Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Barton, Jacqueline K.
Location California Institute of Technology
Primary Field Chemistry
Secondary Field Biochemistry
 Election Citation
Barton has used novel methods to investigate the microstructure and reactions of nucleic acids. In a series of landmark experiments, her team designed transition metal complexes that recognize different DNA sites with high specificity. Using these tools, she demonstrated that DNA-mediated electron transfer occurs over long ranges, leading to oxidative damage at remote sites.
 Research Interests
As a chemist I am interested in nucleic acid structure and reactions, using transition metal complexes as probes. We have designed octahedral metallointercalators and demonstrated enantioselective binding of the small cations to DNA. Rhodium complexes were made that bind avidly and with photoactivation cleave DNA. Ruthenium complexes were prepared as sensitive luminescent probes. Complexes were designed that recognize different DNA sites with high specificity. With these tools I began studies of DNA electron transfer. Stacked DNA base pairs resemble solid-state p-stacked materials. We asked whether DNA as a molecular p-stack could also provide a facile medium to transport charge. DNA assemblies with pendant electron donors and acceptors were constructed and, using spectroscopic and biochemical methods, DNA electron transfer was examined. We learned that this chemistry was exquisitely sensitive to stacking within the helix, and we developed electrochemistry to detect single base mismatches in DNA and to monitor protein/DNA interactions. Long-range charge transport can also be harnessed to carry out chemical reactions at a distance. DNA oxidation can occur through charge transport 20 nanometers from the bound oxidant, and long-range oxidative DNA damage has been seen within the cell nucleus. We are exploring the biological consequences and opportunities for this chemistry.

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