Pictured above is the crystal structure of a pair of gold nanoparticles that exist in a right-handed (bottom) and left-handed (top) configuration. These nanoparticles hold great promise as a chiral catalyst—a tool highly sought-after by the pharmaceutical industry. |
Carnegie
Mellon University’s Roberto R. Gil and Rongchao Jin have successfully
used NMR to analyze the structure of infinitesimal gold nanoparticles,
which could advance the development and use of the tiny particles in
drug development.
Their
approach offers a significant advantage over routine methods for
analyzing gold nanoparticles because it can determine whether the
nanoparticles exist in a both right-handed and left-handed
configuration, a phenomenon called chirality. Determining a
nanoparticle’s chirality is an important step toward developing them as
chiral catalysts—tools that are highly sought-after by the
pharmaceutical industry. Their results are published online at ACS Nano.
Many
drugs on the market today contain at least one molecule that is chiral.
Often only one of the configurations, or isomers, is effective in the
body. In some cases, the other isomer may even be harmful. A striking
example is the drug thalidomide, which consisted of two isomers: one of
which helped pregnant women control nausea while the other caused damage
to the developing fetus. In an effort to create safer, more effective
drugs, drug manufacturers are looking for ways to produce purer
substances that contain only the left- or right-handed isomer.
Huifeng
Qian, a fourth-year graduate student working with Jin, created a gold
nanoparticle that has the potential to catalyze chemical reactions that
will produce one isomer rather than the other. The nanoparticle is
comprised of precisely 38 gold atoms and measures a mere 1.4 nm. Qian
worked diligently for nearly a year to grow the nanoparticles into
high-quality crystals so that he could study their structure using x-ray
crystallography.
“Growing
a pure crystal from nanoparticles is very challenging, and you may not
even be able to get a crystal at all,” said Jin, an assistant professor
of chemistry in CMU’s Mellon College of Science. “In the nanoparticle
community, the crystal structures of only three nanoparticles have been
reported.”
In
Jin’s case, x-ray crystallography revealed that the gold nanoparticle
is chiral. Chemists typically probe the internal chiral structure of
gold nanoparticles using a technique called circular dichoism
spectroscopy. When pure chiral molecules are exposed to circularly
polarized light, each isomer absorbs the light differently, resulting in
a unique—and of opposite sign—spectrum for each isomer. The process of
creating the gold nanoparticles, however, often results in a 50/50 mix
of each isomer, known as racemates.
“Because
the spectrum is of opposite sign for each isomer, they cancel each
other out and the net optical response is zero. This makes circular
dichoism (CD) spectroscopy useless when it comes to determining the
chirality of gold nanoparticles in 50/50 mixtures,” said Gil, associate
research professor of chemistry and director of the Department of
Chemistry’s NMR Facility.
Since
Jin couldn’t use circular dichoism spectroscopy, Gil was able to use
NMR to help Jin distinguish between his gold nanoparticles’ left- and
right-handed isomers.
NMR
spectroscopy takes advantage of the physical phenomenon wherein some
nuclei wobble and spin like tops, emitting and absorbing a radio
frequency signal in a magnetic field. By observing the behavior of these
spinning nuclei, scientists can piece together the chemical structure
of the compound.
In
1957, scientists observed that the hydrogen atoms of a freely rotating
methylene (CH2) group produced two different frequencies if they were
close to a chiral center. Jin’s gold nanoparticles, which have a chiral
core, are cushioned by several chemical groups, including freely
rotating methylene groups. Gil reasoned that the nanoparticles’ chiral
core should induce the methylene group’s two hydrogen atoms to give off
different frequencies, a phenomenon known as diastereotopicity.
Gil
and Jin compared the NMR signal from the hydrogen atoms in a non-chiral
gold nanoparticle with the NMR signal from the hydrogen atoms in chiral
gold nanoparticle. The non-chiral nanoparticle’s NMR spectrum did not
reveal any differences, but the chiral nanoparticle’s NMR spectrum
revealed two different hydrogen signals, providing a simple and
efficient way of telling whether the particle is chiral or not, even for
a 50/50 mixture of isomers.
“NMR
is an alternative—and very efficient—method for providing useful
information about how the atoms in nanoparticles form the molecular
structure. Because NMR can determine chirality in some cases, it can
readily be used to determine the purity of a nanoparticle mixture,” Jin
said.
In
current work, Jin and Qian are striving to turn their 50/50 mixture of
right- and left-handed isomers into a pure solution of one or the other.