Preparation of surface-functional polymer particles

Polymer particles having a hydrophobic core and various surface functional groups, particularly hydrophilic and chiral surface functional groups, are produced by adding a non-emulsified functional polymerizable monomer to the aqueous phase of a dispersion of soluble polymer particles which have previously been swollen with an emulsified-monomer and polymerizing the monomers. Preferably the particles are uniform macroporous beads.

BACKGROUND OF THE INVENTION 
Polymer beads are usually produced by free radical suspension 
polymerization, a well known process developed in 1909. See Hofman et al., 
Ger. Pat. 250,690 (1909). Porous polymer beads based on, for example, 
poly(styrene-co-divinylbenzene) are widely used in the synthesis of 
ion-exchange resins. In addition, significant speciality applications 
exist for the use of such polymer beads in areas related to separation 
science. These applications include separation of enantiomers from racemic 
mixtures, analysis of blood samples, water purification, high-performance 
liquid chromatography, and the like. 
Some of these speciality applications require or would benefit from the use 
of polymer beads which have unique surface properties. For example, when a 
conventional column containing hydrophobic polymer beads is used in the 
analysis of human plasma, the proteins in the blood plasma are denatured 
on the hydrophobic surface of the beads. This eventually destroys the 
column through clogging which increases the back pressure to such an 
extent that the column must often be replaced after only a very short 
useful lifetime. In contrast, a column packed with polymer beads having a 
hydrophobic core and a hydrophilic outer layer does not suffer from the 
same problem because the hydrophilic surface does not react with blood 
protein so as to cause clogging of the column. 
Another speciality application is the separation of enantiomers from 
racemic mixtures. Such chromatographic separations require the use of 
beads with a chiral surface layer. These separations are important for the 
analysis, identification, or preparation of optically active compounds. 
Other possible applications for which polymer beads having a hydrophilic or 
chiral outer surface include catalysis in which it is sometimes desirable 
to segregate an active component at the surface of a solid catalyst. The 
selection of a reactive chiral or hydrophilic group and its placement at 
the surface of a polymer bead could accomplish such an active component 
segregation. In toner chemistry, it is often desirable to modify the 
surface chemistry of toner particles which are generally non-porous 
non-cross-linked polymer particles. Currently this is performed through 
the use of simple mixtures or coatings of the toner particles with the 
desired additives. 
While some polymer beads with hydrophilic surfaces are available, the 
processes used to produce such polymer beads are difficult to perform, are 
limited in the types of monomers and groups which they can introduce, and 
are in many cases not economical. As regards chiral surface groups, 
polymer beads having chiral surface functionality and hydrophobic cores 
and processes for producing such are not known in the prior art. 
Accordingly, the speciality applications discussed previously, which would 
benefit from the use of such polymer beads, remain as theoretical 
applications for polymer beads without suitable polymer beads to perform 
the operation needed by such. 
The production of polymer substrates, particles and/or beads having 
hydrophilic cores and hydrophilic outer layers or hydrophilic surface 
functionality is disclosed in a number of publications. For example, U.S. 
Pat. No. 4,571,390 discloses a porous styrene polymer substrate wherein 
the surface is rendered hydrophilic by chloromethylating it to introduce 
methylol groups onto the polymerized substrate. The substrate is disclosed 
as useful in adsorbing high molecular weight proteins. U.S. Pat. No. 
4,898,913 is directed to a process for altering a macroporous crosslinked 
hydrophobic copolymeric lattice produced by a precipitation polymerization 
of ester monomers. According to the method described therein, the 
copolymeric lattice, after formation, must be separated from the mixture 
in which it is formed, and then, in a separate operation, the surface of 
the copolymer is rendered hydrophilic either by reaction with an aqueous 
alkali or by a second polymerization using a hydrophilic acrylate monomer. 
European Patent No. 0371258 discloses porous polymer substrates comprising 
an acrylonitrile polymer or copolymer core with a hydrolized surface layer 
having post-generated amide surface groups. The porous substrates such as 
beads are disclosed as being useful in chromatography separation 
processes. The amide surface groups are produced by adding a peroxide to a 
polymer suspension and heating for a time sufficient to convert about 15 
mole percent of the total surface nitrile groups to amide groups. This 
process and the resulting product are limited to specific types of surface 
functional groups. 
Another polymer bead material having a hydrophilic surface is disclosed in 
U.S. Pat. No. 4,882,226. The polymer beads comprise (i) a core material 
obtained by the addition polymerization of monomers comprising methacrylic 
acid and (ii) a hydrophilic coating which is covalently bonded to the core 
as a result of complete or partial conversion of the carboxyl function 
with a compound containing at least three carbon atoms and an epoxy group. 
The formation of the covalent bond to create the hydrophilic surface is a 
multi-step and complex process. 
An expensive and complicated process for producing polymer microspheres is 
taught in U.S. Pat. No. 4,170,685. The process involves the production of 
microspheres by the use of ionizing radiation. Hydrophilic characteristics 
are provided by addition of a suitable unsaturated comonomer. See also U.S 
Pat. No. 4,259,223 which discloses a similar process. 
Japanese Patent No. 62046260 discloses still another polymer bead material 
having a hydrophobic core and a hydrophilic surface layer to which a 
polyethylene fiber is laminated. The multilayer material is disclosed as 
being useful in determining components in a blood serum solution. 
