Latex hyperbranched anion exchangers

Abstract

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

Description

[Technical Field]

[0001] The present invention relates to latex particle-based ion exchange packing materials suitable for use in chromatographic media and methods for their preparation. [Background technology]

[0002] Ion chromatography is a powerful technique for measuring a variety of inorganic and organic ions. However, providing anion exchangers that have both high efficiency and selectivity, along with stability in the highly alkaline media required for anion separation, still poses a challenge.

[0003] This is because the separation provided by anion exchangers depends on a variety of parameters, including substrate type, particle size, size distribution, hydrophilicity of the stationary phase, water content of the stationary phase, and packing procedure.

[0004] Therefore, there is a need for stable ion exchange materials that offer both high efficiency and selectivity.

[0005] Latex agglomerated anion exchangers, such as those described in EP 0058358 A1, offer high performance, however the capacity of the latex particles is limited by the fixed size and composition of the latex, typically no more than two amino groups per latex functional group are available.

[0006] Hyperbranched anion exchangers containing sulfonated substrates and bonded hyperbranched condensation polymers, such as those described in C. Pohl and C. Saini, "New developments in the preparation of anion exchange media based on hyperbranched condensation polymers," J. Chromatogr. A1213 (2008) 37-44, also offer high performance. However, to increase capacity, multiple reaction cycles are required, which leads to a high degree of crosslinking, which affects stationary phase selectivity.

[0007] The listing or discussion of an apparently prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

[0008] Since chromatographic selectivity is not only influenced by the properties of the substrate but also depends on the structure of the functional layer, it would be advantageous to provide novel ion exchange materials using new combinations of substrates and hyperbranched layers to provide further options for ion separation. Summary of the Invention

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

[0010] Accordingly, the present invention provides a method for producing modified latex particles, the particles comprising condensation polymers attached to functional groups (particularly amino and / or hydroxyl functional groups) on the latex particles, the method for forming the condensation polymer comprising: (a) Functional groups present on latex particles (i) at least a first multifunctional compound having at least two functional moieties reactive with the functional group; or (ii) reacting with at least a first multifunctional compound having at least two functional moieties reactive with the functional group, and at least a first amine compound containing an amino group selected from the group consisting of ammonia, primary, and secondary amines; forming a first condensation polymer reaction product (CPRP) comprising ion exchange sites and a first unreacted excess functional moiety.

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

[0012] In the method for producing modified latex particles in which 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 condensation polymer can be bonded to functional groups located throughout the latex particle, but at least some must be bonded to functional groups located on the outer surface of the latex particle. For example, at least 25% of the condensation polymer may be bonded to functional groups on the outer surface of the latex particle, for example, at least 50% of the condensation polymer may be bonded to functional groups on the outer surface of the latex particle, or at least 75% of the condensation polymer may be bonded to functional groups on the outer surface of the latex particle.

[0014] The functional (i.e., amino and / or hydroxyl) groups, e.g., primary, secondary, and / or tertiary amino groups, on the latex particles (at least on their outer surface) may already be present on the latex particles (e.g., present after the latex particles are formed) or may be formed by converting functional groups that can be converted to amino or hydroxyl groups. Examples of functional groups that can be converted to amino groups include those that can be converted to amino groups either directly or indirectly, i.e., primary, secondary, and / or tertiary amine groups, via hydrolysis or via reaction with an amine.

[0015] Methods for forming such latex particles are well known to those skilled in the art.

[0016] The amino group may be mono- or polyfunctional, i.e., the amino group may comprise a single primary, secondary, or tertiary amine group, or may 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 that can be converted to an amino group by hydrolysis" is intended to include groups that, upon exposure to acidic or basic media, provide a primary, secondary, or tertiary amino group, e.g., an amide group.

[0018] As used herein, "a functional group that can be converted to an amino group either directly or indirectly via reaction with an amine" is intended to include groups that form primary, secondary, or tertiary amino groups when reacted with an amine, for example, by nucleophilic substitution of a haloalkane, epoxide ring opening, or reductive amination.

[0019] At least two functional moieties of the at least first multifunctional compound may comprise at least one functional moiety selected from the group consisting of epoxide, alkyl halide, benzyl halide, tosylate, methyl sulfide, and mixtures thereof. In a preferred embodiment, at least two functional moieties of the at least first multifunctional compound may comprise an epoxide moiety.

