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Student
Abstracts: Chemistry at BNL
Characterization of Functionalized Carbon Nanoloop-Antibody Structures as Membrane Probes.
CORY DAIGNAULT
(Florida State University,
Tallahassee, FL 32306)
JOHN WARREN
(Brookhaven National Laboratory, Upton, NY 11973).
Carbon nanotubes have recently attracted considerable study in the scientific
community due to their unique structure dependent, mechanical and electrical
properties. Thus far their applications to biology have been limited, though
their robust nature has many potential applications. This investigation
focuses on the functionalized nanoloops by attaching monoclonal antibodies for
the gC1q-R receptor protein (74.5.2 and 60.11) to the surface of nanoloops,
ring-shaped single-walled carbon nanotubes. Atomic force microscopy (AFM) and
transmission electron (TEM) microscopy were used to characterize the protein
functionalized carbon nanotubes loops. The loops were made by treating single
walled nanotubes (SWNT) with acid, heat, and sonication in the presence of
H2O2. These chemically cut tubes were treated with carbodiimide to form loops
and attach the biological proteins. The average widths of the functionalized
loops ranged from 25-36 nm and the heights ranged from 1.6-3.0 nm. The height
value reported refers to the material trapped and apparently bound in the
central cavity, for the loops with protein treatment. These nanoscale
complexes have a size that can be seen using AFM and TEM. Due to these
properties, the antibody-nanoloop complexes may provide for delivery systems
for doing dynamic living cellular experiments.
d-threo-methylphenidate induced increase in striatal dopamine unaffected by l-threo-methylphenidate pretreatment. .
SARA GONZALEZ
(University of Scranton,
Scranton, PA 18510)
MADINA GERASIMOV
(Brookhaven National Laboratory, Upton, NY 11973).
Each year, millions of patients diagnosed with attention-deficit hyperactivity
disorder (ADHD) are treated with methylphenidate (MP, Ritalin®).
Methylphenidate is marketed as a racemic mixture of l-threo-methylphenidate
(l-threo-MP) and d-threo-methylphenidate (d-threo-MP). The d-threo form works
by selectively blocking dopamine (DA) transporters and increasing synaptic DA
concentrations. The l-threo form has been thought to have no significant
effect on DA. In this study, microdialysis and high pressure liquid
chromatography (HPLC) were used to investigate whether l-threo-MP attenuates
the dopaminergic effects of d-threo-MP when administered 15 minutes prior to
the pharmacologically active enantiomer. Effects of MP were evaluated as a
function of the change from the basal levels of extracellular DA in the corpus
striatum of the rat brain. Three groups of 250-300g rats were treated with 5.0
mg/kg of d-threo-MP administered intraperitoneally. One group of animals
received no other treatment, another group received a saline injection 15
minutes prior to injection with d-threo-MP, and a third group was injected with
5.0 mg/kg l-threo-MP 15 minutes prior to injection with d-threo-MP.
Pretreatment with l-threo-MP resulted in a mean initial DA increase of 362% 15
minutes following the administration, which was not significantly different
from the mean initial increase demonstrated in the group with no pretreatment
(471%, p=0.196, two tailed t-test) or in the group pretreated with saline
(431%, p=0.489). This evidence suggests that the l-threo enantiomer does not
reduce the efficacy of the active d-threo form.
d-threo-methylphenidate induced increase in striatal dopamine unaffected by l-threo-methylphenidate pretreatment.
SUZANNE HULME
(McGill University,
Montreal, QC H3A 2T5)
MADINA GERASIMOV
(Brookhaven National Laboratory, Upton, NY 11973).
Each year, millions of patients diagnosed with attention-deficit
hyperactivity disorder (ADHD) are treated with methylphenidate (MP, Ritalin®).
