A crystal structure prediction enigma solved: the gallic acid monohydrate system – surprises at 10 K

Abstract

The seemingly unpredictable structure of gallic acid monohydrate form IV has been investigated using accurate X-ray diffraction measurements at temperatures of 10 and 123 K. The measurements demonstrate that the structure is commensurately modulated at 10 K and disordered at higher temperatures. Aided by charge-density modeling and periodic DFT calculations we show that the disorder gives a substantial stabilization of the structure.

Conformational Polymorphism in Safinamide Acid Hydrochloride (Z′ = 3 and Z′ = 1) and Observation of a Temperature-Dependent Reversible Single-Crystal to Single-Crystal Phase Transformation of High-Z′ form (Z′ = 3 ↔ Z′ = 2 via an Intermediate Z′ = 4)

“…Organic molecules which crystallize with multiple molecules in the asymmetric unit, referred to as Z ′ > 1 or high- Z ′ structures, − continue to fascinate researchers, although several groups in the past have attempted to understand the Z ′ > 1 phenomenon. − The Cambridge Structural Database (CSD) reached a major milestone by depositing the millionth crystal structure in 2019 . The recent statistics of Z ′ > 1 in the CSD continue to be approximately 10–11% in organic structures and 8% in total CSD structures. − ,, A proper understanding of Z ′ and the expectation of a possible Z ′ > 1 crystal structure based on the molecular structure, functional groups, shape, and symmetry is regarded as an important strategy for an accurate crystal structure prediction (CSP) of drug molecules, − a structure determination by the powder X-ray diffraction (PXRD) method, − and the development of chiral materials. , The Z ′ > 1 structures are often termed as “frustrated” structures which are thought to arise from packing difficulties to crystallize as a single molecular entity . Steed wrote two detailed reviews on high- Z ′ structures, and the reasons for Z ′ > 1 occurrence are attributed to awkward molecular shape, the choice of slightly different molecular conformations, conflict from strong intermolecular interactions and crystal packing, pseudosymmetry, disorder, and temperature effects. , Experimental conditions under which the crystals are grown are shown to have a strong correlation with Z ′ > 1 behavior. , The connection between high- Z ′ structures and strong hydrogen bonds was noted by Gavezzotti, Nangia, Desiraju, Brock, , and others. …”

Structural Features of Sulfamethizole and Its Cocrystals: Beauty Within

“…However, the three symmetry-independent SMZ molecules could not be clearly distinguished by the single crystal XRD data due to the higher level of molecular vibrations at temperatures above 100 K. Fortunately, the different local domains were captured by solid state NMR at room temperature due to the short time scale of NMR, on the order of milliseconds. 18,19 A very similar case, gallic acid monohydrate (GAM) form IV, was recently reported, where the accurate Z′ = 3 structure was solved at 10 K. 20 The motivation for investigating the crystal structure of GAM form IV at such a low temperature was its failure in the crystal structure prediction (CSP) blind tests. 21 A mechanistic understanding of these failure cases is essential for the further development of CSP methods.…”

The trimorphism of 3-hydroxybenzoic acid: an experimental and computational study

“…The latter might indicate disorder over two sites of the polar phenol hydrogen atom as seen in related structures (e.g. phloroglucinol, 37,38 gallic acid 17,39 ). In case of form II, no isostructural packings were found in Fig.…”