The prior art processes for forming polymer particles with hydrophobic 
cores and hydrophilic surface layers are either complicated and 
uneconomical or limited to a specific surface functionality. Moreover, 
none of the prior art processes describes a method for introducing a 
chiral functional group to the surface of hydrophobic polymer beads. 
Accordingly, it is one of the objects of the present invention to develop 
an improved process for introducing hydrophilic or chiral surface 
functionality on hydrophobic porous polymeric particles. 
It is another object of the present invention to produce polymeric 
particles that have chiral groups on their surface. 
It is a further object to manufacture polymeric particles from solid 
monomers or monomers having a low solubility in the polymerization 
solvent. 
SUMMARY OF THE INVENTION 
The present invention is directed to a process for the production of porous 
polymer particles having specific surface functionality and the particles 
produced therefrom. The process generally comprises (i) adding a 
non-emulsified functional monomer which also contains at least one 
polymerizable group into the aqueous phase of a dispersion of soluble 
polymer which are insoluble in water and particles which have previously 
been swollen with an emulsified-monomer, (ii) polymerizing the monomers to 
form polymer particles which are insoluble, and preferably (iii) 
extracting the initial soluble polymer particles. The non-emulsified 
functional monomer contains hydrophilic or chiral groups or precursors 
thereto. The non-emulsified functional monomer is preferably added prior 
to the initiation of the polymerization though it may be added shortly 
thereafter. 
Polymer particles produced according to this process generally contain 
hydrophobic cores with an outer layer composed of the polymerized 
non-emulsified functional monomer. The process is particularly useful in 
the production of polymer particles having hydrophilic or chiral group 
surface layers. The polymer particles formed are generally in the form of 
beads having a size of from about 2 to 20 .mu.m. The beads are preferably 
of substantially uniform size and shape although the process is suitable 
for producing beads of varied sizes and shapes. The beads may have no, 
little, or a substantial amount of porosity as desired for a particular 
end use. Preferably the beads are macroporous and have a solvent regain of 
at least about 0.1 ml/g, preferably at least about 0.5 ml/g, and most 
preferably at least about 1.0 ml/g. When macroporous products are 
produced, the macropores often are coated with the polymerized functional 
monomer while the micropores are generally hydrophobic. The polymer beads 
are particularly useful in water purification, high-performance liquid 
chromatography, separation of enantiomers from racemic mixtures, size 
exclusion chromatography, perfusion chromatography, interaction modes of 
liquid chromatography, waste water treatment, polymer-supported organic 
reactions, enzyme immobilization, polymer catalysts, analysis of blood 
plasma, modification of the surface chemistry of toner particles, and 
other such applications.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
More particularly, the process of the present invention comprises adding a 
non-emulsified monomer which contains (i) functionality that is 
hydrophilic or chiral or is a precursor to such functionality and (ii) at 
least one polymerizable group into the aqueous phase of a dispersion of 
soluble polymer particles which are insoluble and in water which have 
previously been swollen with at least one emulsified hydrophobic monomer. 
The emulsified monomer(s) are then polymerized substantially inside the 
soluble polymer particles to form a central portion of the new particles 
and the non-emulsified functional monomer which is in the aqueous phase 
outside of the soluble polymer particles copolymerizes substantially on 
the surface of the particles. The inner emulsified monomer and the outer 
non-emulsified functional monomer surface probably undergo some amount of 
"mixing" (some of the non-emulsified monomer migrates inside before being 
polymerized, generally into macropores but not into any micropores) but 
there is a clear gradient of the composition as one proceeds from the 
center of the particle to the outside. The new copolymer produced is 
insoluble. Thereafter, the initial soluble polymer particles may be 
extracted to produce a porous particle having an outer surface of a 
polymer of the non-emulsified functional monomer and an inner portion of a 
hydrophobic polymer. If the initial soluble polymer is not extracted, the 
resultant particle will still have an outer surface of a polymer of the 
non-emulsified functional monomer. 
Hydrophobic and hydrophilic are relative terms relating to the ability of a 
material to adsorb or absord water. For purposes of this invention a 
material is hydrophilic if it contains at least one water-attracting 
functional group such as hydroxy, carboxyl, amino, amido, imido, sulfonyl, 
epoxy, diol, and the like. Materials which are not hydrophilic are 
hydrophobic for the purposes of this invention. Chiral is used herein to 
mean an optically active or enantiomerically pure or containing one or 
more asymmetric center in a welldefined optically active configuration. 
The non-emulsified functional monomers which result in hydrophilic surfaces 
are those monomers which contain a polymerizable vinyl group as well as a 
hydrophilic group. Suitable such hydrophilic groups include hydroxyl, 
carboxyl, amino, amido, imido, sulfinyl, sulfonyl, nitro, nitrile, oliol, 
aminoacid, epoxy, diol, and the like. Accordingly, suitable such monomers 
include vinyl acetate and other vinyl esters, acrylamide, methacrylamide, 
hydroxyalkylacrylates and methacrylates such as hydroxyethylmethacrylate, 
glyceryl acrylate or methacrylate, glycidyl methacrylate, vinyl phenol and 
esters thereof, acrylic and methacrylic acids and derivatives thereof, 
vinyl pyridine, vinyl pyrrolidone, aminostyrene, p-epoxystyrene, styrene 
sulfonic acid and its derivatives, and mixtures thereof. This listing is 
merely representative of such monomers and not in limitation thereof. 
