Note: Descriptions are shown in the official language in which they were submitted.
13037~5
POST-CROSS-LINKED POLYMERIC GELS
BACKGROUND OF THE INVENTION
The present invention relates to novel solid polymeric
compositions, their preparation and cross-linking, and
their uses.
A well-established method for improvirg the physical
properties and solvent resistance of linear polymers is
cross-linking, in which the individual polymer chains are
joined at many points to yield an interconnected network.
The cross-links may be ionic in character, as in complexes
of poly-acids with poly-bases, but covalent or chemical
cross-linking is strorger, more resistant to hydrolysis,
and more versatile in its applications.
The most common way of achiev~ng covalent cross-linking
~303785
iA to use a polyfunctional monomer in the polymerlzatlon
reactlon itself (e.g., divinylbenzene together with
styrene). Since cross-linked polymers cannot be dissolved,
melted or cast, the polymerization must be carried out in
the final physical shape required. Problems often arise in
the preparation of films and membranes when catalysts must
be introduced or inhibitors such as oxygen excluded from
the polymerization reaction. Furthermore, the monomers
themselves are often too toxic, volatile, or fluid to be
conveniently processed in this manner. All of these
factors make the manufacturing process difficult and
costly.
It is thus often preferable to prepare a linear polymer
or polymers, dissolve them in an appropriate solvent, spray
or cast in the final form required, and only then introduce
the cross-links. A familiar example of such
post-cross-linking is the vulcanization of rubber, in which
linear polyisoprene is mixed with sulfur, molded and then
heat-cured. - Another example is the cross-linking of
various unsaturated polymers by light to produce plates for
photoengraving.
Although many polymers will form loosely cross-linked
gels upon heating, the mechanism is often obscure and the
cross-linking difficult to predict or control. ~he present
invention provides a post-cross-linking method unique in
its mechanism, in the range of polymers to which it
applies, and in its practicality and wide range of
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~303785
application. It iq believed to proceed via the alcoholysiq
of pendant amide or e~ter groups on the polymer with
hydroxyl groups to produce a new ester linkage between
polymer chains, or the amidolysis (or aminolysis) of
pendant amide or ester groups on the polymer with amino
groups to produce a new amide linkage between polymer
chains, or the reaction of pendant carboxyl groups on the
polymer with hydroxyl or amino groups to produce new ester
or amid linkages. Depending on the nature of the reaction
and the leaving group involved, the use of an acid or base
eatalyst or no catalyst at all is employed to obtain
optimal cross-linking.
Alcoholysis of amides and esters is a well-known
reaction in the organic chemistry of small molecules, where
it generally is run in solution at reflux temperature with
strong acid or base catalysis. It is one of several
mechanisms postulated by Kopecek and Bazilova to account
for unusually high molecular weights obtained in the
solution polymerization of N-(2-hydroxypropyl)
methacrylamide (European Polymer Journal, 1973, vol. 9, pp.
10-11.) These authors considered only the possibility of
dimerization, not actual cross-linking, and did not report
any insolubilization taking place. The unusual feature of
the alcoholysis, aminolysis and transamidation reactions
described in this invention is their occurrence in the
solid state in the absence of solvent, a phenomenon
entirely unexpected and heretofore unreported.
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i303785
Similarly, amidolys~s of amide~ and esters i9 a well
known reaction in the organic chemigtry of small molecule~,
generally performed at elevated temperature~, sometime~
with a base cataly~t, other timeg with an acid catalyst or
no catalyst at all depending on the nature of the ~olvent
and the leaving group. The novel post-cross-linking
techniques taught by this invention have many unique
advantage~, particularly in the manufacture of synthetiC
membranes. Conventional membrane~ for rever~e osmosi~ (R0)
and ultrafiltration (UF) are made of polymer~ that are
insoluble in the fluid acted on by the membrane (water, in
mo~t case~). Typically, a linear polyamide, polysulfone,
or cellulose acetate i~ cast from an organic solvent and
coagulated in water. Although ~uch membrane~ are rigid and
physically strong, they are hydrophobic in nature and tend
to foul through adsorption of hydrophobic particles and
solute~ in the feed stream. Such fouling is a major
problem in industrial use of membrane~, making frequent
cleaning or costly pretreatment necessary.
~ .
Strongly hydrophilic polymer~, particularly those
where in at least 80% of their con~tituent unit~ are highly
polar 90 the linear polymer ig highly soluble in water,
which include thoge having a fixed po~itive or negative
charge on each unit or an uncharged specie~ with a
similarly high affinity for water guch as acrylamide, have
been shown to regi~t 9uch adgorptive foullng. However,
they either dis~olve in water or, unle~s ~ubstantially
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1303785
cross-linked, form a soft gel. Useful membranes may be
formed of ~uch polymers only by a high degree of
cros~-linking, so they swell not more than 3-5 times by
weight when soaked in water. Since the pore structure of
such membranes is generally created by coagulation and
since monomers are essentially uncoagulable, the best
practical route is post-cross-linking of the coagulated
linear polymer. Using the techniques taught by this
invention, highly cross-linked UF membranes of controlled
porosity may be cast from very hydrophilic polymers. The
intricate pore structure of these coagulated membranes is
preserved by solid state post-cross-linking. Furthermore,
charged functionalities such as sulfonate or quaterr,ary
ammonium may be incorporated to yield a cross-linked
interpolymer membrane of the type described by Gregor (U.S.
Patent 3,808,305), where the fixed charges serve to re~ect
charged colloidal particles and, to a lesser extent,
dissolved salts.
A typical and commonly employed hydrophilic support
.
medium is -cross-linked polyacrylamide (PAM) beads of
different sizes and different degrees of cross-linking, the
latter acting to control pore size. PAM contains a
hydrocarbor skeletion to which are attached pendant
amidocarbonyl groups which contain an amide ammonia
nitrogen, one readily replaced by certain other nitrogen
compounds, thus permitting the formation of several
derivatives having useful properties. A typical, earlier
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~303785
study by Inman and Dintzis (Biochemistry, 1969, vol. 8, pp.
4074_4082.) showed that commercially available bead~ made
of cross-linked copolymer~ of acrylamide and N,
N'-methylenebisacrylamide could be treated by several
different reactions to make useful products. The~e authors
performed the direct aminoethylation of the beads as well
as the preparation of a number of derivatives from these
beads including those of the: hydrazide; trinitrophenyl;
2,4 dinitrosophenylaminoethyl; succinylhydrazide; sulfo-
ethyl; p-hydroxyphenethyl. Also, these authors found it
was possible to effect the coupling of primary amines via
the general acyl azide procedure employing, in this case,
the hydrazide derivative. These authors also achieved
coupling to proteins such as to serum albumin via the acyl
azide reaction, and to trypsin via the treatment of the
hydrazide derivative with cold nitrous acid, followed by
treatment with a suitable solution of trypsin. These
authors also converted the aminoethyl derivative of PAM
with p-nitrobenzoylazide, followed by triethylamine and
washing with DMF to form the p-nitrobenzamidoethyl
derivative which was then converted to the p-amino-
benzamidoethyl derivative. The latter, after treatment
with nitrous acid was employed for the coupling of bovine
serum albumin via the diazonium intermediate. These
authors then employed some of these derivatives as
immobilized enzymes and as immunoadsorbents.
~303'78~
The materials which can be prepared by the teachings of
the sub~ect invention constitute' particularly useful and
powerful tools for the techniques of modern biochemistry
and molecular biology. Often these require a sequential
and laborious laboratory procedure which usually must be
carried out over a period of several days. Often one
starts with substantial quantities of material,but very
soon this is reduced to a dilute solution containing a
small amount of material, of which a very small fraction is
the desired component. The classical biochemical
techniques which involve salt precipitation, desalting and
successive column chromatography, with a final
concentration often achieved by freeze-drying andsubsequent
procedures, results in both an extremely laborious and
time-consumirg procedure and usually a loss or
denaturization of the very substance which is desired as an
end product of the entire process.
As a typical example, in the isolation of transcription
factors~one first usually uses a large column which can be
cross-linked heparin, ~ hydroxy -a-petite or a phospho-
cellulose, for the purpose of concentrating the DNA binding
proteinst which have an affinity for these columns. The
next step is to elute the active material~usually by the
use of different salt gradients and test each eluted
fraction for specific activity. Once an active fractior is
isolated, it can be separated by using gel permeation
1303785
chromatography to visualise the amount and approximate
molecular weight of the protein in that fraction, and
finally a certain band is isolated which contains
substantial amounts of the activity of the protelns which
constltute a transcription factor. Since none of these
preparatory procedures producesa~ingle band of the desired,
purified protein,ihlvirtually all circumstances the final
purification procedure required consists of growing
antibodies to the protein desired and employing these
antibodies in an affinity chromatography system to finally
obtain the pure protein.Since a desired component is a low
molecular weight material such as a polypeptide present in
a group of highly similar ~olypeptides, the problem is a
particularly difficult one.
All of these proceduresJ involving as they do for
the most part hydrophobic materialsor surfaces to which the
desired proteins may be adsorbed and lost, suffer from that
disadvantage.
-- . . .
,
I303785
SUMMARY OF THE INVENTION
In accordance with the present invention, applicants
have found that substantially improved cross-linked gel~ in
the form of membranes, coatings, and formed ob~ects can be
prepared from a solution of a linear polymer or polymers,
at least one of which has at least 80% of its units
containing pendant amidocarbonyl or oxycarbonyl groups,
with cross~linking affected by either hydroxyl groups,
present as either pendant groups from the polymer, or as
low molecular weight polyols; amino groups, present as
either pendant groups from the polymer, or as low molecular
weight diamines or polyamines. Where a catalyst is
required or advantageous, such a catalyst is generally
strongly acidic and is either of low molecular weight or
may be a pendant group from the polymer. After removal of
the solvent by drying or coagulation, followed by a high
temperature cure, some of the amidocarbonyl or oxycarbonyl
groups are alcoholyzed to form ester linkages that
cross-link and insolubilize the gel, or amide linkages
which similarly cross-link and insolubilize the gel. This
invention allows for the production of membranes, films and
solid gels of excellent strength, controlled pore size, and
controlled swelling, which may incorporate a wide variety
of fixed charges and other functionalities.
~30378S
DETAILED DESCRIPTION OF THE INVENTION
As noted above, the cross-linking reaction described in
this invertion involve the presence of the following
functionalities: pendant amides or esters, alcohols,
amines, and (in most cases) a strong acid. The alcohol or
amine is either itself a pendant function on the polymer
(e.g., hydroxyhexyl acrylamide copolymers) or a low molec-
ular weight polyol (e.g., glycerol or pentaerythritol) or
diamines or polyamines. The alcohol should be primary or
secondary to avoid the side reaction of elimination, and
should be non-volatile and slow to decompose under the
conditions of the high temperature cure. The hydroxyl
group may also be present in an incipient form, such as an
epoxy. It is of course possible to run an inverse reaction
with a low molecular weight bis-amide or bis-ester
cross-linking a polymer with pendant alcohol groups, but no
advantage is obtained and the resins tend to show less
hydrolytic stability than those resulting from the normal
cross-iinking reaction. -Where diamine or polyamine
cross-linking is involved, the amine group is
preferentially a primary amine, but it may be a secondary
amine, but not a tertiary amine and it should be of low
volatility or non-volatile and slow to decompose at
elevated temperatures.
The reaction is greatly facilitated by acid catalysis,
although a few polymers such as polyacrylamide cross-link
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1303785
adequately in the absense of acid catalysts. The acid
should be a strong acid, non-volatile and non-oxidizlng.
The acid may be pendant as in poly(3-sulfopropyl acrylate),
or a separate low molecular weight molecule.
Methanesulfonic acid is ideal for this purpose, but any
similar, strong mineral or organic acid may be used. At
least 0.1 mole acid catalyst per mole of the cross-linking
alcohol functionality should be used, although no advantage
is obtained by exceeding a 1:1 ratio. If the acid catalyst
is a pendant functionality on the polymer, improved
cross-linking results when an additional low molecular
weight acid is used as well, presumably on account of its
ability to become localized at the reactive sites.
