Investigation of an Unusual Crystal Habit of Hydrochlorothiazide Reveals Large Polar Enantiopure Domains and a Possible Crystal Nucleation Mechanism

Abstract

The observation of an unusual crystal habit in the common diuretic drug hydrochlorothiazide (HCT), and identification of its subtle conformational chirality,has stimulated ad etailed investigation of its crystalline forms.E nantiomeric conformers of HCT resolve into an unusual structure of conjoined enantiomorphic twin crystals comprising enantiopure domains of opposite chirality.The purity of the domains and the chiral molecular conformation are confirmed by spatially revolved synchrotron micro-XRD experiments and neutron diffraction, respectively.M acroscopic inversion twin symmetry observed between the crystal wings suggests apseudoracemic structure that is not as olid solution or al ayered crystal structure,but an unusual structural variant of conglomerates and racemic twins.C omputed interaction energies for molecular pairs in the racemic and enantiopure polymorphs of HCT,a nd the observation of large opposing unit-cell dipole moments for the enantiopure domains in these twin crystals, suggest ap lausible crystal nucleation mechanism for this unusual crystal habit.

Structural Self-Destruction of Deep Eutectic Solvents Induced the Formation of Unusual Diamond-Shaped Crystals of Honokiol and Its Mechanistic Study

“…, solvents and additives) determine the development of crystal faces. , Understanding the fundamental crystal growth behavior is crucial for the design and manufacture of crystals with desired habits and properties. − Solution crystallization is the most dominant approach for the morphological regulation of organic crystalline materials, and their regulation mechanism on the growth of anisotropic organic crystals has been widely studied. ,, In recent years, the discovery of several unusual habits ( e.g. , triangular-shaped habit of theophylline and biochanin A, two-winged twin-crystal morphology of hydrochlorothiazide) promotes more in-depth understanding regarding the crystal structure and the solvent effect on the habit modification of crystals.…”

X-ray Natural Circular Dichroism Imaging of Multiferroic Crystals

“…However, these approaches have significant restrictions and require a substantial time investment for data collection and treatment. Meanwhile, these techniques are not always applicable to visualize directly enantiomorphous twinning [24], which is often manifested in a structure formed by alternating enantiomeric domains (a pair of opposite-handed shapes).…”