U.S. patent application number 15/800781 was filed with the patent office on 2019-05-02 for sulfonamide based anion exchange resins.
The applicant listed for this patent is Dionex Corporation. Invention is credited to Melvin Hatch, Manikandan Jayaraman, Christopher A. Pohl.
Application Number | 20190126167 15/800781 |
Document ID | / |
Family ID | 64316259 |
Filed Date | 2019-05-02 |
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United States Patent
Application |
20190126167 |
Kind Code |
A1 |
Hatch; Melvin ; et
al. |
May 2, 2019 |
SULFONAMIDE BASED ANION EXCHANGE RESINS
Abstract
An ion exchange resin for use as a stationary phase in an ion
chromatography column. The ion exchange resin has a negatively
charged substrate particle, a positively charged polymer layer
bound to the negatively charged substrate particle, a linker, and
an ion exchange group. The ion exchange group includes a
sulfonamide group and an amine, in which the ion exchange group is
coupled to the positively charged polymer layer via the linker.
When the sulfonamide is in a neutral form, a positively charged
amine group provides retention; while when the sulfonamide is in an
anionic form, the sulfonamide anion becomes a counter ion to the
positively charged amine group, forming a zwitterion that reduces
retention at that site. Accordingly, the retention time is able to
be controlled by adjusting the mobile phase pH.
Inventors: |
Hatch; Melvin; (Socorro,
NM) ; Pohl; Christopher A.; (Union City, CA) ;
Jayaraman; Manikandan; (San Jose, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Dionex Corporation |
Sunnyvale |
CA |
US |
|
|
Family ID: |
64316259 |
Appl. No.: |
15/800781 |
Filed: |
November 1, 2017 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01D 15/361 20130101;
B01J 41/13 20170101; B01J 41/14 20130101; B01D 15/363 20130101;
B01D 15/364 20130101; B01J 41/20 20130101; B01J 41/05 20170101 |
International
Class: |
B01D 15/36 20060101
B01D015/36; B01J 41/20 20060101 B01J041/20; B01J 41/13 20060101
B01J041/13 |
Claims
1. An ion exchange resin comprising: a negatively charged substrate
particle; a positively charged polymer layer bound to the
negatively charged substrate particle, in which the positively
charged polymer layer includes a linker; and an ion exchange group
including a sulfonamide group and an amine, in which the ion
exchange group is coupled to the positively charged polymer layer
via the linker.
2. The ion exchange resin of claim 1, in which the amine is
selected from a group consisting of a secondary amine, a tertiary
amine, a quaternary amine, and a combination thereof.
3. The ion exchange resin of claim 1, in which the ion exchange
group includes a quaternary amine and the ion exchange group is
configured to be zwitterionic when the sulfonamide is in a
deprotonated state.
4. The ion exchange resin of claim 1, in which the negatively
charged substrate particle is a polymeric particle and the ion
exchange resin is configured to retain the ion exchange group when
subjected to eluent having a pH ranging from 0 to 14.
5. The ion exchange resin of claim 1, in which the negatively
charged substrate particle comprises a sulfonated copolymer of an
ethylvinylbenzene and a divinylbenzene.
6. The ion exchange resin of claim 2, in which the negatively
charged substrate particle comprises a super macroporous
particle.
7. The ion exchange resin of claim 6, in which the super
macroporous particle has a diameter of 4-6 .mu.m, a surface area of
20-30 m.sup.2/g, and pore sizes of 1000 .ANG.-2000 .ANG..
8. The ion exchange resin of claim 1, in which the positively
charged polymer layer comprises quaternary amines.
9. The ion exchange resin of claim 8, in which the positively
charged polymer layer further comprises ether groups and hydroxyl
groups.
10. The ion exchange resin of claim 9, in which the positively
charged polymer layer comprises a structure according to Formula
(I): ##STR00004## wherein n ranges from about 5 to about 150, and R
is an alkyl group.
11. The ion exchange resin of claim 9, in which the positively
charged polymer layer comprises a structure according to Formula
(III): ##STR00005## wherein n ranges from about 5 to about 150, and
R is an alkyl group.
12. The ion exchange resin of claim 1, in which the linker includes
an aromatic ring.
13. The ion exchange resin of claim 1, in which the ion exchange
group comprises a structure according to Formula (II): ##STR00006##
or a salt thereof, wherein R.sub.1 is selected from unsubstituted
alkyl, and substituted alkyl; L.sub.1 is selected from substituted
alkyl, unsubstituted alkyl, substituted aryl, and unsubstituted
aryl; R.sub.2 is selected from the group consisting of H,
unsubstituted alkyl, substituted alkyl, a lone pair of electrons,
and a support structure, in which the support structure includes
the linker, the positively charged polymer layer, and the
negatively charged substrate particle; R.sub.3 is selected from the
group consisting of H, unsubstituted alkyl, substituted alkyl, a
lone pair of electrons, and the support structure, and R.sub.4 is
selected from the group consisting of H, unsubstituted alkyl,
substituted alkyl, a lone pair of electrons, and the support
structure, with the proviso that two or more of R.sub.2, R.sub.3,
and R.sub.4 cannot be lone pair electrons, and with the proviso
that at least one of R.sub.2, R.sub.3, and R.sub.4 comprises the
support structure.
14. The ion exchange resin of claim 13, in which R.sub.1 and
R.sub.2 each include an unsubstituted alkyl containing two to three
carbons and R.sub.3 includes the support structure.
15. The ion exchange resin of claim 13, in which the salt thereof
comprises a quaternary amine and an anion, the anion selected from
the group consisting of a hydroxide ion, a carbonate ion, a
bicarbonate ion, and a combination thereof.
16. A method of using an ion exchange resin packed in a
chromatography column, the method comprising: flowing an eluent
through the chromatography column, in which the eluent comprises
carbonate and bicarbonate, wherein the ion exchange resin
containing a positively charged polymer layer coupled to the ion
exchange resin, in which the positively charged polymer layer
includes a linker; and an ion exchange group including a
sulfonamide group and a positively charged amine, in which the ion
exchange group is coupled to the ion exchange resin via a linker;
and separating a sample that includes a trivalent species.
17. The method of claim 16 further comprising: adjusting a ratio of
a carbonate concentration and a bicarbonate concentration so that a
carbonate peak does not overlap with an analyte peak.
18. The method of claim 16, in which the adjusting a pH value of
the eluent so that a first analyte peak does not overlap with a
second analyte peak.
19. The method of claim 16, in which the trivalent species includes
phosphate or arsenate.
20. An ion exchange resin comprising: a negatively charged
substrate particle; a positively charged polymer layer bound to the
negatively charged substrate particle, in which the positively
charged polymer layer includes a linker; and a first ion exchange
group including a first sulfonamide group and a first quaternary
amine, in which the first ion exchange group is coupled to the
positively charged polymer layer via the linker; and a second ion
exchange group including a second sulfonamide group and a second
quaternary amine, in which the second ion exchange group is coupled
to the positively charged polymer layer via the linker, in which
the first ion quaternary amine is different than the second
quaternary amine.
21. The ion exchange resin of claim 20, in which the first ion
exchange group comprises N,N-dimethylaminopropyl methylsulfonamide
and the second ion exchange group comprises N,N-diethylaminoethyl
methylsulfonamide.
22. The ion exchange resin of claim 20, in which a ratio of the
first ion exchange group to the second ion exchange group is 1:1.
Description
FIELD OF THE INVENTION
[0001] This invention relates to the field of chromatographic
sample separation that includes liquid chromatography and more
particularly ion exchange chromatography. In particular, this
invention relates to material and the synthesis of material for use
as a stationary phase in chromatographic sample separation. The
invention further relates to chromatographic columns containing the
stationary phase and applications thereof.
BACKGROUND OF THE INVENTION
[0002] Hydroxide selectivity is a term that can be used to describe
stationary phases for ion exchange chromatography that exhibit an
unusually high affinity for the hydroxide anion. The earliest
hydroxide selective phases were synthesized in the early 1950s,
which can be referred to as type I anion exchange resins. Hydroxide
selective phases may contain hydroxyl groups positioned near a
quaternary amine ion exchange site of an anion exchange material.
