An analysis of calculated molecular properties further emphasized the difference between the starting library and the compounds that are bona fide RNA binders (Table ). The RNA binders were on average more lipophilic (ClogP = 1.3) and less flexible in terms of having fewer rotational bonds (4.3 vs. 5.7). RNA-binding small molecules also had on average two additional hydrogen-bond donors and have greater polar surface area. Many of the descriptors suggest a planar-like shape preference for the RNA binders. That is, the hits include an additional ring, an increased occurrence of aromatic atoms at the expense of fewer aliphatic atoms as well as fewer chiral centers. The average fraction-sp 3 (a measure on carbon bond saturation) was 0.11, compared to 0.24 for the starting small molecule library. Finally, a large number of RNA binders, 50%, included a basic functionality. These preferences were used to select compound nearest neighbors from the AstraZeneca collection, providing an additional 980 RNA-focused small molecules that were studied by AbsorbArray and 2DCS. [Collectively, the two screens studied a total of 2947 small molecules and >62 million potential binding events.] In this second screen, ten selective RNA-binding small molecules were obtained, providing a hit rate of 1.1%. Tanimoto analysis revealed four additional conserved scaffolds, that avidly bind RNA including 2-guanidino thiazoles, 2-amino quinazolines, 2,4-diamino pyrimidines, and phenyl benzimidazoles, which also includes phenyl-bis-benzimidazoles. (Fig. and).