Elisa Nauha

Kitaigorodsky Revisited: Polymorphism and Mixed Crystals of Acridine/Phenazine

Non-stoichiometric molecular mixed crystals have potential as functional materials, the properties of which can be tailored by rationally changing their composition. The guidelines for their preparation were summarized over thirty years ago by Alexander Kitaigorodsky. Here those principles are revised in light of new studies on the acridine/phenazine system, and solvent-assisted grinding is presented as a convenient synthetic procedure to afford a more homogeneous product than traditional solvent-evaporation methods. Finally, the proposed prerequisite of crystal isostructurality/isomorphicity for the pure compounds, which seems to be violated in the present case, is discussed.

Fine-tuning of a thermosalient phase transition by solid solutions

Thermosalient crystals are solids that exhibit motion at the macroscale as a consequence of a thermally induced phase transition. They represent an interesting scientific phenomenon and could be useful as actuators for the conversion of thermal energy into motion or mechanical work. The potential utilization of these miniature transducers in real-world devices requires a controllable phase transition (i.e. a predetermined temperature). While it is difficult to control these performances with a single-component molecular crystal, “tunable” properties could be accomplished by solid solutions. To verify this hypothesis, the thermosalient material [Zn(bpy)Br2] (bpy = 2,2′-bipyridine) was selected and its synthesis was performed in the presence of chloride ions. The resulting mixed crystals ([Zn(bpy)Br2xCl2(1−x)]) show that the product undergoes the expected thermosalient phase transition, and the temperature of the onset of the phase transition and the transition enthalpy depend on the Cl/Br ratio.

“Predicting” Polymorphs of Pharmaceuticals Using Hydrogen Bond Propensities: Probenecid and Its Two Single‐Crystal‐to‐Single‐Crystal Phase Transitions

The recently developed hydrogen-bonding propensity tool in the Cambridge Structural Database software package (Mercury) was tested to predict polymorphs. The compounds for the study were chosen from a list of approximately 300 pharmaceutically important compounds, for which multiple crystal forms had not been previously reported. The hydrogen-bonding propensity analysis was carried out on approximately 60 randomly selected compounds from this list. Several compounds with a high probability for exhibiting polymorphism in the analysis were chosen for a limited experimental crystal form screening. One of the compounds, probenecid, did not yield polymorphs by traditional solution crystallization screening, but differential scanning calorimetry revealed three polymorphs. All of them exhibit the same hydrogen bonding and transform via two reversible single-crystal-to single-crystal transformations, which have been characterized in detail through three single-crystal structure determinations at appropriate temperatures.

Control of a thermosalient phase transition by solid solutions

Thermosalient crystals that exhibit macro-scale motion upon phase transition could be useful as actuators that are capable of converting thermal energy into motion or mechanical work in macroscopic devices.[1] The application capability of these miniature actuators for energy conversion depends on the temperature range and dynamics of transition. While the thermo-mechanical performance cannot be systematically varied with a pure molecular crystal, solid solutions could present a way to intentionally tune both the dynamics and the temperature of the transition in a continuous manner (Figure 1). To verify this hypothesis, Zn(2,2’bpy)Br2,[2] was selected as a thermosalient material which could form solid solutions (or mixed complexes) with Zn(2,2’-bpy)Cl2. Only one form (isomorphous to one of the two Zn(2,2’-bpy)Br2 forms) has been reported for the chloride.[3] The results indicate that indeed, the two complexes form solid solutions in varying ratios. The mixed crystals undergo the same phase transformation as the pure Zn(2,2’-bpy)Br2 at a Cl/Br-ratio-dependent temperature. The temperature and dynamics of the thermosalient phenomenon correlates with the Cl/Br-ratio.