These hydroxyl groups can be weakly acidic when covalently bound to
the resin such that they are sufficiently close to the anion
exchange site. When the ion exchange site is in the hydroxide form,
some of these hydroxyl groups can be converted into the anionic
form, forming a zwitterion with the associated quaternary amine ion
exchange site, negating the retention at that ion exchange
site.
[0003] Generally, control of hydroxide selectivity is accomplished
by changing the number of hydroxyl groups in the proximity of the
quaternary amine ion exchange site. Hydroxyl groups in the beta
position relative to the quaternary amine ion exchange site are
more acidic than hydroxyl groups in the gamma or delta position
relative to the quaternary ion exchange site so it is the beta
hydroxyl groups that are predominantly responsible for hydroxide
selectivity. The beta position indicates that there is a two-carbon
spacer in between the hydroxyl group and the anion exchange group.
Similarly, the gamma and delta positions respectively indicate that
there is a three and four carbon spacer in between the hydroxyl
group and the anion exchange group. The pKa of a beta hydroxyl
group is believed to be about 13.9, which makes it about 100 times
more acidic than a hydroxyl group not close to a quaternary amine
group. As an example of a beta hydroxyl group with respect to a
quaternary amine, it is worthwhile to note that choline has a
hydroxyl group with a pKa of 13.9. For comparative purposes,
ethanol, which does not have a proximate quaternary amine, has a
hydroxyl group with a pKa of 15.9. The limitation of hydroxide
selective phases, however, is that the pH must be very high in
order to observe the effect of hydroxide selectivity. This renders
such phases suitable for strong base hydroxide eluent systems,
which can produce high pH (e.g., pH 11 to 13.5) in the stationary
phase, but unsuitable for buffered carbonate/bicarbonate eluent
systems which produce much lower stationary phase pH values. While
hydroxide eluent systems in combination with a suppressor provide
the advantages of relatively low background conductivity and
compatibility with gradient elution chromatography, carbonate
eluent systems are still widely used.
[0004] Modern ion chromatography phases may use a hyperbranched
architecture, which can be hydroxide selective and are described in
U.S. Pat. Nos. 7,291,395 and 9,283,494. A side effect of this
hydroxide selectivity is an increase in the effective pH of the
stationary phase when using carbonate-bicarbonate eluent systems.
An undesirable consequence of this property is that phosphate,
which can be partially trivalent and divalent for typical pH values
used in testing, elutes at a time close to the elution time of the
sulfate, which is relatively later than the monovalent ion in the
chromatogram.
[0005] Phosphate is typically present in real drinking water
samples as a minor component. Since carbonate eluent chromatography
is invariably done under isocratic conditions and since peak height
and sensitivity decreases with increasing retention under isocratic
conditions, sensitivity for phosphate is compromised on such
phases. Increasing the amount of bicarbonate (while keeping the
carbonate concentration constant) to move the phosphate earlier in
the chromatogram is one method to resolve the problem but
increasing the amount of bicarbonate in the mobile phase has the
side effect of increasing the background conductivity and the
corresponding detection limit is degraded under these conditions.
Applicant believes that there is a need for ion exchange resins
that can separate divalent and trivalent ions with a carbonate
based eluent under isocratic eluent conditions.
SUMMARY OF THE INVENTION
[0006] Functionalization of reactive monomers with an amino
sulfonamide results in an ion exchange group with an acidic
sulfonamide moiety adjacent to an ion exchange site. The term
"adjacent" used herein throughout the present disclosure includes
next to, nearby, or approximate, such as in the immediately next
position or a position that is two or three atoms apart. Because
sulfonamides have a pKa of approximately 9, this results in a
buffered stationary phase when operating with carbonate eluent.
When the sulfonamide is in a neutral form the adjacent quaternary
side of the stationary phase provides retention; while when the
sulfonamide is in an anionic form the sulfonamide anion becomes a
counter ion to the quaternary ion exchange site, negating retention
at that site. As a consequence, retention can be controlled by
adjusting the mobile phase pH. In addition, this architecture
results in a buffered system which minimizes the retention of
trivalent species such as phosphate and arsenate which become
trivalent at elevated pH.
[0007] Under certain circumstances, samples containing analyte(s)
of interest can have a relatively high ionic strength that
interferes with a quantitative measurement of the analyte(s).
Applicant believes that there is a need for anion exchange
chromatographic resins that can quantitatively measure analyte
concentrations, which is robust to changes in ionic strength by
various anions, when using a carbonate-bicarbonate eluent
system.
[0008] Under certain circumstances, a carbonate-bicarbonate eluent
system can have a disturbance (peak or valley) caused by carbonate
in the sample where such a disturbance can interfere with an
analyte measurement. Applicant believes that there is a need for a
carbonate-bicarbonate eluent system using anion exchange
chromatographic resins that can adjust the retention time of the
carbonate disturbance so that it does not interfere with an analyte
peak of interest by varying the composition of the
carbonate-bicarbonate eluent. Other features and advantages of the
present invention will become apparent after reviewing the detailed
description of the embodiments set forth below.
[0009] In an aspect, an ion exchange resin comprises a negatively
charged substrate particle, a positively charged polymer layer
bound to the negatively charged substrate particle, and an ion
exchange group including a sulfonamide group and an amine, in which
the ion exchange group is coupled to the positively charged polymer
layer via the linker. The positively charged polymer layer includes
a linker.
[0010] In some embodiments, the amine is selected from a group
consisting of a secondary amine, a tertiary amine, a quaternary
amine, and a combination thereof. In other embodiments, the ion
exchange group includes a quaternary amine and the ion exchange
group is configured to be zwitterionic when the sulfonamide is in a
deprotonated state. In some other embodiments, the negatively
charged substrate particle is a polymeric particle and the ion
exchange resin is configured to retain the ion exchange group when
subjected to eluent having a pH ranging from 0 to 14, preferably 1
to 13, and more preferably 11 to 13. It should be noted that silica
particle ion exchange resins are typically stable from pH 2 to 7.
In some embodiments, the negatively charged substrate particle
comprises a sulfonated copolymer of an ethylvinylbenzene and a
divinylbenzene. In other embodiments, the negatively charged
substrate particle comprises a super macroporous particle. In some
other embodiments, the super macroporous particle has a diameter of
4-6 .mu.m, a surface area of 20-30 m.sup.2/g, pore sizes of 1000
.ANG.-2000 .ANG., and a crosslinking mole ratio of 55% of the
divinylbenzene a mole ratio of 45% of the ethylvinylbenzene. In
some embodiments, the positively charged polymer layer comprises
quaternary amines. In other embodiments, the positively charged
polymer layer further comprises ether groups and hydroxyl groups.
In some other embodiments, the positively charged polymer layer
comprises a structure according to Formula (I):
##STR00001##
wherein n ranges from about 5 to about 150, and R is an alkyl
group.
[0011] In some embodiments, the positively charged polymer layer
comprises a structure according to Formula (III):
##STR00002##
wherein n ranges from about 5 to about 150, and R is an alkyl
group. In other embodiments, the linker includes an aromatic ring.
In some other embodiments, the ion exchange group comprises a
structure according to Formula (II):
##STR00003##
or a salt thereof, wherein R.sub.1 is selected from unsubstituted
alkyl, and substituted alkyl, L.sub.1 is selected from substituted
alkyl, unsubstituted alkyl, substituted aryl, and unsubstituted
aryl, R.sub.2 is selected from the group consisting of H,
unsubstituted alkyl, substituted alkyl, a lone pair of electrons,
and a support structure, in which the support structure includes
the linker, the positively charged polymer layer, and the
negatively charged substrate particle, R.sub.3 is selected from the
group consisting of H, unsubstituted alkyl, substituted alkyl, a
lone pair of electrons, and the support structure, and R.sub.4 is
selected from the group consisting of H, unsubstituted alkyl,
substituted alkyl, a lone pair of electrons, and the support
structure, with the proviso that two or more of R.sub.2, R.sub.3,
and R.sub.4 cannot be lone pair electrons, and with the proviso
that at least one of R.sub.2, R.sub.3, and R.sub.4 comprises the
support structure. In some other embodiments, R.sub.1 and R.sub.2
each include an unsubstituted alkyl containing two to three carbons
and R.sub.3 includes the support structure. In some other
embodiments, the salt thereof comprises a quaternary amine and an
anion, the anion selected from the group consisting of a hydroxide
ion, a carbonate ion, a bicarbonate ion, and a combination
thereof.
