Isoenergetic Polymorphism: The Puzzle of Tolazamide as a Case Study.

In the present case study of tolazamide we illustrate how many seemingly contradictory results that have been obtained from experimental observations and theoretical calculations can finally start forming a consistent picture: a "puzzle put together". For many years, tolazamide was considered to have no polymorphs. This made this drug substance unique among the large family of sulfonylureas, which was known to be significantly more prone to polymorphism than many other organic compounds.

Advances in elucidating mechanochemical complexities via implementation of a simple organic system.

Mechanochemistry is becoming increasingly popular amongst both the academic and industrial communities as an alternative method for inducing physical and chemical reactions. Despite its rapidly expanding application, little is understood of its mechanisms, greatly limiting its capacity. In the present work the application of specialty devices allowed submission of the simple organic system, α-glycine + β-malonic acid, to isolated shearing and impact treatment.

Low-temperature phase transition in glycine-glutaric acid co-crystals studied by single-crystal X-ray diffraction, Raman spectroscopy and differential scanning calorimetry.

The occurrence of a first-order reversible phase transition in glycine-glutaric acid co-crystals at 220-230 K has been confirmed by three different techniques - single-crystal X-ray diffraction, polarized Raman spectroscopy and differential scanning calorimetry. The most interesting feature of this phase transition is that every second glutaric acid molecule changes its conformation, and this fact results in the space-group symmetry change from P2(1)/c to P1. The topology of the hydrogen-bonded motifs remains almost the same and hydrogen bonds do not switch to other atoms, although the hydrogen bond lengths do change and some of the bonds become inequivalent.

Solid-state transformations in the β-form of chlorpropamide on cooling to 100 K.

A single-crystal X-ray diffraction study of the effect of cooling down to 100 K on the β-form of chlorpropamide, 4-chloro-N-(propylaminocarbonyl)benzenesulfonamide, has revealed reversible phase transitions at ∼257 K and between 150 and 125 K: β (Pbcn, Z' = 1) ⇔ β(II) (P2/c, Z' = 2) ⇔ β(III) (P2/n, a' = 2a, Z' = 4); the sequence corresponds to cooling. Despite changes in the space group and number of symmetry-independent molecules, the volume per molecule changes continuously in the temperature range 100-300 K. The phase transition at ∼257 K is accompanied by non-merohedral twinning, which is preserved on further cooling and through the second phase transition, but the original single crystal does not crack.

An extended phase transition in crystalline L-cysteine near 70 K.

An anomaly of heat capacity near 70 K was registered in the crystalline L-cysteine (orthorhombic polymorph) by adiabatic calorimetry as a small, 3-5% height, diffuse "jump", or a wide "hump" accompanied by the substantial increase in the thermal relaxation time. The Cp(T) dependence is characteristic for a transformation extended over a wide temperature range and sensitive to the thermal prehistory of the sample, that can be interpreted as nonsimultaneous changes in the dynamics and the orientation of the numerous thiol groups in the structure. The measurements of the cell parameters and cell volume on cooling suggest that a discontinuity in their values over the transition point exists.