[0020] Suitable epoxides include butadiene diepoxide, ethylene glycol diglycidyl ether, butanediol diglycidyl ether, diethylene glycol diglycidyl ether, hexanediol diglycidyl ether, glycerol triglycidyl ether, and many other compounds containing two or more epoxy groups, including epoxy resins commonly used in commercial epoxy formulations. Suitable alkyl halides include dichloroethane, dichloropropane, dichlorobutane, dibromoethane, dibromopropane, dibromobutane, and many other alkyl halides. Suitable benzyl halides include alpha,alpha-dichloroxylene and alpha,alpha-dibromoxylene, as well as many other benzyl halides. Suitable tosylates include ethylene glycol ditosylate, diethylene glycol ditosylate, and the tosylates of various other aliphatic or aromatic polyols. Suitable methyl sulfides include 1,3-bis(methylthio)propane and 1,4-bis(methylthio)butane, as well as many other polymethyl sulfides. Polyfunctional compounds for the purposes of the present invention preferably comprise an epoxide polyfunctional moiety, which is defined to include monoepoxide compounds, diepoxide compounds, and / or polyepoxide moieties in compounds including polymers.

[0021] The size of the polyfunctional compound can vary over a wide range, from simple non-polymeric compounds having a molecular weight of, for example, less than 87, to small polymeric compounds having a molecular weight of 234 to 10,000. Preferably, the polyfunctional compound is water-soluble and consists of a glycidyl ether of a polyol, or contains a glycidyl ether bound to a hydrophilic polymer such as polyethylene glycol or polypropylene glycol, or a combination of all three, such as glycerol propoxylate triglycidyl ether.

[0022] Other polyfunctional reagents capable of forming condensation polymers with either polyfunctional amines or polyfunctional epoxides can also be used in conjunction with, or instead of, materials suitable for reacting with amines or epoxides. Suitable alternative polyfunctional reagents for reacting with polyfunctional amines include 2-methyl-2-nitro-1,3-propanediol, dithiobis(succinimidyl propionate), cyanuric chloride, and polyfunctional acid chlorides (e.g., dimethyl adipimidate dihydrochloride). Suitable alternative polyfunctional reagents for reacting with polyfunctional epoxides include compounds such as polyfunctional thiols. Preferably, suitable reagents are also water-soluble to facilitate water-based synthesis methods.

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

[0024] Suitable amino groups of the primary amine type include methylamine, ethylamine, propylamine, isopropylamine, butylamine, isobutylamine, sec-butylamine, tert-butylamine, amylamine, tert-amylamine, hexylamine, heptylamine, octylamine, benzylamine, phenethylamine, ethanolamine, 3-amino-1-propanol, 1-amino-2-propanol, 2-amino-1-propanol, 2-amino-1,3-propanediol, 4-amino-1-butanol, and many other primary amines with or without additional polar and / or hydrophilic substituents.

[0025] Suitable amino groups of the secondary amine type include dimethylamine, diethylamine, dipropylamine, diisopropylamine, dibutylamine, diisobutylamine, di-sec-butylamine, di-tert-butylamine, di-tert-amylamine, dipentylamine, dihexylamine, diethanolamine, methylethanolamine, ethylethanolamine, 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 benzyldiamines such as m-xylylenediamine, p-xylylenediamine, aliphatic polyamines such as diethylenetriamine, triethylenetetramine and higher polymeric analogs, as well as various other structures containing multiple primary, secondary, and / or tertiary amine groups in a single compound.

[0027] Both primary and secondary amines are inherently polyfunctional in that they each contain at least two functional groups that can react with polyfunctional groups to form CPRPs, as described below. The size of the amine compound can vary over a wide range, from simple non-polymeric compounds with molecular weights of, for example, 17 to small polymeric compounds with molecular weights of 200 to 10,000. Preferably, each amino group in the amine compound should have at least three atoms in the bond between each amino group to achieve good reactivity to each amino group, although polymeric species such as polyamines derived from the hydrolysis of polyethyleneimine and n-vinylformamide polymers are also useful in the present invention.

[0028] In step (a) of the method for producing modified latex particles, functional (i.e., amino and / or hydroxyl) groups present on the latex particles are reacted with either (i) at least a first multifunctional compound having at least two functional moieties reactive with the functional groups, or (ii) at least a first multifunctional compound having at least two functional moieties reactive with the functional groups and at least a first amine compound containing an amino group selected from the group consisting of ammonia, primary, and secondary amines, to form a first condensation polymer reaction product containing ion exchange sites and a first unreacted excess functional moiety.

[0029] The reaction in step (a) is carried out to provide excess unreacted (and therefore reactive) functional moieties. These may be unreacted moieties on the polyfunctional compound in the first CPRP or unreacted moieties on the amine compound. "Unreacted" means that one or more of the functional moieties are unreacted, e.g., not involved in the condensation reaction, and therefore still reactive.

[0030] The reaction in step (a) also provides ion-exchange sites on at least the outer surface of the latex. The term "ion-exchange sites" refers to functional groups present on the condensation polymer that have a positive or negative charge, depending on the desired application. For example, quaternary ammonium sites on the condensation polymer on at least 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 compound used in step (a) may comprise a first amine compound as the only amine compound and a first multifunctional compound as the only multifunctional compound. Alternatively, it may comprise a mixture of the first amine compound and one or more additional amine compounds. Furthermore, it may comprise the first multifunctional compound alone with the first or additional amine compounds, or it may comprise a mixture of the first multifunctional compound and one or more additional multifunctional compounds. In this way, each condensation polymer reaction product can be tailored to contain the desired functional groups.