[0012] In another aspect, a method of using an ion exchange resin
packed in a chromatography column comprises flowing an eluent
through the chromatography column, in which the eluent comprises
carbonate and bicarbonate, wherein the ion exchange resin
containing a positively charged polymer layer coupled to the ion
exchange resin, in which the positively charged polymer layer
includes a linker and an ion exchange group including a sulfonamide
group and a positively charged amine, in which the ion exchange
group is coupled to the ion exchange resin via a linker, and
separating a sample that includes a trivalent species. In some
embodiments, the method further comprises adjusting a ratio of a
carbonate concentration and a bicarbonate concentration so that a
carbonate peak does not overlap with an analyte peak. In other
embodiments, the method comprises adjusting a pH value of the
eluent so that a first analyte peak does not overlap with a second
analyte peak. In some other embodiments, the trivalent species
includes phosphate or arsenate.
[0013] In another aspect, an ion exchange resin comprises a
negatively charged substrate particle, a positively charged polymer
layer bound to the negatively charged substrate particle, in which
the positively charged polymer layer includes a linker, and a first
ion exchange group including a first sulfonamide group and a first
quaternary amine, in which the first ion exchange group is coupled
to the positively charged polymer layer via the linker, and a
second ion exchange group including a second sulfonamide group and
a second quaternary amine, in which the second ion exchange group
is coupled to the positively charged polymer layer via the linker,
in which the first ion quaternary amine is different than the
second quaternary amine.
[0014] In some embodiments, the first ion exchange group comprises
N,N-dimethylaminopropyl methylsulfonamide and the second ion
exchange group comprises N,N-diethylaminoethyl methylsulfonamide.
In other embodiments, a ratio of the first ion exchange group to
the second ion exchange group is 1:1.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Embodiments will now be described by way of examples, with
reference to the accompanying drawings which are meant to be
exemplary and not limiting. For all figures mentioned herein, like
numbered elements refer to like elements throughout.
[0016] FIG. 1 illustrates schematic representations of a
sulfonamide functional group on an ion exchange resin in accordance
with some embodiments.
[0017] FIG. 2A illustrates a process of making a monomer that is
used to be coupled with a positively charged polymer layer in
accordance with some embodiments.
[0018] FIG. 2B illustrates a process of making a
sulfonamide/tertiary amine containing moiety with linker in
accordance with some embodiments.
[0019] FIG. 3 illustrates diamines that are used as part of the
sulfonamide containing moiety in accordance with some
embodiments.
[0020] FIG. 4A illustrates a structure of a base polymer layer in
accordance with some embodiments.
[0021] FIG. 4B illustrates a process of grafting a linking agent of
vinylbenzyl chloride to form the charged polymer layer in
accordance with some embodiments.
[0022] FIG. 4C illustrates a structure of grafted butanediol
diglycidyl ether to form pendant epoxide groups on the base polymer
in accordance with some embodiments.
[0023] FIG. 4D illustrates a structure of pendant amine groups
coupled to the base polymer in accordance with some
embodiments.
[0024] FIG. 4E illustrates a hyperbranched structure of pendant
epoxide groups in accordance with some embodiments.
[0025] FIG. 4F illustrates a pendant epoxide group of the
hyperbranched structure linking with a tertiary amine/sulfonamide
moiety to form a quaternary amine. The squiggle is a shorthand
representation of a portion of the hyperbranched structure shown in
FIG. 4E.
[0026] FIG. 5 shows a resin preparation process in accordance with
some embodiments.
[0027] FIG. 6 shows testing results of an ion exchange
chromatography containing N,N-dimethylaminopropyl methylsulfonamide
moiety in accordance with some embodiments.
[0028] FIG. 7 illustrates a diethyl analog (S-DEAP-Q-VBC) 702 and a
chromatogram using a stationary phase incorporating the diethyl
analog in accordance with some embodiments.
[0029] FIG. 8 illustrates a 50%:50% blend 800 of diethyl analog
(S-DEAP-Q-VBC) and dimethyl compound (S-DMAP-Q-VBC) and
chromatograms using a stationary phase incorporating the 50%:50%
blend in accordance with some embodiments.
[0030] FIGS. 9A-9D illustrate chromatograms testing a possible
matrix effect of a relatively high level of a pre-selected analyte
on the peak areas of other analyte anions in accordance with some
embodiments.
[0031] FIG. 10 illustrate chromatograms testing the possible effect
of adding CO.sub.3.sup.2- to the peak areas of pre-selected
analytes in accordance with some embodiments.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0032] Reference is made in detail to the embodiments of the
present invention, examples of which are illustrated in the
accompanying drawings. While the invention is described in
conjunction with the embodiments below, it is understood that they
are not intended to limit the invention to these embodiments and
examples. On the contrary, the invention is intended to cover
alternatives, modifications and equivalents, which can be included
within the spirit and scope of the invention as defined by the
appended claims. Furthermore, in the following detailed description
of the present invention, numerous specific details are set forth
in order to more fully illustrate the present invention. However,
it is apparent to one of ordinary skill in the prior art having the
benefit of this disclosure that the present invention can be
practiced without these specific details. In other instances,
well-known methods and procedures, components and processes have
not been described in detail so as not to unnecessarily obscure
aspects of the present invention. It is, of course, appreciated
that in the development of any such actual implementation, numerous
implementation-specific decisions must be made in order to achieve
the developer's specific goals, such as compliance with application
and business related constraints, and that these specific goals
vary from one implementation to another and from one developer to
another. Moreover, it is appreciated that such a development effort
can be complex and time-consuming, but is nevertheless a routine
undertaking of engineering for those of ordinary skill in the art
having the benefit of this disclosure.
Definitions
[0033] Herein the term "zwitterionic" ligand refers to a molecule
that contains both positive and negative charges and carries a zero
or substantially zero net charge.
[0034] Herein the term "hydrocarbon" and the like (e.g. hydrocarbon
moiety) includes alkyl and aryl groups as herein defined. Herein,
the term hydrophobic moieties and the like (e.g. hydrophobic
linkers) includes alkyl and aryl groups as herein defined.
[0035] Herein the term "linker" includes any chemical structures,
functional groups, and moiety that is able to connect at least two
chemical moieties. The connection is able to be formed by any type
of chemical reaction, such as polymerization. The linker may be any
hydrophobic chain of chemical structure. In some embodiments, the
linkers and L.sub.1 (FIG. 1) are independently hydrophobic moieties
selected from substituted or unsubstituted alkyl and substituted or
unsubstituted aryl. Herein the term "moiety" includes any selected
portion of a chemical structure.
[0036] Herein the term "alkyl," by itself or as part of another
substituent, means, unless otherwise stated, a straight or branched
chain, or cyclic hydrocarbon radical, or combination thereof, which
is able to be fully saturated, mono- or polyunsaturated and is able
to include di- and multivalent radicals, having the number of
carbon atoms designated (e.g., C1-C10 means one to ten carbons).
Examples of saturated hydrocarbon radicals include, but are not
limited to, groups such as methyl, ethyl, n-propyl (e.g.,
--CH.sub.2--CH.sub.2--CH.sub.3, --CH.sub.2--CH.sub.2--CH.sub.2--),
isopropyl, n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl,
(cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for
example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An
unsaturated alkyl group is one having one or more double bonds or
triple bonds. Examples of unsaturated alkyl groups include, but are
not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl,
2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1-
and 3-propynyl, 3-butynyl, and the higher homologs and isomers. The
term "alkyl," unless otherwise noted, is also meant to include
those derivatives of alkyl defined in more detail below, such as
"heteroalkyl". Alkyl groups that are limited to hydrocarbon groups
are termed "homoalkyl". The term "alkyl" is also able to mean
"alkylene" or "alkyldiyl" as well as alkylidene in those cases
where the alkyl group is a divalent radical.