Any long-chain molecule with pendant amidocarbonyl or
oxycarbonyl groups is suitable for cross-linking under the
teachings of this invention as long as it is stable under
the conditions of the high-temperature cure. The most
common and practical of these are N-substituted
polyacrylamides and polymethacrylamides, esters of poly-
.. . . ..
acrylic acid and polymethacrylic acid or the acids
themselves, and homologs of the following polymers:
R R R R
( C -- C ~n or ( C C )n
R R' R R'
C=O C=O
R 1 R ' I - 1 1 - O - R''
i303785
in which:
each Rmaybethe~sameor different andishYdrOgen,Or an
alkyl radical with up to 10 carbon atoms or aryl
radical with up to 10 carbon atoms,
R' is an alkylene radical
with up to 10 carbon atoms or arylene radical with
up to 10 carbon atoms, and
R " is an alkyl radical with up to lO carbor. atoms, or.
an aryl radical with up to lO carbon atoms, either
of which may have a substituent which imparts a
desirable functionality to the R'' groupJsuch as a
carboxyl, sulfonic acid, amine, ammor.ium, or other
functionality.
Alkyl substituents on the polymer backbone are thus
permissible (e.g., polyethacrylamides or poly~2-propyl-
acrylates)) and the amidocarbonyl or oxycarbonyl
functionality may be suspended from the polymer backbone by
one or more methylene urits, as ir. ami.des or esters of
poly(3-butenoic acid). Since experience has shown that the
solid-state cross-linking reactions of this invention are
quite susceptible to steric hinderance, substituents near
the cross-linking site should be avoided where possible.
A wide variety of functional groups may be present on
the alkyl N-substituents of polyacrylamides, or the alcohol
moiety of polyacrylate esters. Polyacrylamides may have
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~03785
one, two, or no N-substltuents. One notable restr~ctlon
lnvolves the presence of a positlve charge near the
amidocarbonyl functionality in N-substituted polyacryl-
amides. Since a positive charge is presumably developed at
that site in the course of the reaction (appearlng
ultimately on the protonated amine byproduct), a second
positive charge fixed nearby inhibits the cross-linking of
such polymers. In the corresponding polyacrylates esters,
the byproduct is a neutral alcohol and such polymers can in
fact be cross-linked successfully. It should be noted that
physical properties such as hydrophilicity may be affected
by the replacement of pendant functional groups with a
polyhydroxyl alcohol such as glycerol or pentaerythritol.
Indeed, a monofunctional alcohol may be grafted onto a
polymer by the present method, yielding a linear polymer
with altered solubility.
A ma~or advantage of the new cross-linking method is
its occurrence in the solid state in the absence of
solvent. The polymer chains lie entangled and in close
proximity at the time of cross-linking, and therefore form
a t-ight -concatenated net~work-that sweels Iittle in-solvent.
A consequence is the need to have good compatibility on a
molecular level of all polymers and low molecular weight
species in the solid state. If the catalyst or
cross-linking agent gets excluded from the polymer while
drying the reaction cannot be successful. If a matrix
polymer phase-separates it cannot increase strength and
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130378S
reduce swelling as it ought. The rate and manner of drying
affect the chain proximity. A polymer dried ln an expanded
state (e.g., freeze-dried) i9 unlikely to cross-link
~atisfactorily. Since the cross-linking reaction welds the
polymer chains into what i8 in effect a single molecule,
the molecular weight of the polymer ls relatively
unimportant. Very low molecular weight polymers (~50,000)
tend not to be highly entangled in the solid state and give
loose, highly swollen gels.
Other factors influence the tightness of the
cross-linking under the teachings of this invention. The
mole percent of cross-linking agent added and of
cross-linkable pendant amide or ester groups in a copolymer
is of considerable importance. As little as 0.1 mol ~
cross-linking agent or moiety (relative to the polymer's
monomer content) can insolubilize a polymer as a very loose
gel, while any in excess of 50 mol % can in principle no
longer find reactive sites on the polymer. In order to
achieve both the desirable qualities of the predominant
groups in the chain and a high degree of cross-linking, at
least 80% and as much as 100% of the chain units should
consist of reactive sites. The longer the cure and higher
the temperature, the more effective the cross-linking. No
advantage is obtained by curing longer than three hours at
150C, and while the practical, lower limit is one hour at
120C, insolubilization can be achieved at lower
temperatures and longer times.
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1303785
The teachings of this invention are applicable to the
preparation of many kinds of polymer membranes. For
example, conventional RO membranes tend to ~uffer
compaction or swelling over a period of time and are highly
susceptible to biological and chemical attack (particularly
chlorination). The tight cross-linking made possible by
the teachings of this invention provides physical strength
and mitigates the effect of plymer chain scission, thus
enabling RO membranes to keep their selectivity under
conditions of use. Furthermore, one may prepare an RO
membrane with a hydrophilic, nor-fouling coating, thus
reducing the need for pretreatment of the feed stream.
Conventional electrodialysis (ED) membranes contain a
small percentage of charged groups fixed inside the pores
of a hydrophobic polymer matrix. Using the teachings of
this invention, ED membranes with very high fixed charge
densities, tight pore structures and low swelling may be
prepared at low cost. Membrane permeation ~MP) or
pervaporation requires ar extremely thin film which
selectively absorbs one component of the feed stream
without irreversible swelling or shrinking. The teachings
of this invention allow one to incorporate any of a wide
range of polymers with different chemical affinities into a
film whose swelling is determined by the degree of
cross-lirking. Solvent extraction membranes must similarly
resist excessive swelling but with controlled porosity, and
these techniques are again applicable. Finally, the wide
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1303785
range of functional group~ compatible with this method of
post-cross-linking allows for unusual versatility in the
preparation of porous, coagulated membranes for enzyme
coupling.
The teachings of this invention enable one to make a
wide range of novel and highly useful adhesive coatings.
Cross-linked coatings have long been known to exhibit
superior strength and solvent resistance, but their
preparation generally involves either photolytic curing
(as with paints) or noxious chemical monomers (as with
epoxies). The presert invention allows a viscous solution
of a polymer and relatively innocuous cross-linking agents
(which may be incorporated in the polymer) to be applied to
a surface and cured by heat ir a relatively short time.
Polyacrylamide and its homologs may be cast into thin films
suitable for electrophoresis. Coatings containg highly
~ulfonated polymers are anti-fouling, non-thrombogenic, and
resist the adhesion of micro-organisms. They are thus
useful for such purposes as coating heat exchargers,
artificial heart valves, ship bottoms, and screens for
~ . - - - . .
suspended solids removal. It is also possible to make
solid gels according to the teachings of this invention
which combine high water content, high physical strergth,
biocompatibility, and resistance to biocontamiration with
optical clarity, making them ideal for long-wearing contact
lenses and other devices used in eye care.
Other teachings of this invention include the treatment
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1303785
of papers and/or fabrlcs to effect either a surface
cross-linking and~or an alteratlon of the surface
properties of the paper or fabric to produce a deslrable
effect. The polymer of this invention can be used for the
purpose of altering the mechanical properties and surface
charge of a paper so as to improve its appearance, its
receptivity to an ink or its feel or "hand". The same
applies to fabrics for the purpose of improving their dye
receptivity, resistance to creasing and their hand.
One important advantage of these polymers arises
because the cross-linking process does not require the
presence of soluble catalysts or co-reactants. This is an
advantage in avoiding the stream pollution which results
from most surface treatments. The fact that a high level
of cross-linking can result without the evolution of toxic
gases is another and major advantage. Cross-linking
reactions which avoid the evolution of formaldehyde possess
major advantages, for example.
The polymers of this inventior car also be used as
barrier films in the fabrication of microclrcuit devices
and chips, where their cross-linked nature and the ease
with which adhesion is achieved is an important advantage.
Similarly these polymers are highly useful in lithography
where they can impart different levels of adsorptive or
non-adsorptive properties to surfaces.
The teachings of this invention allow, among other
things, the making of special purpose absorbents,
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1303785
part~cularly biochemical absorbents. B~ochemlcal
absorbentq are preferably hydrophilic in nature ~o as to
minimize the non-specific adsorption of proteins, although
most of the carriers commonly employed for these purposes
show an appreciable and deleterious degree of non-specific
ad~orption. Al~o, most of the useful carrier materials
cannot be formed into sheets, films, coatings or membranes
of controlled porosity in the manner in which a wide
variety of hydrophilic materials can be so formed by
post-cross-linking in accordance with the teachings of this
invention.
This invention is advantageous in many respects. First,
it allows for either a dialysis or ulfiltration system which
does not denature proteins, i.e. the active and desired pro-
tein is not lost during the purification procedure. Further,
ulfitration is a rapid technique readily suited to the remo-
val of large amounts of salts and other low molecular weight
foreign bodies from protein solutions. For proteins highly
susceptible to denaturation, a coating applied to the tubing
and cell according to the present invention will minimize or
avoid denaturation. The polymers of the invention are partic-
ularly well suited for large as well as very small scale op-
~rations. Ultrafiltration using polymers according to~~the-in-
vention can be carried out with simple equipment at high
speed.A subsequent example describes a very thin gel electro-
phoresis system suited to the analysis of very small samples.
The examples giver below consist of monomer
preparations, homopolymerizations, copolymerizations,
cross-linking of polymer films and resins, and the casting
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~30378S
and teqting of membranes. The polymerizationq given in the
examples yield polymers of approximately the qame molecular
weight and comonomer composition as those called for ln the
cross-linking and membrane examples. Where differences
occur, the polymerization procedures may readily be
modified according to principles well known to tho~e
skilled in the art. For example, molecular weight may be
increased by using less catalyst or decreased by adding an
appropriate chain-transfer agent such as isopropanol.
Since the reactivity ratios in almost all of the
copolymerizations are comparable, the comonomer composition
may be changed by appropriate adjustments in the initial
amounts of the monomers. Where molecular weights are
given, they were determined by either viscometry or gel
permeation chromatography. Where no molecular weight
standards exist, estimates were made based on the viscosity
or gel permeation volume of similar known polymers. Since
molecular weight may be varied by a factor of at least two
without altering the results, the difference between weight
and number averaging is insignificant.
- All solutions of polymers were prepared on -a
weight/volume basis, with the total solute concentration
given as percent by weight. The ratio of various solutes
to each other is given as parts by weight. Concentrations
of low molecular weight compounds are also given as mol %
relative to the monomer units making up the polymer(s) in
solution. All solvents are reagent grade, but in many
cases practical or even commercial grades may be
substituted. All water used as a solvent or reagent in the
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1303785
exameles is distilled. All ethanol used is 200 proof. The
swelling index is the ratio of the weight or volume of the resin
swollen with solvent to that when dry, a standard measurement.
All resins and membranes containing polyelectrolytes were soaked
in saturated sodium chloride after heat-curing before being put in
distilled water so as to minimize osmotic shock.
The membranes described below are all prepared using
similar, basic techniques well known to those skilled in the art.
Unless otherwise specified, all membranes described in the
examples below are cast on Hollytex 3381*, a calendered non-woven
polyester cloth (Eaton-Dikeman Co.). The casting solution is
filtered through a coarse glass frit, and any bubbles are then
removed by either centrifugation or applying a vacuum. The
viscous liquid polymer films are cast using either manually
operated knives with fixed or adjustable gate openings (available
from Gardner Laboratories) or motorized roller type units
routinely used in the paper and coatings industries (available
from Talboys Engineering Corp., Emerson N.J.).
Casting solutions completely free of any turbidity and
prepared using solvent or solvent mixtures in which the polymers
have a high or nearly maximal viscosity at a given solids content
are very much p~eferred.
Casting and/or coating can also be effected by dipping a
surface or support material into the casting solution: this method
is often preferred when a particularly thin coat or film is
desired, and allows the use of a dilute casting solution.
The pure water flux of the membranes is determined by
mounting them in a standard ultrafiltration cell (Gelman)
*Trade Mark
--~0--
` 1303785
filled with prefiltered distilled water, applying 30-100
psi nitrogen pressure, and measuring the volume permeate
per unit time. Fluxes are expressed as ~sa, or microns per
second atmosphere, and tend to be fairly independent of
applied pressure. An approximation of pore size is
obtained by measuring the percent re~ection of the red dye
erythrosin from a 15 ppm feed solution. The concentration
of the dye (MW 836) is determined photometrically.
Membranes of the R0 type are tested by applying high
pressures (400_800 psi) across the membrane and measuring
the rejection of salt via conductivity.
Membrane porosity varies according to a number of
factors which must be ~udiciously varied and controlled in
order to obtain a desired value. ~or uncoagulated
membranes the higher the solids content in the casting
solution and the wider the gate opening on the casting
knife, the more polymer deposited and the lower the flux.