The non-emulsified functional monomers which result in chiral surface 
functionality are those monomers which contain a polymerizable vinyl group 
and a reactive chiral group. Suitable such reactive chiral groups include 
aminoacids, alcohols, amines, esters, amides, sugars, carboxylic acids and 
esters, and the like. Accordingly, suitable such monomers can be produced 
by the attachment of known optically active (chiral) compounds to 
styrenic, acrylic, methacrylic, or other vinylic structure that can be 
polymerized by conventional free-radical techniques. Generally the 
attachment will result in pendant chiral groups such as those listed 
above. This is intended to be merely representative of the chiral monomers 
and not in limitation thereof. 
To achieve the desired result, the non-emulsified functional monomer is one 
which is not completely water soluble. Rather, it should only be slightly 
soluble in water. It is preferably added in neat form to the aqueous phase 
of a previously prepared swollen polymer dispersion. As defined herein, 
"neat form" means that the monomer is introduced as a pool of liquid or in 
solid form into the dispersion, and not as part of the emulsified monomer 
mixture which is used to swell the soluble polymer particles. 
The non-emulsified functional monomer is generally added in an amount of 
from about 1 to 100%, and more preferably in an amount of from about 3 to 
30 wt %, based upon the total weight of the soluble polymer and emulsified 
monomers, though more or less may be used depending upon the thickness and 
uniformity of the surface layer which is to be produced. Preferably, it is 
added to the aqueous phase of the swollen soluble polymer particle 
dispersion prior to initiating polymerization of the emulsified 
monomer(s), but it may also be added after polymerization has commenced. 
When the non-emulsified functional monomer is added prior to the 
commencement of polymerization, it is desirable to also add a 
polymerization inhibitor to prevent premature polymerization of it. If 
such polymerization were to occur, it may reduce the yield of the surface 
coated particles and also may possibly result in the formation of 
particles which do not have the hydrophobic central portions. Also when 
monodisperse soluble polymer particles are used, it could result in the 
production of particles having different sizes. Suitable inhibitors are 
known in the art and include, for example, sodium nitrite, ferric 
chloride, and hydroquinone. The inhibitors are added in an effective 
amount which is generally of from about 1 to 25 wt % based upon the weight 
of the initiator. 
Initiation is effected in any conventional manner by the introduction of a 
suitable polymerization initiator such as benzoyl peroxide, lauroyl 
peroxide, redox initiator systems, or an azo compound such as 
azobisisobutyronitrile. The initiator is generally present in an amount of 
from about 1 to 2 wt %, based upon the total weight of the polymerizable 
monomers present. 
The polymerization is carried out in a conventional manner, generally at a 
temperature of from about 50.degree. to 90.degree. C. for a period of from 
about 6 to 24 hours, depending upon the initiator and monomers used. 
Polymerization proceeds rapidly within the confines of the swollen polymer 
particles to produce a hydrophobic core which is later made porous by 
extraction of the soluble polymer and any swelling or porogenic solvent. 
While the polymerization within the particles occurs, the non-emulsified 
monomer slowly migrates to the surfaces of the polymerizing particles and 
of the forming macropores where it is copolymerized thereon to form a 
functionalized hydrophilic or chiral outer surface layer. It is believed 
that the inner and outer layers of the particles undergo some amount of 
mixing as some of the non-emulsified monomer migrates further inside the 
polymerizing particle before undergoing polymerization. This creates a 
gradient of composition as one proceeds from the outer surface of the 
particles to the core. This gradient is believed to be rather sharp with 
the surface functional groups not extending very deeply into the core. 
After polymerization is complete, the polymerized dispersion is added to a 
suitable solvent, such as methanol tetrahydrofurane, benzene, toluene, 
dioxane, or mixtures thereof, and the starting soluble polymer particles 
are then extracted therefrom forming a porous final particle. This 
procedure of extraction in a solvent may be repeated numerous times, 
preferably about 2 to 5 times, to produce the desired surface 
functionalized porous polymer particles. Optionally, in the case wherein 
the surface functional groups are hydrophilic, such as when glycidyl 
methacrylate is used, the hydrophilicity may be increased such as by 
opening the glycidyl groups to form diols by acid hydrolysis. 
The initial dispersion of swollen polymer particles in water may be formed 
by a conventional method known in the art. However it is presently 
preferred to carry out the process as set forth hereinafter to produce 
macroporous monodisperse particles. A water dispersion containing 
monodisperse soluble polymer particles, which particles will act as the 
primary porogen in the process, is formed. The particles then go through a 
swelling stage, which may be performed in one or more steps, during which 
the polymer particles solvate. It is presently preferred to carry out the 
swelling in two steps. First, a solvent usually containing a dissolved 
free radical initiator is emulsified in water then a dispersion of the 
polymer particles is added and the polymer particles are allowed to absorb 
the solvent-initiator emulsion. This solvates the polymer particles and 
may even dissolve them, changing the particles to solvated droplets. 