[0037] Typical alkyl groups include, but are not limited to:
methyl; ethyls such as ethanyl, ethenyl, ethynyl; propyls such as
propan-1-yl, propan-2-yl, cyclopropan-1-yl, prop-1-en-1-yl,
prop-1-en-2-yl, prop-2-en-1-yl (allyl), cycloprop-1-en-1-yl;
cycloprop-2-en-1-yl, prop-1 -yn-1-yl, prop-2-yn-1-yl, etc.; butyls
such as butan-1-yl, butan-2-yl, 2-methyl-propan-1-yl,
2-methyl-propan-2-yl, cyclobutan-1-yl, but-1-en-1-yl,
but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl,
but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl,
cyclobut-1-en-1-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-1-yl,
but-1-yn-1-yl, but-1 -yn-3-yl, but-3-yn-1-yl, etc.; and the
like.
[0038] Herein the terms "halo" or "halogen," by themselves or as
part of another substituent, mean, unless otherwise stated, a
fluorine, chlorine, bromine, or iodine atom. Additionally, terms
such as "haloalkyl," are meant to include monohaloalkyl and
polyhaloalkyl. For example, the term "halo(C.sub.1-C.sub.4)alkyl"
is meant to include, bit not be limited to, trifluoromethyl,
2,2,2.-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the
like.
[0039] Herein the term "aryl" means, unless otherwise stated, a
polyunsaturated, aromatic, substituent that is able to be a single
ring or multiple rings (preferably from 1 to 3 rings), which are
fused together or linked covalently. The term "heteroaryl" refers
to aryl groups (or rings) that contain from one to four heteroatoms
selected from N, O, S, Si and B, wherein the nitrogen and sulfur
atoms are optionally oxidized, and the nitrogen atom(s) are
optionally quaternized. A heteroaryl group is able to be attached
to the remainder of the molecule through a heteroatom. Non-limiting
examples of aryl and heteroaryl groups include phenyl, 1-.naphthyl,
2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl,
3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2-oxazolyl,
4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl,
4-isoxazolyl, 5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl,
2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl,
4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl,
2-benzimidazolyl, 5-indolyl, 5-isoquinolyl, 2-quinoxalinyl,
5-quinoxalinyl, 3-quinolyl, and 6-quinolyl. Substituents for each
of the above noted aryl and heteroaryl ring systems are selected
from the group of acceptable substituents described below.
[0040] For brevity, herein the term "aryl" when used in combination
with other terms (e.g., aryloxy, arylthioxy, arylalkyl) includes
both aryl and heteroaryl rings as defined above. Thus, the term
"arylalkyl" is meant to include those radicals in which an aryl
group is attached to an alkyl group (e.g., benzyl, phenethyl,
pyridylmethyl and the like) including those alkyl groups in which a
carbon atom (e.g., a methylene group) has been replaced by, for
example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl,
3-(1-naphthyloxy)propyl, and the like).
[0041] Each of the above terms (e.g., "alkyl," "heteroalkyl,"
"aryl" and "heteroaryl") are meant to include both substituted and
unsubstituted forms of the indicated radical. Preferred
substituents for each type of radical are provided below.
[0042] Substituents for the alkyl and heteroalkyl radicals
(including those groups often referred to as alkylene, alkenyl,
heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl,
heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) are
generically referred to as "alkyl group substituents," and they are
able to be one or more of a variety of groups selected from, but
not limited to: substituted or unsubstituted aryl, substituted or
unsubstituted heteroaryl, substituted or unsubstituted
heterocycloalkyl, OR', .dbd.O, .dbd.NR', .dbd.N--OR', --NR'R'',
--SR', -halogen, SiR'R''R''', --OC(O)R', --C(O)R', --CO.sub.2R',
--CONR'R'', --OC(O)NR'R'', --NR'' C(O)R', --NR'--C(O)NR''R''',
--NR''C(O).sub.2R', --NR--C(NR'R''R''').dbd.NR'''', --NR--C(NR'R'')
.dbd.NR''', --S(O)R', S(O).sub.2R', --OS(O).sub.2R',
--S(O).sub.2NR'R'', --NRSO.sub.2R', --CN and --NO.sub.2 in a number
ranging from zero to (2m'+1), where m' is the total number of
carbon atoms in such radical. R', R'', R''' and R'''' each
preferably independently refer to hydrogen, substituted or
unsubstituted heteroalkyl, substituted or unsubstituted aryl, e.g.,
aryl substituted with 1-3 halogens, substituted or unsubstituted
alkyl, alkoxy or thioalkoxy groups, or arylalkyl groups. When a
compound described herein includes more than one R group, for
example, each of the R groups is independently selected as are each
R', R'', R''' and R'''' groups when more than one of these groups
is present. When R' and R'' are attached to the same nitrogen atom,
they are able to be combined with the nitrogen atom to form a 5-,
6-, or 7-membered ring. For example, --NR'R'' is meant to include,
but not be limited to, 1-pyrrolidinyl and 4-morpholinyl. From the
above discussion of substituents, one skilled in the art will
understand that the term "alkyl" is meant to include groups
including carbon atoms hound to groups other than hydrogen groups,
such as haloalkyl (e.g., --CF.sub.3 and --CH.sub.2CF.sub.3) and
acyl (e.g., --C(O)CH.sub.3, C(O)CF.sub.3, --C(O)CH.sub.2OCH.sub.3,
and the like).
[0043] Similar to the substituents described for the alkyl radical,
substituents for the aryl and heteroaryl groups are generically
referred to as "aryl group substituents". The substituents are
selected from, for example: substituted or unsubstituted alkyl,
substituted. or unsubstituted aryl, substituted or unsubstituted
heteroaryl, substituted or unsubstituted heterocycloalkyl, --OR',
.dbd.O, .dbd.NR', .dbd.N--OR', --NR'R'', --SR', halogen,
--SiR'R''R''', --OC(O)R', --C(O)R', --CO.sub.2R', --CONR.dbd.R'',
--OC(O)NR'R'', --NR''C(O)R', --NR'--C(O)NR''R''',
--NR''C(O).sub.2R', --NR--C(NR'R''R''').dbd.NR''',
--NR--C(NR'R'').dbd.NR''', --S(O)R', --S(O).sub.2R',
--S(O).sub.2NR'R'', --NRSO.sub.2R'--, --CN and --NO.sub.2,
--N.sub.3, --CH(Ph).sub.2, fluoro(C.sub.1-C.sub.4)alkoxy, and
fluoro(C.sub.1-C.sub.4)alkyl, in a number ranging from zero to the
total number of open valences on the aromatic ring system; and
where R', R'', R''' and R'''' are preferably independently selected
from hydrogen, substituted or unsubstituted alkyl, substituted or
unsubstituted heteroalkyl, substituted or unsubstituted aryl and
substituted or unsubstituted heteroaryl. When a compound described
herein includes more than one R group, for example, each of the R
groups is independently selected as are each R', R'', R''' and
R'''' groups when more than one of these groups is present.
[0044] A squiggle line can be used for illustrative purposes and
indicates a bond to an immediately adjacent moiety such as, for
example, an anion exchange group that includes a sulfonamide
group.
[0045] The ion exchange group that is configured to form a
zwitterionic group attached to the surface, e.g., fixed in close
proximity to the surface, of a substrate which thereby imparts
unique phase selectivity towards small ions compared to standard
mono-selective ion-exchange materials. The zwitterionic groups,
which include sulfonamides and positively charged amines, are
attached at the outer surface and/or within the volume of the
stationary phase, e.g., on the surface within the pores of a porous
substrate.
[0046] The ion exchange group that is configured to form a
zwitterionic group is able to be grafted onto a polymer (e.g.,
positive charged or neutral) using one or more unsaturated bonds
via one or more polymerization reactions. Any other processes and
methods that are able to immobilize the ion exchange groups that
are configured to form zwitterionic groups as part of the
stationary phase are within the scope of the present
disclosure.
[0047] A solution to the problem of preparing a suitable stationary
phase for trivalent analytes or partially trivalent analytes (e.g.,
phosphate and arsenate) includes the use of an amino sulfonamide
reagent. The sulfonamide moiety in the reagent is weakly acidic
with a pKa of approximately 9 to 10. The amine functional group in
the reagent is capable of reacting with a linking compound (e.g.,
vinylbenzyl chloride and glycidyl methacrylate) that are typically
used to produce anion exchange sites in anion exchange materials.
