Predicting the Effect of Solvent on the Crystal Habit of Small Organic Molecules

Abstract

In order to develop a practical engineering tool for predicting the relative growth rates and morphology of solution-grown faceted crystals, a method for quickly determining solvent-modified crystal surface energies is required. The bulk interface approximation and model by van Oss, Chaudhury, and Good provides the most practical option available for small organic molecules. Applying these techniques to the mechanistic growth modeling of four centrosymmetric crystal systems provides evidence of the utility of this treatment, since both sublimation and solution growth shape predictions correspond to experimental shapes. The fact that the approach correctly predicts the changes between sublimation and solution growth shapes supports the ability of this technique to accurately account for the solvent effect.

A design aid for crystal growth engineering

“…Surface physics and chemistry (including the growth environment) define the rates of these processes. is, in principle, system-specific but under solution growth for organic molecular crystals typically involves sequential adsorption at the terrace and then the step before entering the kink site [11,14,[72][73][74][75][76]. Steps are generated on F faces as a result of two mechanisms: two-dimensional (2D) nucleation on the surface or screw dislocations (leading to spiral growth); these are discussed in sections section 3.4 & 3.5, respectively.…”

“…We expect organic molecular crystals (with fast surface diffusion) to grow via a 3-event mechanism: terrace adsorption, step adsorption and finally kink incorporation; inorganic crystals are conversely expected to incorporate directly from solution in light of slower surface diffusion. A microkinetic model can be formulated to describe each process within a 3-event mechanism; the resulting kink rate for centrosymmetric crystals is essentially the same as if a single-event mechanism of incorporation directly from solution is adopted [76]. Thus, although incorporation into a kink is expected to be preceded by adsorption onto a step, rate expressions can be simplified by assuming a single-event mechanism.…”

“…ADDICT will attempt to find locations of acid-base interactions by finding those PBCs with a large columbic character in GAFF. This approach was prompted by a recent investigation into the most appropriate way to model solution effects within the mechanistic crystal growth model; a brief summary of the implementation will be presented here with more details appearing in an upcoming paper [76].…”

Crystal Morphology and Interfacial Stability of RS-Ibuprofen in Relation to Its Molecular and Synthonic Structure

“…a Burton, Cabrera and Frank mechanism (BCF) 35 , or by a birth and spread mechanism (B&S) 36 , can be assessed utilising the attachment energy model 30 . Though there have been a number of studies which have successfully predicted the morphology of crystals as a function of solvent environment for surfaces which grow by such mechanisms 12,20,[37][38][39][40][41] , a universal method for predicting the dependence of the crystal morphology as a function of solvent choice is yet to be fully established. It is though well-known that if a crystal surface grows with a roughened interface, then the crystal growth rate can be significantly increased [42][43][44] .…”

An Appreciation of Organic Solid‐State Chemistry and Challenges in the Field of “Molecules, Materials, Medicines”

“…A better understanding of solid‐state phase transformations would enable more confidence in developing metastable polymorphs, stabilising amorphous forms and further work in identifying the types and role of defects in modifying degradation pathways will also be important . Certain crystal attributes can be modelled reasonably well—habit, mechanical properties, dislocation nucleation and dynamics,—that are important in modelling and predicting solubility ,. Combining crystal structure with associated property predictions is likely to be a key driver for future research efforts towards establishing robust development programs.…”