Methylphenidate is marketed as a racemic mixture of l-threo-methylphenidate
(l-threo-MP) and d-threo-methylphenidate (d-threo-MP). The d-threo form works
by selectively blocking dopamine (DA) transporters and increasing synaptic DA
concentrations. The l-threo form has been thought to have no significant
effect on DA. In this study, microdialysis and high pressure liquid
chromatography (HPLC) were used to investigate whether l-threo-MP attenuates
the dopaminergic effects of d-threo-MP when administered 15 minutes prior to
the pharmacologically active enantiomer. Effects of MP were evaluated as a
function of the change from the basal levels of extracellular DA in the corpus
striatum of the rat brain. Three groups of 250-300g rats were treated with 5.0
mg/kg of d-threo-MP administered intraperitoneally. One group of animals
received no other treatment, another group received a saline injection 15
minutes prior to injection with d-threo-MP, and a third group was injected with
5.0 mg/kg l-threo-MP 15 minutes prior to injection with d-threo-MP.
Pretreatment with l-threo-MP resulted in a mean initial DA increase of 362% 15
minutes following the administration, which was not significantly different
from the mean initial increase demonstrated in the group with no pretreatment
(471%, p=0.196, two tailed t-test) or in the group pretreated with saline
(431%, p=0.489). This evidence suggests that the l-threo enantiomer does not
reduce the efficacy of the active d-threo form.
Synthetic Methods and Administration of [11C]Acetone For Positron Emission Tomography.
RYAN MULLER
(College of William and Mary,
Williamsburg, VA 23186)
STEPHEN L. DEWEY
(Brookhaven National Laboratory, Upton, NY 11973).
As acetone has become an increasingly abused inhalant worldwide, researchers
have developed a radiotracer form of the compound, [11C]acetone, for positron
emission tomography (PET) studies. Since the synthetic scheme for [11C]acetone
calls for the rapid delivery of 11CO2 to an isolated reaction vial, a system
was designed to trap and release 11CO2 from cyclotron target gas without the
moisture condensation difficulties of cryogenic trapping. Beyond the target gas
trap, a valve-operated reaction panel was constructed and has successfully
generated radiochemically pure [11C]acetone for PET imaging. This radiotracer
has since been administered to an anesthetized rat and imaging results
demonstrate high uptake in the brain. Pharmacokinetic analysis indicated an
8-minute washout half-time in the striatum and cerebellum. Encouraging results
from these initial imaging studies indicate the potential for [11C]acetone to
be imaged further in primate and human protocols.
Synthesis of a Novel Boron-Containing Porphyrin.
JARED NIED
(Long Island University, Southampton College,
Hampton Bays, NY 11946)
MICHI MIURA
(Brookhaven National Laboratory, Upton, NY 11973).
Gliblastoma multiforme is a virulent, aggressive type of brain cancer that
arises from the astrocystes that for the blood-brain barrier and protect the
brain's neurons. GBM is so malignant and lethal that the median survival time
after diagnosis is a mere 8.6 months, with a totally negligible percent of
patients surviving to 5 years. Conventional treatments, consisting of surgery
to remove most of the tumor mass and radiation therapy to attempt to kill any
remaining cells, shows little if any promise of extending survival times. A
promising possible therapy for these types of cancer is boron-neutron capture
therapy, which is a bimodal therapy consisting of a boron-10 containing
compound and a beam of thermal neutrons. When the neutrons encounter the
boron-10, the boron splits into a lithium-7 nucleus, an alpha particle, and
gamma radiation. The damage that these particles cause is entirely confined to
the cell containing the boron. If boron compounds are selected that will
preferentially accumulate in tumor cells, the therapy will prove extremely
lethal to those cells, while leaving healthy tissue unscathed ? since it does
not contain boron, the neutrons pass through it uneventfully. Porphyrins are
one class of chemical that has been found to selectively uptake into tumor
cells. This project focuses on the total synthesis of a novel boron-containing
porphyrin for BNCT.
Modification of FORTRAN Code to Analyze Data of Pulse Radiolysis Method.
BHAUTIK PATEL
(Rutgers University,
Jersey city , NJ 07307)
DR. JOHN MILLER
(Brookhaven National Laboratory, Upton, NY 11973).