Functionalization of reactive monomers with a tertiary amino
sulfonamide may result in a quaternary ion exchange site with an
acidic sulfonamide moiety adjacent to the quaternary ion exchange
site. Because sulfonamides have a pKa of approximately 9 to 10,
this results in a buffered stationary phase when operating with
carbonate eluent.
[0048] When the sulfonamide is in a neutral form and the amine
group has a positive charge, the charged amine group of the
stationary phase provides anion retention; while when the
sulfonamide is in an anionic form, the sulfonamide anion becomes a
counter ion to the positively charged ion exchange site, negating
retention of anions at that site. As a result, anion retention can
be controlled by adjusting the mobile phase pH.
[0049] In addition, this architecture results in a buffered system
which reduces the retention of trivalent species such as phosphate
and arsenate which can become partially or fully trivalent at
elevated pH. Materials using the combination of sulfonamide and
anion exchange sites have been produced using a pre-functionalized
sulfonamide-quaternary anion exchange monomer via graft
polymerization and by hyperbranched condensation polymerization.
Materials have also been prepared by functionalizing latex
particles prepared from reactive monomers with the tertiary amino
sulfonamide reagent. Materials produced using both synthesis
methods exhibit significantly reduced retention time of phosphate
relative to sulfate anions that are both commonly of interest in
the analytical chemistry of drinking water.
[0050] Another advantage of this ion exchange site is the
relatively early elution of carbonate in the chromatogram.
Carbonate in a sample containing an analyte is generally
"invisible" when using carbonate eluents but small baseline
disturbances are often observed with samples that are at extremes
with regard to pH or ionic strength. By using a buffered stationary
phase, this carbonate disturbance can be moved earlier in the
chromatogram where it is easier to position the carbonate baseline
disturbance a suitable distance away from other common anions.
[0051] Thus, a buffered stationary phase is disclosed in accordance
with some embodiments that allows for reduced retention of
partially trivalent species such as phosphate and arsenate when
using carbonate eluent.
[0052] FIG. 1 illustrates a process of making ion exchange sites,
that can form zwitterionic state, of an ion exchange resin in
accordance with some embodiments.
[0053] In an aspect, the ion exchange resin has a negatively
charged substrate particle, a positively charged polymer layer
bound to the negatively charged substrate particle, a linker, and
an ion exchange functional group. In some embodiments, the ion
exchange group includes a sulfonamide group and an amine that is
either secondary, tertiary, or quaternary. In some embodiments, the
ion exchange group is linked/coupled to the positively charged
polymer layer via the linker.
[0054] Chemical structure 102 shows an exemplary structure of the
ion exchange functional groups in accordance with some embodiments.
In some embodiments, the R.sub.1 is selected from a group
consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, and
heptyl. Preferably, R.sub.1, may be an unsubstituted alkyl ranging
from C.sub.1 to C.sub.3. A person of ordinary skill in the art
appreciates that any other alkyl groups are within the scope of the
present invention. L.sub.1 is selected from a group consisting of
substituted or unsubstituted alkyl and substituted or unsubstituted
aryl. Preferably, L.sub.1, may be an unsubstituted alkyl ranging
from C.sub.2 to C.sub.3. R.sub.2, R.sub.3, and R.sub.4 are selected
from a group consisting of unsubstituted alkyl (e.g., C.sub.1 to
C.sub.3) and a lone pair of electrons. In some embodiments, at
least one of the R.sub.2, R.sub.3, and R.sub.4 includes the linker.
In addition, at least one of the R.sub.2, R.sub.3, and R.sub.4
includes the linker, the positively charged polymer, and the
negatively charged substrate particle. R.sub.2, R.sub.3, and
R.sub.4 are selected such that two or more of R.sub.2, R.sub.3, and
R.sub.4 cannot be a lone pair of electrons. Preferably, when two of
R.sub.2, R.sub.3, and R.sub.4 are unsubstituted alkyls, the
unsubstituted alkyls range from C.sub.2 to C.sub.3 and one of
R.sub.2, R.sub.3, and R.sub.4 includes a support structure. The
support structure can include the linker, the positively charged
polymer, and the negatively charged substrate particle. When each
of L.sub.1, R.sub.2, R.sub.3, and R.sub.4 have an alkyl portion
attached to the nitrogen group, chemical structure 102 includes a
quaternary amine in a salt form. Examples of quaternary amine salt
counterions may include hydroxide, carbonate, bicarbonate, or a
combination thereof, where carbonate is a preferred embodiment.
[0055] The chemical structure 104 shows an exemplary structure of
the chemical structure 102 when R.sub.3 of the ion exchange moiety
106 is directly connected to or coupled with a linker 108. The
linker 108 is directly connected to and/or coupled with a
positively charged polymer layer 110. The positively charged
polymer layer 110 is directly connected to or coupled with the
negatively charged substrate particle 112.
[0056] In some embodiments, the ion exchange moiety 106 is directed
connected to a substrate (e.g., the negatively charged substrate
particle 112 and any other substrates via covalent bonds, ionic
bonds, or hydrogen bonds.) Any other variations of the connectivity
of the ion exchange moiety 106 are within the scope of the present
disclosure.
[0057] FIG. 2A illustrates a process 200 of making a monomer 202
that can be coupled with a positively charged polymer layer in
accordance with some embodiments. The monomer 202 is able to be the
sulfonamide-quaternary anion exchange monomer, which is able to be
formed by reacting a sulfonamide/tertiary amine containing moiety
204 and a linking agent 206. In some embodiments, the
sulfonamide/tertiary amine containing moiety 204 can be formed by
reacting one amine group of a diamine with sulfonyl chloride.
[0058] FIG. 2B illustrates a process of making a
sulfonamide/tertiary amine containing moiety with linker in
accordance with some embodiments. In some embodiments, the
sulfonamide/tertiary amine containing moiety with linker 214 can be
formed by reacting one amine group of a diamine 212 with a
vinylarylsulfonyl chloride, such as 4-vinylbenzylsulfonyl chloride
210. The "n" number of the diamine 212 can be 1, 2, 3, 4, or 5,
which is the length of the carbon chain between the two nitrogens
of the diamine 212, and preferably n ranges from 2 to 3. The R of
the diamine can be an unsubstituted alkyl or substituted alkyl, and
preferably a C1 to C3 unsubstituted alkyl. In some embodiments, one
amine of diamine 212 can be quaternized. In some embodiments, the
diamine compound is in the form of an asymmetric diamine. In some
embodiments, the diamine compound comprises a diamine 302 and 304
of FIG. 3.
[0059] In an exemplary embodiment, the sulfonamide containing
moiety 204 is N,N-dimethylaminopropyl methylsulfonamide and the
linking agent 206 is 4-vinylbenzyl chloride. The reaction of the
sulfonamide/tertiary amine containing moiety 204 and the linking
agent 206 forms the monomer 202, which is able to be used to be
grafted onto a positively charged polymer layer (e.g., the polymer
110 of FIG. 1 or 406 of FIG. 4B), which is able to be used as a
resin containing the quaternary ion exchange sites for an ion
chromatography column. The vinyl group of monomer 202 can react and
bind to the vinyl group of positively charged polymer 406.
[0060] FIG. 3 illustrates various diamines 300 that can be used for
synthesizing the sulfonamide containing moiety 204 of FIG. 2 in
accordance with some embodiments. In some embodiments, the diamines
include asymmetric diamines. The asymmetric diamines include
trialkyl amines 302. In some embodiments, R of the trialkyl amine
includes CH.sub.3, C.sub.2H.sub.5, C.sub.3H.sub.7 and n=2, 3. A
person of ordinary skill in the art appreciates that any trialkyl
amines are within the scope of the present disclosure. For example,
C.sub.xH.sub.2x-1 (wherein x=1, 2, 3, 4, or 5) and n=1, 2, 3, 4, or
5), wherein n is the length of the carbon chain between the two
nitrogens of the diamine 302, are within the scope of the present
disclosure.