Slow evaporation of the solvent and a high degree of
cross-linking produce non-porous gels with little swelling
and low flux.
The flux of coagulated membranes depends on the
fineness of the pore structure, which depends in turn on
the speed of coagulation. A highly porous support such as
Hollytex 3329 allows rapid attack on the cast film from
both sides and results in larger pores. Membranes cast on
dense supports such as Hollytex 3396, glass or "MYLAR'~ tend
to have much lower fluxes. Wetting a porous support with
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*Trade ~lark
~303785
the coagulating solvent causes some immediate coagulatlon
upon casting and hlgher ultimate ~lux. The hlgher the
temperature of the coagulatlng bath, the higher the flux,
and where coagulation is ~low, a longer reqldence time
helps ensure complete extraction of the casting solvent.
Allowing the cast film to partially dry before coagulation
results in a finer pore structure on top and lower flux.
If a coherent skin is allowed to form, a low-flux membrane
of the Loeb-Sourira~an type is obtained.
The most reliable way of controlling porosity is by
increasing or decreasing the solids content of the casting
solution. High solids films coagulate more slowly and
leave behind a denser pore structure. The higher the
molecular weight of the polymer, the lower the solids
content possible without changing the viscosity, and the
higher the potential flux. There is generally a minimum
molecular weight (MW) below which coagulation is poor and a
maximum above which the solids content must be too low to
give a coherent film structure. The polydispersity of the
polymer should not be too high or the low molecular weight
"tail" will cause anomalous coagulation. Tight
cross-linking of hydrophilic, coagulated membranes keeps
the pores from becoming excessively small due to swelling
when the membrane is put in water, and thus improves the
flux.
The examples given herin constitute orly a small
fraction of the monomers which car be polymerized to give
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1303785
materials which can be cross-linked in accordance with the
teaching~ of thls invention. For purpoqes of specific
applications, one can choose optlmal materia 1Q made from a
number of monomer~ which are either described in the
literature andJor available commercially. For example,
acrylic and methacrylic acids are available as esters or
amides having a wide range of substituents bonded to the
oxygen or nitrogen atom, respectively. These include alkyl
or aryl groups to which can be attached a wide range of
ionic and non-ionic groups. One of the important
advantages of the subject invention is that a very wide
range of compounds having a number of specific uses can be
employed as post-cross-linkable polymers, in accordance
with the sub~ect invention.
Similarly, the physical properties of the final product
can be modified by the nature of the cross-linking agent
used and the reaction employed. Cross-linking agents with
longer chains between the reactive groups generally produce
looser gels, while those with short distances between the
tow reactive sites produce materials of lower degrees of
- .. . . ., . , , ~ ~
swelling in solvents in which the non-cross-linked polymers
are soluble. One of the unique advantages of this par-
ticular invention is the fact that a bifunctional
cross-linking agent has a multiplicity of sites on the
reactive polymer wherein cross-linking can take place, and
this allows a particularly high degree of cross-linking to
be effected.
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~30378S
In the preparation of the numerous films, coatings,
membrane~ and other materials described in the sub~ect
invention,usually lt is es~ential that in the casting or
formation of a polymer solution on a surface,~h~C adequate
wetting of that surface through the drying and the final
post-cross-linking process. In order to employ the
manifold polymers and solvents useful for the purposes of
this invention, the modification of common polymers is
advantageous. For example, many aqueous solutions are not
easily cast onto a PAN support membrane of the UF variety,
so the use of a 15:1 copolymer P(AN-AMPS) or of
P(AN-MAPTAC) is advantageous.
G~OSSARY
The following abbreviations are used in the examples
given below.
DES is diethylsuccinate, El Paso Products Co.
DMAC is dimethyl acetamide, Aldrich.
DMF is dimethylformamide, Fisher.
TCE is sym. tetrachloroethane, Fisher.
THF is tetrahydrofuran, Fisher.
TMP is trimethylol propane, Celanese.
A number of monomers are listed below, designated by
the abbreviations used in the examples. Some are from the
commercial sources specified, and the remainder have their
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~30378S
preparations and phyqical properties 31ve ln the examples.
AM is acrylamide, PolyscienceQ.
AMPS is 2-acrylamido-2-methylpropane qulfonic acld,
Lubrizol Corp., Special Reaction Grade.
DMAM ls N,N-diomethylacrylamide, Polyqciences.
DNBAM is N,N-di-n-butylacrylamide, described herein.
HEA is hydroxyethyl acrylate, Pfaltz and Bauer.
HPA is hydroxypropyl acrylate, Pfaltz and Bauer.
HHAM is N-(6-hydroxyhexyl acrylamide), described
herein.
MAPTAC is methylacrylamidopropyltrimethylammonium
chloride, Texaco Chem.
NBAM is N-n-butyl acrylamide, described herein.
NBMAM is N-n-butyl methacrylamide, described herein.
NMAM is N-methyl acrylamide, Polysciences.
SEM is 2-sulfoethyl methacrylate, Dow Chem.
SPAtNa) is 3-sulfopropyl acrylate, sodium salt?
described herein.
SSA(K) is styrenesulfonic acid, K+ salt, described
hereir,.
TMEAC is trimethylaminoethylacrylate chloride,
Monomer-Polymer.
Some of the polymers employed in the practice of this
invention were prepared as described in the following
examples, and are abbreviated by preceding the monomer name
with a letter P. Others are commercially available
materials from the suppliers indicated below.
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"KYNAR" is polyvinylidene fluoride, Pennwalt Corp.,Grade 301 of MW 375,000.
PA~ is polyacrylamide, American Cyanamid, Cyanamer
P-250, MW 5,000,000, unless otherwise designated.
PAN is polyacrylonitrile, DuPont, Neutral Modified Type
A, M~ 150,000, unless otherwise designated
PSSA is polystyrenesulfonic acid, available from
National Starch and Chem. of molecular weight
70,000, and prepared as described herein.
In addition, several other commercially available
substances were employed:
AIBN is azobisisobutylnitrile, Eastman.
DNPD is N,N-di-2-naphthyl-p-phenylenediamine, Pfaltz
Bauer.
EPON 1031 is a tetrafunctioral epoxide resin~ Shell
Chem.
Molecular Sieves is a drying agent with nominal 3 or 4
Angstrom pores, Davison Division of Grace Chemical.
MSA is methanesulfonic acid, Fisher.
Witcamide 511 is an emulsifying agent, Witco Chem.
EDA is ethylenediamine, DAH is diaminohexane and DAO is
diaminooctane, Aldrich.
The invertion will now be described with reference to the
following non-limiting examples.
EXAMPLES
Example 1
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130378S
Preparation of N~N-di-(n-butyl) acrylamide (DNBAM?
In a 2 liter 3-necked flask were comblned 129 g (1 mol)
di-~n-butyl)amine (Fi~her Scientific) and 0.5 l dry toluene
and cooled to 5-C. 46 g (0.5 mol) acryloyl chloride
dissolved in 50 ml toluene were added ~lowly so the
temperature remained below 10-C. After the addltion the
flask was warmed to 25-C and the precipitate removed by
filtration. 1 g DNPD was added, and after concentration on
a rotary evaporator the product was distilled at 20 torr
and 61-63-C. Yield 77 g (84~).
Example 2
PreParation of N-(6-hydroxyhexyl acrylamide) (HHAM)
150 g 6-aminohexanol (Pfalz & Bauer) was distilled,
ground, and dried overnight under vacuum. 1 liter dry THF
was added at 40-C and the solution cooled to 10C, causing
partial precipitation. 52 ml (57.9 g) acryloyl chloride
was dripped in with stirring at 10-15C over a period of
2.5 hours, with 200 ml additional THF added after 2 hours.
- The whit~e precipit-ate of aminohexanol hydrochloride
formed was filtered, washed with 100 ml THF and then
stirred with 300 ml THF. The latter portion of THF was
filtered, treated with 5 grams silica gel, and refiltered
into the main portion of the solution. Then 1 g
hydroquinone was added and the THF solutior evaporated
under vacuum to an oil. Recrystallization from 500 ml
ethyl acetate yielded 79.4 g of a white crystalline
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product. The mother liquor was evaporated and
recrystallized from 75 ml ethyl acetate to yleld an
additional 4.0 g of product, m.p. 57.5-58.5-C.
Example 3
Preparation of N-n-butyl acrylamide (NBAM)
146 g of n-butylamine (dried over 4 A Molecular Sieves)
was dissolved in 1 liter of toluene (dried over calcium
hydride) in a 2 liter 3-necked flask equipped with an
ice-acetone bath, a mechanical stirrer, a thermometer and a
dropping funnel. The solution was stirred and cooled to
0C. 90.5 g distilled acryloyl chloride dissolved in 100
ml dry toluene was added slowly so that the temperature did
not go above 10C. After addition, the solution was
allowed to come to room temperature and was then filtered
through medium porosity filter paper. Then 1.5 g of the
non-volatile inhibitor DNPD was added and the solution
concentrated on a rotary evaporator. Distillation at 0.05
torr and 85C yielded 115 g, a yield of 90.5%.
.
Example 4
Preparation of N-n-butyl methacrylamide (NBMAM)
In a 1 liter 3-necked flask were combined 400 ml dry
THF and 40 ml distilled n-butylamine (0.405 mol). After
coolirg to 5C in an ice bath, 20 ml (0.205 mol)
methacryloyl chloride was added slowly so as to keep the
temperature below 10~C. The precipitate was removed by
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filtration, and the filtrate concentrated on a rotary
evaporator. 1 g DNPD wa~ added and the oil dictilled at
76_78-C and 20 torr. Yield 24.3 g (84%)
Example 5
Preparation of 3-sulfoPropyl acrylate, Na ,~alt
(SPA(Na))
19 g sodium acrylate, 7.5 g acrylic acid, 60 ml
tert-butanol, and 0.1 g p-methoxyphenol were heated to
reflux in 500 ml 3-neck flask. 25 g propanesultone
(Aldrich) was added dropwise over a period of 2 hours, with
more tert-butanol added as needed to maintain stirring.
The precipitate was collected by filtration and vacuum
dried to yield 40 g product.
Example 6
Preparation of styrene sulfonate, K salt SSA(K)
In a 3 liter 4-necked flask were combined 372 g (2.0
molj 2-bromoethyl benzene (RSA Corp) and 135Q ml
1,2-dichloroethane, both having been dried over 4 A
Molecular Sieves. The flask was warmed to 60-C and flushed
with nitrogen. 240 g (2.07 mol) chlorosulfonic acid
(Eastman) dissolved in 150 ml 1,2-dichloroethane was added
dropwise with rapid stirring. Stirring was continued at
60C until no additional hydrogen chloride was evolved. A
partial vacuum was applied to remove residual HCl, and the
flask was chilled to 10C. A chilled solution of 135 g KOH
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~30~785
in 750 ml distilled water was added, and the flask cooledto O-C. The precipitate wa~ collected u~ing a Puchner
funnel cooled wi.th ice water, and then dried under vacuum
to yield 440 g crude product. This was dissolved in a
solution of 95 g 86% aqueous KOH and 750 ml distilled
water, warmed to 65-C, and filtered though a heated Buchner
funnel. The filtrate was cooled slowly to 5C, and the
precipitate was collected and dried as before. Yield 300 g
(67~).
Example 7
Preparation of_ Poly(2-acrylamido-2-methylPropane
sulfonic acid) (PAMPS)
50 g of AMPS was dissolved in 100 ml of distilled water
and then purged 30 minutes with nitroger. at ambient
temperature. 3.2 mg potassium peroxydisulfate dissolved ir.
1 ml water was added, purging continued for 10 minutes, and
the container sealed and allowed to stand at 40C for 16
hours. The polymer was isolated by diluting to less than
1Q~ solids and. freeze-drying. ._
Example 8
Preparation of Poly(methacrylamidopropyltrimethyl-
ammonium chloride) (PMAPTAC)
Here, 100 g of a 50% (w/w) solutior of MAPTAC ir water
was warmed with 2 g activated charcoal, stirred and
filtered. The solutior. was purged with ritroger for 15 mir
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~303785
and warmed to 40-C under nltrogen. A solution of 100 mg
ammonium peroxydisulfate in 1 ml water was added, followed
by a solution of 10 mg sodium metabisulfite in 1 ml water.
