Geckeler K.E., Nishide H. (Eds.) Advanced Nanomaterials
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References 649
Borja - Aburato , V. and Diaz - Brriga , F.
( 2001 ) Environ. Res. , 85 , 69 .
61 Denizli , A. , Buyuktuncel , E. , Tuncel , A. ,
Bektas , S. and Genc , O. ( 2000 ) Environ.
Technol. , 21 , 609 .
62 Li , Y.H. , Di , Z. , Ding , J. , Wu , D. , Luan , Z.
and Zhu , Y. ( 2005 ) Water Res. , 39 , 605 .
63 Li , Y. , Zhu , Y. , Zhao , Y. , Wu , D. and
Luan , Z. ( 2006 ) Diamond Relat. Mater. ,
15 , 90 – 4 .
64 Katz , S.A. and Salem , H. ( 2006 ) J. Appl.
Toxicol. , 13 , 217 .
65 Di , Z.C. , Li , Y. , Luan , Z. and Liang , J.
( 2004 ) Adsorpt. Sci. Technol. , 22 , 6 .
66 Di , Z.C. , Ding , J. , Peng , X. - J. , Li , Y. - H. ,
Luan , Z. - K. and Liang , J. ( 2006 )
Chemosphere , 62 , 861 .
67 Mohan , D. and Singh , K.P. ( 2002 ) Carbon ,
36 , 2304 .
68 Li , Y. , Wang , S. , Luan , Z. , Ding , J. , Xu , C.
and Wu , D. ( 2003 ) Carbon , 41 , 1057 .
69 Toles , C.A. , Marshall , W.E. and Johns ,
M.M. ( 1999 ) Carbon , 37 , 1207 .
70 Wu , C.H. ( 2007 ) J. Colloid Interface Sci. ,
311 , 338 .
71 Rainbow , P.S. , Hopkin , S.P. and Crane ,
M. ( 2001 ) Forecasting the Environmental
Fate and Effects of Chemicals , John Wiley
& Sons, Inc. , New York .
72 Lu , C. and Chiu , H. ( 2006 ) Chem. Eng.
Sci. , 61 , 1138 .
73 Lu , C. , Chiu , H. and Liu , C. ( 2006 ) Ind.
Eng. Chem. Res. , 45 , 2850 .
74 Kadirvelu , K. , Senthilkumar , P. ,
Thamaraiselvi , K. and Subburam , V.
( 2002 ) Bioresour. Technol. , 81 , 87 .
75 Lu , C. and Liu , C. ( 2006 ) Chem. Technol. ,
81 , 1932 .
76 Li , Y. , Ding , J. , Luan , Z. , Di , Z. , Zhu , Y.
and Xu , C. ( 2003 ) Carbon , 41 , 2787 .
77 Hsieh , S.H. , Horng , J. - J. and Tsai , C. - K.
( 2006 ) J. Mater. Res. , 5 , 1269 .
78 Peng , X. , Luan , Z. , Di , Z. , Zhang , Z. and
Zhu , C. ( 2005 ) Carbon , 43 , 855 .
79 Hichour , M. , Persin , F. , Molenat , J. ,
Sandeaux , J. and Gavach , C. ( 1999 )
Desalination , 122 , 53 .
80 Hichour , M. , Persin , F. , Sandeaux , J. and
Gavach , C. ( 2000 ) Sep. Purif. Technol. , 18 , 1 .
81 Bishop , P.L. and Sansoucy , G. ( 1978 )
J. Am. Water Works Assoc. , 70 , 554 .
82 Buchanan , W.D. ( 1962 ) Toxicity of Arsenic
Compounds , Amsterdam , New York .
83 Peng , X. , Luan , Z. , Ding , J. , Di , Z. , Li , Y.
and Tian , B. ( 2005 ) Mater. Lett. , 59 , 399 .
84 Zhang , Z. , Liu , L. , Zhao , H. et al . ( 1996 )
J. Colloid Interface Sci. , 182 , 158 .
85 Wang , X. , Chen , C. , Hu , W. , Ding , P. ,
Xu , D. and Zhou , X. ( 2005 ) Environ. Sci.
Technol. , 39 , 2856 .
86 National Primary Drinking Water
Regulations, U.S. Environmental
Protection Agency 816 - F - 03 - 016, June
2003. http://www.epa.gov/safewater/
contaminants/index.html#listmcl .