[0061] In some embodiments, the diamines for the sulfonamide
containing moiety 204 of FIG. 2 include heterocyclic amines 304,
such as five-membered heterocyclic amines (e.g., azolodine),
six-membered heterocyclic amines (e.g., piperidine and heterocyclic
diamines). A person of ordinary skill in the art would appreciate
that any diamines are within the scope of the present disclosure,
so long as the diamines are able to react to form a base structure
(e.g., containing at least one sulfonamide and at least one amine)
of the ion exchange containing moiety 204.
[0062] In some embodiments, linking agents for forming linker 206
of FIG. 2 include vinylbenzyl chloride (VBC), vinylbenzyl bromide
(VBB), glycidyl methacrylate, aromatic linkers, diglycidyl ethers,
vinylbenzyl glycidyl ether, 2-(4-Vinylbenzyloxy)ethyl glycidyl
ether, and glycidyloxy ethyl methacrylate. A person of ordinary
skill in the art appreciates that any chemical structures that are
able to serve as a linker/connector between the sulfonamide
containing moiety and the positively charged polymer layer are
within the scope of the present disclosure. For example, the
linking agent 206 of FIG. 2 is able to contain a vinyl group and a
nitrogen reactive group. In some embodiments, the nitrogen reactive
group is selected from the group consisting of an epoxide, an alkyl
halide, a benzylhalide, and a combination thereof. Specific
examples of linking agents include, for example, 2-glycidyloxyethyl
methacrylate, 3,4 epoxybutyl methacrylate, 4,5-epoxypent-2-yl
methacrylate, 4,5-epoxypentyl methacrylate, and 2-glycidyloxyethyl
methacrylate, 4-vinylbenzylsulfonyl chloride, and amido- and
keto-derivatives of the above.
[0063] In some embodiments, the sulfonamide monomers similar to
monomer 202 of FIG. 2A can be prepared by the reaction using
predetermined precursor molecules with tertiary amine and include,
without being limiting to the present disclosure, quaternary
ammonium salts of epoxy- or halo-alkyl acrylates or methacrylates
where alkyl comprises straight or branched chain alkyl groups with
from about 4 to about 13 carbon atoms and optionally containing
from 0 to about 3 heteroatoms.
[0064] FIG. 4A illustrates a structure 400 of the base polymer
layer, which is a precursor to positively charged polymer layer 110
of FIG. 1 in accordance with some embodiments. The structure 400 is
one of the exemplary embodiments. In some embodiments, one or more
linkers are between the sulfonamide containing moiety and the
positively charged polymers. In some embodiments, one or more
linkers are between the substrate and the positively charged
polymers. In some embodiments, the structure 400 comprises one or
more tertiary amines, one or more ether groups, one or more
hydroxyl groups, or a combination thereof. As shown in the
structure 400, repeating units of the structure range from 5 to
about 150.
[0065] In some embodiments, the negatively charged substrate
particle 112 of FIG. 1 contains one or more super macroporous
particles (SMP). Some exemplary processes of preparing the SMP is
further illustrated in the Example 1 below in the section of
General Synthetic Procedure. In some alternative embodiments, the
SMP are obtained from commercial sources, including Agilent
PLRP-s1000A and Waters Styragel HR4-HR6. The super macroporous
particle can have a diameter of 4-6 .mu.m, a surface area of 20-30
m.sup.2/g, pore sizes of 1000 .ANG.-2000 .ANG., and a crosslinking
mole ratio of 55% of the divinylbenzene and a mole ratio of 45% of
the ethylvinylbenzene.
[0066] FIG. 4B illustrates a process 400A of grafting a linker
vinylbenzyl chloride 402 to a polymer chain 404 in accordance with
some embodiments. The linking agent 402 is grafted onto the polymer
chain 404 forming the positively charged polymer 406, which is able
to be the positively charged polymer layer 110 of FIG. 1. In FIGS.
4A to 4E, R can be an unsubstituted alkyl, substituted alkyl, or
H.
[0067] In the following, a process of making a resin with an ion
exchange group capable of forming a zwitterionic functional groups
that is used as a stationary phase of an ion chromatography is
provided in accordance with some embodiments.
[0068] FIG. 5 shows a resin preparation process 500 in accordance
with some embodiments. The resin is used as a stationary phase of
an ion chromatography. At a Step 502, a super macroporous particle
(SMP) is prepared. At a Step 504, SMP was sulfonated with sulfuric
acid. Some exemplary processes of preparing the sulfonated SMP
resin are illustrated in the Example 2 below.
[0069] In some embodiments, the SMP has a particle size of 4-6
.mu.m, a surface area of 20-30 m.sup.2/g, pore size of 1000
.ANG.-2000 .ANG., and a crosslinking rate of 55%. A person of
ordinary skill in the art would appreciate that any other polymer
particles are within the scope of the present disclosure, so long
as the substances are suitable for serving as the substrate for an
ion exchange chromatography. In some embodiments, hyperbranched
structures are used as the substrate. Reaction materials,
conditions, and procedures for preparing the SMP and hyperbranched
structures are further disclosed in the U.S. Pat. No. 7,291,395,
titled "Coated ion exchanged substrate and method of forming" and
U.S. Pat. No. 9,283,494, titled "Agglomerated ion exchange particle
bed and method," which are incorporated by reference in their
entirety for all purposes.
[0070] In some embodiments, the sulfonated SMP resin is grafted
with a monomer (e.g., the monomer 202 (FIG. 2) having one or more
sulfonamide contained moiety) using a free radical grafting. At a
Step 506, the sulfonated SMP resin is coated with a positively
charged polymer layer (e.g., layer 406 of FIG. 4B). In an
embodiment, the SMP resin can be packed into a chromatography
column and particular reagents flowed through the column to form
the positively charged polymer layer in situ. For example, a
reagent solution can include the butanediol diglycidyl ether (BDGE)
and methyl amine (MA) to form base layer 400, as illustrated in
FIG. 4A. At a Step 508, a linker is attached to the based layer by
reacting with vinylbenzyl chloride (VBC) to form the positively
charged polymer 406, as illustrated in FIG. 4B. At a Step 510, a
free radical grafting process is performed, in which the sulfonated
SMP resin is grafted with the sulfonamide/ion exchange group
contained moiety. Some exemplary processes of preparing a
sulfonated SMP resin complexed to a positively charged polymer
grafted with the linker VBC using the free radical approach is
illustrated in the Example 4 below.
[0071] In some other embodiments, the sulfonated SMP resin complex
is grafted with sulfonamide contained moiety using a layer by layer
approach, which forms a hyperbranched platform. Some exemplary
processes of preparing the sulfonated SMP resin grafted with a
chain having sulfonamide and quaternary amine moiety using the
layer-by-layer approach is illustrated in the Example 5 below.
EXAMPLE 1
Sulfonation of SMP Resin
[0072] 25 g of SMP resin was dispersed in 125 g of glacial acetic
acid. 500 g of concentrated sulfuric acid was slowly added to the
dispersion. Next, it was thoroughly mixed and sonicated in a water
bath at room temperature for 60 minutes. The reaction mixture was
poured over .about.1000 g of ice. Once the reaction mixture
equilibrated to room temperature, the reaction mixture was
filtered, and washed with DI water (deionized water) until the
washing showed a pH close to neutral. The resin was isolated for
further functionalization.
EXAMPLE 2
Procedure For Making Sulfonated Resin with Positively Charged
Polymer that Includes Grafted VBC
[0073] 20 g of sulfonated SMP resin was packed into a 9.times.250
mm column. A combination of 72% 1,4-butanediol diglycidyl ether (10
wt % solution in DI water) and 28% methyl amine (4 wt % solution in
DI water) was pumped through the column while being maintained at
65.degree. C., at a flow rate of 0.5 ml/min for 60 min. The column
was then unpacked and the resin was slurried in 100 mL of DI water
with sonication for 30 seconds with a probe sonicator and sieved
through a 38 .mu.m sieve and filtered. Next, the resin was then
dispersed in 100 mL of methanol and filtered. It was then rinsed
with 2 aliquots of 50 mL of methanol. The resin was then stirred
gently in 100 ml of a 5% solution of vinylbenzylchloride (VBC) in
methanol for 3 to 4 hrs at 60.degree. C. The mixture was filtered
and the resin washed with 4 aliquots of 50 ml of MeOH (methanol)
and 3 aliquots of 50 ml of DI water. The sulfonated resin with a
positively charged polymer that included grafted VBC was then
isolated.
