammonium sites on the latex particles and sulfo groups on the support resin.

[0072] The support resin can generally be substantially spherical, and / or can have a particle size of from about 2 to about 100 microns, preferably from about 4 to about 10 microns.

[0073] The support resin can be insoluble or substantially insoluble in any solvent system that can subsequently be used therewith.

[0074] In the method of preparing the ion exchange chromatography packing, the support resin and the latex particles are mixed / combined together prior to step (a) or after formation of the necessary polycondensation reaction product. This can be done in situ in a conventional ion exchange column by slurrying the support resin in a non-solvent liquid, packing the slurry in the ion exchange column, and subsequently passing a suspension of the latex particles through the column. By continuously monitoring the column effluent for breakthrough of latex particles, it can be determined when formation of the latex particles is complete, once substantially all of the available sites on the support resin have been engaged by the latex particles.

[0075] When the latex particles have (irreversibly) engaged the support resin, the combination can be washed with a suitable amount of non-solvent liquid to remove excess latex particles. The ion exchange packing is then ready for use, without further treatment. If separation of the ion exchange component is desired, it can be separated from the liquid, drained and dried at room temperature for storage, transport, etc.

[0076] The present application also provides a modified latex particle, by the method defined herein, wherein the latex particle comprises: (i) forming a first condensation reaction polymer product comprising ion exchange sites and first unreacted excess functional groups, wherein the first condensation reaction polymer is formed by reacting the functional groups (i.e. amino and / or hydroxyl groups) on the latex particle with: i. at least a first polyfunctional compound having at least two functional groups; or ii. at least a first polyfunctional compound having at least two functional groups and at least a first amine compound comprising an amino group selected from the group consisting of an amine, a primary amine and a secondary amine.

[0077] Finally, the present application provides an ion exchange chromatography packing which comprises: (i) a support resin having ion exchange sites on at least its available surface; and (ii) a modified latex particle as defined herein, wherein an ionic attractive force is formed between the ion exchange sites on the support resin and the ion exchange sites on the latex particles.

[0078] The modified latex particles can have other features as defined in the method of making modified latex particles as defined herein.

[0079] The foregoing description of specific exemplary embodiments of the application has been presented for the purposes of illustration and description. They are not intended to be exhaustive or to limit the application to the precise forms disclosed, and various modifications and variations are possible in light of the above teachings or can be acquired from practice of the application. One skilled in the art will recognize that many

[0080] For the avoidance of doubt, in the present specification, where the term "comprising" or "including" is used, it is meant that the methods or products described are not limited to the listed components, but can optionally include additional components. "Comprising" shall be taken to mean "consisting of" or "consisting" in which the described method or product must only include the listed components.

[0081] For the avoidance of doubt, unless the context clearly indicates otherwise, the recitation of preferences, options, specific features etc. in relation to a given aspect, feature or parameter of the application shall be taken to have been disclosed in combination with any and all other preferences, options and specific features etc. recited in relation to the same or other aspects, features and parameters of the application.

[0082] As used herein, the term "about", e.g. in reference to a measurable value such as an amount or parameter, is meant to encompass variations that can exist in the values that can occur in a laboratory determination or in a commercial production environment. Sometimes animals, cells, or tissues are used as the source of a value being measured, and variations in the values obtained from such sources are expected and are meant to be encompassed by this term. The term "about" is intended to cover statistical variance, in addition to experimental error associated with determination of a particular value. About also covers round-off error that can result from the use of round-off techniques in the presentation of data.

[0083] The methods and apparatus of the present application have other features and advantages which will be apparent from or which will be elucidated in the accompanying drawings and in the following detailed description of the application, which are to be considered in conjunction with the appended claims, together with the

[0084] The application will now be described with reference to the following non-limiting drawings and examples. BRIEF DESCRIPTION OF DRAWINGS

[0085] Figure 1 : Chromatogram showing the separation of inorganic anions using ion chromatography packing formed by the method of the present application, the method comprising sulfonated EVB-DVB as the matrix, a vinyl chlorobenzyl based latex and 1 pass hyperbranching cycle using methylamine (4% in water) and 1,4-butanediol diglycidyl ether (10% in water).

