Harnessing microscopic agents
Researchers at the University of Canterbury are
investigating ways to improve drug delivery
methods and assist medical diagnoses by using
magnetically switchable microscopic agents.
Professor Paul Kruger (Chemistry), who is also
a Principal Investigator at the MacDiarmid
Institute, heads a UC research group that
recently received $750,000 in funding from the
Marsden Fund for its work to see if molecules
can be altered to become better drug delivery
agents or more effective contrast agents for
magnetic resonance imaging (MRI) to aid
medical diagnoses.
Kruger, whose research focus is on inorganic
supramolecular chemistry, says the group is
looking at how metal-organic molecular cages,
created in the lab, can be used to trap molecules
then release them under an external influence
such as heat or light.
50oC, the molecule obtains its open state and the
cage releases its guest. That’s pretty cool.”
“These Trojan horse complexes would be capable
of controllably releasing their contents via an
external stimulus and would represent a great
advance towards the development of novel drug
delivery agents. Such novel agents could reduce
the harmful side effects that result from the
indiscriminate delivery of drug molecules to sites
within the body not associated with disease.”
Kruger says an advantage of using magnetic
metal ions in the synthesis of these cage
molecules is that the research group could
also develop MRI contrast agents that can be
switched on when they are needed and off when
their task is complete.
Kruger is also making molecular cages which
exploit the spin state of metal ions within
them, but instead of using just one metal ion,
he’s using two, or four, or more, to increase the
number of switching points.
“We’re interested to see how they interact with
each other — how the switching in one of
the metal sensors influences each neighbour,”
he says.
Molecular cages are 3D constructs that consist
of organic components (ligands) held together
by metal ions so that an internal cavity of a
predetermined size is formed. They are typically
synthesised through self-assembly, whereby
the ligand components and the metal ions
are simply mixed in solution and they “selfassemble”. The structural outcome of the
assembly process is controlled by careful ligand
design and by using appropriate metal ions to
direct the order of assembly.
“We’re trying to design systems where the metal
ions know what their nearest neighbours are
doing, and then they can potentially co-operate
with each other.”
“Synthetic chemists have the ability to make
molecular cages of any size and can adapt them
to capture molecules of many shapes and sizes,”
says Kruger.
Similar molecular cages could be used to lock
molecules inside. With changes in temperature,
light or pressure, the spin state of the metal ions
change, and a guest molecule could be trapped
or released from a molecular “cage”.
“We will develop functional, responsive and
adaptable molecular cages able to reversibly
switch their properties and behaviour through
light irradiation or by a change in temperature.
38 “Light and heat are then the keys that open and
shut the cages.
University of Canterbury
Kruger is trying to build molecular cages which
change properties due to a spin state change of
metals when they capture other molecules.
“So the binding event happens and we can pick
that up through a noticeable change in one of
the properties like colour, magnetism or size.”
“So, let’s says at 10oC the molecule is trapped
within that cage. We can have it so we heat that
solution and then at a differing temperature, say
Current state-of-the-art MRI contrast agents
use expensive and toxic metal ions that cannot
be switched off. Kruger says the development
of a new type of contrast agent will not only
reduce costs in the health sector, but also be of
benefit to patients by replacing these toxic metal
ions. Switching MRI “on and off” should allow
clinicians to access much better contrast images
whereby the contrast can be variably tuned.
Kruger says molecular cages could have other
uses outside the medical industry. There is also
the potential for these cages to be modified
to behave like sensors to detect the presence
of harmful environmental pollutants, such as
anions, when they are trapped inside the cage.
“Anions, such as phosphate and nitrate, are
found in fertilisers and are detrimental to
waterways when present in an overabundance,
and can cause damage to river and lake quality
as a result of run-off from dairy farms,” says
Kruger.
“Access to molecules capable of selectively and
specifically sensing these ions may lead to the
development of test kits for on-site real-time
analysis.”
Research supported by:
• Marsden Fund
By Stacey Doornenbal
Professor Paul Kruger
Research Report 2014
39