EXAMPLE 3
Procedure For Grafting Sulfonamide/Quaternary Amine/VBC Monomer
[0074] 1.7 g of N,N-Dimethyl-N-vinylbenzyl-aminopropyl
methylsulfonamide monomer 202 was dissolved in 10 g of DI water. 5
g of the resin from Example 2 was then dispersed in this solution
and 0.2 g of initiator (e.g.,
2,2'-Azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride, Wako
VA-044) is added and thoroughly mixed. The mixture was then tumbled
at 52.degree. C. for 12-16 hrs. The reaction mixture was then
diluted to 100 ml with DI water, filtered and washed with 1) DI
water, 2) Acetone, 3) DI water, 4) 0.5M NaOH, 5) DI water and
finally 0.5M Na.sub.2CO.sub.3. The resin was then isolated for
testing.
EXAMPLE 4
Procedure for Forming Hyperbranched Resin with Grafted
Sulfonamide/Quaternary Amine
[0075] 20 g of sulfonated SMP resin was packed into a 9.times.250mm
(diameter.times.length) column and the following solutions were
pumped through the column at 65.degree. C. at a flow rate of 0.5
mL/min (unless stated otherwise). The reaction is performed based
on the steps, reaction conditions, and reagents described below.
[0076] E1: DI water [0077] E2: 10% 1,4-Butanediol diglycidyl ether
[0078] E3: 4% Methyl amine [0079] E4: 5% N,N-Diethylaminoethyl
methylsulfonamide
TABLE-US-00001 [0079] Steps E1 E2 E3 E4 Comments 1. 0 72 28 0 60
minute duration--create base layer polymer. See FIG. 4A. 2. 100 0 0
0 DI water for 5 minute duration 3. 0 100 0 0 20 minute
duration--create pendant epoxide groups. See FIG. 4C. 4. 100 0 0 0
DI water for 5 minute duration 5. 0 0 100 0 20 minute
duration--methyl amine react with pendant epoxide groups to form
secondary amine. See FIG. 4D. 6. 100 0 0 0 DI water for 5 minute
duration 7. 0 100 0 0 20 minute duration--react up to two epoxide
groups with secondary amine to form two branches. See FIG. 4E. 8.
100 0 0 0 DI water for 5 minute duration 9. 0 0 0 100
N,N-Diethylaminoethyl methylsulfonamide for 30 minute duration at
1.5 ml/min. See FIG. 4F. 10. 100 0 0 0 DI water rinse for 30 minute
duration at 3 mL/min 11. 100 0 0 0 Turn the pump flow to 0 mL/min
and take out the column from water bath. Let it sit overnight at RT
before resin clean-up.
The column was then unpacked and the resin was slurried in 100 mL
of DI water with sonication for 30 seconds with a probe sonicator
and sieved through a 38 .mu.m sieve and filtered. Next, the resin
was then isolated for testing.
EXAMPLE 5
[0080] FIG. 6 shows three chromatograms (604, 606, and 608) of an
ion exchange chromatography column containing
N,N-Dimethylaminopropyl methylsulfonamide moiety 602 in accordance
with Examples 1-3. The analysis was carried out on a Thermo Fisher
Scientific ICS 5000 system. The analysis conditions are listed
below. The carbonate/bicarbonate eluent was manually prepared.
[0081] Column Dimensions: 2.times.250 mm [0082] Eluent : 4.5 mM
Na.sub.2CO.sub.3/1.4 mM NaHCO.sub.3 (unless stated otherwise)
[0083] Flow Rate: 0.25 mL/min [0084] Injection Volume: 2.5 .mu.L
[0085] Temperature: 30.degree. C. [0086] Detection: Suppressed
Conductivity, Dionex AERS 500, 4 mm, AutoSuppression, recycle mode
[0087] Suppressor Current 10 mA [0088] The elution order and
concentration for the 7 anion standard solution are listed
below.
TABLE-US-00002 [0088] Peaks Concn (ppm) 1. Fluoride 5.0 2. Chloride
10.0 3. Nitrite 15.0 4. Phosphate 40.0 5. Bromide 25.0 6. Nitrate
25.0 7. Sulfate 30.0
[0089] The chromatograms 604 and 606 were performed on a resin
having a surface area of 24 m.sup.2/g. The chromatogram 608 was
performed on a resin having a surface area of 33 m.sup.2/g.
[0090] As shown in the chromatograms 604, 606, and 608, the
S-DMAP-Q-VBC-VBC-Q-SO3-SMP (512 of FIG. 5) contained stationary
phase column was able to elute phosphate (e.g., peak #4) before
Br.sup.- (e.g., peak #5) and NO.sub.3.sup.- (e.g., peak #6). The
peaks of phosphate in the experiments of 604, 606, and 608 are
clearly separated from the peaks of Br.sup.- and
NO.sub.3.sup.-.
EXAMPLE 6
[0091] FIG. 7 illustrates a diethyl analog (S-DEAP-Q-VBC) 702 that
replaced the two methyl groups of N,N-Dimethylaminopropyl
methylsulfonamide with two ethyl groups in the stationary phase in
a manner similar to Examples 1-3. The chromatogram 704 was tested
in a manner similar to Example 5 and showed that the peak of
Br.sup.- (peak #5) is separated from the peak of NO.sub.3.sup.-
(peak #6), while the peak of Br.sup.- overlaps with the peak of
SO.sub.4.sup.2- (peak #7).
EXAMPLE 7
[0092] FIG. 8 illustrates a 50%:50% blend 800 of diethyl analog
(S-DEAP-Q-VBC) 804 and dimethyl compound (S-DMAP-Q-VBC) 802 was
reacted at the same time with the stationary phase in a manner
similar to Examples 1-4. A person of ordinary skill in the art
would appreciate that any ratio of the blend (such as the blend
800) are within the scope of the present disclosure. The
chromatograms 812 show that the peak of Br.sup.- (peak #5),
NO.sub.3.sup.- (peak #6), SO.sub.4.sup.2- (peak #7) were separated
from each other. The chromatograms 812 also show that the
concentration of bicarbonate in the eluent affects the peak timing
of CO.sub.3.sup.2- peak. As shown in the chromatogram 806, the peak
of CO.sub.3.sup.2- overlaps with peak #6 of NO.sub.3.sup.- when the
concentration of bicarbonate is 1.5 mM and the concentration of
carbonate is 3 mM. As shown in the chromatogram 808, the peak of
CO.sub.3.sup.2- overlaps with peak #5 of Br.sup.- when the
concentration of bicarbonate is 2.5 mM and the concentration of
carbonate is 3 mM. As shown in the chromatogram 810, the peak of
CO.sub.3.sup.2- does not overlap with any of the peaks of
NO.sub.3.sup.- and Br.sup.- when the concentration of bicarbonate
is 3.5 mM and the concentration of carbonate is 3 mM.
[0093] Accordingly in some embodiments, the concentration of the
bicarbonate or the molar ratio of carbonate/bicarbonate in the
eluent is able to be adjusted to avoid the peak of
CO.sub.3.sup.2-overlapping with any of the peaks of substances
tested here within. In some embodiments, the molar ratio of
carbonate/bicarbonate is in a range between 3/2.5 (or 1.2) and
3/3.5 (or 0.875), such as 1.1, 1, 0.9, 0.880. In some embodiments,
the molar ratio of carbonate/bicarbonate is in a range between
3/3.5 (or 0.875). A person of ordinary skill in the art would
appreciate that any other ratios are within the scope of the
present disclosure, so long as the peaks eluted do not overlap with
the peak of interest. In some embodiments, the ionic strength of
the eluent concentration is adjusted to move the peak of carbonate
to not overlap with the peak of nitrate when a testing sample
contains a relatively high ionic strength.
[0094] The ion exchange chromatography using a stationary phase
with the blend of 800 is advanced in that the peak of
CO.sub.3.sup.2- is able to be moved ahead of the peaks of Br.sup.-
and NO.sub.3.sup.-. Further, the peak of Br.sup.- is not
overlapping with the peak of NO.sub.3.sup.-.
