This award to University of Wisconsin-Madison by the Solid State Materials Chemistry program in the Division of Materials Research is to investigate the polymorphism of organic materials. Polymorphism is the ability of the same molecule to crystallize in different structures with distinct properties, as the ability of carbon to crystallize as diamond, graphite, and C60. This project will synthesize novel polymorphs by cross-nucleation and will use polymorphs to understand an unusual mode of crystal growth from amorphous solids. The project builds on recent observations that rare crystal forms of chiral molecules may be discovered by seeding and that some polymorphs show fast, diffusionless crystal growth from the glassy state, while others do not. This project will study two broad fundamental questions in the crystallization of organic and pharmaceutical materials: (i) synthesis of solid solutions of enantiomers, with an enhanced excess of one enantiomer, and (ii) the crystallization of amorphous materials. The first project focuses on the seeding-induced crystal growth of chiral molecules. The second part of the project will be on the crystal growth of polymorph-forming molecules from supercooled liquids. Both projects seek to address fundamental mechanisms of crystal growth.
Studying crystal polymorphs serve two missions of materials research: to synthesize new materials and to understand structure-property relations. It is anticipated that this research will impact several technological areas. The discovery and control of polymorphs is critical in developing drugs, pigments, explosives, and other materials. Better understanding of the crystallization of amorphous materials will advance the ability to develop amorphous drugs, silicon, metals, ceramics, and polymers. This research spans materials science and chemistry and will provide multidisciplinary educational opportunities for undergraduate and graduate students. The research will involve students from the Undergraduate Research Scholars program, which helps first- and second-year undergraduates to gain hands-on experience in research by working with the faculty and research staff at University of Wisconsin-Madison campus.
. Polymorphism is the ability of the same substance to crystallize in different structures with distinct properties. This phenomenon is illustrated by the ability of carbon to crystallize as diamond, graphite, and C60. The team observed that even though polymorphs share the same liquid, they can grow at remarkably different rates. They used this polymorphic dependence to understand the dependence of the crystal growth process on the structure being developed. One conclusion is that organic glasses can rapidly crystallize in structures that have more isotropic packing of molecules. Polymorphs were also used to understand fast crystal growth at the free surface of organic glasses. The team established that the surface enhancement of crystal growth is not caused by the easier release of crystallization-induced tension, but better explained by surface molecular mobility and the possibility for surface crystals to grow toward free space. The workers determined that in contrary to a widely held view, the selective crystallization of a centro-symmetric polymorph of glycine is not a consequence of the formation of molecular dimers. Their research findings have been presented in 17 papers in high-impact journals of basic and applied science. Crystal polymorphism is an important phenomenon in the fabrication of many products, including drugs, pigments, and explosives, and in the study of structure-property relations in materials. This project has advanced the understanding of polymorphism and its control during crystallization processes. Although the traditional control strategy emphasizes the nucleation of target polymorphs, this work has shown the importance of controlling the relative growth rates of polymorphs; fast nucleater need not be fast grower. The stability of amorphous materials against crystallization is essential for all amorphous materials, including drugs, silicon, metals, ceramics, and polymers. This work has improved the understanding of crystal growth in organic glasses and the knowledge gained will guide the production of stable amorphous materials. For example, this work has raised questions about an influential model of surface crystallization in the ceramic and metallurgical communities, which gives importance to the crystal-glass density difference. This work has shown instead that surface crystallization is facilitated by surface molecular mobility. This research has spanned materials science and chemistry and provided multidisciplinary educational opportunities for six graduate students, three postdoctoral researchers, and four undergraduate students. The participants have won prestigious awards and fellowships on the strength of their accomplishments, and are now independent research scientists in academia and industry. The team played a key part in the University of Wisconsin Pre-college Enrichment Opportunity Program for Learning Excellence (PEOPLE) each summer during the grant period, which provides experiences that help minority and low-income high-school students to become scientifically literate citizens and encourages them to consider careers in science and engineering. The research findings have been incorporated into the course materials for Molecular Solids, a graduate course taught by Lian Yu to students from Pharmaceutical Sciences, Chemistry, Chemical Engineering, and Food Science, and from local companies, and into short courses to industrial scientists organized by University of Wisconsin Extension Service and the Association of American Pharmaceutical Scientists. It is significant that this NSF-supported project has been augmented by additional industrial funding to develop the technology of stable amorphous pharmaceuticals for delivering poorly soluble drugs.
