Formation
and Characterization of Molecularly Imprinted Nanoparticles and Nanoparticle Growth
This project will: Develop technology for formation and
characterization of nanoparticles and nanoparticle
growth. The skills developed will be
applied to determining the role of size of particles synthesized on the
properties exhibited.
Primary
Faculty co-Advisors
David A. Spivak, Department of Chemistry,
LSU (Organic Polymer Synthesis)
Off-campus
Participant: Pat Cotts (Dupont)
Technical Proposal:
INTRODUCTION
Molecularly imprinted polymers (MIP’s) can be tailored to bind specifically a targeted molecule or catalyze a desired reaction. Barriers to implementing imprinted polymers in industrial applications are related to the following disadvantages:
·
Distribution
of Sites providing "good" sites and "bad" sites that
combine to show an overall poor performance (there are many more
"bad" sites than "good" sites).
·
Low Affinities
due to the distribution of sites.
·
Slow Mass
Transfer Kinetics that lower the rate of catalysis and sensor response due
to slow diffusion in and out of the polymer matrix.
The goal of this research is the development of molecularly imprinted nanoparticles, followed by separation of particles with "good sites" from the particles with "bad sites"-- which is anticipated to solve the major problems of MIP's.
RESEARCH PLAN
Developing
EGDMA Microemulsions for Molecular Imprinting. Although it has been determined that
molecular imprinting is optimized by using ethylene glycol dimethacrylate
(EGDMA) as the cross-linking monomer, very few small particle polymerizations
have been reported using EGDMA. All have
been suspension polymerizations, not emulsion polymerizations. One of the reasons has been the problem of
removing the surfactant from the emulsified particles once polymerized. Precipitation of microsuspension
particles using methanol has been reported, but this technique was not
successful, under any conditions, for a clear emulsion made with DTAB (dodecyl trimethyl ammonium
bromide) and thermally polymerized in our lab.
Alternatively, we have developed ultrafiltration
methods to separate small particles regardless of precipitation properties.
Design of template-monomer emulsion system. Scheme 1 outlines the strategy described in this proposal; the key is the covalent complex 1 (synthesized as shown
Scheme 1. Outline of strategy for imprinted
nanoparticles by emulsion polymerization.
in scheme 2), between benzophenone and glycerol monomethacrylate. Removal of the benzophenone template by hydrolysis leaves diol functionality in the polymer which is anticipated to have size selectivity. The imprinted nanoparticle will be tested for rebinding that is selective for the smaller benzophenone versus the larger methyl-pyrene ketone (figure 1).
Scheme 2.
Synthesis of the covalent template.
Evaluation of Particle Size. Evaluation of particle size by Dynamic Light Scattering (DLS) and TEM has shown the process described above to give particles in the range of 20-40 nm.
Imprinting and Rebinding Studies. The incorporation of the ketal monomer into the polymer matrix was not a problem, as shown by HPLC data of the hydrolysis showing high yields of acetophenone recovery. The rebinding of ketones has so far proven to be very difficult, most likely due to the low yielding ketal formation reaction. Initial attempts at rebinding acetophenone to reform the ketal have so far not been successful using traditional methods. To quantify the amount of selectivity for different ketones within the polymer particles will require further study (for example, figure 1).
Figure 1. Different sized ketones to determine size selectivity of particles.
Continuing Goals of Project. Demonstration of size selectivity will be achieved either by the system at hand, or another related system. Upon successful demonstration of size selection, we will separate particles with "good sites" using affinity chromatography and affinity immobilization methods.
Consistency with the Macromolecular
Education, Research & Training theme:
The training and development of
How does the project form a vector
cross-product of existing research themes by the participants?
Existing research
directions. Broadly defined, research in the
Spivak group involves the development of synthetic methodology applied to
construction of organic and bioorganic polymers with engineered architecture,
functionality and function. Potential
applications are in the areas of chromatography, catalysis, biomedical
materials, molecular recognition and sensor technology. The Russo group is interested in what might
be called "complex" solutions and the materials that can be made from
them. For example, high-performance aramid fibers are
processed from solutions of rigid rodlike polymers. The dynamics of such
solutions is a major question in polymer physical chemistry, and one of our
main areas of interest. By laser light scattering and fluorescence
photobleaching recovery methods, we can assess the mobility of rodlike polymers
and other species, such as small dyes, in very crowded solutions, gels, and
even melts.
