The binding of heavy metal complexes to nucleic acid constituents and polynucleotides is being studied in aqueous solution primarily using Raman and Raman difference spectroscopies. The effect of polynucleotide secondary and tertiary structure on the binding sites and the extent of reaction is being studied using the substitutionally inert (PtCl2(NH3)2) and (Pt(OH2)2(NH3)2)2ion complexes as well as the labile (CH3HgOH2)ion and H3Oion moieties. For these comparisons the structureless polynucleotides, e.g. poly(C), poly(A), and poly(A). poly(U), as well as triple stranded structures are being employed. The sensitivity of Raman spectroscopy in the detection of phosphate binding is being evaluated by the determination of crystal spectra of (enPtCMP).2H2O. Raman spectrophotometric and biochemical titrations of purified calf thymus DNA and Simian virus DNA with labile (H3CHgOH2)ion and inert (PtCl2(NH3)2) are being studied to understand the binding reactions and denaturing effects of these two metal complexes. Finally, the utility of Raman difference spectroscopy in supressing troublesome fluorescence backgrounds in other biological samples will be examined.