[0033] Furthermore, the amino group in each amine compound and the two functional moieties in the multifunctional compound may be the same or different from each other. For example, the first amine compound may contain at least primary amine groups only, secondary amine groups only, one or more primary and / or secondary groups, etc. Similarly, the first multifunctional compound may contain at least two functional moieties reactive with amino groups of the same or different types, and may additionally contain more than two functional moieties.

[0034] Subsequent CPRPs can be formed after step (a) by reacting the unreacted excess functional moieties of the first CPRP with additional multifunctional compounds and / or amine compounds. The compounds used to form subsequent CPRPs will depend on the non-reactive moieties present on the previous CPRP. For example, if the first CPRP is formed via step (a)(i), the subsequent CPRPs can be formed using an excess of amine compounds or an excess of both multifunctional and amine compounds. Alternatively, if the first CPRP is formed via step (a)(ii), the subsequent CPRPs can be formed using an excess of multifunctional compounds or an excess of both multifunctional and amine compounds.

[0035] Thus, the above-defined method may further comprise step (b)(i) or (b)(ii), in which in step (b)(i), the unreacted excess functional moieties on the CPRP of step (a)(i) may be reacted with at least a second amine compound or with both at least a second multifunctional compound and at least a second amine compound to form a second CPRP comprising ion-exchange sites and second unreacted excess functional moieties, and in step (b)(ii), the unreacted excess functional moieties on the CPRP of step (a)(ii) may be reacted with at least a second multifunctional compound or with both at least a second multifunctional compound and at least a second amine compound to form a second one comprising ion-exchange sites and second unreacted excess functional moieties.

[0036] In this manner, the multifunctional compound and the amine compound can be added sequentially or in one pot to form a continuous CPRP.

[0037] This process can be repeated as many times as desired to achieve the desired properties in the final product.

[0038] Thus, the method may further include reacting additional amine compound and / or polyfunctional compound with unreacted excess amine compound moieties or polyfunctional compound moieties from the first or second condensation polymer reaction product in step (a) or (b).

[0039] With reference to step (b)(i) or (ii), and any subsequent iterations, if any, the at least second amine compound or second multifunctional compound can be characterized in a manner similar to the first amine compound and first multifunctional compound. Thus, the second amine compound can be a mixture 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 multifunctional 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 multifunctional compound" includes a second multifunctional compound that is the same as or different from the first multifunctional compound.

[0041] As noted above, at any point in the above process, the outer layer of the condensation polymer reaction product on the latex particles contains ion exchange sites, such as cationic functional groups of amine groups. The product of this reaction can be used directly in this form without further modification. In this case, the product of this reaction will contain both strong and weak base anion exchange sites, which may be advantageous for some separations.

[0042] However, strong base anion exchange sites may be introduced into the outer layer of the condensation polymer by a capping reaction by reacting with a capping compound containing tertiary amine groups. In this way, the reaction is capped or stopped, and the ion exchange coating contains a greatly increased number of quaternary amines conventionally used for the separation of anions, such as when the substrate is used in the form of anion exchange packing for a chromatography column or the like.

[0043] The condensation polymer on the latex particles can be converted for use as a cation exchange substrate by reacting the excess amine-reactive functional groups on the exterior surface of the coated substrate with an amine-containing cationic functional compound. Suitable amine-containing cationic functional groups include sulfonic acid, phosphonic acid, and carboxylic acid, or a combination thereof. Preferably, the amine-containing cationic functional compound contains two or more cationic functional groups so that the total number of cationic functional groups exceeds the number of anion exchange sites previously formed. Suitable compounds include γ-carboxyglutamic acid, nitrilotriacetic acid, 3,3′,3″-nitrilotripropionic acid, N-(2-carboxyethyl)iminodiacetic acid, N-(phosphonomethyl)glycine, 2-amino-3-phosphonopropionic acid, iminodi(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 amine-containing cationic functional compounds. Other suitable cationic functional groups include sulfonic acid, phosphonic acid, and carboxylic acid. Other suitable cationic functional compounds include chloroacetic acid, bromoacetic acid, chloropropionic acid, bromopropionic acid, sodium 2-chloroethanesulfonate, sodium 2-bromoethanesulfonate, or 1,4-butanesultone. Phosphonic acid cationic functional groups can be introduced using a suitable reagent such as phosphorus pentachloride or phosphorus oxybromide, followed by hydrolysis.

[0044] One or more of the condensation polymer functional groups may be branched and / or crosslinked. For example, the second, third, or more CPRPs can be branched and crosslinked by appropriate selection of reagents and adjusting the ratio of reagents, and by providing an excess of one or other of the amine compounds and polyfunctional compounds described below.

