Self-Assembled Monolayers as Nucleating Surfaces to Study Early Formation Pathways of Crystallographic Poylmorphs

Executive Summary

The understanding and control of crystallographic polymorphism and crystal habit of organic as well as inorganic compounds is scientifically and technologically important to a number of industries. To date, however, the experimental control of polymorphs (crystalline solids with different arrangements of the same constituents) is difficult. Since a polymorph is determined at the nucleation of a crystal, methods that lead to an advanced understanding of early crystal formation pathways and mechanisms are highly desirable. Towards this aim, in this project we employ arrays of self-assembled monolayers (SAMs).

Self-assembled monolayers (SAMs) are well-defined surfaces that can be used to study the relationship between the nucleation event and the final polymorph selection. Furthermore, by tuning the substrate-crystal interface energy, potentially crystalline order of SAMs can promote the nucleation of polymorphs not accessible via solution methods. It is these two advantages, i.e. the establishment of scientific correlations between nucleation and observed polymorph and access to polymorphs not accessible via solution methods, that have led us in this project to choose heterogeneous surface nucleation via SAMs as the primary means to study polymorph selection.

In the first-year of work, we have selected three types of SAMs, two hydrophilic (carboxylic acid terminated surface and hydroxyl terminated surface) and a hydrophobic (methyl terminated) surface to investigate their ability to influence the nucleation, crystal growth, and polymorph selection of a common drug, acetaminophen (ACM). It turns out that the hydrophilic surface tends to promote the formation of the monoclinic form of ACM, while the hydrophobic surface induces the formation of the less thermodynamically stable orthorhombic form of ACM. We hypothesize that this selection is due to the energetic preference of certain crystal facets interacting with the chemically specific SAMs surface. By studying the known relationships between the structure of the crystal and the nucleating surface, we will gain insights into molecular-scale recognition events that can lead to polymorphism which is a promising step to the final goal: understanding early formation pathways of crystallographic polymorphs.