Support is requested for fundamental studies of the vibrational spectra of purine and pyrimidine bases, ribose, phosphates, nucleosides, nucleotides and homopolymeric nucleotides eventually extending to include DNA and RNA. Both experimental studies (primarily of matrix-isolated and hydrogen-bonded species) and theoretical studies of both are planned. It is expected that a theory for accurate prediction of both frequencies and intensities in the vibrational spectra of these molecules will be developed, calibrated and adjusted until it can successfully be applied to any molecule in this series, in any tautomeric form, or to any hydrogen-bonded or """"""""stacked"""""""" form. Ab initio quantum mechanical calculations will be made to predict quantitatively the spectra of small molecules; the results from this are expected to guide the devlopment of transferable force constants and intensity parameters which will lead to general methods for confident prediction of the spectra of these large molecules. The advantage for this particular approach is that ab initio calculations can be made accurately enough for these small molecules to allow recognizable comparison with experimental spectra of small molecules isolated in rare gas matrices at 10 degree K, thus eliminating effects due to the hydrogen bonding that occurs for these molecules in the crystal. Hence the theory can be directly tested against the experimental data, and also the effects due to hydrogen bonding including interaction with water, tautomerism, chemical substitution of CH3 for H or of S for O, can be identified and compared with predictions of the theory. In this way it is expected to be possible to achieve an understanding of vibrational spectra in these molecules to a greater depth than has heretofore been possible. Furthermore, it is expected that the process of theoretical modeling of the spectra of nucleosides and comparison with experiment will provide understanding of the intramolecular perturbation of the vibrational spectrum when the ribose and the pyrimidine react to form the nucleoside. If so, the theory can be extrapolated with confidence to predict quantitatively the vibrational spectra of almost any molecule of interest in nucleic acid chemistry. Ultimately, it may be possible from this study to use the vibrational spectrum to characterize the average evironment of appropriate probe molecules as they exist in truly biological environments. One may expect to model different situations with the theory; comparison of predictions from different models with experimental measurements may provide direct structural information concerning the probe molecule, for example in the presence of drugs, in double-strand interactions, or in other health-related applications requiring knowledge on a molecular level of DNA or RNA behavior.
| Kwiatkowski, J S; Person, W B; Szczepaniak, K et al. (1987) On tautomerism of the cytosine molecule. Acta Biochim Pol 34:165-81 |
