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RESEARCH ARTICLE
Contents Vol 70(5)

Weak Intermolecular Forces, but High Melting Points*

Jiabin Gao A , Djamal Djaidi A , Christopher E. Marjo B , Mohan M. Bhadbhade B , Alison T. Ung C and Roger Bishop A D
+ Author Affiliations
- Author Affiliations

A School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.

B Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia.

C School of Mathematical and Physical Sciences, University of Technology Sydney, PO Box 123, Broadway, NSW 2007, Australia.

D Corresponding author. Email: r.bishop@unsw.edu.au

Australian Journal of Chemistry 70(5) 538-545 https://doi.org/10.1071/CH16565
Submitted: 5 October 2016  Accepted: 6 December 2016   Published: 9 January 2017

Abstract

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°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⋯π, aromatic π⋯π, and C–H⋯N interactions. The alternating layers of opposite handedness are then crosslinked by means of aza-1,3-peri hydrogen interactions. This bifurcated C–H⋯N⋯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.


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