The impact of systematic structural variation on the energetics of π-π stacking interactions and associated computed charge transfer integrals of crystalline diketopyrrolopyrroles

Investigating crystal nucleation at the nanoscale is of significant interest, in particular as more complex, non-classical routes have roused questions about the classical view of homo-and hetero-nucleation processes. Here, we report the direct observation of a two-step nucleation mechanism during the transformation of anhydrous olanzapine to olanzapine dihydrate. Atomic force microscopy studies of the dominant (100)OZPNI face of olanzapine form I single crystals in contact with water show the formation and growth of dense nanodroplets concentrated around ledge sites. In unstirred solution, apparent ordering and crystallisation from these droplets occurs with olanzapine dihydrate D produced by the templating effect of the underlying olanzapine I lattice. In contrast, under stirred conditions a kinetic dihydrate polymorph, dihydrate B, nucleates probably due to the detachment of nanodroplets from the surface during stirring and a consequent loss of template effect. Computational modelling of the binding of olanzapine growth units on crystal ledges reveals many strongly bound dimer positions unrelated to either crystal structure. This impedes surface integration and contributes to the growth of disordered clusters at the ledge site. Nanocrystal modelling shows that the (100)OZPNI surface favours the nucleation of dihydrate D over the kinetic form. This work gives an important insight into heterogeneous two step nucleation where the first step, the formation of a prenucleation droplet, can in the second step, bifurcate, either to produce the stable form by templating, or the kinetic form on detachment of the nanodroplets.

Sensitive optical detection of nitroaromatic vapours with diketopyrrolopyrrole thin films is reported for the first time and the impact of thin film crystal structure and morphology on fluorescence quenching behaviour demonstrated.

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An organic molecule may crystalize in numerous distinct lattices and the slow and unpredictable transitions between multiple crystal forms is a significant concern in its pharmaceutical application. Recent results indicate that the transformation of olanzapine (OZPN) from anhydrous to hydrate crystals is mediated by mesoscopic solute-rich clusters. Here we demonstrate the existence of such clusters in undersaturated OZPN solutions in purely aqueous and mixed EtOH/aqueous solvents. The clusters occupy about 10-8-10-7 of the solution volume and capture ca. 10-7-10-5 of the dissolved OZPN. The average cluster radius is steady in time at about 35 nm and independent of the OZPN concentration and the solvent composition, whereas the OZPN fraction captured in the clusters is dictated by the solution thermodynamics. Both behaviors are in dire conflict with classical theories of phase transformation and recent aggregation models. They are, however, consistent with the predictions of a model that assumes the formation of OZPN dimers and their decay upon exiting the clusters. We propose that a transient dimer, which may be akin to the centrosymmetric dimer present in all of the 60 known OZPN crystal structures, may underlie cluster formation. The finding of cluster formation in organic systems and the proposed cluster mechanism provide guidance towards enhanced control over nucleation, molecular transitions, and the solid forms in molecular systems. 