Chiral recognition during crystal growth of chiral molecules : Impact of the counter enantiomer on the crystal habit of pure mandelic acid

During the past decades, the rapid development in diffraction techniques has provided lot of information about intermolecular interactions in the solid state and crystal growth mechanisms. An interesting and challenging approach in this field is the understanding of structural recognition processes (i. e. molecular and chiral recognition) related to the solvent, undesired or intentionally introduces impurity molecules (tailor-made additives) [1,2]. Such knowledge allows both prediction and comprehension of crystal morphologies. Indeed, nucleation and growth rate associated to the resulting crystal habit, can be independently modified by adding specific modifiers. Associated to the progress of molecular modeling tools and establish procedures, crystal engineering approach appears to be a powerful and efficient technology [3]. In spite of the large number of publications describing the influence of structurally related compounds, the particular situation of enantioselective crystallization in presence of the counter-enantiomer was not studied in detail, whereas the chirality impact of the additives has been lighted on, involving selective chiral recognition mechanisms as function as the faces nature [4]. Indeed, in chiral systems, the antipode can be considered as an impurity with important structural similarities. During experimental studies of growth kinetics of pure mandelic acid in water, the presence of the ocunter-enantiomer in the biphasic domain of the ternary phase diagram (pure solid enantiomer in equilibrium with saturated solution) has been highlighted as an important factor, resulting in growth rate modifications and changes in crystal morphology [5]. With the aim to correlate these results with structural features, molecular modeling tools were applied to evaluate the crystal faces ability for the stereodiffernciation. For this purpose, different approaches have benn used, pointing out weak energy differences between the desired and the counter-enantiomer, without disturbing the hydrogen bond network. Some tendencies in good agreement with the experimental data can be deduced and related to the disappearance of two crystal faces. Moreover, the existence of structural similarities between the crystal structure of pure mandelic acid and a metastable racemate modification [6] have triggered our investigations in different solvents to isolate clearly the phenomena. [1] Lahav M., Berkovitch-Yellin Z., van Mil J., Addadi L., Idelson M., Leiserowitz L. Isr. J. Chem. 1985, 25, 353; Berkovitch-Yellin Z., van Mil J., Addadi L., Idelson M., Lahav M., Leiserowitz L. J. Am. Chem. Soc. 1985, 107, 3111 [2] Clydesdale G., Roberts K. J., Lewtas K., Docherty R. J. Cryst. Growth 1994, 141, 443 [3] Clydesdale G., Hammond R. B., Roberts K. J. J. Phys. Chem. B 2003, 107, 4826 [4] Shimon L. J. W., Lahav M., Leiserowitz L. Am. Chem. Soc. 1985, 107, 3375 [5] Perlberg A., Lorenz H., Seidel-Morgenstern A. Ing. Eng. Chem. Res. 2005, 44, 1012 [6] Profir V. M., Rasmuson A. C. Cryst. Growth Des. 2004, 4, 31