Abstract:
Long-distance electron transfer has been studied in several systems in which D
and A have been kept apart by a rigid spacer group or by incorporating them in
rigid glass or polymers. Recent crystallographic work and kinetic measurements
on photosynthesis reaction centers have shown that nature makes use of LDET in
on of the most important processes known, photosynthesis. Our research involves
the synthesis of suitable molecules, tailor-design to measure intermolecular
electron-transfer rates of the type
A1 '- Sp '- A2- -A1 '- Sp '- A2
where A1 and A2 are group with finite electron and Sp is a rigid spacer with no
electron affinity of its own. The experiment involves the generation of
negative radical ions from the molecules by pulse radiolysis and the kinetic
measurement of the intermolecular electron-transfer rates establishing
equilibrium by optical absorption. This chemical reaction is measured by
passing radiation beam light through mixture. In this experiment, chemical
reaction happens within nanoseconds or Picoseconds over the time period, and
this data are collected in VAX machine to observe the result by using FORTRAN
code. This code execute on legacy Vax system. Plotting and graphing data
hauling of data require detail instructions (calls). This problem resolved by
using IGOR software, which especially made for research purpose and has
constructive options like graphics, procedure window, built in functions.
Research Category: Computer science
Is this being submitted for publication? No
DOE Program: Energy Research Undergraduate Laboratory Fellowships
Investigation of Electromagnetic Spectrum of HCBr Radical.
PINTO ROSANGELY
(University of Purto Rico, Cayey Campus,
Cayey, P.R. 00736)
SEARS TREVOR
(Brookhaven National Laboratory, Upton, NY 11973).
Bromomethylene (HCBr) is a reactive species belonging to the carbene (divalent
carbon containing compounds) family. It is formed as a short-lived
intermediate in the burning of bromine-containing fuels and in the chemistry of
the polluted atmosphere. Spectroscopic methods may be used to monitor the
presence and concentration of this species in chemical reaction systems, and we
reported the observation and rotational analysis of part of the visible
spectrum of the radical for the first time. HCBr was made by photolysis of
bromoform (CHBr3), in an excess of Helium in a slow-flow gas mixture, at 193 nm
using a pulsed excimer laser. The HCBr radical was detected by the absorption
of single frequency continuous-wave dye laser pumped by an Argon ion laser.
The weak absorption lines were measured using frequency modulation of a dye
laser beam followed by demodulation of the signal from a fast photodiode
detector monitoring the transmitted laser beam. The spectrum was measured
relative to the well-known spectrum of iodine and the line positions were
estimated to be accurate to within 0.02 cm-1. Approximately 100 rotational
lines in the 060 '000 band (here the numbers correspond to the three
vibrational quantum numbers in each electronic state) were assigned. Their
positions were used to determine the upper state rotational energy levels and
thereby estimate the structure of the radical in this state. These results
will be useful for future studies of chemical reactivity of this species and
for monitoring the radical in chemical reaction systems.
Synthesis of [11-C]Nisoxetine for PET Study of Norepinephrine Transporters.
DAVA SZALDA
(Syracuse University,
Syracuse, NY 13210)
DR. YU-SHIN DING
(Brookhaven National Laboratory, Upton, NY 11973).
Positron Emission Tomography (PET) is a valuable medical imaging tool in
studying the functions of various neurotransmitters in the brain. Nisoxetine,
a potent norepinephrine reuptake inhibitor, can potentially be used to study
the norepinephrine transporters using PET. In order to label nisoxetine, a
precursor must be made through the demethylation of nisoxetine. The precursor
will react with [11C]CH3I in order to create [11C]nisoxetine for PET studies.
The synthesis of the precursor was attempted using both N-demethylation and
O-demethylation techniques. N-demethylation was carried out using the reagent
1-chloroethyl chloroformate while O-demethylation was attempted using a
diphenyl phosphine and butyllithium complex. A desired product was obtained in
model reactions, however, demethylation of nisoxetine did not afford the
desired precursor. These studies provide valuable information in choosing an
appropriate protecting group for the amino function before the O-demethylation.
Further investigations are underway.
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