Thereafter, an emulsified monomer or monomer mixture which may also 
contain a porogenic solvent and a free radical initiator if none was added 
earlier is added and the swelling (size extension) is completed by 
absorption of the monomer or monomer mixture by the solvated polymer 
droplets. In an alternative, the emulsified monomer or monomer mixture may 
be added first and then followed by the solvent and initiator, or both the 
solvent and monomer with initiator may be added simultaneously. The 
monomers and solvents have to be miscible and be capable of solvating the 
polymer of the primary particles. When particles of a very small size are 
desired or when only a small enlargement of the size of the primary 
particle is desired, the addition of the organic solvent may be omitted 
thus simplifying the process. After absorption of the monomer or mixture 
of monomers, initiator, and optional solvent into the polymer particles, 
the dispersion of swollen polymer particles is ready for the introduction 
of the non-emulsified functional monomer. 
The starting soluble polymer particles used in the process of the present 
invention serve to control the shape and size distribution of the final 
product. They also serve as a primary component of the porogen. Soluble 
polymer particles useful herein are insoluble in water but soluble in 
various organic solvents and include polymers and copolymers containing, 
for instance, styrene or ring substituted styrenes, acrylates, 
methacrylates, dienes, vinylchlorides, or vinylacetate. It is presently 
preferred to employ a polystyrene or an acrylic polymer. The starting 
polymer particles can be prepared by any technique producing very 
uniformly sized particles, e.g. by conventional techniques such as 
emulsion or dispersion polymerizations. The polymer particles initially 
generally have a diameter of from about 0.5 to 10 .mu.m, more preferably 
of from about 1 to 6 .mu.m, and most preferably of from about 2 to 5 
.mu.m. The initial particle size will, of course, depend upon the intended 
end use and size of the final particles. For example, to obtain a final 
bead having a size of about 5 .mu.m, an initial bead size of about 2 .mu.m 
is recommended. A 5 .mu.m bead is typically used in high-performance 
liquid chromatography. If uniformity is not desired, the initial bead size 
is not as important and can, of course, vary resulting in a final product 
having variable size particles. 
The soluble polymer particles must be solvated by the solvent employed in 
this stage of the process or by the monomer mixture if no solvent is used. 
The organic component of the emulsified liquid phase is allowed to diffuse 
or absorb slowly into the polymer particles solvating them and increasing 
their size in a very uniform manner. Accordingly, the polymer particle 
size is increased during solvation without any appreciable change in the 
overall size distribution of the solvated particles. The polymer particles 
are generally present in the three phase dispersion in an amount of from 
about 1 to 5% by volume. 
In the process of the present invention, the amount of soluble polymer 
remaining in the polymer particles after polymerization is completed is 
generally from about 6 to 50 wt %, preferably from about 10 to 30%. 
The swelling solvent employed in the present invention contributes to both 
swelling or solvation of the soluble polymer particles and to the 
formation of pores during the polymerization reaction. This may be any 
suitable solvent such as toluene, 1-chlorodecane, 1-bromodecane, 
dibutylphthalate, chlorobenzene, or mixtures thereof which can solvate the 
polymer particles used. The solvent is generally present in an amount of 
from 10 to 80% by volume of the volume of the initial polymer particles, 
preferably about 10 to 60%. 
Suitable monomers which may be used to form the particle core include vinyl 
monomers or more usually a mixture of vinyl monomers consisting of both a 
di- or polyvinyl monomer and a monovinyl monomer. Suitable divinyl 
components include, e.g. divinylbenzene, divinylpyridine, ethylene 
dimethacrylate, ethylene diacrylate and divinylether. The monovinylic 
monomers will generally be chosen from the group comprising styrene, ring 
substituted styrenes, methacrylates, acrylates, conjugated dienes, and the 
like. The crosslinking monomer is present in the monomer mixture in an 
amount of from about 10 to 100% by volume. The total amount of monomers 
present in the three phase dispersion is calculated from the expected 
particle size taking into account the volume of the inert solvent and the 
volume of the primary particles themselves. 
In addition to the primary components of the three phase dispersion, the 
dispersion will also generally include both an emulsifier and a suspension 
stabilizer. Suitable ionogenic or non-ionogenic emulsifiers include such 
as sodium dodecyl sulfate, alkyl- or dialkyl phenoxypoly(ethyleneoxy) 
ethanol, and polyoxyethylene sorbitan esters of fatty acids. Suspension 
stabilizers of the sterical type which may be employed include polymers 
such as polyvinylalcohol, polyvinylpyrrolidone, polydiethylacrylamide, 
poly(2-hydroxypropyl methacrylamide), and hydroxypropyl cellulose. The 
emulsifier is generally present in an amount of from 1 to 5 g/l of the 
water phase while the concentration of the steric suspension stabilizer 
generally ranges from 5 to 30 g/l of the water phase. 
The process of the present invention will now be described with reference 
to the following non-limiting examples in which all parts and percents are 
by weight unless otherwise specified. 
EXAMPLE I 
Preparation of Soluble Polymer Particles 
Monodisperse polystyrene primary particles with a diameter of 1.5 .mu.m 
were prepared by a standard emulsifier-free emulsion polymerization as 
follows: in a 1000 ml round bottom reactor containing 700 ml of distilled 
water in which 0.65 g of sodium chloride was dissolved, 85 g of purified 
styrene was added. The mixture was flushed with nitrogen gas for 30 min 
and then heated to 75.degree. C. under stirring (350 rpm) and a nitrogen 
flushed solution of 0.5 g of potassium persulfate in 65 ml of distilled 
water was admixed. The polymerization proceeded at 75.degree. C. and 350 
rpm for 24 hours. The product was purified from the remaining salts by 
repeated centrifugation and redispersion by sonication in water until the 
supernatant was clear. The final dispersion contained 7.2% solids after 
evaporation. The yield from several different emulsifier-free emulsion 
polymerization runs ranged from 75 up to 86% based on the amount of 
styrene monomer. 