87 Hileman , B. ( 2000 ) Chem. Eng. News , 29 ,
13 .
88 Yang , R.T. , Long , R.Q. , Padin , J. ,
Takahashi , A. and Takahashi , T. ( 1999 )
Ind. Eng. Chem. Res. , 38 , 2726 .
89 Kang , H.S. ( 2005 ) J. Am. Chem. Soc. , 127 ,
9839 .
90 Fagan , S.B. , Santos , E.J. , Filho , A.G. ,
Filho , J.M. and Fazzio , A. ( 2007 ) Chem.
Phys. Lett. , 437 , 79 .
91 Roberge , F. , Gravel , M.J. , Deschenes , L. ,
Guy , C. and Samson , R. ( 2001 ) Water Sci.
Technol. , 44 , 287 .
92 Hill , G.A. , Tomusiak , M.E. , Quail , B. and
Cleave , K.M.V. ( 1991 ) Environ. Prog. , 10 ,
147 .
93 Fagan , S.B. , Gira , E.C. , Mendesfi lho , O.J.
and Souzafi lho , A.G. ( 2006 ) Int. J.
Quantum Chem. , 106 , 2558 .
94 Rook , J.J. ( 1974 ) Water Treatment Exam. ,
23 , 234 .
95 Bull , R.J. , Brinbaum , L.S. , Cantor , K.P. ,
Rose , J.B. , Butterworth , B.E. , Pegram , R.
and Tuomisto , J. ( 1995 ) J. Fundam. Appl.
Toxicol. , 28 , 155 .
96 Lu , C. , Chung , Y. and Chang , K. ( 2006 )
J. Hazard. Mater. , 138 , 304 .
97 Yang , K. , Zhu , L. and Xing , B. ( 2006 )
Environ. Sci. Technol. , 40 , 1855 .
Molecular Imprinting with Nanomaterials
Kevin Flavin and Marina Resmini
651
Advanced Nanomaterials. Edited by Kurt E. Geckeler and Hiroyuki Nishide
Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
ISBN: 978-3-527-31794-3
20
20.1
Introduction
Molecular recognition plays a key role in the natural world, from DNA transcrip-
tion to immune responses and enzyme substrate recognition. Important biological
processes depend on the capability of small molecules to recognize their targets
in a selective and effi cient manner. During the past century, a great deal of
research was performed involving molecular recognition, not only to further our
comprehension of its role in biological processes but also to translate any fi ndings
to practical applications. The design of artifi cial receptors, capable of selective
molecular recognition, has been a goal of research groups in different disciplines
for use in a variety of processes such as catalysis, sensing, biological assaying, and
the separation of complex chemical mixtures.
One interesting approach for the development of artifi cial receptors is molecular
imprinting , and its application to polymeric materials. In this chapter we will
discuss the concept of molecular imprinting, and highlight recent advances in the
synthesis of molecularly imprinted polymer s ( MIP s) on the nanoscale. Included
will be methodologies for the preparation of nanoparticles, with a view to a more
rational and commercially viable receptor design, and imprinting methodologies
which utilize various other nanomaterials, such as nanowires, quantum dots,
fullerene, and dendrimers. The applications of these imprinted nanomaterials will
be discussed, highlighting those properties which are advantageous to each appli-
cation, together with details of the changes that will be needed in future in order
to maintain the practical potential of molecular imprinting.
20.1.1
Molecular Imprinting: The Concept
Molecular imprinting is a process where functional and crosslinking monomers
are copolymerized in the presence of the target analyte (the imprint molecule),
which acts as a molecular template [1] . The functional monomers initially form a
652 20 Molecular Imprinting with Nanomaterials
complex with the imprint molecule and, following polymerization, their
functional groups are held in position by the highly crosslinked polymeric struc-
ture. Upon removal of the imprint molecule, a cavity or recognition site is created
which is complementary to the original template used. A molecular memory is
therefore created in the polymeric matrix, which is now capable of recognizing
and rebinding the analyte with a very high specifi city. The interaction between
the template and the functional monomers can be either covalent, noncovalent,
or combinations of both, and the choice is largely dependent on the chemical
structure of both the template and monomers, and the intended application
(Figure 20.1 ).
The evolution of molecular imprinting, as a technique, will be briefl y discussed
in the following sections, together with descriptions of some of the chemical strate-
gies utilized for molecular imprinting, in terms of imprint molecule – monomer
interactions.