[0045] For example, the "second CPRP" of step (b)(i) or (ii) can be prepared using a mixture of a polyfunctional amine and a polyfunctional epoxide compound. The composition of this layer can be adjusted so that the mixture does not form a gel under the application conditions of the "second CPRP." For example, methylamine (a trifunctional amine capable of reacting with a total of three epoxy groups to form quaternary ion exchange sites) is preferably combined with a water-soluble diepoxide (difunctional epoxide), in a preferred embodiment, butanediol diglycidyl ether. When these two components are combined in a ratio of 2 moles of methylamine to 3 moles of butanediol diglycidyl ether, they tend to form a crosslinked gel because they are combined together in a stoichiometry that complements their functionality. Such a reaction mixture in either slurry mode or flow-through "packed column" mode can be undesirable in that, in the former case, gelation results in substrate particles suspended in a stable gel unsuitable for use in liquid chromatography, and in the latter case, it results in the generation of very high pressures, precluding the use of pumps as a means of delivering the reagents and rendering the material unsuitable for use in liquid chromatography. Alternatively, if the ratio of the two reagents is adjusted so that a gel is not formed (preferably using a composition close to the gellable composition, rather than using a gellable composition), the solution can be passed through a "packed column" without experiencing the high pressure characteristic of gelation. Furthermore, the coating thickness will continue to increase as the solution passes through the column.

[0046] Useful "CPRP coatings," e.g., first and / or second and / or subsequent CPRP coatings, can be achieved by using a 1:1 molar ratio of the preferred reagents and reacting the reagents in the presence of the product of step (a) or (b) at 65° C. for 1 hour. Use of this composition allows for the formation of a predominantly linear CPRP when subsequent CPRPs are formed on the product of step (a) or the product of steps (b)(i) or (b)(ii).

[0047] Condensation polymers formed using this composition contain a significant number of ion exchange sites (ie, reactive amine sites) because under these conditions the amine reactant is in excess relative to the functionality of the reagent.

[0048] For example, when methylamine (a trifunctional reagent) and butanediol diglycidyl ether (a bifunctional reagent) are combined in a 1:1 ratio, a polymer is formed with, on average, two butanediol diglycidyl ether reagents attached to each methylamine reagent, forming a largely linear polymer. The resulting polymer is primarily an alternating polymer with amine and butanediol diglycidyl ether groups alternating in the polymer chain. While the majority of all amine groups thus formed are tertiary upon completion of the "CPRP" preparation process, some of the amine groups at this point are quaternary and some are secondary. These tertiary amine groups (as well as secondary amine groups) remain available for further reaction, forming quaternary moieties at each reactive site. Thus, a "CPRP," such as a "first CPRP" or a "second CPRP," is available for subsequent treatment with a multifunctional epoxide.

[0049] In one embodiment of the method for producing modified latex particles, latex can be reacted with a large excess (e.g., 50-200%) of a polyfunctional epoxide (polyfunctional compound), preferably butanediol diglycidyl ether. By utilizing a large excess of the polyfunctional epoxide, the latex is now modified with pendant unreacted epoxide groups. After treatment with a large excess (e.g., 50-200%) of the polyfunctional epoxide, the substrate can then be treated with a large excess of a polyfunctional amine (amine compound), preferably methylamine. This leaves a surface modified with pendant groups containing amine functional groups with two remaining reactive sites.

[0050] Repeated cycles using a large excess of multifunctional epoxide followed by a large excess of multifunctional amine result in branching of all amines with quaternary moieties at the branching point. In theory, alternating the reaction using butanediol diglycidyl ether and methylamine doubles the number of branches in each layer. By using this method, 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 times). In practice, the situation is significantly more complicated than this, since as branching increases, so does the probability that branches will be crosslinked together. Thus, materials produced using preferred embodiments tend to have an increasing amount of crosslinking with increasing cycle number (assuming at least one of the reagents utilized has a functionality >2). However, when layers are alternated with both difunctional amines and difunctional epoxides, chain growth is primarily linear, and crosslinking side reactions are greatly reduced.

[0051] An additional potential complication in this reaction chemistry is the tendency of epoxides to undergo base-catalyzed polymerization. Because condensation polymers using this synthetic strategy are in the hydroxide form, they can, under some conditions, induce polymerization of multifunctional epoxy monomers in the absence of any amines. The final condensation polymer may contain a fraction of polyepoxide formed via this polymerization side reaction, which also modifies the surface. The existence of these additional reaction pathways does not in itself limit the utility of this method, as the examples provided in the bonded coated examples demonstrate. Useful compositions can be made by varying different combinations, including varying the nature of either the amine or epoxide in each layer, or by utilizing any combination of amines or epoxides in each layer.