Preparation of Swollen Soluble Polymer Particles 
An emulsified mixture of solvent and initiator was prepared from 1.6 ml of 
dibutyl phthalate, 0.15 g of benzoyl peroxide, 10 ml of distilled water, 
and 0.075 g of sodium dodecyl sulfate by sonication using an ultrasonic 
homogenizer. To the emulsified mixture was added 3.5 ml of the dispersion 
of monodisperse polystyrene primary particles (7.2 wt %, solid=0.26 g, 1.5 
.mu.m in size, Mn=133,400). The mixture was stirred slowly for 5 hours at 
room temperature. 
After the adsorption of the solvent and initiator, to this mixture was 
added an emulsified mixture of monomers and porogenic solvent prepared 
from 1.5 ml of styrene, 4.8 ml of commercial divinylbenzene, 12.5 ml of 
toluene, 50 ml of distilled water, and 36 ml of a 10 wt % solution of 
poly(vinyl alcohol), (PVA), in water [87-89% hydrolyzed poly(vinyl 
alcohol) with molecular weight 85,000 to 146,000] by sonication using an 
ultrasonic homogenizer. The mixture was stirred slowly for 39 hours at 
room temperature. 
Preparation of Glycidyl Methacrylate Coated Particles 
To the above prepared swollen particles, 0.005 g of sodium nitrite was 
added and the dispersion was flushed with nitrogen gas for 20 minutes, 
then 2 ml of neat glycidyl methacrylate, a hydrophilic monomer which forms 
a hydrophilic surface layer on the styrene-divinylbenzene crosslinked 
copolymer core, was added to the reaction vessel. The heterogeneous 
mixture was heated to 70.degree. C. for 22 hours while stirring slowly to 
effect polymerization of the emulsified monomers and the nonemulsified 
glycidyl methacrylate. 
The polymerized dispersion was poured into 300 ml of methanol and the 
supernatant liquid was removed and discarded after sedimentation. The 
polymer particles were redispersed in 300 ml of tetrahydrofuran then 
allowed to sediment again and the supernatant liquid was discarded again. 
This procedure was repeated with 2 portions of tetrahydrofuran. Since the 
volume ratio of porogenic solvent to monomers was 63:37, the final polymer 
had approximately 60 vol % porosity. The final macroporous particles were 
essentially monodisperse with a size of 5 5 .mu.m while the yield was 85% 
based on the total weight of monomers. 
Ring Opening of Epoxide Group 
In order to increase the hydrophilicity of the polymerized glycidyl 
methacrylate surface, the epoxy rings of the glycidyl groups were opened 
to diol groups by acid hydrolysis as follows: 4.02 g of the macroporous 
particles were treated with 20 ml of 0.1 M H.sub.2 SO.sub.4 aqueous 
solution at 80.degree. C. for 4 hours with intermittent shaking, then the 
polymer particles were washed with water, followed by 50% aqueous 
methanol, methanol, and acetone and dried. A quantitative yield of 
macroporous polymer particles with a size of 5.5 .mu.m were recovered. 
Analysis of Particles Formed 
To confirm that hydrophobic core particles with a hydrophilic outer layer 
had been formed, the hydrophobicity and other properties of columns packed 
with the particles was tested in reversed-phase mode and compared to (i) 
particles having no hydrophilic outer layer and (ii) simple mixtures of 
hydrophobic and hydrophilic particles. Chromatographic tests were 
performed with the separation of a series of small molecules, i.e. 
alkylbenzenes, the mobile phase selected was 80% aqueous acetonitrile at 1 
mL/min. 
The test results demonstrate the production of the desired 
hydrophobic-hydrophilic layer structure as follows: 
(1) The particles exhibit a more hydrophilic character than particles 
having only a hydrophobic composition. In other words, measurements of 
hydrophobicity showed a lower value for the particles with the hydrophilic 
surface than for untreated hydrophobic particles. FIG. 1 plots the log k' 
(the capacity factor) as a function of the length of the carbon chain 
pendant on the benzene rings of the alkylbenzenes. The higher the slope of 
the line, the higher the hydrophobicity. As can be seen, the particles 
having a hydrophobic layer only are the most hydrophobic. 
(2) Since the hydrophilic outer layer particles produced also have 
hydrophobic cores, small molecules such as alkylbenzenes should be 
retained within the inner pores of the particles. As such, the retention 
time of the alkylbenzenes should be longer than would be the case if a 
mere mixture of hydrophobic and hydrophilic particles were present. This 
is actually observed. 
(3) The hydrophilic outer layer particles exhibit water-wettability while 
both hydrophobic particles and mixtures of hydrophobic and hydrophilic 
particles are non-water-wettable. 
These findings demonstrate that the particles produced have a hydrophilic 
outer layer and a hydrophobic core. 