Figure 20.1 Schematic representation of the imprinting
process showing some of the interactions used in creating
affi nity in the binding site for the template. I, reversible
covalent interaction; II, semicovalent method; III, electrostatic
interaction with an oppositely charged monomer; IV,
noncovalent H - bonding.
20.1 Introduction 653
20.1.1.1 History of Molecular Imprinting
Towards the beginning of the last century, much effort was devoted to the develop-
ment of new materials and techniques for applications in chromatography [2] .
Among many of those scientists active in this fi eld was the soviet chemist M.V.
Polyakov, who reported unexpected absorption properties in silica particles pre-
pared by a novel synthetic procedure [3] . Silica prepared, in the presence of
benzene, toluene or xylene, was observed to selectively readsorb the additive
present during the preparation [4, 5] . This appears to be the fi rst point in the lit-
erature at which selective adsorption to polymeric materials had been observed
and explained in terms of a template effect [6] .
During the following decade, Pauling developed a theory of the structure and
process of formation of antibodies that laid the foundations for the development
of molecular imprinting [7] . Dickey, in 1949, reported the preparation of silica gel,
having specifi c affi nities for their predetermined substrates, using the same mech-
anistic approach described by Pauling [8] . Silica gels were prepared in the presence
of four different dyes, namely methyl - , ethyl - , n - propyl - and n - butyl orange (Figure
20.2 ). The dye was subsequently removed and in rebinding experiments the pres-
ence of any of these “ pattern molecules ” would bind the pattern molecule in
preference to the other three dyes. Several research groups pursued the prepara-
tion of specifi c adsorbents utilizing Dickey ’ s method [9, 10] . After a steady fl ow of
publications for 15 years, interest in imprinted silica materials experienced a
decline as a result of limitations in the stability of these preparations and the
reproducibility of the results obtained [2] .
The decline in research into imprinting with silica coincided with the publica-
tion of a report by Wulff and Sarhan in 1972, on the fi rst example of molecular
imprinting in synthetic organic polymers [11] . This report has been accredited
with stemming the current interest in imprinted materials as artifi cial antibodies.
By utilizing a covalent imprinting approach, Wulff and Sarhan succeeded in pre-
paring polymers with chiral cavities for the separation of racemic mixtures.
Research with imprinted materials accelerated when Mosbach et al . introduced a
simpler synthetic approach, which utilized noncovalent interactions of the “ tem-
plate ” species with the functional monomers [12] . At present, research groups
worldwide are focusing attention on the preparation of novel imprinted polymers
and new analytical and synthetic applications of molecularly imprinted materials.
In the following sections, we describe the covalent and noncovalent imprinting
approaches initially reported by Wulff and Mosbach, respectively, which are
Figure 20.2 Chemical structures of the alkyl orange dyes.
654 20 Molecular Imprinting with Nanomaterials
widely accredited to be the foundation for the fi eld of molecular imprinting, as it
is known today.
20.1.1.2 Covalent Imprinting
In the covalent imprinting strategy, the key step is the formation of a reversible
covalent bond between the template and the functional monomer. After polymeri-
zation the template is removed, leaving the binding site with the functional group
available for further covalent rebinding. Wulff utilized the reversible formation of
boronate ester - linkages very successfully, initially for the imprinting of glyceric
acid [11] , and later for a number of carbohydrate derivatives [13, 14] . In one
example, Wulff described the imprinting of a sugar (phenyl - α - D - mannopyranoside)
which was coupled with a vinyl - derivatized phenylboronic acid [13] . The template
monomer, illustrated in Figure 20.3 , was polymerized by free radical initiation in
the presence of a porogenic solvent and a large amount of crosslinking agent. The
template was subsequently removed through hydrolysis with water or methanol,
resulting in a template specifi c cavity.
The major advantage of the covalent approach is that the high - energy interac-
tions will lead to high association constants, and therefore increase template rec-
ognition and reduce nonspecifi c binding between the template and polymer.
Although, covalent strategies have been used successfully with boronate esters
[13] , Schiff ’ s bases (imines) [15] , ketals and acetals [16] , only certain compounds
such as alcohols, aldehydes, ketones, amines and carboxylic acids can be imprinted
using this approach. Moreover, the synthetic diffi culties associated with the prepa-
ration of a suitable polymerizable unit limit the applicability of this approach.
