Predicting Cocrystallization Based on Heterodimer Energies: The Case of N,N′‑Diphenylureas and Triphenylphosphine Oxide

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 meta-substituted N,N′-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
[R21(6)] dimers
between the urea hydrogens and the phosphine oxygen. Heterodimer (mXPU···TPPO)
and homodimer (mXPU···mXPU) interaction energies, ΔEint, 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, ΔΔEint,
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 ΔΔEint between heterodimers
and homodimers is
a good predictor of cocrystal formation in this system.

Diarylureas 常常聚集形成具有一维氢键链式结构的结构。本研究中，我们探讨了三苯基氧化膦 (TPPO) 对 14 种不同取代位置的 N,N'-二苯基脲 (mXPU) 中氢键模式的破坏能力，并形成共晶；在所考察的 14 种情况下，有 9 种获得了 1:1 的 mXPU:TPPO 共晶（成功率为 64%）。共晶采用五种不同的晶格类型，所有这些类型均显示出不规则的氢键 [R21(6)] 二聚体，存在于脲氢与膦氧之间。使用密度泛函理论 (DFT) 在 B3LYP/6-31G(d,p) 水平上计算的异二聚体 (mXPU···TPPO) 和同二聚体 (mXPU···mXPU) 相互作用能 ΔEint，被用于解释实验结果。观察到一种明显的趋势，即仅在异二聚体与同二聚体能量差 ΔΔEint 大于约 5.3–6 kcal/mol 的情况下，才能实验性地实现共晶。尽管计算出的相互作用能是对系统热力学的一种简化度量，但这些结果表明，异二聚体与同二聚体之间相对 ΔΔEint 的差异是预测该体系中共晶形成的一个良好指标。