Nucleic acids, such as DNA and RNA, are very important pharmaceutical targets. Over the past several years, efforts at targeting nucleic acids have focused on sequence specificity, in an effort to target a specific gene, or on specific structures such as the a triple helix or G-quadruplex, with the hope to regulate gene expression and to combat various genetic diseases or cancer. The competition dialysis assay was developed in our laboratory to rapidly analyze a compound’s structural and sequence selectivity to nucleic acids. In the typical experiment, an array of nucleic acid structures and sequences is dialyzed and equilibrated against a common test ligand solution, and the amount of ligand bound to each structure or sequence is then determined spectrophotometrically. Since all structures and sequences are in equilibrium with the same free ligand concentration, the amount bound is directly proportional to the ligand binding affinity. The first generation assay contains binding affinities for 126 compounds binding to 13 unique nucleic acid structures. Each of the compounds was grouped by structural similarity and correlation plots were made to compare the binding of compounds to each unique structure. The Specificity Sum, SS, was developed and calculated for each compound, which allows a direct, normalized comparison of selectivity for each compound to one of the 13 nucleic acid structures. Additionally, difference plots were calculated for all of the compounds binding to each sequence, which allow us to visually compare the binding of each compound to each sequence. This analysis can then be used in the development of new QSAR experiments and to search for new, more potent DNA-binding compounds.