20.1.1.3 Noncovalent Imprinting
Currently, the most widely used technique to generate molecularly imprinted
binding sites is represented by the noncovalent approach developed by Mosbach
Figure 20.3 Schematic representation of a covalent imprinting
approach, using a sugar coupled with a vinyl - derivatized
phenylboronic acid [13] .
20.1 Introduction 655
[17] . This is based on a noncovalent self - assembly of the template with functional
monomers prior to polymerization with a crosslinking monomer and subsequent
template extraction, followed by rebinding via noncovalent interactions, such as
H - bonding, ion pairing, and dipole – dipole interactions. The most widely used
functional monomer for noncovalent imprinting is methacrylic acid ( MAA ), which
was initially proposed by Mosbach et al . [18] ; however, many other functional
monomers, such as 4 - vinylpyridine [19] and acrylamide [20] are commercially
available. A number of custom - designed functional monomers, such as N , N ′ -
diethyl(4 - vinylphenyl)amidine [21] , for use in catalysis, and trans - 4 - [ p - ( N , N -
Dimethylamino)styryl] - N - vinylbenzylpyridinium chloride [22] , used for fl uorescent
sensing, have also been reported.
Figure 20.4 illustrates the well - known noncovalent imprinting strategy of theo-
phylline using MAA as the functional monomer and ethylene glycol dimethacr-
ylate as the crosslinker [23] .
The monomer – template association complex can be obtained in situ simply by
adding the components to the reaction mixture. After polymerization, the template
is removed by extracting the polymer with acidifi ed methanol. The guest binding
Figure 20.4 Noncovalent imprinting of theophylline, using
methacrylic acid as the functional monomer and ethylene
glycol dimethacrylate as the crosslinker [23] .
656 20 Molecular Imprinting with Nanomaterials
by the polymer occurs through the corresponding noncovalent interactions. The
carboxylic acid function of the methyl methacrylate forms ionic interactions with
the amino groups and hydrogen bonds with polar functions. Dipole – dipole and
hydrophobic interactions are also thought to contribute.
The advantages of the noncovalent strategy are that the synthesis of covalent
monomer – template conjugates is unnecessary, and that the imprint molecule
is easily removed from the polymer under very mild conditions, as it is only
weakly bound by noncovalent interactions. Also, guest binding and guest release
via noncovalent interactions result in faster binding kinetics than occur in the
covalent approach. The main disadvantages are that the imprinting process may
not be very effi cient, as the monomer – template adduct is labile and not strictly
stoichiometric. In order to overcome these limitations, the polymerization condi-
tions must be carefully chosen so as to maximize noncovalent adduct formation
in the mixtures.
20.1.1.4 Alternative Molecular Imprinting Approaches
The two most extensively used strategies for molecular imprinting have been the
noncovalent and covalent approaches, respectively. However, a number of varia-
tions of these methods have been investigated in recent years, with the intention
of overcoming the disadvantages inherent in each approach. One such strategy
employs the stoichiometric noncovalent approach [24] , in which the complex
between the functional monomer and template is strong enough to ensure that
the equilibrium lies well in favor of complex formation; this can be achieved when
the association constant is ≥ 10
3
M
− 1
[25] . Semicovalent imprinting is another fre-
quently used strategy, which attempts to merge the advantages of the covalent and
the noncovalent approach. In this method, the template is bound covalently to the
functional monomer, either directly [26] or via a spacer [27] ; however, rebinding
occurs via noncovalent interactions only.
20.1.2
Towards Imprinting with Nanomaterials
The fi nal application of a target - imprinted polymer plays a key role in determining
the type of polymeric matrix to be used. Since the fi rst report of an example of
molecular imprinting, “ bulk ” polymerization has been the most frequently used
method for the production of MIPs. However, in this method the “ bulk ” material
must be ground mechanically, which results in a large size distribution of irregu-
larly shaped particles and sieved; this is not only time - consuming but can also
result in a substantial loss of material. Considerable advances have been made
over the past decade, in the basic methodologies available for the production of
receptor sites, and in the optimization of conditions for imprinting and subse-
quent rebinding [28] . In order to avoid the disadvantages associated with “ bulk ”
polymerization, alternative polymeric materials have been used, for example,
imprinted microbeads, fi lms, and membranes [28, 29] . In the case of beads that
are designed for chromatographic purposes, particle diameters of 25 – 38 μ m are
20.2 Molecular Imprinting in Nanoparticles 657
suitable for effi cient separation with reasonable back - pressures [30] . However,
when considering MIPs intended for catalysis, facilitated synthesis, sensing and
assaying, a progression from the micro - to the nanoscale has been a major aim of
many research groups. Aside from the obvious advantages that miniaturization
presents, good accessibility to as many recognition sites as possible and shorter
diffusion times to facilitate faster equilibrium between release and reuptake of the
template in the cavity, are central to requirements [31] . Ultimately, improvements
in the effi ciency of synthetic receptors, with respect to response times and reaction
rates, may depend on how closely the actual biological systems can be mimicked.