[0052] Epoxy monomers can be used to prepare hydroxide-selective materials. Hydroxide selectivity requires a hydroxyl functionality located near the quaternary center of each anion-exchange site.

[0053] Epoxy monomers provide such hydroxyl groups as a by-product of the reaction of epoxides with amines. Therefore, such condensation polymers are particularly useful for preparing hydroxide-selective anion-exchange phases. However, this does not limit the usefulness of the present invention to epoxy monomers and amines. In fact, similar condensation polymers can also be prepared using, for example, polyfunctional alkyl halides with polyfunctional amines. While such condensation polymers are not hydroxide-selective, they are still useful for preparing anion-exchange phases.

[0054] As noted above, conditions that result in gel formation should generally be avoided, but particularly in the case of slurry grafting, useful synthesis methods include the use of combinations that ultimately result in gel formation by simply reducing the exposure time of the substrate to the reaction mixture so that the exposure time is shorter than the gelation time of the reaction mixture.

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

[0056] This allows large amounts of latex particles to be packed into a bed, coated in a large flow-through column, and removed in large quantities as the feed for a packed smaller analytical column.

[0057] While the method of the present invention can utilize methylamine, as noted above, a wide variety of alternative multifunctional amines, including simple diamines, triamines, and higher polyamines, are also suitable for the present invention. Propagation of the polymer growth process requires that the amine contain at least two available reactive sites. Termination of polymer growth can be achieved by a final reaction step using a tertiary amine-containing compound, or the reaction can be completed without such a termination reaction.

[0058] An advantage of the present invention is that when the condensation polymer 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 resumed. However, because epoxides undergo hydrolysis under alkaline conditions, it is generally preferable to interrupt the reaction after the reaction with the polyfunctional amine-containing reagent rather than immediately after the reaction with the polyfunctional epoxy-containing reagent. Similarly, while the preferred polyfunctional epoxide is butanediol diglycidyl ether, a wide variety of polyfunctional epoxides can be used in the present invention. Ideally, the polyfunctional epoxide should be water-soluble to facilitate condensation polymer formation under aqueous conditions, but any of the many available polyfunctional epoxides can be used for this purpose. Furthermore, a wide variety of polyglycidyl reagents that are not readily available can be easily synthesized using standard synthetic methods. While in-situ column preparation of condensation polymers is a convenient way to rapidly evaluate different formulations, in-situ column preparation is generally not as efficient as batch synthesis. However, by utilizing either slurry grafting techniques or, preferably, large packed-bed reactors, optimal coating chemistries can be easily transferred to larger-scale batch processes.

[0059] Generally, epoxides and amines react as shown below:

[0060] [ka]

[0061] In the above-defined method, the latex particles may have an average diameter of from about 0.01 to about 0.5 microns.

[0062] Typically, the latex particles may include styrene and / or methacrylate monomers. For example, the latex particles may include polyvinylbenzyl chloride crosslinked with divinylbenzene or ethylenediamine.

[0063] As previously mentioned, functional groups on the latex particles may be already present on the latex particles or may be formed by converting functional groups that can be converted to amino or hydroxyl groups. For example, the latex particles may include epoxide functional groups on at least the outer surface of the latex, which can be converted to amino functional groups via reaction with, for example, methylamine.

[0064] The modified latex particles defined above can be utilized to provide an ion exchange chromatography packing material. Accordingly, a method for producing an ion exchange chromatography packing material is also defined, the method for producing a packing material comprising the latex particles obtained as defined herein, the latex particles comprising: (i) prior to step (a), ionically bound to a support resin having ion exchange sites (hereinafter "available sites") on at least its available surface; or (ii) After formation of the first, second, or subsequent condensation polymer reaction product, it is ionically bonded to a support resin having ion exchange sites (hereinafter "available sites") on at least its available surface.

[0065] In the method for producing ion exchange chromatography packings, the support resin may be a synthetic ion exchange resin.

[0066] A wide variety of condensation and addition polymers having ion exchange sites of the desired type (i.e., anion or cation exchange) are known in the art. These synthetic resins and their preparation are described in detail in Wheaton and Hatch in Chapter 6 of "Ion Exchange," Vol. 2, J. Marinsky Ed. (New York 1969). For example, synthetic ion exchange resins such as poly(phenol-formaldehyde), polyacrylic or polymethacrylic acid, or nitrile, amine-epichlorohydrin resins, graft polymers of styrene on polyethylene or polypropylene, poly(2-chloromethyl-1,3-butadiene), and especially poly(vinyl aromatic) resins, such as those derived from styrene, alpha-methylstyrene, chlorostyrene, chloromethylstyrene, vinyltoluene, vinylnaphthalene, or vinylpyridine (all of these resins are suitably crosslinked to render them insoluble in the solvent medium with which they come into contact, and which have the desired ion exchange sites) are suitable synthetic resins that can form the carrier resin. The synthetic resin used can be a macroporous or gel type resin well known in the art.

