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

Publication Reference
FRR-30-16
Author Last Name
Wiesner
Authors
Ulrich B. Wiesner
Publication Year
2021
Country
United States

look at early formation stages of crystallization.

to study polymorph selectivity in different solvents or solvent mixtures as well as to

appropriate conditions, nucleation and growth on SAMs can function as a model system

interpretations. Overall, the two-part project clearly established, however, that under

were the basis for the designs of all experiments conducted and associated

Covid-19 shutdown). This may have led to variations in the solubility curves, which

that only a small amount of ultrapure ROY was available (in part as a result of the

crystallization experiments reported with ROY on SAMS were also plagued by the fact

likely caused by crystals falling off of the substrate into the solution. Furthermore, all

phenyl SAMs). The growth possibility dropped as supersaturation increased, which was

secondary polymorphs typically increased with increasing supersaturation (exception:

observed as a function of SAM chemistry. The possibility of occurrence of these

dominant polymorph, irrespective of SAM. However, secondary polymorphs were

with longer incubation time. When the solvent changed to toluene, Y was still the

(exception: phenyl SAMs). The growth possibility showed an overall increasing trend

polymorphs were not frequently observed, even at higher supersaturation levels

benzyl alcohol, Y was the dominant polymorph, irrespective of SAM. Secondary

applied for polymorph characterization of the resulting nucleated crystals. For ROY in

induced on the SAM surface by generating temperature jumps. Raman microscopy was

part of the project. SAMs were placed vertically in the solution and the nucleation was

conducted instead of the solvent evaporation-based crystallization employed in the first

control the level of supersaturation, crystallization experiments upon cooling were

in toluene and benzyl alcohol were determined. In this part of the project, in order to

on polymorph selection in concert with SAMs. To that end, solubility curves for ROY

chemistry, and both polar and nonpolar solvents were again chosen to study their effects

different terminal (omega) functional groups were used to control nucleating surface

(ROY), was chosen for in depth studies. Alkane-thiols based SAMs on gold with

organic model system, 5-methyl-2-[(2-nitrophenyl) amino]-3-thiophenecarbonitrile

other model compounds. In the second part of the project, to that end a more complex

formation stages of the crystallization of ACM and may be used to extend to studies of

suggested, that our methodologies are effective to gain insights into the earliest

possible existence of structural transformations at these early stages. These results

occurring. Further analysis and corroboration via additional data sets pointed to the

nucleation, we identified unusual shifts along scattering vector, q, of the earliest peaks

totally in-plane orientation. Studying crystallization of Form I by spontaneous

crystallographic orientation, directing the (002) planes from slightly out-of-plane to a

(trichloro(phenyl)silane) terminated SAM surface has a strong influence over

the substrate-solution interface than in the bulk above, and that a PTS

crystallization of Form II by seeded nucleation, we verified that crystals grow faster at

of Form I and II crystallization events of ACM under these conditions. Studying

Cornell’s High Energy Synchrotron Source (CHESS) to study the early formation stages

We then introduced time-resolved in situ wide-angle X-ray scattering (WAXS) at

surface chemistry and solvent conditions work together to control crystal polymorph.

degree of supersaturation. Under these conditions, we first demonstrated that both SAM

and growth were induced by simple solvent evaporation, i.e. without control of the

predominant crystal forms, Form I and Form II, was investigated. In this part, nucleation

part of the project, a pharmaceutical compound, acetaminophen (ACM), with two

chosen to study their effects on polymorph selection in concert with SAMs. In the first

used to control nucleating surface chemistry. Both polar and nonpolar solvents were

gold or silanes on glass, each with different terminal (omega) functional groups, were

in order to control crystal polymorphs. To that end, either alkane-thiol based SAMs on

monolayers (SAMs) in conjunction with varying solvents or solvent mixtures

mechanisms are highly desirable. In this project, we used a combination of selfassembled

methods that lead to an advanced understanding of early crystal formation pathways and

industries. Since a polymorph is determined at the early stages during crystallization,

of organic compounds is scientifically and technologically important to several

Understanding and control of crystallographic polymorphism and crystal habit

SUMMARY