This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor Achim at Carnegie Mellon University to synthesize hybrid inorganic-peptide nucleic acid (PNA) structures. PNA is a synthetic analogue of DNA that has a pseudo-peptide backbone to which nucleobases are attached. The comparative study of the structure and thermodynamics of formation of non-modified and ligand-modified PNA duplexes, in the absence and presence of metal ions is used to create metal-containing PNAs capable of undergoing structural changes in response to external stimuli. This research developed at the interface between bio-organic and -inorganic chemistry offers to undergraduate and graduate students a unique opportunity to learn about both research fields. The students in the Achim group interact with research groups in the Center for Nucleic Acids Science and Technology at Carnegie Mellon, which exposes them to a broad range of tools for the synthesis and characterization of nucleic acids and gives them a wide perspective of chemistry. The hybrid inorganic-PNA structures synthesized have relevance and potential applications in nanotechnology and molecular electronics.
The goal of the research sponsored by this grant was to create nanometer-size molecules capable of responding in a predicted and detectable way to changes in the environment in which they are placed. We used as main component of these molecules a nucleic acid called PNA, which resembles DNA (Figure 1). We chose PNA specifically because (1) just like DNA, it can store information and be "programmed" to assemble in certain shapes; and (2) in contrast to DNA, it is charge neutral and resistant to degradation in biological environments. We developed the synthetic ability to place metal atoms in these novel PNA-based molecules at specific positions and used physical methods to determine the structure of the PNA before and after metal binding (Figure 2). Intellectual merit of the research. Our research produced PNAs that undergo changes induced by a change in the chemical environment, such as the addition of a transition metal ion or of a reductant or an oxidant. In a specific example presented in laymen terms, we succeeded to make a 3-nanometer molecule change shape between two forms each of which bears resemblance to the right- and left- hand in response to the binding to- or release from- the molecule of a copper atom (Figure 3). Besides providing information useful for scientists, such molecules may be useful for applications in nano- and bio-technology, some of which are currently pursued. Broader impact of proposed research. Our research developed at the interface between two areas of chemistry, namely bio-organic and bio-inorganic chemistry was conducted by six undergraduate and five graduate students, who learned about both fields and gained a wide perspective of chemistry. All of these students are currently employed or are pursuing Ph.D. or M.D.s. The majority (82%) of these students was women and one of the students was from a population group underrepresented in science. We have also contributed to the development of the DNAZone, an educational outreach program for 4th-12th grade students (Figure 4). Faculty and students who participate in the program create age-appropriate experiments and demonstrations that can be used in the schools to teach science concepts.