To do so would require signifi cant developments of MIPs on the nanoscale.
20.2
Molecular Imprinting in Nanoparticles
A variety of approaches for preparing imprinted particles in the nanometer size
range have proved successful. In this section we will review the various approaches,
and highlight recent developments and important applications.
20.2.1
Emulsion Polymerization
The fi rst reported synthesis of imprinted nanoparticles was over a decade ago by
Takagi and coworkers [32] , who successfully prepared a Cu
2+
- selective resin using
a novel template polymerization technique. Here, the target molecule (hydrophilic)
and the host – monomer (amphiphilic) approach and arrange themselves at the
interface of an oil - in - water emulsion. The oil phase, containing the monomer
and crosslinker, was subsequently polymerized, the result being a resin with par-
ticle sizes ranging from 400 to 500 nm. Although standard emulsion polymeriza-
tion has proved successful for molecular imprinting in nanoparticles [32 – 34] ,
core – shell emulsion polymerization is probably a more useful approach, as it
enables a much better control over particle size, polydispersity, and the location
of recognition sites.
20.2.1.1 Core – Shell Emulsion Polymerization
Core – shell emulsion polymerization consists of two steps that begin with the
preparation of a core latex in the absence of an emulsifi er. The core, which may
be prepared from a variety of materials [35 – 37] , is then mixed with another
monomer or mixture of monomers that produces the shell. The core – shell parti-
cles possess two types of property, one being endowed by the core (spherical
monodisperse nanoparticles) and the other by the shell (recognition layer).
P é rez et al . reported the synthesis of core – shell particles, in which a sacrifi cial
spacer method was used, for the imprinting of cholesterol [38] . Initially, 30 – 40 nm
MMA or styrene core particles were prepared, which were subsequently used in
a second - stage polymerization with ethyleneglycol dimethacrylate ( EGDMA ), in
658 20 Molecular Imprinting with Nanomaterials
the presence of a polymerizable cholesterol derivative (Figure 20.5 ). Following
template cleavage (carbonate ester hydrolysis) and removal, the recognition prop-
erties of the imprinted core – shell polymers were evaluated.
On comparison of the imprinted and nonimprinted polymers, a considerably
greater binding of cholesterol to the imprinted core – shells was evident. Similar
imprinted nanoparticles were also prepared with a magnetic core, which demon-
strated similar cholesterol rebinding properties to those particles prepared with
nonmagnetic cores; however, in the presence of a magnetic fi eld, a more effi cient
particle sedimentation – and thus removal from solution – was demonstrated. Sub-
sequently, P é rez et al . reported the preparation of imprinted nanoparticles char-
acterized by a poly(divinylbenzene) shell over a crosslinked poly(styrene) core [39] .
In this case, the second - stage polymerization was performed in the presence of
polymerizable surfactants (pyridinium 12 - (4 - vinylbenzyloxycarbonyl)dodecanesul-
fate (PS) and pyridinium 12 - (cholesteryloxycarbonyloxy)dodecanesulfate (TS), that
also acted as a template. Figure 20.6 illustrates the noncovalent imprinting
approach used, where the surfactant - like template aligns itself at the polymer –
water interface with the template region in the monomer phase. Following polym-
erization of the monomer phase, template removal creates hydrophobic recognition
sites at the surface of the beads. As the polymerized surfactant tails are also hydro-
lyzed, a polar surface is exposed which differentiates it from the imprinted regions.
P é rez and Mayes subsequently reported the successful imprinting of propranolol
by the more classical noncovalent approach in core – shell nanoparticles [40] .
Although, the binding capacity was lower than that usually measured for bulk
polymers imprinted with propranolol, this investigation proved that noncovalent
imprinting in core – shell particles was possible, despite the fact that they were
Figure 20.5 Schematic diagram of core – shell nanoparticles
with cholesterol - imprinted shells Adapted from Ref. [38].