Concomitant polymorphism and chirality studies on self-assembled monolayers

The ability of a compound to exist in more than one crystal structure is known as polymorphism. Polymorphism is a result of differences in the molecular packing arrangement and/or molecular conformation. Concomitant nucleation of polymorphs is an interesting phenomenon which involves the appearance of more than one polymorph of a substance under seemingly identical conditions. In this work, we studied concomitant nucleation using a high throughput method consisting of patterned substrates of self-assembled monolayers with contrasting wetting properties. We were able to obtain 6 out of the 7 stable polymorphs of the compound 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) under seemingly identical conditions. Form YT04 crystals, previously prepared by melt crystallization and seeding methods, were obtained in very low percentages in our experiments from solution crystallization. Form ORP crystals were obtained in very low percentages only when we carried out more than 10000 trials. The low probability of obtaining crystals of forms YN and ORP on an island means that they could be missed even if 1000 trials are carried out.Chiral drugs are a subgroup of drug substances that contain one or more chiral centers. From the points of view of safety and efficacy, the pure enantiomer is preferred over the racemate in many marketed dosage forms. Thus, resolution of enantiomer mixtures is an active area of research. In this work, we used chiral self assembled monolayers (SAMs) on gold as resolving auxiliaries in the crystallization of the amino acid valine. We were able to obtain one enantiomer in excess on the crystals obtained on the chiral SAMs when starting with racemic solutions. The enantiomer obtained in excess was the one having opposite chirality to the monolayer being used. Significantly, we were also able to obtain crystals of the pure enantiomer when starting with a solution having an enantiomeric excess value of 50%. Control experiments carried out without any chiral SAMs showed that at equilibrium, mixtures of the pure enantiomer and racemic compound were obtained under these conditions. The enantiomer obtained on the chiral SAMs was the one that was initially present in excess regardless of the chirality of the monolayer being used.