Lian Yu

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4119 Pharmacy
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Yu L Group
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B.S. Peking University (China)                           
Ph.D. Ohio State University

Also: Professor of Pharmacy

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Research Description

We study the solids of organic molecules, with special attention to the different solids of the same molecules. A key property of solids is the ability of the same substance to form different and long-lasting structures. Carbon can crystallize as diamond and graphite; silicon dioxide can solidify as quartz (crystalline) and glass (amorphous). The discovery of new solid forms provides new materials (e.g., C60 and carbon nanotubes) and new knowledge of materials. Our study of organic solids is also motivated by their importance in developing drugs, organic electronics, and other soft materials. Recent studies have revealed new and surprising features of organic solids unknown for inorganic solids. In this laboratory, physical measurements and crystallization experiments are combined to understand how different solid forms can result from the same liquid and transform among themselves. Our major techniques are crystallography, calorimetry, spectroscopy, and microscopy.

Three areas of current research:
(1) Polymorphism of Organic Materials. Polymorphism, the ability of the same molecule to crystallize in different structures, is important to the makers of pharmaceuticals and specialty chemicals. Our work aims to discover unusual polymorphs, understand how polymorphic systems crystallize, and use polymorphs as a tool to understand the process of crystallization. A polymorphic system discovered in this laboratory (ROY) has the largest number of coexisting polymorphs of solved structures. Such a system helps elucidate the origin of polymorphism and study structure-property relations. Some questions being investigated include: Why do some molecules have many polymorphs and others seemingly none? Why do polymorphs grow from the same liquid at rates orders of magnitude different? What determines the probability of one polymorph nucleating on another during crystallization?

(2) Crystallization of Organic Glasses. For many applications, amorphous solids (glasses) are preferred over crystalline solids. Amorphous drugs, for example, are more soluble than crystalline drugs, a property useful for delivering the increasing number of highly potent but poorly soluble drugs. Any amorphous material must be stable against crystallization for crystallization negates its advantages. We are interested in how organic glasses crystallize. It is remarkable that despite the freezing of liquid-like molecular mobility, a glass can still crystallize, even at rates faster than permitted by diffusion. We are studying two mechanisms leading to fast crystal growth: transition from diffusion-controlled to “diffusionless” crystal growth and surface-enhanced crystal growth. To our knowledge, these phenomena have been observed only for organic glass formers. Some questions being investigated include: Is crystal growth from glasses controlled by crystal/liquid structural similarity? How does crystal growth from glasses differ from diffusion-controlled growth in low-viscosity liquids? Is surface-enhanced crystal growth caused by high surface molecular mobility? Can surface crystallization be suppressed with a coating? How does surface-enhanced crystallization differ from bulk crystallization?

(3) Molecular Motions in Organic Solids. Molecular motions in a solid controls how fast it undergoes physical and chemical changes. We are studying two types of molecular mobility in organic glasses: surface diffusion and moisture diffusion. The method of surface grating decay is used to measure the surface molecular mobility of organic glasses. This property is of interest because crystal growth can occur orders of magnitude faster at the surface than in the bulk of organic glasses. Raman microscopy is used to measure moisture diffusion in sugar glasses. This property is of interest because the interaction with water is a major mechanism for the degradation of pharmaceutical and food products.

Awards and Honors

David Grant Research Achievement Award in Physical Pharmacy, American Association of Pharmaceutical Scientists 2011
Invited Visiting Professor, University of Manchester, United Kingdom 2009
Elected Fellow, American Association of Pharmaceutical Scientists 2006
Lilly Research Laboratories President's Award 2003