EXAMPLE 8
[0095] FIGS. 9A-9D illustrate the effects of a high level of
pre-selected analytes using an ion exchange chromatography column
containing anion exchange resin made in accordance with Example
4.
[0096] FIG. 9A shows an exemplary result 900A of adding various
levels of PO.sub.4.sup.3- (peak #6). The chromatograms 902A, 904A,
906A, and 908A were performed using a sample having 40 ppm, 140
ppm, 240 ppm, and 440 ppm of HPO.sub.4.sup.2-/PO.sub.4.sup.3-
respectively. The peaks are denoted as 1) F.sup.- 5 ppm, 2)
Cl.sup.- 10 ppm, 3) NO.sub.2.sup.- 15 ppm, 4) Br.sup.- 25 ppm, 5)
NO.sub.3.sup.- 25 ppm, 6) HPO.sub.4.sup.2-/PO.sub.4.sup.3- 7) and
SO.sub.4.sup.2- 30 ppm.
[0097] The peak areas of NO.sub.3.sup.- (peak #5) are 0.988, 0.948,
0.926, and 0.904 for experiments 1002A, 1004A, 1006A, and 1008A
respectively, which show that the area of the NO.sub.3.sup.- peak
was relatively unaffected by the amount of PO.sub.4.sup.3- (<10%
change across the tested range of 40 ppm to 440 ppm phosphate).
[0098] FIG. 9B shows an exemplary result 900B of adding various
levels of Br.sup.- (peak #4). The chromatograms 902B, 904B, 906B,
and 908B were performed using a sample having 40 ppm, 140 ppm, 240
ppm, and 440 ppm of Br.sup.-, respectively. The peak areas of
NO.sub.3.sup.- (peak #5) are 0.987, 0.955, 0.927, and 0.970 for
experiments 902B, 904B, 906B, and 908B respectively, which show
that the area of the NO.sub.3.sup.- peak was relatively unaffected
by the amount of Br.sup.- (<10% change across the tested range
of 40 ppm to 440 ppm Br.sup.-).
[0099] FIG. 9C shows an exemplary result 900C of adding various
levels of NO.sub.3.sup.- (peak #5). The chromatograms 902C, 904C,
906C, and 908C were performed using a sample having 40 ppm, 140
ppm, 240 ppm, and 440 ppm of NO.sub.3.sup.-, respectively. The peak
areas of Br.sup.- (peak #4) are 0.786, 0.773, 0.751, and 0.720 for
the experiments 902C, 904C, 906C, and 908C, respectively, which
show that the Br.sup.- peak was relatively unaffected by the amount
of NO.sub.3.sup.- (<10% change across the tested range of 40 ppm
to 440 ppm NO.sub.3.sup.-).
[0100] FIG. 9D shows an exemplary result 900D of adding two
different combinations of Cl.sup.- (peak #3) and SO.sub.4.sup.2-
(peak #8). The chromatogram 902D has 110 ppm of Cl.sup.- and 130
ppm of SO.sub.4.sup.2- added to a sample containing six other types
of anions. The chromatogram 904D has 210 ppm of Cl.sup.- and 230
ppm of SO.sub.4.sup.2- added to a sample containing six other types
of anions. The peak areas of NO.sub.3.sup.- (peak #5) are 1.000 and
0.974 for the experiments of 902D and 904D, respectively, which
show that the NO.sub.3.sup.- peak was relatively unaffected
(<10% change in peak area) by the combination of Cl.sup.- and
SO.sub.4.sup.2- added up to 210 ppm and 230 ppm, respectively.
TABLE-US-00003 TABLE 1A Peak Area Data of FIG. 9A PO4 concentration
(ppm) Largest % 40 140 240 440 Change F (5 ppm) 0.501 0.490 0.474
0.471 6% Cl (10 ppm) 0.699 0.674 0.659 0.645 8% NO2 (15 ppm) 0.672
0.655 0.639 0.626 7% Br (25 ppm) 0.773 0.744 0.730 0.705 9% NO3(25
ppm) 0.988 0.948 0.926 0.904 9% PO4 0.790 3.288 5.963 11.851 n/a
SO4 (30 ppm) 1.568 1.483 1.464 1.423 9%
TABLE-US-00004 TABLE 1B Peak Area Data of FIG. 9B Br concentration
(ppm) Largest % 25 125 225 425 Change F (5 ppm) 0.506 0.500 0.481
0.461 9% Cl (10 ppm) 0.702 0.690 0.656 0.680 7% NO2 (15 ppm) 0.691
0.662 0.635 0.656 8% Br 0.770 4.842 8.939 19.263 n/a NO3(25 ppm)
0.987 0.955 0.927 0.970 6% PO4 (40 pppm) 0.795 0.778 0.757 0.774 5%
SO4 (30 ppm) 1.542 1.508 1.443 1.488 6%
TABLE-US-00005 TABLE 1C Peak Area Data of FIG. 9C NO3 concentration
(ppm) Largest % 25 125 225 425 Change F (5 ppm) 0.512 0.524 0.502
0.478 9% Cl (10 ppm) 0.711 0.703 0.679 0.649 9% NO2 (15 ppm) 0.683
0.681 0.663 0.635 7% Br (25 ppm) 0.786 0.773 0.751 0.720 8% NO3
1.005 6.515 12.788 25.189 n/a PO4 (40 ppm) 0.807 0.806 0.769 0.740
8% SO4 (30 ppm) 1.579 1.559 1.490 1.441 9%
TABLE-US-00006 TABLE 1D Peak Area Data of FIG. 9D Cl & SO4
concentration (ppm) Largest % 10, 30 110, 130 220, 230 Change F (5
ppm) 0.518 0.498 0.502 3% Cl 0.716 11.201 24.382 n/a NO2 (15 ppm)
0.699 0.648 0.67 7% Br (25 ppm) 0.795 0.758 0.757 5% NO3(25 ppm)
1.008 0.974 0.974 3% PO4 (40 ppm) 0.845 0.765 0.761 10% SO4 1.589
7.876 14.768 n/a
[0101] FIG. 10 illustrates the effects 1000 of added
CO.sub.3.sup.2- concentration to a sample containing 7 anions at
predetermined concentrations using an ion exchange chromatography
column containing anion exchange resin made in accordance with
Examples 4. The peaks of chromatograms 1002, 1004, and 1006 are
denoted as: 1) F.sup.- 5 ppm, 2) Cl.sup.- 10 ppm, 3) NO.sub.2.sup.-
15 ppm, 4) Br.sup.-25 ppm, 5) NO.sub.3.sup.- 25 ppm, 6)
HPO.sub.4.sup.2-/PO.sub.4.sup.3- 7) and SO.sub.4.sup.2-30 ppm.
Different levels of CO.sub.3.sup.2- were added to the injected
sample of chromatogram 1002 (CO.sub.3.sup.2-: 0 pm), chromatogram
1004 (CO.sub.3.sup.2-: 100 pm), and chromatogram 1006
(CO.sub.3.sup.2-: 200 pm), respectively.
[0102] As shown in the Table 1000A, the peak areas of all the peaks
(#1 - #7) showed less than a 10% area changes across the range of
tested carbonate levels, which show that the stationary phase
prepared herein can accurately measure anions and be robust to a
wide range of matrix ions that may be present.
[0103] The resin prepared herein is able to be utilized in
preparing a stationary phase of an ion chromatography, which has a
controllable retention time of trivalent analytes and ions that are
partially trivalent.
[0104] In operation, ion exchange resin capable of forming a
zwitterionic state is prepared. The resin is used to prepare a
column for ion chromatography. Analytes that are passing through
the stationary phase are eluted at different times, due to the
different affinity of the analytes and the stationary phase. In
some embodiments, the pH is adjusted to control the elution
time.
[0105] The present invention has been described in terms of
specific embodiments incorporating details to facilitate the
understanding of principles of construction and operation of the
invention. Such reference herein to specific embodiments and
details thereof is not intended to limit the scope of the claims
appended hereto. It is readily apparent to one skilled in the art
that other various modifications can be made in the embodiment
chosen for illustration without departing from the spirit and scope
of the invention as defined by the claims. Features in various
examples or embodiments are applicable throughout the Present
Specification.
* * * * *