Catechol and beta-ketoenol are important pharmacophores of HIV-1 integrase (IN) inhibitors. We investigated their recognition of the divalent metals, Mg and Mn, and of hydrogen bond donors (HBD) and acceptors (HBA). We used data retrieved from the Cambridge Structural Database (CSD), applying a 3-D structure-based, in silico-driven approach. We found that both biophores were stabilized by intramolecular H-bonding (IHB), which was weak in catechols and very strong in beta-ketoenols. Catechols tended to recognize environmental HBD and HBA, demonstrating their ability to make use of both hydroxyl groups to form multiple, strong intermolecular H-bonds. In contrast, beta-ketoenols stabilized by strong IHB inefficiently formed intermolecular H-bonds. beta-Ketoenolate chelated both Mg and Mn ions much more efficiently than dioxolene, which was highly selective for Mn cations. The significant differences in the ability of these two pharmacophores to bind HBD and HBA and in their ability to chelate Mg and Mn have important consequences for competitive inhibitor binding and selectivity for metals and integrase DNA-binding sites.