[0086] Figure 2: Chromatogram showing the separation of small molecule organic acids using the ion chromatography packing formed by the method of the present invention, which comprises sulfonated EVB-DVB, a vinyl chlorobenzyl based latex and dimethylamine and 1,4-butanediol diglycidyl ether for the formation of a polycondensate as the matrix.

[0087] Figure 3 : Chromatogram showing the separation of small molecule organic acids using the ion chromatography packing formed by the method of the present invention, which comprises sulfonated EVB-DVB, a vinyl chlorobenzyl based latex and dimethylamine and 1,4-butanediol diglycidyl ether for the formation of a polycondensate as the matrix.

[0088] To illustrate the present invention, the following non-limiting examples thereof are given Example 1

[0089] A 10 g vinyl chlorobenzyl (VBC) and divinylbenzene (DVB) based latex was mixed with 3.1 g of a 40% methylamine (MA) solution and 6.9 g of deionized water and allowed to react at 65°C for 4 hours. Glacial acetic acid was then added to the aminated latex until a pH of 5 was reached. The resulting sulfonated ethyl vinylbenzene-divinylbenzene matrix particles (55% crosslinking, 6.45 μm average diameter and 20 m2 / g surface area) were then packed into a 4 x 250 mm column and the prepared latex was passed through the column.

[0090] A hyperbranched layer was formed on top of the latex by running a reaction cycle using the following steps: a 10% 1,4-butanediol diglycidyl ether solution was passed through the column at a flow rate of 0.25 mL / min for 20 minutes, allowed to react in the column for 40 minutes, the column was rinsed with deionized water for 10 minutes; a 4% methylamine solution was passed through the column for 20 minutes, allowed to react for 40 minutes and the column was rinsed with deionized water for 10 minutes. The column was then rinsed with 10 mM KOH. Figure 1 Chromatogram showing the separation of some monovalent inorganic anions in a suppressed ion chromatography mode using the column prepared in Example 1 with 10 mM KOH as the eluent along with a flow rate of 1 mL / min. Example 2

[0091] The same as Example 1 but the number of reaction cycles in the hyperbranching process was 2. Figure 2 Chromatogram showing the separation of some monovalent inorganic anions in a suppressed ion chromatography mode using the column prepared in Example 1 with 20 mM KOH as the eluent along with a flow rate of 1 mL / min. Example 3

[0092] A 10 g vinyl chlorobenzyl (VBC) and divinylbenzene (DVB) based latex was mixed with 3.1 g of a 40% methylamine (MA) solution and 6.9 g of deionized water and allowed to react at 65°C for 4 hours. Glacial acetic acid was then added to the aminated latex until a pH of 5 was reached. The resulting sulfonated ethyl vinylbenzene-divinylbenzene matrix particles (55% crosslinking, 6.45 μm average diameter and 20 m2 / g surface area) were then packed into a 4 x 250 mm column and the prepared latex was passed through the column.

[0093] A solution 1 of 9 g 40% dimethylamine (DMA) in 20 g deionized water and a solution 2 of 14.7 g 1,4-butanediol diglycidyl ether in 20 g deionized water were added simultaneously at a flow rate of 0.25 mL / min each at 65 °C to a latex while stirring. The process was continued for 40 minutes, then the reaction mixture was kept in an oven at 65 °C for 2 hours. The prepared latex with bonded polymer chains was passed through a 4 x 250 mm column packed with sulfonated ethyl vinyl benzene-divinyl benzene matrix particles (crosslinking degree 55%, average diameter 6.45 μm and surface area 20 m2 / g). The column was rinsed with 10 mM KOH.