New research direction. Combining the expertise of the Spivak and
Russo groups will allow development of novel nanosized
materials and their characterization.
How do students benefit from the
team-oriented research, beyond what would be available to them from either
advisor separately?
The
students benefit from the team-oriented approach by receiving training in
different areas of polymer technology from experts in the field. This affords rapid advancement of the student
through qualified mentorship unavailable from just one advisor. Without this team-approach, students are left
on their own to learn skills and technology through long and painstaking
trial-and-error approaches. There will
still be plenty of room for trial and error, but students will have seen how
research master craftspersons handle those
disappointing times.
Support level available to each
individual faculty:
Funding
from Professor Spivak's group for this project comes
from two sources:
1. Oak Ridge Associated Universities, Ralph E. Powe Junior Faculty Enhancement Award: "Nano-imprinting: Formation of Molecularly Imprinted Nanoparticles," 61/00-5/31/03, $10,000, PI: David A. Spivak.
2. Research Corporation, Cottrell Scholar Award: "Controlling the Molecular Architecture of Functionalized Organic Materials using Fluoro-Organic Mesophases," CS0801, 6/1/01 - 5/1/03, $75,000, PI: David A. Spivak.
Funding in the Russo Group includes the following:
1. Inhibition of Fibrillogenesis with beta-Strand Mimics, NIH, $1,200,000 (06/01/00-05/30/03), with PI Robert Hammer (LSU) and co-investigators R. L. McCarley and Mark L. McLaughlin.
2. Complex Fluids with Extended, Rigid Components, NSF, $330,000 (06/01/00-05/30/03)
3. Synthesis and Characterization of Composite Polypeptide-Silica Colloidal Particles, ACS, $60,000 (07/15/99 - 06/30/01).
4. Macromolecular Development Fund, Dow, $30,000 (open-ended)
5. Polymer Characterization, Dow, $25,000 (09/01/00 - 08/31/01)
6. Mechanism of Action of Insecticidal Toxin CYT1A, a Biophysical and Biochemical Approach, USDA, $19,040 (08/01/00 - 07/30/03). A subcontract with principle investigator Peter Butko (University of Southern Mississippi).
Interdisciplinary strengths of the team
project: Professor
Spivak's group provides support for learning the
synthetic organic aspects of macromolecular chemistry. Mr. Campbell will learn all aspects of
organic synthesis with an emphasis on monomer synthesis and
characterization. Mr. Campbell will go
on the learn methods of polymer synthesis and modification, directed toward the
research goals. Under Professor Russo's
tutelage, Mr. Campbell will be able to perform in-depth analysis of size,
composition, and dynamics of the polymer products. The strength of this joint venture is the
ability to train Mr. Campbell in the full spectrum of polymer development, from
design to synthesis to characterization.
Commitment of faculty & off-campus participants to work side-by-side with apprentices:
During the Summer
2001, Prof. Spivak will spend 2-3 weeks with
For a total of ten days during the summer
of 2001, Mr. Campbell will work with Prof. Russo to design, construct and test
improvements to the dynamic light scattering (DLS) apparatus. It is anticipated that Prof. Russo can work
5-6 hours per day on task (in the laboratory, working directly with the
student). The nature of this type of
research is stop and go. For example,
after designs are submitted to the machine shop, there is a delay in the
project until the designs are completed.
Some portion of the testing may be conducted using human influenza
virus, a singularly monodisperse preparation that undergoes changes that should
be captured by Laplace inversion. That
portion of the research would be done under the joint tutelage of Prof. Russo and
Prof. Richard Epand of McMaster University,
Canada. Dr. Rafael Cueto
of the Basic Sciences/Chemistry technical staff will also participate in the
training. Mr. Campbell will also undergo
apprenticeship training with Prof. Spivak (next paragraph). He will "shadow" the DOSY/FPR/DLS
project of student Nadia Edwin and the Small Angle X-ray Scattering
construction project, which involves Professors Thomas, Russo and Negulescu
plus off-campus participant Greg Beaucage and
trainees Thomas Morgan, Mariah Mc Masters, and