EXAMPLE II 
An emulsified mixture of solvent and initiator was prepared from 1.9 ml of 
dibutyl phthalate, 0.17 g of benzoyl peroxide, 15 ml of distilled water, 
and 0.08 g of sodium dodecyl sulfate by sonication using an ultrasonic 
homogenizer. To this emulsified mixture was added 4.0 ml of the dispersion 
of monodisperse polystyrene primary particles prepared in Example I (7.2 
wt %, solid +0.3 g, 1.5 .mu.m in size, Mn=133,400 Daltons). The mixture 
was stirred slowly for 23 hours at room temperature. After the adsorption 
of the solvent and initiator, an emulsified mixture of monomers and 
porogenic solvent was added. This mixture was prepared from 8.5 ml of 
divinylbenzene (80%), 9.7 ml of toluene, 50 ml of distilled water, and 40 
ml of a 10 wt % solution of poly(vinyl alcohol) in water [PVA ca. 88% 
hydrolyzed with MW ca. 70,000 to 150,000 Daltons] by sonication using 
ultrasonic homogenizer. The mixture was stirred slowly for 47 hours at 
room temperature, then 0.01 g of sodium nitrite was added and the 
dispersion was flushed with nitrogen gas for 20 minutes. Then 1 ml of 
ethylene glycol dimethacrylate (neat liquid) was added and the whole 
heterogeneous mixture was heated to 70.degree. C. for 24 hours while 
stirring slowly to effect the polymerization. 
The polymer particles having hydrophilic groups on their surfaces were 
recovered as in Example I. The volume ratio of solvents to monomers in the 
above polymer preparation was 55:45 and thus the final polymer had about 
55 vol % porosity. The final macroporous particles were essentially 
monodisperse with a size of 6.5 .mu.m while the yield was 96% based on the 
total weight of monomers. 
Analysis of Particles Formed 
The particles were evaluated as in Example I. Although the monomer utilized 
to form the outer layer is not very hydrophilic, it exhibits the same 
relative benefits as in Example I. FIG. 2 is a plot of the log k' as a 
function of the length of the carbon chain pendant on the benzene rings of 
the alkylbenzenes. As can be seen, the particles having a hydrophobic-only 
composition are the most hydrophobic. 
EXAMPLE III 
An emulsified mixture of solvent and initiator was prepared from 1.9 ml of 
dibutyl phthalate, 0.17 g of benzoyl peroxide, 15 ml of distilled water, 
and 0.08 g of sodium dodecyl sulfate by sonication using an ultrasonic 
homogenizer. To this emulsified mixture was added 5.8 ml of the dispersion 
of monodisperse polystyrene primary particles prepared by a method similar 
to that of Example I (5.0 wt %, solid=0.3 g, 1.2 .mu.m in size). The 
mixture was stirred slowly for 24 hours at room temperature. To this 
mixture was added an emulsified mixture of monomers and porogenic solvent 
prepared from 9.2 ml of divinylbenzene (80%), 9.7 ml of toluene, 50 ml of 
distilled water, and 40 ml of a 10 weight % solution of poly(vinyl 
alcohol) in water [PVA ca. 88% hydrolyzed with MW ca. 70,000 to 150,000 
Daltons]0 by sonication using an ultrasonic homogenizer. The mixture was 
stirred slowly for 46 hours at room temperature. Then 0.01 g of sodium 
nitrite was added and the dispersion was flushed with nitrogen gas for 20 
minutes. Then 0.48 g of finely powdered solid 
(S)-N-methacryloyl-.alpha.-methylbenzylamine was added and finally the 
whole heterogeneous mixture was heated to 70.degree. C. for 10 hours while 
stirring slowly to effect the polymerization. 
The polymer particles having chiral groups on their surfaces were recovered 
as in Example I. Since the volume ratio of solvents to monomers was 52:48, 
the final polymer had about 50% porosity. The final macroporous particles 
were essentially monodisperse with a size of 4.4 .mu.m while the yield is 
89% based on the total weight of monomers. 
Analysis of Particles Formed 
The particles were evaluated as in Example I and the results of the 
hydrophobicity are shown in FIG. 3. In this case, the monomer used to form 
the outer layer, (S)-N-methacryloyl-.alpha.-methylbenzylamine, also 
contains a relatively hydrophobic phenyl group. Accordingly, the 
differences in the graphs are still evident, but less pronounced. This is 
however necessary for chiral separations due to the occurrence of pi-pi 
interactions. 
EXAMPLE IV 
An emulsified mixture of solvent and initiator was prepared from 1.9 ml of 
dibutyl phthalate, 0.17 g of benzoyl peroxide, 15 ml distilled water, and 
0.08 g of sodium dodecyl sulfate by sonication using an altrasonic 
homogenizer. To this emulsified mixture was added 5.8 ml of the dispersion 
of monodisperse polystyrene primary particles (5.0 wt %, solid=0.3 g, 1.2 
.mu.m in size). The mixture was stirred slowly for 24 hours at room 
temperature. 
