Weak Intermolecular Forces, but High Melting Points

The poorly soluble racemic compound 6,6a,13,13a-tetrahydropentaleno[1,2-b:4,5-b']diquinoline (4) has an exceptionally high melting point range of 352-354 degrees C despite its low molar mass (308.38) and a structure containing only 40 atoms (38 of which are C and H). Analysis of the X-ray crystal structure and Hirshfeld surface of 4, along with comparison with its isostructural homologue 2, reveals how this occurs in the absence of Pauling-type hydrogen bonding. Excellent complementarity between homochiral molecules of 4 allows formation of enantiomerically pure layers using C-H center dot center dot center dot pi, aromatic pi center dot center dot center dot pi, and C-H center dot center dot center dot N interactions. The alternating layers of opposite handedness are then crosslinked by means of aza-1,3-peri hydrogen interactions. This bifurcated C-H center dot center dot center dot N center dot center dot center dot H-C motif acts as a molecular clip creating a highly rigid network structure. The role of weaker intermolecular forces in influencing the solubility and bioavailability of potential drug molecules is discussed in the context of the popular Lipinski 'rule of 5' guidelines.