[0067] As used herein, the term "available surface" means the surface of the carrier resin that contacts the latex particles (as defined herein) when the carrier resin is in contact with the latex particles, for example, as a suspension of the latex particles.

[0068] For example, if the carrier resin is made from beads of gel-type resin, the available surface area is essentially the outer surface of those beads. If the carrier resin is from a macroporous resin, the available surface is both the outer surface of the resin and the inner surface of the microscopic channels that penetrate the structure of the resin and have pore sizes larger than the particle size of the latex particles.

[0069] In a preferred embodiment of the present invention, the carrier resin may comprise about 4-10 micron beads of a crosslinked poly(vinyl aromatic) resin, most preferably a styrene-divinylbenzene copolymer containing about 25 to about 55 weight percent divinylbenzene monomer and having anion or cation exchange sites on their available surfaces.

[0070] The ion-exchange sites on the support resin typically comprise negatively charged functional groups, preferably sulfonic acid, carboxylic acid, and / or phosphonic acid functional groups. For example, the ion-exchange sites on the available surface of the support resin may be sulfonic acid groups.

[0071] The ion exchange sites on the available surface of the carrier resin can then be utilized to form (irreversible) ionic bonds between the ion exchange sites on at least the outer surface of the latex and sites of opposite charge on the available surface of the carrier resin.

[0072] For example, if the ion exchange sites on at least the outer surface of the latex particles are cationic, the ion exchange sites on the carrier resin are anionic, such as quaternary ammonium sites on the latex particles and sulfonic acid groups on the carrier resin.

[0073] The carrier resin may typically be substantially spherical and / or have a particle size of from about 2 to about 100 microns, preferably from about 4 to about 10 microns.

[0074] The carrier resin may be insoluble or substantially insoluble in any solvent system with which it may subsequently be used.

[0075] In the process for producing ion exchange chromatography packing material, the support resin and latex particles are mixed / combined together either before step (a) or after formation of the required condensation polymer 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 into the ion exchange column, and then passing a suspension of latex particles through the column. By continuously monitoring the column effluent for breakthrough of latex particles, completion of latex particle formation can be determined when substantially all available sites on the support resin have been bound by latex particles.

[0076] When the latex particles are (irreversibly) bound to the carrier resin, the combination can be washed with a suitable amount of non-solvent liquid to remove excess latex particles. The ion exchange packing material is then ready for operation and can be used without further treatment. If desired, the ion exchange composition can be separated from the liquid, drained, and dried at room temperature for purposes such as storage, transportation, etc.

[0077] Through the methods defined herein, the present invention also provides modified latex particles, the latex particles comprising: (i) a first condensation reaction polymer product comprising ion exchange sites and a first unreacted excess functional moiety, the first condensation reaction polymer being a functional group (i.e., amino and / or hydroxyl) on the latex particles; i. at least a first multifunctional compound having at least two functional moieties; or ii. a first condensation reaction polymer product formed by reacting at least a first multifunctional compound having at least two functional moieties and at least a first amine compound comprising an amino group selected from the group consisting of ammonia, primary and secondary amines.

[0078] Finally, the present invention provides (i) a support resin having ion exchange sites on at least its available surface; and (ii) providing an ion-exchange chromatography packing material comprising modified latex particles as defined herein, wherein an ionic attraction is formed between the ion-exchange sites on the support resin and the ion-exchange sites on the latex particles;

[0079] The modified latex particles may have further characteristics as defined in the method of making the modified latex particles defined herein.

[0080] The foregoing description of specific exemplary embodiments of the present invention has been presented for purposes of illustration and description. It is not intended to be exhaustive or to limit the invention to the precise form disclosed, and obviously, many modifications and variations are possible in light of the above teachings. The exemplary embodiments were chosen and described in order to explain certain principles of the invention and their practical applications, thereby enabling those skilled in the art to make and utilize various exemplary embodiments of the invention, and various alternatives and modifications thereof. It is intended that the scope of the present invention be defined by the appended claims and their equivalents.

[0081] For the avoidance of doubt, when the terms "comprising" or "comprises" are used herein, the process or product being described must contain the recited components, but may, optionally, contain additional components. "Comprising" should be considered to include the terms "consisting of" or "consists of" when the process or product being described must contain only the recited components.

[0082] For the avoidance of doubt, any preference, option, particular feature, etc. stated with respect to a given aspect, feature, or parameter of the invention should be deemed to be disclosed in combination with any and all other preferences, options, particular features, etc. stated with respect to the same or other aspects, features, and parameters of the invention, unless the context indicates otherwise.

[0083] As used herein, the term "about," for example, when referring to a measurable value (such as an amount or parameter), refers to a variation of ±20%, ±10%, ±5%, ±1%, ±0.5%, or particularly ±0.1% of the specified amount.

