TESTING 49
Deuterium isotope labelling of colloidal mixtures
n Dr Tamim Darwish – ANSTO, Australia
Deuteration is the process in which all or some of the hydrogen (1H or H) atoms of a compound are replaced by the stable (non- radioactive) heavier isotope of hydrogen, deuterium (2H or D). Different isotopes of the same element exhibit nearly identical chemical behaviour. This makes deuterated and protonated compounds almost identical in chemical properties, however they still differ in some physical and nuclear properties which make them useful in a number of characterisation techniques. For example, neutrons interact with (and scatter from) nuclei, rather than with electrons, which makes neutrons extremely sensitive to the difference between the hydrogen atom and its deuterium isotope, since the mass difference between the two nuclei is so pronounced. In biological systems which are typically rich in hydrogen, selective substitution of hydrogen with deuterium can therefore be used to create contrast and highlight the position, structure, interactions or dynamics of individual components within complex macromolecular systems or assemblies. This is particularly useful in applications using small-angle neutron scattering, neutron reflectometry, neutron protein crystallography and neutron spectroscopy. Deuteration is not limited to neutron studies but is also effective in conjunction with nuclear magnetic resonance (NMR) and vibrational spectroscopies, which are used to study the structure and function of synthetic polymers or other nanotechnology or biotechnology-relevant materials.
In addition to its use as a
characterisation tool, deuteration has been used to enhance the properties of end-use products. For example, the kinetic isotope effect has been recognised broadly, to improve the metabolic fate of numerous drug and healthcare entities. A non- exhaustive list of deuteration applications in this area is summarised below. l Slowing the rate of oxidation and destruction of materials under ambient or extreme conditions.
l Improving the biological stability of September 2019
Thin Film Nanotech Devices
Drug Delivery Food-Lipid Digestion
Energy and Gas Storage Materials
NDF
Biopolymer and Biotechnology
Catalysis and mechanism
Figure 1: The types of applications that the National Deuterium Facility (NDF) has been involved with since 2010.
molecules in living systems (slowing the rate of enzymatic breakdown by the kinetic isotope effect) or forcing a switch to another metabolic pathway.
l Tuning intra- and intermolecular interactions (modifying the hydrogen bonding network to modify the stability, reactivity, and self-assembly of materials).
l Altering bond strength (frequency of vibrations), electronic structure (transitions/excitations), physical structure, density, and refractive index (optics).
l Internal standards in analytical chemistry (mass spectrometric quantification of biological analytes).
The diversity of techniques that benefit
from deuteration inspired the Australian Nuclear Science and Technology Organisation (ANSTO) to build capability in the biological applications of deuteration to neutron and X-ray scattering in 2002. This positioned ANSTO as the only experienced player when, in 2006, the Australian Government’s National Collaborative
Research Infrastructure Strategy (NCRIS) identified the need for a national deuteration facility to meet demand from the Australian research community. The NCRIS scheme allowed ANSTO to expand its scope to include not only biological deuteration but also chemical deuteration.
National Deuteration Facility: mission and role
A key part of the mission of the NDF is to expand the range and complexity of applications of the neutron scattering instruments at OPAL for the study of biological, organic and polymeric molecules, opening up new avenues for researchers in the fields of soft-matter and colloids in Australia. The facility aims to provide access to specialist laboratory space, equipment, staff and expertise to enable deuteration of biological and organic molecules for investigation using neutron scattering and other techniques, such as NMR and IR spectroscopies. The NDF has also identified that deuteration technology remains relatively untapped in
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