Roberto R. Gil, PhD, and Rongchao Jin, PhD, of Carnegie Mellon University of Pittsburgh have used nuclear MR (NMR) to analyze the structure of infinitesimal gold nanoparticles, which could advance the development and use of the tiny particles in drug development.
The researchers reported that 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 in December’s 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. An 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.
"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 Carnegie's Mellon College of Science. "In the nanoparticle community, the crystal structures of only three nanoparticles have been reported."
"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 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.
NMR spectroscopy takes advantage of the physical phenomenon wherein some nuclei wobble and spin like tops, emitting and absorbing a radiofrequency signal in a magnetic field, according to the researchers. By observing the behavior of these spinning nuclei, scientists can piece together the chemical structure of the compound.
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 research, 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.