The main focus of research in her laboratory has been the development of chiral NPs for enantioselective chemical processing. Chiral NPs have atomic structures with a specific “handedness” that allows them to discriminate between the handedness of complex chemicals such as biomolecules and pharmaceuticals. Enantioselective production of chiral chemicals requires the use of chiral media such as chiral catalysts.
Research Faculty, Engineering Research Accelerator
Nisha Shukla is a research faculty member with Engineering Research Accelerator and courtesy appointment in the Department of Chemical Engineering in the College of Engineering at Carnegie Mellon University. Her research interests are focused on nanomaterials, nanotechnology applications in pharmaceuticals, catalysis, disk drives, and quantum dots.
The goal of this project is to develop improved methods for synthesis of tetrahexahedral and hexoctrahedral Au chiral NPs and in particular those that have naturally homochiral facets. These have the capacity to be significantly more enantioselective than those prepared in prior work in our lab or anywhere in the world. A new methodology has been developed over the past year for optical rotation measurements of enantiospecific adsorption of chiral probe molecules on the surfaces of these particles. These efforts are to be targeted towards the development of these chiral NPs for applications in enantiospecific centrifugal separations and purification processes and drug separations.
In this project, we are trying to develop a new type of quartz crystal sensor that can be used in quartz crystal microbalance (QCM) systems for detection of analytes in water-based systems and for enantiospecific adsorption of chiral pharmaceuticals. The sensor will be based on a standard quartz crystal but with electrodes manufactured from nanoporous gold (np-Au) rather than dense gold. The nanoporosity of the Au films increases their surface area by 100-fold, and it has been demonstrated that this can increase QCM sensitivity by an order of magnitude (and probably by significantly more) over commercially available QCM systems. More importantly, the np-Au sensors to be developed in this project will significantly improve the operation of QCMs for measurement of adsorption from liquids. QCMs detect mass adsorbed onto smooth Au electrode surfaces by extremely sensitive measurement of shifts in the resonant frequency of the quartz crystal. In the presence of liquids, however, there are shifts in the frequency that also arise from dissipation due to the viscosity of the liquid.
Chiral molecules are those that have structures that are not superimposable on their mirror images. Thus, like the human hands, they come in right- and left-handed forms. Typically, chiral organic compounds have carbon atoms that are tetrahedrally bonded to four different atoms or substituents. These molecules are denoted as R- or S- enantiomers, depending on the arrangement of the atoms around the central carbon atom, and have identical physical properties other the fact that they rotate polarized light in opposite directions.
Furthermore, their chemical properties are identical unless they are in an environment that has a net chirality. This is a critical point because living organisms are environments with a net chirality. This becomes important because most of the pharmaceuticals used in modern medicine are chiral; however, they are synthesized by methods that produce a racemic (equimolar) mixture of both enantiomers. If ingested or administered as the racemic mixture, the two enantiomers can have drastically different physiological impact. An infamous example is the case of the drug thalidomide used to relieve morning sickness in pregnant women. It was discovered that while one enantiomer relieved the morning sickness, the other caused birth defects. As consequence of that tragedy, chiral pharmaceuticals must now be prepared in enantiomerically pure form, a very challenging task. The resulting market for enantiomerically pure drugs is ~$225 billion per year.
There is a great need in the pharmaceutical industry and all its supporting industries for the development of chemical processing methods and chemical detection methods that are enantiospecific; in other words, methods that are sensitive to the handedness of chiral molecules and can be used for the selective preparation of the desired enantiomer. Chiral pharmaceuticals are often synthesized as racemic mixtures and then separated into the two pure enantiomers using difficult, enantioselective separations methods. The need exists for enantioselective catalytic catalysts, enantioselective separations media, and rapid, sensitive methods for enantiospecific detection of chiral molecules. The ability to prepare pure enantiomers using enantioselective chemical processing techniques will enable heightened purity and thus, improved effectiveness of many pharmaceuticals.
Feature story: Carnegie Mellon University, Engineering Magazine, “Nanotechnology—Engineering Better Health,” January 2012.
JACS article: “Enantioselective separations using chiral Au nanoparticles” (2010-2011)
Media coverage
Editorial Board: Nanotechnology, Science and Applications - Dove Press
CMU Engineering
Engineering students at Carnegie Mellon are often involved in research labs with faculty, post-doctoral researchers, and graduate students. But Marcus Yu had the unique experience of working in a lab that included researchers who were entirely undergraduate students.
CMU Engineering
Zachary Blonder’s experience conducting research on processes relevant to pharmaceuticals synthesis with Nisha Shukla as an undergraduate steered him toward a position in the pharma industry after graduation.
CMU Engineering
Nisha Shukla and Andrew Gellman have developed a number of new, easier methods for making naturally chiral metal surfaces.