The solution was stirred at 40-C under nitrogen until its
viscosity increased significantly, and then covered and set
in an oven at 60-C for 1 hour. The polymer was isolated by
drying in a vacuum oven or diluting to 500 ml with water
and freeze-drying. Its intrinsic viscosity was 769 ml/g
for a 0.1% solution in water at 25C.
Example 9
Preparation of Poly(N-n-butyl acrylamide) and Poly(N-n-
butyl methacrylamide) (PNBAM ard PNBMAM)
Distilled NBAM was extracted with 0.1 N sulfuric acid,
washed with saturated sodium sulfate, dried over anhydrous
sodium sulfate and filtered. Then 40 g was combined with
80 ml degassed, distilled water and 1.2 g sodium lauryl
sulfate to yield a mixture of pH 4Ø The mixture was
heated to 40C with stirring and nitrogen was bubbled
through - for- ~Q min-utes. Then 50 mg of ammonium
peroxydisulfate was added dissolved in 1 ml water. A
latex formed within 10 minutes and polymerization was
continued overnight. Ethanol was added to the latex to
coagulate the polymer, which was then dissolved in 500 ml
ethanol, precipitated into distilled water in a blender>
and dried overnight under high vacuum to yield 32.2 g
polymer.
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The polymerization of NBMAM proceedq exactly the same
way, with the n-butyl methacrylamide monomer subqtltuted
and the reactior, run at 50-C.
Example 10
P tion of Pol (N N-di-n-but lacr lamide) (PDNBAM)
repara y , _ Y Y
g of DNBAM monomer were combined with 375 ml
distilled water, 8 g sodium lauryl sulfate, and 100 mg
ammonium peroxydisulfate and the pH adjusted to 4.0 wi.th
phosphoric acid. It was stirred with r.itrogen bubbling
though at 60C for 18 hours. The polymer was coagulated
with methanol and blended with water to remove detergert
and harden the polymer. It was dried under vacuum. Yield,
64g.
Example 11
Preparation of Poly(2-sulfoethyl methacrylate) (PSEM)
A 30% solution in water of the SEM monomer was purged
with nitrogen bubblir.g, then polymerized with the additior.
Of 0.2% w/w (relative to the monomer) of ammonium
peroxydisulfate at 50-C for 16 hours. The solution was
passed though a weak base ion-exchange column (Rohm & Haas
IRA 60) to remove residual monomer and then freeze-dried.
The molecular weight was estimated at 100,000 by
viscometric comparisor with similar, knowr polymers.
Example 12
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Preparation of Poly(3-sulfopropyl acrylate) (PSPA)
To 20 ml water purged with nitrogen was added 10 g
SPA(Na) with stirring. The solution was warmed to 50-C,
1.0 mg ammonium peroxydisulfate was added, and the solution
left covered in a 50-C oven overnight. The solutlon was
diluted to 5% solids, freeze-dried, re-dissolved to 5%
solids in water, and acidified by passage through a strong
acid ion-exchange column ("Amberlite 200n, Rohm & Haas).
The polymer was recovered by freeze-drying-the diluted
solution.
Example 13
Preparation of Poly(styrene sulfonic acid) (PSSA)
In a 500 ml 3-necked flask were combined 1~0 g xylene,
20 g Witcamide 511 and 40 mg AIBN, and warmed to 55-C under
nitrogen. Stirring was maintained at 450 rpm using a
stirring blade which largely filled the flask. The monomer
charge of 30 g potassium styrene sulfonate in 90 ml water
was added dropwise (0.5 ml/min), ard the reaction cortinued
for 72 hours. The emulsion was broken by pouring into 1
liter of acetone. The precipitate was removed, blended
with 1 liter acetone, filtered and dried, yielding 31.6 g.
This was dissolved in 600 ml water and precipitated into
1.3 liters absolute ethanol in a blender. The supernatant
solvent was discarded and replaced by 1.5 liters absolute
etharol, which was blended until a finely divided material
was obtained. This was filtered and dried yielding 21 g.
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~303785
Its MW was determined to be about 2 millior by comparison
with sulfonated polystyrene standard~ uAing gel permeation
chromatography. The polymer was di~solved in water to 5%
solids, converted to the acid on a strong acid ion exchange
column tAmerlite 200, Rohm ~ Haas) and then freeze-dried.
Example 14
Preparation of Poly(trimethylaminoethylacrylate
chloride) (PTMEAC)
20 g of a 40% aqueous solution of TMEAC was treated
with 1 g activated charcoal for 20 minutes and filtered.
The filtrate was purged with nitrogen, 5 mg ammonium
peroxydisulfate was added, and the solution was left
overnight at 50-C. The polymer was precipitated with
acetone, filtered, and dried, yielding 6 g (75%).
Example 15
Preparation of P(AMPS-HHAM), 9:1 Copolymer
67.5 g AMPS, 6.14 g HHAM, and 300 ml water were
combired..ir. a 5~00 mi res~ri kettle fitted with a heating
mantle, cooling coil, thermometer, overhead stirrer and
fritted gas bubbler. Nitrogen was bubbled through the
solution for one hour while the temperature was maintained
at 58C. Then, 35 mg ammonium peroxydisulfate and 15 mg
sodi.um metabisulfite were each dissolved in 6 ml of
degassed distilled water, and 2 ml of the peroxydisulfate
solution was added to the kettle followed by 2 ml of the
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metabi~ulfite solution. The add~tion of 2 ml aliquots waArepeated after 1.5 minutes and 5.5 minutes while the
temperature was maintained as near 58-C as possible.
After 1 hour, 300 ml distilled water was added and the
viscou~ solution freeze-dried at _20-C. The resulting
polymer had an inherent viscosity of 227 ml/g when measured
as a 0.5% solution ir 3~ NaCl.
Example 16
Preparation of PtNBAM-HEA), 9:1 Copolymer
For a 10 mol% copolymer, the inhibitor in the ~EA
monomer was removed by dissolving 1.79 g (0.0154 mol) of
HEA in 13 ml water and treatment with activated charcoal
followed by filtration. This was combined with 40 ml
methanol, 17.67 g NBAM (0.139 mol) and 90 mg AIBN. The
polymer was isolated by additor of water in a blender
followed by filtration and drying under vacuum at 45-C.
The yield was 17.2 g (88%).
Example 17
Preparation of P(AMPS-SSA)~ 1:1 Copolymer
22 g of the sodium salt of AMPS and 24 g of SSA(K)
(Fluka) were combined with 80 g water and purged with
nitrogen at 40C. 3 mg ammonium peroxydisulfate was added
and purging was continued until the start of
polymerizatior. The container was covered and left at 40C
for 18 hours. Gel permeation chromatography revealed
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~30;~785
con~iderable monomer remaining. The solution waq thus
dialyzed against distilled water and the polymer isolated
by freeze-drying. Yield 38 g.
Example 18
Preparation of P(SSA-HEA), 4:1 CoPolymer
In a 500 ml 3-necked flask were combined 130 g xylene
and 13 g Witcamide 511 with 15 mg AIBN and then stirred at
50~C under nitrogen. An aqueous phase was prepared by
combining 21.5 g potassium styrene sulfonate, 65 ml water
and 2.8 g HEA with charcoal and filtering. This was added
dropwise (about 0.5 ml/minute) to the xylene phase with
stirring at 450-500 rpm. After 48 hrs the polymer was
isolated by pouring into 1 liter absolute ethanol in a
blender, decanting the solvent and reblending with 700 ml
ethanol. The yield was 15.4 g. Gel permeation
chromatography showed the MW to be about 900,000.
Example 19
Freparation of -PAM, PNMAM,- PDMAM; Cros-sIinkirg o-f PAM- -~
with Glycerol from Water
To prepare PAM of MW 1,000,000, 100g of AM, 2.5 ml of 2
propanol (less or none give a higher MW, more a lower MW),
water to 750 ml total, ther purged with nitrogen gas. A
solution of 50 mg of ammonium peroxydisulfate in 1 ml of
purged water w~s followed by 25 mg of sodium metabisulfite
in 1 ml purged water, then the solution under nitrogen was
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~303785
stirred anlkept in a water bath at 25-C. As the reactior
proceeded the temperature rose to 34-C even with bath
cooling, and it proceeded for 3 hours. Then water was
added, the viscous solution stirred well and finally
freeze-dried, mixed with 3 liters of methanol in a blender,
filtered and dried.
PNMAM and PDMAM were prepared by identical procedures
except that with increasing substitition a somewhat higher
temperature was needed to maintain miscibility and no 2
propanol was added. The reaction was carried out at 50C
for 16 hours under nitrogen, and the product recovered by
dilution with an excess of water followed by freeze-drying.
PAM is readily soluble in water, ethylene glycol and
glycerol. With increas~ng substitution of methyl groups on
the nitrogen, the polymer becomes soluble in many polar
organic solvents (DMF, phenol:TCE, ethanol) and can be
coagulated by organic~olvents as by diethylether.
To a 5% solution of 5,000,000 MW PAM in water was added
2.5 mol 5 of glycerol. The clear solution was dried in an
aluminum dish at 60C and then cured for 3 hours at 140~C.
After soaking in water at 80C for several hours the gel
swelled slightly and was quite firm. When the preparation
was repeated with 10 mol % glycerol, a hard, slippery gel
was formed. When 50 mol % glycerol ard 50 mol % MSA were
used, the resulting gel appeared ro different from the one
made with 10 mol % glycerol alone.
PAM, PNMAM, and PDMAM could all be cross-linked by the
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13037~5
same reactions as the other non-ionic substituted
acrylamides. Films or membranes cast from PAM appeared to
be the most hydrophilic, from PNMAM only slightly less
hydrophilic and from PDMAM somewhat less hydrophilic, but
all were strongly hydrophilic as contrasted wlth most
polymers containing alcohol or amino groups on most links.
Example 20
Cross-linking of PNBAM and PNBMAM from Ethanol
1.50 g PNBAM was dissolved in a solution with 0.11 ml
glycerol and 0.34 ml MSA in 28.5 ml absolute ethanol. The
viscous solution was poured to a thickness of 1 mm on an
aluminum sheet, dried 30 min at 60~C, and then cured 3
hours at 140-C. The film was soaked in ethanol for a week;
its weight swelling index was 4.5 in that solvent.
In a second experiment, 1.50 g PNBMAM was dissolved in
a solution of 0.12 ml glycerol and o.38 ml MSA in 13.5 ml
ethanol. The solution was dried and cured as above, giving
a fi-lm-with a weight~sw~l~ ng index of 4.5 in ethanol.
In a third experiment, three solutions of PNBAM were
prepared, each 8~ in ethanol. The first contained no
cross-linking agents, the second contained 3 mol ~ each of
glycerol ard MSA, and the third contained 20 mol % each of
glycerol and MSA. Each solution was cast at a thinkness of
7 mils on a film of carboxymethylcellulose laid over glass,
dried at 60C, and cured at 140C for three hours. After
soaking in distilled water for rine days the water contents
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by weight were determined: uncro~s-linked,12.9%; 3%
cross-linked, 12.5%; 20% cross-linked,30~ water content.
Example 21
Crocs-linking of PDNBAM; Comparison with PNBAM
To a 5% solution of PDNBAM in 1:1 phenol:TCE was added
40 mol ~ each of MSA and glycerol. A similar solution was
prepared of PNBAM. Each clear solution was poured into an
alumi.num di.sh, dried at 60C and cured 3 hours at 14-C.
When 1:1 phenol:TCE solvent was added and the gels stirred
overnight at 50C, neither polymer di.ssolved. A coherent
and strong film structure was observed with PNBAM, while
PDNBAM swelled much more and had a loose, gel-like
structure.
Example 22
Cross-linking of PAMPS with Glycerol from Ethanol
To a solution of 10 g of PAMPS (MW 1,000,000) in 90 ml
ethanol was added ~Ø8~ ~g glycerol~ (20. mole .%). The
solution was cast at a thickness of 6 mils onto a glass
plate, dried at 60C and then cured 3 hours at 150-C.
After soaking briefly in saturated sodium sulfate, the film
was soaked overnight in distilled water. The resin was
firm and highly hydrophilic and swelled so little it did
not lift of the plate unless peeled off. Its swellirg
index was 3.1. When glycerol was omitted from the reaction
mixture, the cured film dissolved completely, showing no
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~30~7~
cross-llnking.