After the adsorption of the solvent and initiator, to this mixture was 
added an emulsified mixture of monomers and porogenic solvent prepared 
from 9.2 ml of ethylene glycol dimethacylate, 9.7 ml of toluene, 50 ml of 
distilled water, and 40 ml of a 10 wt % solution of poly(vinyl alcohol) in 
water (PVA ca. 88% hydrolyzed with MW ca. 70,000 to 150,000 Daltons) by 
sonication using ultrasonic homogenizer. The mixture was stirred slowly 
for 46 hours at room temperature, then 0.01 g of sodium nitrite was added 
and the dispersion was flushed with nitrogen gas for 20 minutes. Then 0.48 
g of finely powdered solid (S)-N-methacryloyl--methylbenzylamine was added 
and the heterogeneous mixture was heated to 70.degree. C. for 23 hours 
while stirring slowly to effect polymerization. 
The polymer particles having chiral groups on their surfaces were recovered 
as in Example I. Since the volume ratio of solvents to monomers was 52:48, 
the final polymer had about 50 vol % porosity. The final macroporous 
particles were essentially monodisperse with a size of 4.4 .mu.m while the 
yield was 98.6% based on the weight of monomers. 
EXAMPLE V 
An emulsified mixture of solvent and initiator was prepared from 1.9 ml of 
dibutyl phthalate, 0.17 g of benzoyl peroxide, 15 ml distilled water, and 
0.08 g of sodium dodecyl sulfate by sonication using an altrasonic 
homogenizer. To this emulsified mixture was added 5.8 ml of the dispersion 
of monodisperse polystyrene primary particles (5.0 wt %, solid=0.3 g, 1.2 
.mu.m in size). The mixture was stirred slowly for 24 hours at room 
temperature. 
After the adsorption of the solvent and initiator, to this mixture was 
added an emulsified mixture of monomers and porogenic solvent prepared 
from 8 ml of divinylbenzene (80%), 9.7 ml of toluene, 50 ml of distilled 
water, and 40 ml of a 10 wt % solution of poly(vinyl aloohol) in water 
[PVA ca. 88% hydrolyzed with MW ca. 70,000 to 150,000 Daltons] by 
sonication using ultrasonic homogenizer. The mixture was stirred slowly 
for 46 hours at room temperature. Then 0.01 g of sodium nitrite was added 
and the dispersion was flushed with nitrogen gas for 20 minutes. Then 1 g 
of powdered (1R,2S)-2-[N-(4-vinyl)-benzoylamino]-1-phenylpropyl-(4-v and 
finally the whole heterogeneous mixture was heated to 70.degree. C. for 23 
hours while stirring slowly to effect polymerization. The polymerized 
dispersion was poured into 300 ml of methanol and the supernatant liquid 
was removed and discarded after sedimentation. 
The polymer particles having chiral group surfaces were recovered as in 
Example I. Since the volume ratio of solvents to monomers was 52:48, the 
final polymer had approximately 50 vol % porosity. The final macroporous 
particles were essentially monodisperse with a size of 4.5 .mu.m while the 
yield is 81% based on the total weight of monomers. 
Analysis of Particles Formed 
The particles were evaluated as in Example I and demonstrated the same more 
hydrophilic behavior than the hydrophobic "core-only" particles. 
EXAMPLE VI 
An emulsified mixture of solvent and initiator was prepared from 1.9 ml of 
dibutyl phthalate, 0.17 g of benzoyl peroxide, 15 ml distilled water, and 
0.08 g of sodium dodecyl sulfate by sonication using an altrasonic 
homogenizer. To this emulsified mixture was added 5.8 ml of the dispersion 
of monodisperse polystyrene primary particles prepared in Example III (5.0 
wt %, solid=0.3 g, 1.2 .mu.m in size). The mixture was stirred slowly for 
24 hours at room temperature. 
After the adsorption of the solvent and initiator, to this mixture was 
added an emulsified mixture of monomers and porogenic solvent prepared 
from 8 ml of divinylbenzene (80%), 9.7 ml of toluene, 50 ml of distilled 
water, and 40 ml of a 10 wt % solution of poly(vinyl alcohol) in water 
[PVA ca. 88% hydrolyzed with MW ca. 70,000 to 150,000 Daltons] by 
sonication using ultrasonic homogenizer. The mixture was stirred slowly 
for 46 hours at room temperature. Then 0.01 g of sodium nitrite was added 
and the dispersion was flushed with nitrogen gas for 20 minutes. Then 1 g 
of powdered (1R, 2S)-2-(N-methacryloylamino)-1-phenylpropyl methacrylate 
was added and the heterogeneous mixture was heated to 70.degree. C. for 10 
hours while stirring slowly to effect polymerization. 
The polymer particles having chiral groups on their surfaces were recovered 
as in Example I. Since the volume ratio of solvents to monomers was 52:48, 
the final polymer had about 50 vol % porosity. The final macroporous 
particles were essentially monodisperse with a size of 4.0 .mu.m while the 
yield is 95% based on the total weight of monomers. 
EXAMPLE VII 
An emulsified mixture of solvent and initiator was prepared from 1.9 ml of 
dibutyl phthalate, 0.17 g of benzoyl peroxide, 15 ml distilled water, and 
0.08 g of sodium dodecyl sulfate by sonication using an altrasonic 
homogenizer. To this emulsified mixture was added 5.8 ml of the dispersion 
of monodisperse polystyrene primary particles prepared in Example I (5.0 
wt %, solid=0.3 g, 1.2 .mu.m in size). The mixture was stirred slowly for 
24 hours at room temperature. 
