Can molecular flexibility control crystallization? The case of<i>para</i>substituted benzoic acids

Abstract

substituted benzoic acids are compared, two of which have substituents with flexible chains. In making this comparison, the importance of normalizing data to account for differing solubilities is highlighted. These data have allowed us to go beyond popular qualitative descriptors such 'crystallizability' or 'crystallization propensity' in favour of more precise nucleation rate data. Overall, this leads to definite conclusions as to the relative importance of solution chemistry, solid-state interactions and conformational flexibility in the crystallization of these molecules and confirms the key role of intermolecular stacking interactions in determining relative nucleation rates. In a more general sense, conclusions are drawn as to conditions under which conformational change may become rate determining during a crystallization process.