Example 23
Cros~-linking of PAMPS with Diols from DMF
To 5% solutions of PAMPS in DMF were added 50 mol~ of
either 1,3-butanediol or 1,4-butanediol, together with 50
mol % MSA. The soluti.ons were dried at 60~C in aluminum
dishes, and then cured at 140-C for 3 hours. Water was
added and the dishes heated at 60-C for 4 hours with
stirring. In both cases the gels were insoluble, coherent
films that appeared as firm as when corresponding amounts
of glycerol were used, with swelling indices of 3.0 and 3.1
for the 1,3 and 1,4 diols.
-
Example 24
Cross-linking of P(AMPS-HHAM) from Water
A 200 mg sample of P~ANPS-HHAM) copolymer of 90:10 mol~
composition was di.ssolved in 2 ml distilled water, dried at
~- 60-C and then heated 1.5 hours at 150C. After soaking in
= . = . . , _ .
saturated sodium sulfate and ther. in water, a cross-l-inked-
resin was obtained with a volumetric swelling index in
water of 5Ø The same procedure was repeated except that
curing for 2 hours at 145C was used. The swelling index
was then 4.7.
Example 25
Cross-linkin of P(AMPS-HHAM) blended with PAN from
g
_40-
~a3~
DMAC
A copolymer of 85 mol S AMPS and 15 mol % HHAM was
dissolved in DMAC to 10% ~olids content. To five parts of
this solution were added one part of a 10% solution in DMAC
of PAN. The final solution was cast at 6 mils onto glass.
After drying 30 minutes at 60-C the film was cured 3 hours
at 125-C. After soaking in saturated sodium sulfate, the
film was soaked in distilled water. Its lateral swelli,ng
was 12.5% and its volumetric swelling index 2.3.
The preceding experiment was performed in the same
manner except that a copolymer 20 mol % in HHAM was used.
The resulting cross-linked film showed a lateral swelling
of 6~ and a volumetric swelling index of 2.1.
Example 26
Cross-linking of PSPA with Glycerol and MSA and MSA
from Water
A 2% solutior of PSPA (MW about 1,000,0C0) was prepared
in~waer.- ~hen-samples--of this solution were dried at 90C
and cured at 140-C for 3 hours, the polymer remained fully
soluble in water. When 50 mol % MSA was added, the polymer
again did not cross-link, but when 50 mol ~ MSA plus 50
mol% glycerol were added, the cured polymer was a hard
coherent solid which softened slightly in hot water but did
not swell perceptibly.
Example 27
_41-
Cross-linking of PSEM with Glycerol and MSA from
Ethanol
A 10% ethanolic solution of PSEM was prepared
containing 50 mol % each of glycerol and MSA. After drying
at 60-C and curing 3 hours at 140-C, a weakly cross-linked
gel resulted. If the glycerol was omitted the cured
polymer dissolved in ethanol.
Example 28
Cross-linking of PTMEAC with Glycerol and MSA from
Phenol: TCE; Non-cross-linking of PMAPTAC under
similar similar conditions
To 10 ml of a 5% solution of PTMEAC in water was added
100 mol % of glycerol and 100 mol % of MSA. Drying and
then curing at 140C for 3 hrs yielded a resin showing
little swelling in water. The positive charge on this
acrylate side chain apparently did not inhibit
cross-linking.
Two 5~ solutions were Frepared-of PMAPTAC in ethanol at
room temperature and in 1:1 phenol:TCE at 75~C. To each
was added 50 mol % glycerol and 50 mol % MSA. These
solutions were each poured into aluminum dishes, dried at
60~C and cured at 140~C for 3 hours. Water, ethanol, and
the 1:1 solvent were each added to different samples of the
cured resins. In each case the polymer dissolved quickly.
It is presumed that the positive charge on the side chains
of this N-substituted acrylamide inhibited the
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~303785
cross-linking reaction as discussed above.
Example 29
Cro s-linking of P(SSA-HEA)
A 1% aqueous solution was prepared of a copolymer with
mole ratio 4:1 of SSA:HEA and molecular weight about 1
million. The solution was divided into three parts. To
the first part nothing was added. To the second was added
0.5 mole MSA per mole HEA monomer, and to the third was
added 0.5 mole MSA and 0.5 mole glycerol per mole HEA. The
samples were poured into aluminum dishes, dried, and cured
at 140-C for 3 hours. Water was then added to the dishes
and they were heated to 60-C. The untreated copolymer
swelled to form a weak gel, but would not dissolve. The
copolymer treated with MSA formed a somewhat harder gel.
The copolymer treated with MSA and glycerol formed a very
hard gel that did not appear to swell significantly.
Example 30
= . . .
Cross-linking of PAM with Diamines from Water
The crosslinking of PAM of MW 5,000,000 was effected as
follows. A 2~ solution of this polymer in water was made.
To it was added a 28 weight ~ solution of each of three
diamines in an amount equal to 25 mole % of the PAM (based
upon monomeric units). The three amines were EDA, DAH and
DA0. The solutiors remained entirely clear after combinin6
the diamines with the polymer. The samples were poured
-43-
lnto aluminum di~hes to a depth of about 2 mm and dried for
6 hours at 70-C to remove moisture, then cured for 3 hourQ
at 140-C. The swelling indices were 2.2 with EDA, 4.3 with
DAH and 4.8 with DA0. Hydrazine may also be employed for
cross-linking and makeQ extremely ~hort cro~s-links with
advantages where very low swelling is desired.
Example 31
Crosslinking of PAM with EDA and MSA from Water
25 mole% each (based on PAM) of EDA and MSA were added
as 20 wt% aqueous solutions to a 3% aqueous solution of
5X106 MW PAM. The sample was poured to a depth of about 2
mm in an aluminum dish, dried 6 hours at 70C and then
cured 3 hours at 140-C. The sample was cooled and water
added. The resin swelled to form a coherent film with a
swelling index of 5.5. When the experiment was repeated
with 50 mole% MSA added rather than 25~, again a coherent
film structure was obtained with a swelling index of 4.5.
, -- . . .......... . . . _
Example 32
Cross-linking of PMAPTAC with Diamines from Water
The crosslinking of PMAPTAC having an approximate
molecular weight of 5Xl06 in a 5% aqueous solution was
carried out as follows. A 20~ solution of each of three
diamines, namely EDA, DA~ and DA0 were added to the polymer
solution ir an amount equal to 25 mole ~ of the PMAPTAC
units to form a clear solution. These were poured into
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i303785
aluminum disheq to a depth of about 2 mm, dried for 6 hoursat 70-C and then cured for 3 hour~ at 140-C. The EDA
crosslinked resin~ were the most hard and firm, with the
swelling increasing slightly with increasing methylene
chain length of the diamineY. Swelling indices were as
follows: with EDA, 3.0; with DAH, 3.4; with DA0, 3.5.
Example 33
Cross-linking of Polyesters with Diamines from Toluene
Poly(methylacrylate) (PMA) was a 25% solids solution in
toluene. Some was poured to a depth of about 3 mm in an
aluminum dish.
To another portion of this PMA so'lution was added 35
mole~ of EDA as a 20% solution in DMF, one which was
miscible with 'the PMA solution. This was similarly poured
into an aluminum dish. To a third portion of PMA solution
was added 35 mole~ EDA and 35 mole% MSA, both in DMF and as
a 20% solution. An insoluble salt formed immediately, and
since one phase was not attainable, the sample was
discarded~'.
The two aluminum dishes containing the polyester
samples were dried overnight at 70C and then cured at
140C for three hours. Toluene was added to the two
dishes, they were then heated to 60C and magnetically
stirred. The PMA sample by itself dissolved completely.
The PMA plus EDA sample formed a semi-hard gel with a
swelling index in toluene (wet weight of resin divided by
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its dry weight) of 4.9.
Example 34
Cross-llnking of P(AN-HPA) with EDA from DMF
Two polymers were compared, P(AN-HPA) of 100,000 MW, 95
mole% AN and 5 mole% HPA, and PAN. Each polymer was
dissolved separately to 14% solids in DMF, then poured to a
depth of about 3 mm in an aluminum dish. A third solution
was made by adding 35 mole~ EDA (based on the HPA content)
to an appropriate amount of this copolymer solution, and
was poured into an aluminum dish. The three dishes were
dried at 70C for 5 hours and then cured at 140-C for 3
hours.
Excess DMF was added to each dish, they were heated
to 60'C and magnetically stirred for several hours. The
PAN homopolymer dissolved completely. The P(AN-HPA)
copolymer alone swelled to form a soft, gelatinous material
with a swelling index in DMF of 8.3, and that with added
EDA maintained a firm, coherent film structure with a
swelling index of 3.~-- in DMF. -Thus, -the- use of EDA
substantially increased the degree of crosslinking. The
P(AN-HPA) copolymer itself was able to crosslink presumably
some because of the hydroxyl groups reacted with the
oxycarbonyl group of the HPA.
Example 35
Attempted Cross-linking of PAMPS _with Diamines from
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Water
25 mole% each of EDA, DAH and DA0 were added (a~ 20 wt%
aqueous solution) to three different 5% solutions in water
of 3x106 MW PAMPS. The EDA-PAMPS sample precipitated
immediately; DA0 and DAH-PAMPS became turbid after a minute
of stirring, but no precipitate formed. The three samples
were each poured to a depth of about 2 mm in aluminum
dishes, dried 6 hours at 70-C and then cured for 3 hours at
140-C. Swelling indices in water were: EDA-PAMPS, fluid
gel, 30; DA0-PAMPS, weak gel, 15; DAH-PAMPS, weak gel, 10.
The high degree of swelling and poor mechanical properties
of these resins was due, in all probability, to ionic
precipitation of polymer by protonated amine of opposite
charge.
Example 36
Attempted Cross-linking of NaPAMPS with EDA with Water
When to 10% aqueous solution of the sodium form of
PAMPS was added 25 mole% of EDA as a 20% solution, the
solution was clear and was~poured to a depth of about~ 2 mm~ --- -
in an aluminum dish, dried for 6 hours at 70-C, then cured
for 3 hours at 140-C. A very soft gel resulted which
fragmented and had a swelling index greater than 50.
ExamPle 37
Attempted Cross-linking of PMAPTAC with EDA and MSA
from Water
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Attempts were also made to crosslink PMAPTAC present ln
a 5% aqueous solution by the addition of 20% aqueous
solutions in an amount equal to 25 mole~ based on MAPTAC
units of EDA and also of MSA, each. Clear solutions were
obtained and were poured to a depth of about 2 mm in an
aluminum dish and dried for 6 hours at 70 DC and then cured
for 3 hours at 140-C. The samples were cooled and water
was added. In each case a loose gel formed with a swelling
index of 20. When the experiment was repeated with 50
mole~ MSA as the only change, the polymer dissolved and it
appeared that no crosslinking took place. It was
postulated that the excess of acid made the crosslinking
reagent positive in charge so it was repelled by the
positive polymer and no crosslinking took place.
Example 38
PAMPS PAN Thin film Com osite R0 Membrane
on _ p
A 9% solution of PAN was prepared by heating and
stirring the poiymer in DMF at 60~C for several hours.
After cooling to room temperature, the clear solution was
cast onto Hollytex 3329 using a Gardner knife at 7 mils.
The film was immersed in water for 10 minutes to coagulate
it, then dried at room temperature. Its initial water flux
was 150 ~sa at 50 psi.
A 7% solution in methanol of 1.0 parts of 5 million MW
PAMPS and 0.13 parts glycerol was cast 7 mils thick onto
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the PAN support membrane, dried at 60-C and cured at 140-C
for 3 hours. The membrane gave a flux of 0.22 ~sa with 76%
salt re~ection when subjected to a feed solution of 0.02 N
KCl at 400 psi.
Example 39
PNBAM on PAN Thin-film Composite R0 Membrane
A 10~ solution of PNBAM in DMF containing 10 mol % each
of glycerol and MSA was cast at 8 mils on a PAN support
membrane of 1000 ~sa pure water flux. The film was
air-dried for 10 minutes, oven-dried at 60-C for 3 hours,
then cured at 140-C for 5 hours. The membrane was soaked
in distilled water 24 hours, then mounted in an R0 test
cell (Gelman) with a 3000 mg/l NaCl feed solution. At 200
psi the initial flux was 0.35 ~sa with 87~ rejection, at
400 psi it was 0.14 ~sa at 92% rejection, and at 500 psi it
was 0.1 ~sa at 97% rejection.
