Comparison of Polymorphic Molecular Crystal Structures through Hirshfeld Surface Analysis

Abstract

Graphical tools based on Hirshfeld surfaces and two-dimensional (2D) fingerprint plots are shown to be valuable for visualizing and analyzing intermolecular interactions in polymorphs of molecular crystals and make the task of polymorph comparison easier and considerably faster. This is the direct result of the underlying principle behind the Hirshfeld surface, which embraces a “whole of structure” view of intermolecular interactions, rather than concentrating exclusively on assumed important (i.e., short) interactions. The subtle relationships between polymorphs of tetrathiafulvalene and p-dichlorobenzene are more easily discernible through comparison of Hirshfeld surfaces and fingerprint plots, rather than solely through conventional structure viewing, and differences and similarities among clearly distinct polymorphs of oxalic acid, terephthalic acid, and p-dichlorobenzene more readily emerge and can be easily catalogued in terms of specific atom···atom interaction types. Conformational polymorphism makes the comparisons more challenging, and Hirshfeld surfaces provide sufficient information for piracetam, while for ROY (5-methyl-2-((2-nitrophenyl)amino)-3-thiophenecarbonitrile, nicknamed ROY due to its red, orange, and yellow crystal forms) fingerprint plots are preferred, summarizing the major features of each crystal structure in a single, colored 2D plot. In addition to the successful applications to polymorph discrimination, improvements to the Hirshfeld surface approach are identified, the most notable being the breakdown of 2D fingerprint plots into specific atom···atom contacts in the crystal.