The first specific aim of this research is to obtain and interpret experimental vibrational spectra in inert rare gas matrices of isolated molecules that are components of nucleic acids. The interpretation consists of (1) reliable assignments, (2) determination of force constants and infrared intensity parameters, (3) measurement of spectra of related model compounds, (4) study of tautomerism including experimental spectra with spectra from ab initio molecular orbital calculations and (6) examination of substituent effects to provide as basis for predicting effect of intermolecular interaction.
The second aim i s to determine the effect on force constants and vibrational frequencies when component molecules are coupled together to form nucleosides and nucleotides. Related to this will be a theoretical and experimental study of changes in the spectra as purines and pyrimidines from self-associated dimers, complexes with small probe molecules (H20, CO, HCl, etc.), with complementary bases, or with drugs. These systems will be studied in a controlled way isolated in an inert matrix to determine specific sites of interaction on a pyrimidine molecule with the different probe molecules. One by-product is the dynamic electronic charge distributions for these molecules. An ultimate aim for the study is to obtain the test possible sets of parameters (force constants and intensities) for use in future moleculer dynamics calculations of properties of large molecules, including vibrational spectra. Probably the most startling result from our earlier studies has been the discovery that guanine and the guanosine analogue 9- methylguanine (9-MeG) isolated in an inert matrix exist in tautomeric equilibrium between the oxo and hydroxy tautomers in approximately equal concentrations (oxo:hydroxy is approximately equal to 1:3) while only the oxo form is present in polar environments. A primary aim of the present study must be to investigate this equilibrium further. It is imperative to understand more about the effect of the environment on this equilibrium. Questions concern the effect of specific interactions on the tautomeric equilibrium. For example, does hydrogen bond formation with thymine stabilize the hydroxy form of 9-MeG? Does intramolecular hydrogen bonding at the N7 position stabilize the hydroxy form? We expect to make experimental studies of these and other generally applicable questions to obtain their answers.
| Kwiatkowski, J S; Person, W B; Szczepaniak, K et al. (1987) On tautomerism of the cytosine molecule. Acta Biochim Pol 34:165-81 |
