FY2010 - Oak Ridge National Laboratory

Seed Money Fund—
Neutron Scattering Science Division
well as from NMR data acquired by us at 0.88 M. Further EPSR refinements on the φ–ψ angles (the
torsional angles that make up the glycosidic linkage of the two sugar residues) are under way. A
manuscript is in preparation.
Synthetic studies in the preparation of deuterated methyl cellobioside and methyl cellooligosaccharides
have been carried out. We have refined the procedures for selective hydrolysis of cellulose to produce
cellooligosaccharides of DP 2–6, with a preference for producing the DP 4 (tetrasaccharide) compound. A
Raney nickel exchange process is then used on their methyl glycosides to exchange D or H at most C–H
sites on the molecules that are attached to –O– groups. To date we have deuterated samples of the methyl
(and deuteriomethyl) di-, tri- and tetrasaccharides with precise levels of deuteration that are available for
neutron studies. The overall synthetic process to the cello-oligosaccharides includes isolation and
purification as their peracetates. The peracetates are then converted to their respective methyl glycosides
and deuterium exchanged by the Raney nickel process in D 2 O.
00500
Neutron Scattering Characterization of Sol-Gel Drug Delivery Systems
Hugh O’Neill, Gary A. Baker, Eugene Mamontov, and Volker S. Urban
Project Description
The aim of this project is to investigate the diffusive properties of model drugs within sol-gel drug
delivery systems of relevance in bone repair and joint replacement, using a combination of quasi-elastic
neutron scattering (QENS) and small-angle neutron scattering (SANS). This project addresses a major
scientific bottleneck in drug delivery research, namely, the ability to characterize the distribution and
diffusion of guest molecules in host carriers. We anticipate that the combination of QENS and SANS can
provide unheralded benefits in the characterization of both the structural and dynamic properties of
realistic drug delivery materials, by providing information where other characterization techniques used
to date have provided only indirect or qualitative evidence, or in cases where other approaches have failed
entirely. This will be the first demonstration of using QENS to measure the dynamics and diffusion of
pharmaceuticals within confined environments relevant to drug-delivery platforms.
Mission Relevance
The DOE Office of Basic Energy Sciences, particularly the Chemical Sciences, Geosciences and
Biosciences Division, has active programs that focus on the investigation of interactions at interfaces and
also the influence of weak interactions on transport in complex, real-world materials. Demonstration of
the unique capabilities of neutron science for biomedical research would attract future funding and also
generate a new user community at the neutron facilities in ORNL. The National Institute of Biomedical
Imaging and Bioengineering (NIBIB) recently had several calls for proposals in areas such as
“Biomaterials and Biointerfaces,” “Enabling Technologies for Tissue Engineering and Regenerative
Medicine,” and “Bioengineering Grants.” The work proposed here would be well suited to these calls.
Results and Accomplishments
The structure and dynamic properties of a sodium benzoate–silica composite material, a model drug
delivery system, were analyzed by QENS and SANS. SANS showed that the gels are highly branched
structures with relatively large pore sizes (550 nm). Using QENS, it was possible to extract the diffusion
coefficients for three solutes in the composite material that can be related to D 2 O, benzoic acid, and
glycerol. The lowest sodium benzoate concentration contributed ~50% of the elastic signal, indicating
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