After the adsorption of the solvent and initiator, to this mixture was 
added an emulsified mixture of monomers and porogenic solvent prepared 
from 8.5 ml of ethylene glycol dimethacylate, 9.7 ml of toluene, 50 ml of 
distilled water, and 40 ml of a 10 wt % solution of poly(vinyl alcohol) in 
water [PVA ca. 88% hydrolyzed with MW ca. 70,000 to 150,000 Daltons] by 
sonication using ultrasonic homogenizer. The mixture was stirred slowly 
for 46 hours at room temperature. Then 0.01 g of sodium nitrite was added 
and the dispersion was flushed with nitrogen gas for 20 minutes. Then 1 g 
of finely powdered 
(1R,2S)-2-[N-(4-vinyl)-benzoylamino]-1-phenylpropyl-(4-vinyl)-benzoate was 
added and the heterogeneous mixture was heated to 70.degree. C. for 24 
hours while stirring slowly to effect polymerization. The polymerized 
dispersion was poured into 300 ml of methanol and the supernatant liquid 
was removed and discarded after sedimentation. 
The polymer particles having chiral group surfaces were recovered as in 
Example I. Since the volume ratio of solvents to monomers was 52:48, the 
final polymer had about 50 vol % porosity. The final macroporous particles 
were essentially monodisperse with a size of 4.3 .mu.m while the yield is 
98% based on the total weight of monomers. 
EXAMPLE VIII 
This example is similar to Example V with the exception that a much larger 
amount of the functional monomer was added as a solid chunk. Also, as the 
amount of functional monomer was very large (50% of the total monomer 
content) some acetone was added as the polymerization was initiated to 
assist in transport of the non-emulsified functional monomer from the 
solid chunk to the polymerizing droplets. 
An emulsified mixture of solvent and initiator was prepared from 1.9 ml of 
dibutyl phthalate, 0.17 g of benzoyl peroxide, 15 ml distilled water, and 
0.08 g of sodium dodecyl sulfate by sonication using an altrasonic 
homogenizer. To this emulsified mixture was added 5.8 ml of the dispersion 
of monodisperse polystyrene primary particles prepared in Example I (5.0 
wt %, solid=0.3 g, 1.2 .mu.m in size). The mixture was stirred slowly for 
24 hours at room temperature. 
After the adsorption of the solvent and initiator, to this mixture was 
added an emulsified mixture of monomers and porogenic solvent prepared 
from 4.8 ml of divinylbenzene (80%), 9.7 ml of toluene, 50 ml of distilled 
water, and 40 ml of a 10 wt % solution of poly(vinyl alcohol) in water 
[PVA ca. 88% hydrolyzed with MW ca. 70,000 to 150,000 Daltons] by 
sonication using ultrasonic homogenizer. The mixture was stirred slowly 
for 46 hours at room temperature. Then 0.01 g of sodium nitrite was added 
and the dispersion was flushed with nitrogen gas for 20 minutes. Then 4.8 
g of chunk (1R, 
2S)-2-[N-(4-vinyl)-benzoyl-amino]-1-phenylpropyl-(4-vinyl)-benzoate and 5 
ml of acetone were added and heated to 70.degree. C. for 24 hours while 
stirring slowly to effect polymerization. The polymerized dispersion was 
poured into 300 ml of methanol and the supernatant liquid was removed and 
discarded after sedimentation. 
The polymer particles were recovered as in Example I. Since the volume 
ratio of solvents to monomers was 52:48, the final polymer had about 50 
vol % porosity. The final macroporous particles were essentially 
monodisperse with a size of 4.5 .mu.m while the yield was 72% based on the 
weight of monomer. 
Analysis of Particles Formed 
Examination by optical microscopy visually confirmed that the final 
particles contained different outer and inner layers (core-shell type). 
The low yield obtained is due to the fact that incomplete transfer of the 
large chunk of monomer was achieved. Some unreacted functional monomer was 
recovered at the end of the process. 
EXAMPLE IX 
A separation of chiral compounds was performed using a column packed with 
the material produced as described in Example V. The hplc chromatographic 
testing was performed in normal phase mode using a non-aqueous organic 
solvent (n-hexanetetrahydrofuran 4:1 v/v) at 0.5 mL/min with a column 4.6 
mm ID X 150 mm long, peak detection was carried out using a UV detector at 
254 nm. The solutes were .alpha.-methylbenzylamine derivatives in which 
.alpha.=k'.sub.R /k'.sub.S, wherein R and S are the two enantiomers being 
separated. For sample 1 (FIG. 5, Z=H) the .alpha. value was determined to 
be 0.99. For sample 2 (FIG. 5, Z=NO.sub.2) the .alpha. value was 1.05. 
EXAMPLE X 
In Example III only 5 wt % of the chiral monomer was used. When the 
resultant particles were evaluated for chiral recognition, it was 
determined that they were relatively ineffective. Accordingly, the 
procedure of Example III was repeated except that the amount of the chiral 
monomer introduced was increased to 20 wt %, i.e. the amount of divinyl 
benzene was 7.76 mL and the amount of chiral monomer was 1.94 g. The yield 
of final particles was 65% due to some loss of material from the outer 
non-crosslinked layer during the tetrahydrofuran washing. The final 
particles showed more hydrophilicity than did those particles of Example 
III. 
The resulting particles were evaluated as in Example IX above for chiral 
separation performance. The results of the two separations afforded 
.alpha. values of 0.94 for each of the samples.