Example 40
Polyacrylamide UF-Mem~rane
A 5% solution of PAM in water was prepared by adding
the polymer granules slowly to a blender containing the
water and blending at high speed until the solutior just
began to boil (about 15 min). The blending reduced the
inherent viscosity from 3000 ml/g to 2600 ml/g, measured at
25~C at 0.005% in water. 50 mol~ glycerol was added to the
blended 5% solution, and it was cast at a thickness of 8
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mils on base-treated Hollytex 3396 (~oaked 3 days in 3N
NaOH). The fil~ was dried at 90~C and cured 3 hours at
140-C, giving an initial water flux of 340 ~sa at 45 p~i.
When 50 mol % pentaerythritol was substituted for the
glycerol, the same flux was observed.
Example 41
PAMPS UF Membrane Coagulated in DES
A 3% solution of PAMPS (5 million MW) in 1:1 phenol:TCE
was divided into four parts, and 5, 10, 25, and 50 mol %
each of glycerol and MSA were added. After casting at 8
mils onto either dense (3396) or medium porosity (3381)
Hollytex, coagulating for 2 minutes in room temperature
DES, drying and curing for 3 hours at 140aC, followed by
soaking in water, the membrane layers adhered strongly to
the support and could not easily be rubbed off. All of the
membranes were hard, smooth and strongly hydrophilic.
Differer.t mol % cross-linking gave the following pure
water fluxes (in ~sa): on Hollytex 3381, 5% gave 482, 10%
gave 500, 25% gave-5-80, and _50- gave-675 llsa-. -On Hollytex
3396, 5% gave 58, 10% gave 58, 25% gave 195, and 50% gave
385 ~sa.
Example 42
PAMPS/Kynar UF Membrane Coagulated in DES
A solution 10~ solids in DMAC was prepared consi.sting
of 5 parts PAMPS (1 million MW), 1 part Kynar and 0.45 part
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Epon 1031. It was cast at 7 mils onto Hollytex dampenedslightly with DES, then immersed in DES at 80-C for 20
ceconds to coagulate the PAMPS, then dried and cured at
140-C for 3 hours. The membrane had a flux of 1.5 ~sa with
93% dye re~ection at 100 psi.
Example 43
P(AMPS_HHAM)~Kynar UF Membrane Coagulated in DES
The same procedure as Example 42 was followed except
that the casting solution was 10% in DMAC and consisted of
parts P(AMPS-HHAM) copolymer (9:1 mole ratio, 1 million
MW) and 1 part Kynar. DES was used for coagulation and the
flux was 2.1 ~sa with 90% dye rejection at 100 psi. This
membrane showed poor stability in base and disintegrated
fairly rapidly in a pH 11 buffer. It is postulated that
the hydroxyhexyl groups on the polymer reacted with the
diethyl succinate coagulation solvent during curing to
yield exposed ester linkages that were easily hydrolyzed.
EXam~-le 44
_, . _
P(NBAM-HEA)/PSSA UF Membrane Coagulated in DES
A 6% casting solution in DME consisting of 3.25 parts
PSSA of 1 million MW, 1 part P(NBAM-HEA) of 300,000 MW and
a 9:1 mole ratio, 0.3 parts glycerol and 0.19 part MSA was
cast at 7 mils, coagulated for 2 min in DES at 25C, and
then dried and cured at 140C for three hours. This
membrane had a flux of 30 ~sa at 50 psi.
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Example 45
P(SSA_AMPS)/PNBAN UF Membrane Coagulated in DES
A solution in DMF having a total solute concentratior
of 4.5% was prepared by combining 0.8 part of P(SSA-AMPS)
(M~ about 250,000; contained 50 mol % AMPS), 1 part of
PNBAM having an intrinsic viscosity of 65 ml~g in DMF at
25-C, 0.36 part glycerol and 0.38 part MSA. This solution
was cast at 5 mils onto Hollytex 3396 and then immediately
immersed into DES for two minutes. The membrane was then
heated in a 140-C oven containing vapors of DES for 20
minutes, and then cured by heating in a dry oven for three
hours at 140C. After soaking for 10 minutes in brine, the
membrane was washed in water and found to have a water flux
of 200 ~sa.
Example 46
Ultrafiltration of Primary Sewage Effluent
A comparison was made of three membranes used for the
UF of primary sewage effluent at 50 psi. The first (A) was
a commercially available polysulfone UF membrane made by
Osmonics, Inc. (SEPA 20* KPS). Membrane B was cast from a
solution composed of 2 parts PMAPTAC, 1 part PNBAM, 0.36
parts glycerol and 0.15 parts MSA, all made up to 3.2~
solids in 1:1 phenol:TCE, coagulated in DES, and dried and
cured 3 hours at 140-C. Membrane C was ider.tical to B
except for the use of 1 part glycerol and 0.19 part MSA in
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the casting solution, the total solids being 3.7%. The
membranes were mounted in rectangular cells with an
effective area of 12 square inches and a cross-flow of 100
cm/sec across the membrane surface. After more than 100
days of constant ultrafiltration of primary effluent from
the Wards Island (New York City) plant, the fluxes of the
three membranes at 50 psi were: A, 1.0 ~sa; B, 2.8 ~sa; C,
3.2 ~sa. The chemical oxygen demand (COD) of the primary
sewage feed was 1100 mg/l; that of the permeates averaged
only 88 mg/l.
Example 47
Surface Treatment of Reverse Osmosis (RO) Membranes
RO membranes of those types which will withstand the
thermal treatment required for the cross-linking reaction
can be rendered hydrophilic. One class of such RO
membranes is those prepared from the polymer
polybenzimidazole(PsI)(U.S.Patent 3~699?308, October 17,
1972). These membranes have a high thermal stability.
Further, often they are annealed by treatment with an
organic liquid which can be ethylene glycol and other
diols.
A sample of a PBI RO membrane was treated with two
solutions by the dip-coating method. The first consisted
of a 5,000,000 MW PAM containing 20 mol % EDA (based on
PAM units), at a concentration of 0.75% in total solids in
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ethylene glycol. The second casting qolution was a 1%~olution of PAMPS of MW 5,000,000 dissolved in the same
solvent, with 20 mol % glycerol added as cro~s-linking
agent.
The dry PBI membrane was dip-coated by each of the two
casting qolutions, with excess solution allowed to run
off. The membrane was first dried at 90-C for 4 hours at
which point both membranes appeared quite dry. Following
this, the membranes where heat-cured for 3 hours at 140-C.
The PBI membrane was kept under tension on a glass plate
during the casting, drying and curing processes and it did
not become deformed as a result of thetreatment. Following
the cure, the membranes were each immersed into distilled
water and the surface examined. In both cases, a thin but
coherent , highly hydrophilic coating was observed on each
coated surface, one which did not become discolored by
treatment with a test fouling solution, diluted blackstrap
molasses.
Example 48
Preparation of Electrodia~ysis (ED) Membranes
ED membranes of low cost suitable for applications
which include the use of ED to obtain electrical energy
from the mixing of salt solutions of different
concentrations, could be prepared by this
invention. It is known that the mixing of concentrated and
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dilute solution~ of common ~alts, such as mixing river
water with sea water or mixing concentrated brines wlth sea
water, can be employed in a membrane-type battery to
produce electric power. Since the diffusive processes
w~ich control the rate of this power generating system are
relatively slow, it is critical that thin membranes of low
cost be available. A particularly useful embodiment of
this concept can be made by the use of a support material
of high porosity but calendered on both sides. A porous
calendered spun-bonded polyester can serve for this
purpose, as well as can other support materials of other
compositions. For this ED applicatior, a PAMPS
composition identical to that of example 22 is applied to
one side- of the support sheet and then dried, following
which the opposite side of the support sheet is treated
with a PMAPTAC composition with EDA of the kind shown in
example 33, and then dried. Following this, both sides can
be simultaneously cured to form a porous support matrix
with a cation-permeable membrane on one face and an
-- ,. . . . . .
anion-permeable of strong ~base character on the opposite
face.
In the device itself, these membranes are separated by
conventional netted plastic spacers of a kind used in
conventional ED equipment, with the dilute salt solution of
higher ohmic resistance passing through the interior of the
support sheet and the concentrated salt solutior ~assing
though the netted plastic material which separates one
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sheet from the next. The sheets are oriented so that thediffusion of ions results in the generation of a potential
which gives rise to a current across the stack, from whence
electrical energy can be derived from electrodes on
opposite ends of the stack. A prime advantage of this
system is its low cost and geometry which takes advantage
of the different ohmic resistances of the two salt
solution~. A low device cost is the principal factor in the
commercial utilization of this kind of system for power
generation.
Example 49
Preparation and Use of Bipolar Ion-exchange
Membranes
Bipolar ion-exchange membranes are ones which are
cation-permeable on one side and anion-permeable on the
other, with the two halves ~oined together so the
resistance of the bipolar membrane is as low as possible
and the two halves are chemically cross-linked together.
Bipolar membranes have been described~among others, by the
patents of Chlanda et. al. (U.S. Patent 4,116,889) and Dege
et. al (U.S. Patent 4,253,900) , these are so~e of the
useful embodimerts of this overall concept. Using the
teachings of examples 22 and 33 of the instant invention,
bipolar membranes were prepared by casting onto a glass
plate a PAMPS sulfonic acid membrane of the kind shown in
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example 22, but cast at a gate opening such its final
thickness in the dry state was 20 microns. After this
membrane had been cast and dried but not cured, then a
quaterna~y ammonium anion-permeable membrane was cast on
top of it, employing the formulation of example 33,
and casting to a dry thickness of about 20 microns, also.
After it was dried and the bipolar membrane cured at 140C
for 3 hours, the film was ready for use. Where a stronger
mechanical film is desired, each half can be cast by
impregnatior and the use of a doctor blade onto a fabric of
suitable size, strength and non-solvency in the casting
solution.
The final bipolar membrane, when mounted in a typical
water-splitting cell, between platinum electrodes, could
convert a feed of 6% sodium chloride into two product
streams of sodium hydroxide and hydrochloric acid at
concentrations of approximately 5~ at current efficiencies
greater than 85 %. Because part of the rate-determining
step in the operation of bipolar membranes is their
hydraulic permeability which allows water from the ambient
solutions to replace that pumped out of the center of the
membrane by electro-osmosis, it was found that these
membranes would withstand currents higher that 100 amperes
per square foot without demonstrating losses in current
efficiency or increases in ohmic resistance over a period
of two months. The low cost of these bipolar membranes
make them particularly attractive for certain applications.
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Example 50Facilitated transport and solvent-extraction membranes
Membranes suitable for purpose of solvent extraction
and facilitated transport can be prepared employing cert~n
of the example~ of this invention. For example, when
solvent extraction is to be employed using a thin
water-insoluble- solvent film separating two aqueous
solutions, the formulations of examples 20 and 21 car be
employed, as examples. A membrane is cast from a PNBAM
polymer using the formulation of example 20 onto a Hollytex
support at a solids composition and gate opening selected
so that its final, dry thickness was estimated to be in the
order of 2 microns. In order to obtain a particularly thin
film, the membrane could also be cast employing the thin
film composite teachings of example 39. Follow casting,
drying and curing, the membrane was swollen in a solvent of
suitable properties, of which Decalin has been found useful
for a number of solvent extraction processes because of its
solvent power, its physical and chemical stability, its
insolubility in water and its very low vapor pressure. The
membrane swelled to approximately three times its original
volume so the volume fraction of polymer in the membrane
was approximately 25 %. This membrane could then be used
for solvent extraction processes where the feed was placed
on one side of the membrane and the stripping solvent on
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the opposite side, with both feed and stripping solventsnot dissolving the Decalin to an ap~reciable extent.
In the same manner, ar, ident~cal membrane was employed
for purposes of facilitated transport as described by Kuo
and Gregor (Separation Science Technology, 18, (5), 421
(1983)). A solution of trioctylphosphineoxide as carrier
was used a 25 % solution in Decalin sorbed by the membrane
to form the facilitated transport system. The membrane was
then washed with water and used for the extraction of
~cetic acid from a feed containing various solutes
... ~ . . . . . . . . . . =
including acetic acid, circulated or one side of the
membrane, with an aqueous, alkaline solution on the other
side of the membrane which converted the acetic acid
transported across the membrane into sodium acetate, and
thus allowed for its extraction as an acid from the feed
and its concentration and separation as the salt in the
stripping solution.