[0094] Figure 3 A chromatogram of separation of some small molecule organic acids in a suppressive ion chromatography mode using a prepared column with 20 mM KOH as an eluent along with a flow rate of 1 mL / min is presented in FIG. 2. Example 4

[0095] An electrostatically bonded base layer was prepared according to US 7291395 (4.5 g of sulfonated ethyl vinyl benzene-divinyl benzene matrix particles (crosslinking degree 55%, average diameter 6.45 μm and surface area 20 m2 / g) were placed into a scintillation vial; 0.368 g of 1,4-butanediol diglycidyl ether, 3.277 g of water, 1.5 g of 4% methylamine were added to the matrix and mixed well. The mixture was then placed in a teflon cup in an oven at 65 °C for 2 hours, then removed from the oven and cooled for 10-15 minutes. 6 grams of deionized water were added to the vial, mixed and the slurry was packed into a 4 x 250 mm column. The reaction cycle described in Example 1 to form a hyperbranched layer was performed 3 times on the base coating. The capacity of this column was comparable to the latex-based column prepared in Example 1 using only 1 reaction cycle, which indicates that the attachment of the hyperbranched layer to the latex can allow for a reduction in the number of steps to prepare a high capacity column.

Claims

1. A method for preparing modified latex particles, wherein the particles comprise a condensation polymer bonded to functional groups on the latex particles and the method for forming the condensation polymer comprises: (a) reacting the amino groups present on the latex particles with: (i) at least a first polyfunctional compound having at least two functional groups reactive with said functional groups of the latex, or (ii) at least a first polyfunctional compound having at least two functional groups reactive with said functional groups of the latex, and at least a first amine compound comprising an amino group selected from the group consisting of ammonia, primary amines and secondary amines to form a first polycondensate reaction product comprising ion exchange sites and first unreacted excess functional groups.

2. The method according to claim 1, wherein the amino groups on the latex particles are primary and / or secondary or tertiary amino groups or hydroxyl groups.

3. The method of claim 1, wherein at least two functional groups of at least the first polyfunctional compound comprise at least one functional group selected from the group consisting of epoxides, alkyl halides, benzyl halides, tosylates, dimethyl sulfides, and mixtures thereof.

4. The method of claim 3, wherein at least two functional groups of at least the first polyfunctional compound comprise epoxide functional groups.

5. The method of claim 1 , wherein the method further comprises step (b)(i) or (b)(ii), wherein in step (b)(i), unreacted excess functional groups on the CPRP of step (a)(i) are reacted with at least a second amine compound or both at least a second polyfunctional compound and at least a second amine compound to form a second CPRP; and in step (b)(ii), unreacted excess functional groups on the CPRP of step (a)(ii) are reacted with at least a second polyfunctional compound or both at least a second polyfunctional compound and at least a second amine compound to form a second CPRP.

6. The method of claim 1 further comprising reacting another amine compound and / or polyfunctional compound with unreacted excess amine compound functional groups or polyfunctional compound functional groups from the first or second polycondensate reaction product in step (a) or (b).

7. The method of claim 5 further comprising repeating step (b)(i) or (ii) at least once more and reacting the amine-reactive functional groups on the external condensation polymer reaction product with an amine-containing cation-functional compound to convert the latex into a cation exchange material.

8. The method of claim 1, wherein the first, second, or subsequent condensation polymers comprise cross-linked functional groups.

9. The method of claim 1, wherein the first, second or subsequent condensation polymer comprises functional groups comprising branched polymer chains.

10. The method of claim 1 wherein the step of forming the first, second or subsequent condensation polymer is performed in a flow-through chamber by sequentially flowing (i) the at least first polyfunctional compound, or (ii) the at least first polyfunctional compound and at least a first amine compound through the latex particles or the first, second or subsequent condensation polymer reaction product.

11. The method of claim 1, wherein the substrate comprises a flow-through monolithic medium or a wall of a flow-through hollow tube.

