Self-association during heterogeneous nucleation onto well-defined templates.

We investigated the interplay between self-associates in solution and surface templating by studying the crystallization behavior of isonicotinamide (INA) and 2,6-dihydroxybenzoic acid (DHB) in the presence of self-assembled monolayers (SAM). The end group of the SAM as well as the hydrogen-bonding capabilities of the solvent and self-association of INA and DHB were found to be important in polymorph crystallization on SAMs. In the case of INA in ethanol, both chain and dimer self-associates are present in the solution. In the absence of SAMs the polymorph form II (dimer structure) is the crystallization outcome. In ethanol the 4-mercaptopyridine and 4-mercaptobenzoic acid SAMs organize INA chain associates at the template surface and enable the crystallization of form I while the 16-mercaptohexadecanoic acid SAM results in the crystallization of form II. Raman spectroscopy suggests that molecular interactions between INA and the SAM are responsible for the formation of specific polymorphs. XRPD results in the identification of the orientation of the crystal on the surface that further verified the results obtained by Raman spectroscopy. In nitrobenzene and nitromethane INA associates in solution only as chains and crystallization results in the formation of form IV and form I, respectively (both chain forms). The crystals formed in the bulk solution and on SAMs were the same, which seems to indicate that the self-association in nitrobenzene and nitromethane is not influenced by the presence of templates. In the case of DHB in toluene and chloroform, all three SAMs nucleated only one type of polymorph (stable form 2). In the case of toluene the polymorphic outcome was stable form 2 instead of metastable form 1, which is favored in toluene in the absence of the SAMs. Again, Raman spectroscopy and XRPD suggest that DHB-SAM molecular interactions may be responsible for the formation of form 2.