The question of the relationship between intermolecular forces and crystal packing has been well studied over the last decades (1, 2). This work has facilitated both the sub set of crystallography, now referred to as crystal engineering (3) and the activity of crystal structure prediction (4). From this work has come the notion (5) of a crystal as a supramolecular entity created from structural synthons – building blocks which may be single molecules or intermolecularly bonded groups of molecules.
In the much older field of crystal nucleation, however, the emphasis has traditionally been on kinetics rather than structure and indeed the general behaviour of supersaturated solutions is well described by the rate equations originating from the work of Volmer in the 1930s (6, 7). It is only recently that attention has begun to focus on structural aspects of the nucleation process (8, 9). Two phenomena are of particular interest – the first concerns the nature of molecular packing within a potential nucleus (10) and the second, the link between structural synthons, as identified by crystallography, and growth synthons present in solution as a consequence of thermodynamically driven self-association equilibria (11,12). It is the second point which concerns us here. This link has been addressed previously in the case of -glycine where the facile nucleation of this metastable form from aqueous solution is thought to result from the presence of cyclic dimers in solution, an idea supported by both diffusion data (13) and surface diffraction from single crystal surfaces (14). Using the measured concentration dependence of proton NMR chemical shift in sulphamerizine Spitaleri et al (15) have noted a direct correlation between dimers in the solution phase and those on the resulting crystal. More recently (16), molecular dynamics simulations of 5-fluorouracil in aqueous and nitromethane solutions have found that the while in nitromethane the doubly H-bonded dimer is favoured, the presence of water hinders its formation and promotes a hydrophobic F…F contact between molecules. This outcome is consistent with the observed nucleation of Form I from aqueous solutions and Form II from nitromethane. In the current work we have chosen to study three mono carboxylic acids- benzoic acid, tetrolic acid and mandelic acid, for a number of reasons. Firstly, their crystallography and intermolecular H-bonding has been well studied and modelled (17, 18). Secondly, the identification of H-bonding motifs in such systems may be carried out relatively easily using FTIR and indeed the early literature on IR spectroscopy contains much work on solutions of carboxylic acids (19, 20), suggesting the possibility that for theses systems it might be possible to make direct observations of self association in concentrated solutions. Finally, in the solid state, the specific acids chosen demonstrate three major features of more general interest. Benzoic acid crystallises in the centrosymmetric space group P21/c (21) in only one known structure constructed from the classic ( ) 2 R 2 8 carboxyl dimer synthon.