In a similar manner, other fac~litated transport agents
can be employed, such as the liquid ion exchangers or LIX
reagents which can be employed for the selective extraction
of copper from copper leach liquors with the copper
extracted and concentrated in a stronger acid solution used
as stripping solution.
Example 51
Protective Coatings
Protective coatings can advantageously be prepared from
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a blend of a particularly inert polymer which has apropensity to swell in certain solvents, such as oils,
together with one capable of being cross-linked. A useful
protective coating can be prepared by dissolving 5 parts of
Rynar with 1 part of PNBA (or similar hydrophobic polymer)
in a solvent such as DMF, adding a cross-linking agent such
as a short-chain diol or a diamine such as hydrazine or
EDA. Casting, drying and curing produces a film or coating
whi.ch swells but slightly in a mineral oil, and serves as
an excellent protective coating under:such-circumstances. :=
Example 52
Pervaporatior. Membranes Selectively Permeable to Water
Pervaporation (PV) membranes selectively permeable to
certain components of a solvent mixture can be prepared by
the teachings of this invention by the use of very thin
films used in the TFC (thin film composite) configuration
cast from polymers which strongly sorb the component whose
selective evaporation is desired and thus allow for its
selective transport. A high degree of cross-linking is
necessary so polymer-permeable component interactions
predominate, for swelling opens up pores and allows mixed
solvents to premeate.
A PV membrane was prepared by first casting and
coagulating a PAN film to form the UF support on Hollytex
3381. Ther, the PV barrier membrane was prepared by
dissolving 5 parts of PAMPS, 1 part of PNBAM and o.B parts
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each of glycerol and MSA to a total ~olids content of 0.5%in ethanol, dip cast and drained from the support membrane.
After drying and curing (3 hours at 140-C), differert
m~xtures of water and alcohols were circulated at room
temperature across the Hollytex side of the membrane, a 1mm
torr vacuum maintained on the other and the vapors trapped,
collected and analyzed. The ratio (by weight) of alcohol
in the permeate divided by that in the feed was, at 0.5
ard 0.9 weight fraction of alcohol in the liquid feed, the
following: methanol-water, 1 and 5; ethanol-water9 5 and
20; propanol-water, 12 and 40. At 10% butanol-water in the
feed the ratio was 7, while at 95% in the feed the ratio
was about 400. With very thin and highly cross-linked PV
barrier membranes, these highly selective permeabilities
can be maintained along with high fluxes.
Example 53
Cross-linked polymer blend membranes
Another of the advantages of the post-cross-linkirg
procedures of this inventior. is that they allow for a wide
combination of homopolymer or copolymer mixtures with other
polymers to produce materials designed to fit specific
applications.
For example, a useful monomer is polyglycolmethacryl-
amide (PGNAM), made by combining 163g polyglycolamine
(H-163*, Urion Carbide) with lOlg triethylamine~ 600ml
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ethanol and 0.2g p-methoxyphenol tFisher), then allowed to
react at -50-C under nitrogen upon the Alow addition of
100g methacryloyl chloride. The product was then filtered
at -lO-C, and the flltrate passed through a strong base
anion exchange resin in the hydroxide state, diluted with
methanol and pa~sed through a weak base anion exchange
resin, finally concentrated and dried.
A casting solution was prepared from DMF and contained
1 part of PAMPS to 5 of P(AN-PGMAM), with 1 mol ~ of
glycerol and- MSA--added --(based on-PAMPS). The-fi-lm was~
cast, then coagulated in water and used as a UF membrare to
treat a diluted blackstrap molasses feed. After 23 days of
use with this very dark and highly fouling feed, during
which time the flux remained constant, the cell was opened
and the membrane was found to be still entirely clean,
white and free of any evidence of fouling. This
formulation employs an insoluble matrix polymer containing
polyol side charges which can also cross-link to a strongly
hydrophilic polymer such as PAMPS.
Where a cation-exchange membrane useful for ED is
desired, different ratios of PAMPS to P(AN-PGMAM) can be
employed to give different degrees of swelling and
porosity, useful for different applications. The same is
true for PMAPTAC anion-exchange membranes. The poly-
electolytes can also be selected from a wide range of
polymers which do not cross-link themselves. PSSA and a
copolymer of P(AN-PNBA) or PNBA form a highly cross-linked
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cage-type membrane of useful properties, as an example.
Example 54
Analytical and Preparative Chromatography Systems
This invention lends itself to the preparation of
particularly useful chromatographic systems, both of the
analytical and preparative varieties. Since the invention
allows one to make very thin films by a casting procedure
wherein the pore structure of the film can be controlled by
coagulation procedures or by the degree of cross-linking,
and where the films can be highly hydrophilic and contained
fixed charges of positive, negative or zero charge,
chromatography systems of unusual utility can be prepared.
For analytical purposes a high speed for the procedure
is most important, and this is achieved by having a very
short path for the diffusive processes into and out of a
pore or gel-like stationary phase. The use of kinds of
thin films of the sub~ect invention iq particularly
advantageous but the problem of provlding for the flow of
the mobile phase across the face of the stationary phase so
that the "front" of fluid flow is not appreciably distorted
must be solved.
Stationary phases having a thickness of 2 or 3 microns
are highly desirable because they allow a high speed to the
system, but it is also desirable to be able to control at
will the volume of the mobile to the stationary phase and
_63-
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keep the driving pressure within rea~onable bounds. The
following formulation was found to be highly u~eful; it is
by no means is the only procedure which can be employed.
First, a very smooth glass plate was coated with a
smooth film of paraffin and scribed with a stylus, making
parallel lines 50 as to expose the glass at spacings deemed
convenient, ranging from a few mm up to a cm or so. The
surface was then treated with hydrofluoric acid or a paste
of hydrofluoric acid and a suitable salt so the glass was
etched to a thickness of- from -1 ~micron up to several
microns. The etched grid was usually rectangular or a
parallelogram in nature so that both the vertical and
lateral flow of the mobile phase could take place
uniformly. At that point the paraffin layer was dissolved,
the plate cleaned and a uniform layer of one of the several
formulations of the sub~ect invention was cast upon it. The
formulations of Examples 19, 22, 23, 26, 28, 30, 31, 32,
and the like could be employed. By varying the conditions
of casting and the percent solids of the casting solution,
films of different thickness are prepared. Coagulation
produces different degrees of porosity, again controllable
within certain ranges. At this point the film is dried,
cured, wetted with water and the film containing a grid of
corrugations on one surface, entirely composed of the same
material, is the result.
To make a chromatographic device, it sufficed to
carefully wind the partially dried film onto a cylinder and
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place this onto another cylinder slightly larger in size.
With the membrane now mounted in a device having suitable
entrance and exit ports for distribution of the solvent,
and then wetted lt swelled appropriately and may serve as
an admirable analytical chromatography system. Its high
speed results from the extremely 3hort diffusion paths; its
configuration with channels running down through and across
the column makes for a system which does not require a high
pressure in contrast to the usual HPLC devices which
employs very fine beads of uniform diameter, ones difficult
to prepare~, a~nd aIso~giving rise to a-hi6h pressure.~
The advantage of the corrugated stationary phase makes
it possible to have very fine spacings which are highly
hydrophilic without the necessity for employing very fine
fabrics or the like, which usually have a minimal thickness
of at least 5 microns and are usually several times that
thickness.
The ~ame general procedures apply to the making of
preparative chromatography columns but her since larger
dimensions are allowed, one can wind either coagulated or
non-coagulated membranes about a cylinder, with the latter
employing very fine cloth as the spacer material. However,
since the denaturation of proteins onto almost all surfaces
constitutes such a ma~or problem in biochemistry and
-molecular biology, it is advantageous to employ fine
fabrics which are coated to make them strongly hydrophilic.
Or, fibers can be spun from the polymeric formulations of
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the various exampleA an woven into fabrics. Or, the
stationary phase can be a fabric which can be quite uniform
and which can ~erve for both a stationary phase and a
spacer.
Since the casting of membrane films is a highly
developed technology which can be carried out on a large
scale with good control over the various physical
properties of the film, it is obvious that large scale
preparative chromatography systems are readily prepared by
the teachings of this invention.
Of particular interest are chromatographic systems
which separate low molecular weight materials of highly
similar nature, such as polypeptides and oligomers of low
molecular weight carbohydrates, as an example. These are
important materials in molecular biology. Also, the
analysis of ions by ion-exchange HPLC ~ystems has many
uses, and the materials described heretofore will find a
application here, also.
Example 55
Polymer Sheets of Specific Affinity
The techniques of modern molecular biology frequently
make use of sheets of nitrocellulose, as an example,
because this material has a high affinity for small
fragments of RNA or DNA, as for nucleic acids of molecular
weight of the order of about 12,000. Nitrocellulose is
commonly used to hold the polymer on the surface while
reactions are carried out with it. More recently, some
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qynthetic treated nylons and other materlals have beenemployed for this purpose, as has been DEAE cellulose
paper, polylysine bound paper and the like.
The teachings of this invention lend themselves
particularly well to the making of surfaces having groups
on them with specific affinity, but holding the material
such that denaturation is absent. With only certain groups
of the nucleic acid held to the surface in a selective
manner, reactions can be performed to advantage.
-- The teachings of this invention also allow for-the
.. . . . . . . . . ........................... . . . . .
cross-linking of nucleic acids to the paper, employing the
typical post-cross-linking or binding reactions employed
for the immobilization of enzymes and proteins. These
reactions, when combined with the highly hydrophilic and
non-denaturing action of the surface give to the
investigator a powerful tool for the modification of the
nucleic acids. The absence of non-specific binding of
proteins and similar molecules constitutes a major
advantage.
Example 56
Sheets for PAGE
Polyacrylamide gel electrophoresis (PAGE) is a commonly
employed technique to identify small amounts of protein in
a complex mixture, usually employed a detergent such as SDS
to form rod-like molecules so the protein migrates at a
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speed characteriqtic of its moleeular weight. PAGE platesare usually highly fragile and sometimes difficult to
prepare. When a further identification of a particular
species is desired, the removal of a specific slice of the
plate is a tedious and somewhat difficult procedure.
Very thin and highly stable PAGE plates can be prepared
from sheets of thin and qtrong pla~tics (such as elongated
polyesters or Mylar (DuPont). These can be coated directly
by a polymer dissolved in an organic solvent which wets the
plastic and-forms a bond between the active material of the
PAGE film and the base plastic. Or, as an example, Mylar
sheets can be treated on one side by a strongly alkaline
solutior for a short period of time to hydrolyze some of
the ester bonds and render the material readily wetted by
water and susceptible to chemical bonding by the casting
formulations of the sub~ect invention.
These PAGE ~heets may be made by casting or dip-coating
onto them one of the polymers quitable for the separation
desired, to produce a thin gel film either of zero charge,
negative or positive charge and of a porosity that can be
set by coagulation. Then the film is dried and cured in the
~tandard manner. PAGE films having a thickness of 1-2
microns and upwards to several microns are readily prepared
by this procedure. The dried and cured films can be stored
dry and made ready for the PAGE procedure by immersion in
buffer, placing the base film on a glass plate with another
glass plate on top to eliminate dead spaces and provide
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uniformity of thickness and rigidity. Then the sample ofunknown is applied, the current passed and the separation
takes place. At that point the system is simply
disassembled and stained. These PAGE gels are firm and can
have wide pores and still have a reasonable mechanical
strength due to their mode of fabrication. After the
staining procedure has been applied, sections of the sheet
are cut out for subsequent purposes. The small thickness
and nature of this PAGE system lends i.tself to the
i:solaion-and--- id~ntiicatio~---with.extremely small samples
of materials of similar nature, such that often other
limitations such as the sensitivity of the analytical
procedures which are available become limiting factors.
Example 57
Desalting and Concentration of Protein Solutions
Proteins are readily desalted and/or concentrated by
the use of a hydrophilic UF membrane either having a fixed
charges of the same sign as that of the protein, or
preferably the material of choice is an uncharged membrane
made from PAM, PNMAM or PDMAM. Ultrafiltration is a
preferred method of desalting/concentration because it is
rapid. Ordinary dialysis can be employed, but it is slow by
comparison.
