Microwave Spectroscopy Measurements on the Hydrogen Bonding of Nucleic Acid Base Pairs and Base Pair Analogs

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In this project funded by the Chemical Structure, Dynamics, and Mechanisms A (CSDM-A) program of the Chemistry Division, Professor Stephen Kukolich of The University of Arizona is using sensitive, high-resolution microwave spectrometers to obtain new data that can be related to the structures and hydrogen bonding interactions of molecules important in molecular genetics. Hydrogen bonding is a specific kind of intermolecular interaction where a partially positively charged hydrogen atom on one molecule is attracted to a partially negatively charged oxygen atom on another molecule. In living systems, hydrogen-bonding interactions are the key interactions for making copies of the genetic information in DNA (deoxyribonucleic acid) - the molecules that make up our genes. Changes in the rotational motions of nucleic acids and their hydrogen-bonded pairs correspond to energies in the microwave region of the light spectrum. Microwave absorption by these molecules and complexes are analyzed to provide detailed structure information. The fundamental principle that the DNA bases form specific pairs responsible for copying and transcribing the genetic code was discovered may years ago by Watson and Crick. However, the details of the structures and hydrogen bonding interactions between the individual base pairs have not been completely determined. This project involves the study of individual hydrogen-bonded complexes that have been evaporated into the gas phase where they are free of the external water-filled biological environment. The research is thus revealing the intrinsic properties of the basic hydrogen bonding interactions. Revealing the intrinsic properties and behaviors of DNA molecules and base pairs has important consequences for our understanding of biomolecules in general, as well as the fundamental processes underlying living systems. The students engaged in this research project are gaining valuable experience in experimental spectroscopy and computer interfacing and calculations of molecular structures. The structures and other properties of the hydrogen-bonded complexes are being studied using three sensitive, high-resolution microwave spectrometers to accurately and precisely measure microwave rotational transition frequencies. The hydrogen-bonded complexes are formed in supersonic expansions so the rotational spectra can be measured in cold molecular beams or isolated molecules and complexes. The volatility of these larger molecules is low so higher- temperature and laser-ablation beam sources must be constructed and tested. The new moments of inertia and distortion constants obtained can be analyzed, in combination with theoretical results to yield new structure and hydrogen bonding parameter information on these important molecules. New data on multiple structural isomers may be obtained. The use of 15N substituted isotopologues substantially improves the observed signal strengths and simplify the analysis. For the smaller complexes this improves the prospects for measuring single 13C isotopologues in order to obtain more structural information. For some cases, nitrogen quadrupole coupling strengths can be obtained and provide data on the local electronic structure. Extensive theoretical calculations are also being performed along with the experiments to guide the experiments and test theoretical methods. The results of this research are likely to provide additional insights into abnormal DNA binding structures which underlie mutations and errors in transcription; these in turn underpin our understanding of biological evolution and diseases arising from genetic disorders. The graduate and undergraduate research students working in our labs can learn fundamentals of chemistry, quantum mechanics and methods and techniques involved in computer work, microwave electronics and making physical measurements through direct involvement in the proposed projects.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.