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
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 molecularscale
recognition events that can lead to polymorphism which is a promising step to the
final goal: understanding early formation pathways of crystallographic polymorphs.