Predicting Cocrystallization Based on Heterodimer
Energies: The Case of <i>N</i>,<i>N</i>′‑Diphenylureas and Triphenylphosphine Oxide
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Abstract
Diarylureas
frequently assemble into structures with one-dimensional
H-bonded chain motifs. Herein, we examine the ability of triphenylphosphine
oxide (TPPO) to disrupt the H-bonding motif in 14 different <i>meta</i>-substituted <i>N</i>,<i>N</i>′-diphenylureas
(mXPU) and form cocrystals; 1:1 mXPU:TPPO cocrystals were obtained
in 9 of 14 cases examined (64% success rate). Cocrystals adopt five
different lattice types, all of which show unsymmetrical H-bonded
[R<sub>2</sub><sup>1</sup>(6)] dimers
between the urea hydrogens and the phosphine oxygen. Heterodimer (mXPU···TPPO)
and homodimer (mXPU···mXPU) interaction energies, Δ<i>E</i><sub>int</sub>, calculated using density functional theory
at the B3LYP/6-31G(d,p) level were used to rationalize the experimental
results. A clear trend was observed in which cocrystals were experimentally
realized only in cases in which the differences in heterodimer versus
homodimer energy, ΔΔ<i>E</i><sub>int</sub>,
were greater than ∼5.3–6 kcal/mol. Although calculated
interaction energies are a simplified
measure of the system thermodynamics, these results suggest that the
relative ΔΔ<i>E</i><sub>int</sub> between heterodimers
and homodimers is
a good predictor of cocrystal formation in this system