The sizing of the membrane pores can be done in a
reliable manner only by empirical means, namely by making
membranes of differing porosity and testing these for the
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non-passage of the desired protein. Since protelns are
usually highly deformable, gel-like molecules the
techniques employed are important. A low pressure is
usually used so as not to deform the protein and force it
through the pores. The use of a high rate of cross-flow or
other means to minimize concentration polarization are
employed to keep the flux high and minimize the formation
of a gel layer on the membrane. Where the loss of protein
by surface denaturation is required, the walls of the UF
cell-can be coated with a strongly hydrophilic material of
the kind described in other examples. The inner lumen of
connecting tubing can be similarly treated.
The simplicity of this procedure and its speed makes it
particularly useful when valuable materials which are
labile and easily denatured or which deteriorate rapidly
are involved.
Example 58
Hydrophilic Microfiltration Screens
Microfiltration screens of high mechanical strength and
highly precise openings can be prepared by the present
invention by coating the screen itself with several of the
formula given as examples in this invention. Common
articles of commerce are fine screens fabricated from metal
wire and a number of polymers including polyoleofins,
polyesters and nylons, usually made for purposes of silk
screening or ultrafine filtration. However, all of these
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suffer from the di~advantage in that hydrophobic andgelatinous materials adhere to the openings of these
screen~, clog them and are difficult to dislodge by
backwa~hing. The same applies to wider screens employed
for the dewatering of cakes and other semi301id material~,
u~ually containing water as the liquid.
It has been found that particularly useful microfilters
can be formed by coating these fine screens with
hydrophilic polymers. With monofilament screens of
polyester and nylons, the procedure is particulary simple
and a wide variety of casting formulations are available.
Care must be employed not to use solvents which attack the
monofilament screens rapidly. In the case of polyolefinic
screens, a prior treatment with one of the conventional
procedures which includes the use of chromic acid dip or a
corona discharge serves to make the surface receptive to
wetting and subsequent adhesion of the coating. Wire
screens usually require a precoat which can be one of the
commercially available epoxide formulations used as primer
coats. These can be extremely thin and adhesion to these
by the formulations of this invention are excellent.
A typical application is a polyester screen obtained
from Tetko (Ardsley, New York), first dipped irto the
casting solutions and then passed through a casting device
to remove excess solution. Sometimes it is necessary to
apply a gentle vacuum to the film to remove excess droplets
of casting solution. Following this, the film is dried for
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2 hours at 63-C and then cured for 3 hours at 140-C.
Microscopic examination of the screen showed that when the
coating waY properly applied, the screen was entirely
coated with the hydrophilic polymer, ascertained by
employing a dye which strongly dyes the screen material
itself but not the polymer eoating. The coating process is
usually carried out with the screen being passed over a
roller under appropriate tension with the doctor blade
passing over the top of the screen; and in this way the
oops--between~ ad-~acent fibers- are d-raw~- tight and the
casting solution not only coats the screen but acts as an
adhesive to close off loops and seal them.
Following the usual drying and curing procedure, it is
found that these screens are highly effective for the
microfiltration of such materials such as cell suspensions
resulting from the fermentation of beverage alcohols,
primary and secondary sewage sludge as well as raw water
from which removal of cells and other suspended ~olids is
to be desired.
One of the particularly useful manifestations of this
invention is the use of such screens mounted on the outside
of a rotating, porous cylinder which spins in an annular
space through which the feed suspension is pumped under
pressure. A double effect can be achieved by coating both
the rotating surface and the stationary porous surface with
the same screen. This mechanical arrangement gives rise to
a highly effective stirring at the surface of the screen, a
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phenomenon well known a~ Taylor's Vortices. Under thelnfluence of ~uch vortices, the suspended solids are
collected in bands which, under the influence of an upward
or downward flow of the feed though the annulus, produce a
"rope" of concentrated, suspended solids which exits from
the port and a substantial concentration of material is
achieved thereby. The pressures employed can be low. By
the use of the hydrophilic surfaces of the subject
invention where adhesion of suspended solids is not a
problem, spinning-rates of only 300-600 RPM have been found
- ~ . . - = .
to be effective. An excellent concentration of the
suspended solids in a stillage gained from the ~anufacture
of beverage alcohol was achieved, from 5 to 18% solids.
When the same, hydrophilic material is employed as a
coating on a cylinder or flat plate device under ordinary
conditions of cross-flow, the rate of cross-flow must be
high becauqe the flow of permeate forces the suspended
solids against the surface of the microfilter, and leads to
a slow rate of filtration through the surface layer.
When a wire or polymeric screen not of strongly
hydrophilic nature is used in the splnning device, speeds
of rotation upwards of 2000-3000 RPM are required to
produce enough shear to allow the filtration process to
take place at an acceptable rate. Thus, it is only by a
combination of configurations such as lead to vorticies
such as those of Taylor's and the hydrophilic materials,
the making of which are taught by this inventior, is a
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~a~or advantage for the removal of suspended solids
achieved.
The same considerations apply to ultrafiltration
processes such as tho~e which involve the removal of low
molecular weight solids from solutions of proteins or, in
the ease of more porous membranes, for the separation of
protein~ from one another. In many of these separations
the extent of convection at the membrane or
mi.crofilter-solution or suspension interface is critical,
and it is by a combination of a hydrophilic sur~ace and a
moving surface that high flux rates results can be
obtained.
Example 59
Surfaces, Ultrafilters and Microfilters to which
Proteins, Enzymes, Antibodies and other Biopolymers
are bound and their use in affinity sorption and
enzymatic conversion processes
.
The use of an insolublized polymer or copolymer
containing substituents to which biomaterials such as
enzymes, proteins, antibodies and the like can be bound and
used for a variety of purposes ranging from the making of
assays for specific materials to their use as bioreactors
is well known. Reference can be made to the several
patents of Gregor and more recently to U.S. Patent No.
4,705,753 of ¢regor et al. All of these systems, based as
they are upon polymers which are either hydrophobic or not
s ~ ng~ hydrophilic, suffer
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from the disadvantage of non-specific adsorption. The
U.S. Patent No. 4,705,753 make~
reference to a number of known coupling chemi~tries such as
those which employ an aryl amine, a pyridine, a hydroxyl-
containing olefin such as N-hydroxy sub~tituted acrylamide
and the like. These systems are similar to some of the
chemical binding reactions of Inman and Dintizis, already
cited. The co-pending application refers to the use of a
functional co-monomer containing an arylamine, a pyridine
or a substituent containing a hydroxyl group which may be
part of the co-monomers N-(5-hydroxy-3-oxa-pentyl)
acrylamide and N-(9-hydroxy-4-7-dioxa-nonyl~ metha-
crylamide. Thus, either by a substitution reaction on a
linear or cross-linked polymer containing a pendant
amidocarbonyl or oxycarbonyl group suitable for
cross-linking under the teachings of this invention,
strongly hydrophilic polymers which can be insolubilized by
the teachings of this invention can be made into useful
surfaces, microfilters, membranes and the like.
These surfaces, membranes and microfilters can be
activated by those skilled in the art, as by
trichlorol-s-triazine, by diazotization, by cyanogen
bromide activation of a pyridyl-containing polymer or by
other known coupling reactions.
A very wide range of biopolymers including
chymotrypsin, glucose isomerase, protein A, bovine serum
albumin and the like maybe coupled.
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These biopolymer-coupled sy~tems may be applled to the
separation and isolation of soybean trypsin inhibitor by
coupled chymotrypsin, in a manner such that non-specific
adsorption does not interfere and all of the soybean
trypsin inhibitor sorbed by the membrane can be desorbed by
conventional techniques which include changes in pH as well
as the use of decoupling agents such as urea.
Similarly, protein A can be immobilized to a
hydrophilic support material, then an antibody such as IgG
-bound to it an~d if neëded, coupled by techniques known to~ -
.
those skilled in the art. Such immobilized antibodies may
be employed for purposes of analysis, separation and
purification.
The process of affinity adsorption similarly maybe
applied to the removal of ~ibronectin by a hydrophilic
polymer to which the protein gelatin has been coupled.
As another example, protein A may be immobilized,
then allowed to bind to anti-human Qerum albumin IgG. Then
the antigen HSA in IgG binding buffer is applied to the
carrier system, washed free of undesired materials and
eluted in a pure and concentrated form. sorption.
It is well recognized that the micro-environment of an
enzyme, as an example, can influence its catalytic
activity. The teachings of the sub~ect invention not only
provide for a highly hydrophilic environment but also one
where a net charge which is either positive or negative can
be placed in the vicinity of the couplirg group, thus
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making for an optimal micro-environment for the process.
Example 60
Surface Treatment of Fabrics and Papers
The teachings of the sub~ect invention may be applied
to the surface treatment of fabrics and papers of
cellulosic and non-cellulosic origin, for several purposes.
These include the imparting a variable degree of
hydrophilicity and/or resistance to the accumulation of
static charges by virtue of the electrical conductivity
give to the material resistance to creasing and receptivity
to fillers. Other desirable properties such as receptivity
to dyes and inks can similarly be obtained by a surface
modification using the teachings of the sub~ect invention.
Since by a subsequent thermal treatment it is possible to
produce chemical bonds between the polymers and the
substrate paper or fabric, these surface treatments are
relatively permanent and will not be removed by washing or
similar cleansing procedures. The fact that some of the
materials of the sub~ect invention consist of a single
polymer dissolved in a common solvent makes the application
particularly convenient and the release of soluble products
which usually cause stream pollution is minimized.
Two washed fabrics, one of a polyester (Dupont Dacron)
ard another of a polyamide (Dupont Zytel) were dipped into
a 0.5% solution in water of P(AMPS-HHAM) (example 15), the
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excesA solution shaken off and the fabric wa~ dried at 60-C
and then cured for 3 hours at 140-C. They were then rinsed
briefly with a dilute sodium bicarbonate solution, then
w~th water and dried. The finished fabrics were found to
have acquired a different "hard" in that they did not
cling, felt more like cotton than a synthetic material, and
absorbed water more like a cellulosic material than a
synthetic one.
Example 61
Determining Extent of Cross-linking.
The extent of cross-linking of a polymer car be
estimated in several different ways. A practical test is
to determine the swelling index of the resin in a solvent
in which the polymer is highly soluble. Quantitative
experiments were performed where the amount of the group
displaced from the polymer by the cross-linking reaction
was determined. In one series, P~M of 3X106 MW was
dissolved in water in a closed flask along with varying
amounts of several polyol cross-linking agents, including
glycerol, TMP and pentaerythritol, the solution dried at
60-C, followed by curing at 140-C for 3 hours. Then the
flask was cooled and the ammonia released by the
cross-linking reaction was neutralized with an excess of
standard hydrochloric acid, and an aliquot of this solution
(plus that used to rinse the insoluble resin) was
back-titrated with standard base to measure released
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ammonia. The mole ratlo of released ammonia to polyol or
to PAM units was calculated as a function of mole ratio of
polyol to PAM and from these data it was concluded that the
degree of cross-linking varied from about 4 to 11~. This
procedure does not show cross-linking between different PAM
chains as contrasted with cross-links formed between two
groups on the same chain. However, since a solvent in
which PAM is highly soluble (and elongated) was used and
steric effects with certain polyols favor inter-chain
cross-linking, --it ~was c-oncluded that inter-polymer
crosslinks predominated.
Similar experiments were performed with PAMPS and a
fully-substituted C14 glycerol (along with ordinary
glycerol) in water with MSA catalyst. After drying and cure
the radioactive incorporation in the washed resins was
measured. A high level of cross-linking was present,
estimated from 8~ to 15~ as inferred from the data.
A number of experiments were also performed wherein to
PAMPS in DMF and to PAM in ethylene glycol were added
varying amounts of glycerol and MSA. After drying at 80C
for 5 days and curing at 140-C for 3 hours, the swelling
index in water was measured. Under favorable conditions,
swelling indices of 2.4 to 3.0 were found for PAMPS, and
2.1 to 3.0 for PAM, indicative of the very high degrees of
cross-linking attainable by employing the teachings of this
invention.
The choice of solvent influences, to some extent, the
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swelling index. PAMPS appears to be more hlghly cros~-
linked from water than from DMF, probably becau~e it ls
more elongated in water.
It will be appreciated that the instant specification
and examples are ~et forth by way of illustration and not
limitation, and that various modifications and changes may
be made without departing from the spirit and scope of the
present invention.
. _ = . ~ . = . . . . .
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