Download Shooting molecules with big guns

Shooting molecules with big guns
Dr Sarah Masters from the
Chemistry department employs
electron guns to determine the
structure of molecules that are too
small to be seen by the naked eye.
“We do this by photographing them in the gas
phase. We generate an electron beam that we
fire at the gaseous molecules, with a camera
at the other end with photographic film in it.
This is easier with smaller molecules, but the
larger a molecule is, the more complicated the
process becomes.”
The technique that Dr Masters uses to look at
very large and biologically relevant molecules
is called gas electron diffraction. In diffraction,
electrons are fired at the molecules, to then
scatter off the molecules and hit a detector,
forming a pattern. From that pattern, researchers
can interpret and work back to what the
structure of the molecule was.
“You can infer behaviour of molecules from their
structure. The structure of a molecule defines its
function, and the way the atoms join together
to make the molecule will dictate how it will
behave in certain circumstances.
“A lot of structural analysis techniques are
actually undertaken on samples in the solid
state. Chemically, salt – or sodium chloride – is a
large regular array of both sodium and chlorine
atoms held together very tightly by electrostatic
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University of Canterbury
“If you want to design an
effective drug molecule,
you need to know both
the structure of the drug
molecule and the fragment
of the protein that the drug
molecule is going to sit in.”
“If you want to design an effective drug
molecule, you need to know both the structure
of the drug molecule and the fragment of the
protein that the drug molecule is going to sit in.
This is because there are important interactions
that hold them together. It is like a lock and a
key. We can currently determine what receptor
sites on proteins look like, but to get molecular
structure on that scale is quite difficult.”
interactions to form a solid. In the gas phase, you
just get two molecules of sodium chloride stuck
together, rather than the regular array.”
Through collaboration with a team at the
Deutsches Elektronen–Synchrotron (DESY) in
Germany, Dr Masters has access to a more
powerful ultra-bright electron gun that can also
pulse the electrons, enabling the team to time
when the molecules go into the machine, and
when the electrons will hit them.
“Because the environment is different for the
molecule, it adopts a different shape. This is why
it is important to study things in the gas phase
as well. In your body for example, molecules
naturally exist with water all around them.
Molecules in gaseous and fluid states tend to
behave in similar ways because the strong forces
that hold molecules together in the solid state
are absent.”
“This means we can look at things in different
stages of solvation as well. We aim to keep the
molecules in their natural environment as much
as possible. By using molecules in solution
(called solvated molecules), ablating them into
a vacuum using a laser, then timing when the
electrons come in, the water molecules will come
off and we can capture images of the molecules
at different stages of being desolvated.”
Dr Masters and her team are researching
the structure of small, biologically relevant
molecules such as adenosine triphosphate
(ATP) with the aim of applying their techniques
to proteins, ultimately to provide essential
information to the pharmaceutical industry so
they can design drugs to fit the receptor sites of
those proteins.
The internuclear distance information given by
gas electron diffraction is one dimensional.
Dr Masters says that, in contrast, crystallography
techniques generate two dimensional
information from molecules that are stationary
and are hit from different angles to build
up a picture, or a series of spots from which
molecular structure is determined.
“In the gas phase molecules are not stationary.
They are at random orientations relative to the
electron beam. Our one dimensional data is
in the form of a series of concentric rings. We
analyse the data from the centre of the pattern
to the outside, and obtain a series of intensities.
We can then use Fourier Transform methods to
produce a vibrationally averaged structure from
which we generate three dimensional pictures of
the molecules.”
It is this information that is so valuable to the
pharmaceutical industry, who would find it
much harder to conduct their own research and
development without such detailed knowledge
of key target proteins.
By Jann O’Keefe
Research into particle
processes using advanced
measurement and modelling
techniques is used to develop new
processes or improve existing ones for
industries ranging from fertilisers to
petrochemicals and carbon capture.
Research Report 2015
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