12. The method of claim 1, wherein the latex particles have an average diameter of about 0.01 to about 0.5 microns.

13. The method of claim 1, wherein the latex particles comprise styrenic monomers and / or methacrylate-based monomers.

14. Modified latex particles, wherein the latex particles comprise: (i) forming a first condensation reaction polymer product comprising ion exchange sites and first unreacted excess functional groups, wherein the first condensation reaction polymer is formed by reacting the functional groups on the latex particles with: i. at least a first polyfunctional compound having at least two functional groups; or ii. at least a first polyfunctional compound having at least two functional groups and at least a first amine compound comprising an amino group selected from ammonia, a primary amine, and a secondary amine.

15. The modified latex of claim 14, wherein the particles have a median diameter of about 0.01 to about 0.5 microns.

16. The modified latex particles of claim 14, wherein the modified latex particles comprise a styrenic monomer or a methacrylate-based monomer.

17. The modified latex particles of claim 14, wherein the two functional groups of the polyfunctional compound comprise at least one functional group selected from the group consisting of epoxides, halogenated hydrocarbons, benzyl halides, tosylates, dimethyl sulfides, and mixtures thereof.

18. The modified latex particles of claim 14, wherein at least one of the two functional groups of the polyfunctional compound comprises an epoxide.

19. The modified latex particle of claim 14, wherein unreacted excess functional groups on the first CPRP can (i) react with at least a second amine compound or both at least a second polyfunctional compound and at least a second amine compound to form a second CPRP, or (ii) can react with at least a second polyfunctional compound or both at least a second polyfunctional compound and at least a second amine compound to form a second CPRP comprising ion exchange sites.

20. The modified latex particle of claim 14, further comprising repeating step (b)(i) or (ii) at least once more and reacting the amine-reactive functional groups on the external condensation polymer reaction product with an amine-containing cationically functional compound to convert the filler into a cation exchange matrix.

21. A method for preparing an ion exchange chromatography filler, wherein the method for preparing the filler comprises preparing the latex particles according to any one of claims 14, wherein the latex particles: (i) ionically bonded to a support resin prior to step (a); or (ii) Ionically bonded to the carrier resin after the first, second or subsequent polycondensation product is formed.

22. The method of claim 21, wherein the support resin is a synthetic ion exchange resin.

23. The method according to claim 21, wherein the support resin has a surface comprising an organic polymer, preferably selected from ethylvinylbenzene-divinylbenzene (EVB-DVB), polystyrene-divinylbenzene (PS-DVB) and polyvinyl alcohol (PVA).

24. The method according to claim 21, wherein the support resin comprises negatively charged functional groups, preferably sulfonic functional groups, carboxyl functional groups and / or phosphonic acid functional groups.

25. The method of claim 21, wherein ionic bonds are formed between ion exchange sites on at least the outer surface of the latex and oppositely charged sites on the support resin.

26. The method of claim 21, wherein the support resin is substantially spherical.

27. The method of claim 21, wherein the carrier resin has a particle size of about 2 to about 100 microns, preferably about 4 to about 10 microns.

28. An ion exchange chromatography filler, comprising: (i) a support resin having ion exchange sites at least on its available surface; and (ii) The modified latex particles according to any one of claims 14 to 19, wherein ionic attraction is formed between the ion exchange sites on the supporting resin and the ion exchange sites on the latex particles.

29. The packing material of claim 28, wherein the carrier resin is substantially spherical.

30. The filler of claim 28, wherein the carrier resin has a particle size of about 2 to about 100 microns, preferably about 4 to about 10 microns.

31. The packing of claim 28, wherein the support resin is a synthetic ion exchange resin.

32. The filler of claim 28, wherein the carrier resin has a surface comprising an organic polymer, preferably selected from ethylvinylbenzene-divinylbenzene (EVB-DVB), polystyrene-divinylbenzene (PS-DVB) and polyvinyl alcohol (PVA).

33. The filler according to claim 28, wherein the carrier resin comprises negatively charged functional groups, preferably sulfonic functional groups, carboxyl functional groups and / or phosphonic acid functional groups.

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