[0084] The method and apparatus of the present invention have other features and advantages that will be apparent from, or will be more fully described in, the accompanying drawings incorporated herein and the following detailed description of the invention, which together serve to explain certain principles of the invention.

[0085] The invention will now be illustrated, but not limited to, by reference to the following figures and examples. [Brief explanation of the drawings]

[0086] [Figure 1] Chromatograms of the separation of inorganic anions using an ion chromatography packing formed by the method of the present invention containing sulfonated EVB-DVB as a substrate, a vinylbenzyl chloride-based latex, and one cycle of hyperbranching using methylamine (4% solution in water) and 1,4-butanediol diglycidyl ether (10% solution in water). [Figure 2] Chromatograms of the separation of inorganic anions using an ion chromatography packing formed by the method of the present invention containing sulfonated EVB-DVB as a substrate, a vinylbenzyl chloride-based latex, and two cycles of hyperbranching using methylamine (4% solution in water) and 1,4-butanediol diglycidyl ether (10% solution in water). [Figure 3] FIG. 1 shows a chromatogram of the separation of small organic acids using an ion chromatography packing formed by the method of the present invention containing sulfonated EVB-DVB as a substrate, a vinylbenzyl chloride-based latex, and dimethylamine and 1,4-butanediol diglycidyl ether to form a condensation polymer. DETAILED DESCRIPTION OF THE INVENTION

[0087] To illustrate the invention, the following non-limiting examples of its implementation are given. Example 1: Ten grams of vinylbenzene chloride (VBC) and divinylbenzene (DVB)-based latex was mixed with 3.1 g of a 40% solution of methylamine (MA) and 6.9 g of deionized water and reacted 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 ethylvinylbenzene-divinylbenzene-based particles, with 55% crosslinking, an average diameter of 6.45 μm, and a surface area of ​​20 m / g, were then packed into a 4 × 250 mm column, and the prepared latex was passed through the column.

[0088] The hyperbranched layer on the latex was formed using the following procedure to perform one reaction cycle: a 10% solution of 1,4-butanediol diglycidyl ether 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, rinsed with deionized water for 10 minutes, passed a 4% methylamine solution through the column for 20 minutes, allowed to react for 40 minutes, and rinsed with deionized water for 10 minutes. The column was then rinsed with 10 mM KOH. A chromatogram of the separation of several monovalent inorganic anions in suppressed ion chromatography mode using the prepared column with 10 mM KOH as the eluent at a flow rate of 1 mL / min is shown in Figure 1.

[0089] Example 2: The same as in Example 1, but the number of reaction cycles in the hyperbranching process was 2. The chromatogram of the separation of several monovalent inorganic anions in the suppressed ion chromatography mode with the prepared column using 20 mM KOH as the eluent at a flow rate of 1 mL / min is shown in Figure 2.

[0090] Example 3: 10 g of vinylbenzene chloride (VBC) and divinylbenzene (DVB) based latex was placed in a scintillation vial.

[0091] Solution 1, containing 9 g of 40% dimethylamine (DMA) in 20 g of deionized water, and Solution 2, containing 14.7 g of 1,4-butanediol diglycidyl ether in 20 g of deionized water, were simultaneously added to the latex at a flow rate of 0.25 mL / min, respectively, while stirring at 65°C. This process was carried out for 40 minutes, and then the reaction mixture was kept in an oven at 65°C for 2 hours. The prepared latex with attached polymer chains was passed through a 4 x 250 mm column packed with sulfonated ethylvinylbenzene-dimethylvinylbenzene substrate particles with 55% crosslinking, an average diameter of 6.45 μm, and a surface area of ​​20 m / g. The column was rinsed with 10 mM KOH.

[0092] The chromatogram of the separation of several small organic acids in suppressed ion chromatography mode on the prepared column using 20 mM KOH as the eluent at a flow rate of 1 mL / min is shown in Figure 3 .

[0093] Example 4: An electrostatically bonded base layer was prepared according to U.S. Patent No. 7,291,395. (4.5 g of sulfonated ethylvinylbenzene-divinylbenzene base particles with 55% crosslinking, an average diameter of 6.45 μm, and a surface area of ​​20 m / g were placed in a scintillation vial. 0.368 g of 1,4-butanediol diglycidyl ether, 3.277 g of water, and 1.5 g of 4% methylamine were added to the base and mixed thoroughly. The mixture was placed in a tumbler in a 65°C oven for 2 hours, then removed from the oven and allowed to cool for 10-15 minutes. 6 g of deionized water was 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 the hyperbranched layer was performed three times on the base coating. The capacity of such a column is comparable to that of the latex-based one prepared in Example 1 using only one reaction cycle, indicating that the attachment of a hyperbranched layer to the latex allows for the preparation of higher capacity columns in fewer steps.

