Abstract
Aspirin has been used and studied for over a century but has only recently been shown to have an additional polymorphic form, known as formII. Since the two observed solid forms of aspirin are degenerate in terms of lattice energy, kinetic effects have been suggested to determine the metastability of the less abundant formII. Here, first-principles calculations provide an alternative explanation based on free-energy differences at room temperature. The explicit consideration of many-body vanderWaals interactions in the free energy demonstrates that the stability of the most abundant form of aspirin is due to a subtle coupling between collective electronic fluctuations and quantized lattice vibrations. In addition, a systematic analysis of the elastic properties of the two forms of aspirin rules out mechanical instability of formII as making it metastable.
Highlights
The ability of molecules to yield multiple solid forms, or polymorphs, has significance for diverse applications ranging from drug design and food chemistry to nonlinear optics and hydrogen storage [1]
Aspirin is a widely used analgesic that clearly illustrates many of the challenges of understanding polymorphism
State-of-the-art quantum-chemical calculations predict very small energy differences of the order of Æ0.1 kJ=mol between the two polymorphs [12,13], making both solid forms essentially degenerate in terms of lattice energy
Summary
Week ending 1 AUGUST 2014 in predicting absolute and relative stabilities of molecular crystals [7,17,20,21]. In this contribution, we apply the DFT þ MBD method to aspirin, showing that the role of many-body vdW interactions goes beyond lattice stabilities and energies to affect vibrational and elastic response properties, revealing an entropically driven mechanism behind the relative stability of form-I aspirin. We begin by putting our approach in the context of other calculations of the relative stabilities of aspirin These calculations have typically considered the energy differences between the computationally optimized, 0 K lattice of the two polymorphs.
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