Nucleic acids are biopolymers of obviously great importance, since they carry information including the genetic code, but the role of structure and particularly secondary structure is perhaps less obvious (or immediate) with regard to their function. While the various duplex DNA forms are well known, the stereochemical issues involved with them are mainly ones of stability, i.e. detecting interconversion and "melting'" or disordering the structure under perturbation. The heterogeneity of the nucleic acids, since they are linked therough the bases, leads to a different level of complexity for secondary structure studies, especially using VCD, which was our contribution to this field. In peptide based systems, there are 20+ amino acids to consider, but only one link, the amide bond which provides the chromophore of most spectroscopic interest. In nucleic acids there are only 4 bases (and varients), and a uniform ribose phosphate link, which sounds simpler, but the bases provide the chromophores, thus are variable, and couple to each other not only by the Watson-Crick hydrogen bonds, but also through stacking interactions, which can particularly affect electronic spectra (hence ECD). At the same time the phosphate and sugar groups are not very useful chromophores for ECD (uv-vis). In this light vibrational spectra has an advantage, and IR, Raman and the associated VCD and ROA techniques have been used to study nucleic acid structure and stability by a number of groups. In our group related studies were done in the early 90s and involved determination of typical VCD patterns for single strand RNAs, duplex DNA in A, B and Z-conformations, triplex RNA and DNAs, and characterization of phase transitions between these states. Most studies focused on base modes, which proved to be sequence specific but did discriminate various helical forms and strand numbers, and phosphate modes, which were not, but discriminated helical sense (handedness) very well, but not duplex vs. other forms. Efforts to look at peptide-nucleic acid binding with VCD have found only modest success. Determination of triplex forms and left-handed Z-forms werea large successes, but only worked well if all (or a large fraction of) the sample was in that conformation, so identification of small segments of unusual conformation remained ellusive. Our papers in this field are clustered under Nucleic Acids, in the publications list, mostly by Lijiang Wang, whose thesis is on Nucleic Acid VCD, and two other papers by A. Annamalai and Ligang Yang. Other groups, particularly Max Diem, Hunter College, CUNY (early) and Hal Wieser, Calgary (more recently) have done more VCD work on these sorts of systems, while that of Laurence Barron, Glasgow have used ROA and George Thomas at Kansas City established many of the basic Raman correlations earlier.

To learn more about our research in nucleic acids, please check out our publications in this area.