Claims

1. 1. A method for producing modified latex particles, the particles comprising a condensation polymer attached to a functional group on the latex particles, the method for forming the condensation polymer comprising: (a) The functional groups present on the latex particles are (i) at least a first multifunctional compound having at least two functional moieties reactive with the functional groups of the latex; or (ii) reacting with at least a first multifunctional compound having at least two functional moieties reactive with the functional groups of the latex, and at least a first amine compound containing an amino group selected from the group consisting of ammonia, primary, and secondary amines; The method includes forming a first condensation polymer reaction product comprising ion exchange sites and a first unreacted excess functional moiety.

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

3. 3. The method of claim 1 or 2, wherein the at least two functional moieties of the at least first multifunctional compound comprise at least one functional moiety selected from the group consisting of epoxide, alkyl halide, benzyl halide, tosylate, methyl sulfide, and mixtures thereof.

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

5. 10. The method of claim 1, further comprising step (b)(i) or (b)(ii), wherein in step (b)(i), the unreacted excess functional moieties on the CPRP of step (a)(i) can be reacted with at least a second amine compound or both at least a second multifunctional compound and at least a second amine compound to form a second CPRP, and in step (b)(ii), the unreacted excess functional moieties on the CPRP of step (a)(ii) can be reacted with at least a second multifunctional compound or both at least a second multifunctional compound and at least a second amine compound to form a second CPRP.

6. 10. The method of claim 1, further comprising reacting additional amine compounds and / or polyfunctional compounds with unreacted excess amine compound moieties or polyfunctional compound moieties from the first or second condensation polymer reaction products in step (a) or (b).

7. 7. The method of claim 5 or 6, further comprising repeating step (b)(i) or (ii) at least one more time to react amine-reactive functional moieties 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 polymer comprises functional groups that are crosslinked.

9. The method of claim 1 , wherein the first, second, or subsequent condensation polymer comprises a functional group that includes a branched polymer chain.

10. 10. The method of claim 1, wherein the step of forming the first, second, or subsequent condensation polymer is carried out in a flow-through chamber by continuously flowing (i) the at least first multifunctional compound, or (ii) the at least first multifunctional compound and at least a first amine compound, past 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 media 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 styrene-based and / or methacrylate-based monomers.

14. Modified latex particles, the latex particles comprising: (i) a first condensation reaction polymer product comprising ion exchange sites and a first unreacted excess functional moiety, said first condensation reaction polymer being a functional group on said latex particles; i. at least a first multifunctional compound having at least two functional moieties, or ii. Modified latex particles comprising a first condensation reaction polymer product formed by reacting at least a first multifunctional compound having at least two functional moieties and at least a first amine compound comprising an amino group selected from the group consisting of ammonia, primary and secondary amines.

15. 15. The modified latex particulate of claim 14, wherein the particulate has a median diameter of from about 0.01 to about 0.5 microns.

16. 15. The modified latex particulate of claim 14, wherein the modified latex particulate comprises a styrene-based or methacrylate-based monomer.

17. 15. The modified latex particulate of claim 14, wherein the two functional moieties of the multifunctional compound comprise at least one functional moiety selected from the group consisting of epoxide, alkyl halide, benzyl halide, tosylate, methyl sulfide, and mixtures thereof.

18. 15. The modified latex particulate of claim 14, wherein at least one of the two functional moieties of the multifunctional compound comprises an epoxide moiety.

19. 15. The modified latex particulate of claim 14, wherein the unreacted excess functional moieties on the first CPRP are capable of reacting (i) with at least a second amine compound or both at least a second multifunctional compound and at least a second amine compound to form a second CPRP, or (ii) with at least a second multifunctional compound or both at least a second multifunctional compound and at least a second amine compound to form a second CPRP comprising ion-exchange sites.

20. 15. The modified latex particulate of claim 14, further comprising repeating step (i) or (ii) at least one more time to react amine-reactive functional moieties on the external condensation polymer reaction product with an amine-containing cationic functional compound to convert the packing into a cation exchange substrate.

21. A method for producing an ion exchange chromatography packing material, comprising producing latex particles according to any one of claims 14 to 20, wherein the latex particles are (i) ionically bound to the support resin prior to step (a); or (ii) the first, second, or subsequent condensation polymer product is ionically bonded to said support resin after formation.

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

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

24. 22. The method of claim 21, wherein the support resin comprises negatively charged functional groups, preferably sulfonic acid, carboxylic acid, and / or phosphonic acid functional groups.

25. 22. The method of claim 21, wherein the ionic bonds are formed between ion-exchange sites on at least the outer surface of the latex and sites of opposite charge on the carrier resin.

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

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

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

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

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

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

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

33. 29. The loading material of claim 28, wherein the carrier resin comprises negatively charged functional groups, preferably sulfonic acid, carboxylic acid, and / or phosphonic acid functional groups.

Images