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Education:

• Ph.D. Physical Chemistry Ohio State University
• B.S. Chemistry Peking University

Overview

Lian Yu joined the School of Pharmacy in 2004. Before then he was a research scientist in Eli Lilly and Company (1991-2003). He is a Fellow of the American Association of Pharmaceutical Scientists and recipient of Lilly Research Laboratories President's Award. He has an affiliate appointment in the Department of Chemistry.

We study the solids of organic molecules, with special attention to the different solids of the same molecule. A key property of solids, in contrast to liquids and gases, is that the same substance can produce many solids of different structures. Carbon can crystallize as diamond and graphite; silicon dioxide can crystallize as quartz and can solidify without crystallizing to yield a glass or amorphous solid. 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 further motivated by their importance in the development of drugs, organic electronics, and other soft materials. Recent studies have revealed new and surprising features of organic solids unknown for inorganic solids; for example, a transition from diffusion-controlled to diffusionless crystal growth in organic glass formers. In this laboratory, physical measurements and crystallization experiments are performed 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.

(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 (Figure 1). 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 (Figure 2)?

(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.

Figure 1. The simple molecule ROY forms at least ten polymorphs with different colors and molecular conformations; the structures of seven polymorphs (shown) have been solved.

Figure 2. Crystal seeds in a supersaturated medium are expected to grow in the same lattice. We found, however, that seeds of one polymorph can nucleate another polymorph. D-mannitol crystallized first as the delta polymorph and then as the alpha polymorph, with alpha nucleating on delta. This phenomenon is relevant to understanding and controlling crystallization in polymorphic systems.

Work-Related Interests/Research:

Crystallization, polymorphism, amorphous solids, solid-state chemistry.

Highlighted Publications:

• Chen, S.; Guzei, I. A.; Yu, L. New Polymorphs of ROY and New Record for Coexisting Polymorphs of Solved Structures. J. Am. Chem. Soc. 2005, 127, 9881-9885.
• Chen, S.; Xi, H.; Yu, L. Cross Nucleation between ROY Polymorphs. J. Am. Chem. Soc. 2005, 127, 17439-17444.

• Tao, J.; Yu, L. Kinetics of Cross-Nucleation between Polymorphs J. Phys. Chem. B 2006, 110, 7098-7101.
• Wu, T.; Yu, L. Origin of Enhanced Crystal Growth Kinetics near Tg Probed with Indomethacin Polymorphs. J. Phys. Chem. B 2006, 110, 15694-15699.
• Wu, T.; Yu, L. Surface Crystallization of Indomethacin below Tg. Pharm. Res. 2006, 23, 2350-2355.
• Huang, J.; Chen, S.; Guzei, I. A.; Yu, L. Discovery of a Solid Solution of Enantiomers in a Racemate-Forming System by Seeding. J. Am. Chem. Soc 2006, 128, 11985-11992.
• Huang, J.; Yu, L. Effect of Molecular Chirality on Racemate Stability: alpha-Amino Acids with Non-polar R Groups. J. Am. Chem. Soc. 2006, 128, 1873-1878.
• Swallen, S.; Kearns, K.; Mapes, M.; McMahon, R.; Kim, S.; Ediger, M.; Yu, L.; Wu, T.; Satija, S. Extraordinarily Stable Glassy Materials Prepared by Vapor Deposition. Science 2007, 315, 353 - 356.
• Ediger, M.; Harrowell, P.; Yu, L. Crystal Growth Kinetics Depend on Liquid Fragility. J. Chem. Phys. 2007, 128(3) , 034709/1-034709/6.
• Wu, T.; Sun, Y.; Li, N.; de Villiers, M.; Yu, L. Inhibiting Surface Crystallization of Amorphous Indomethacin by Nanocoating. Langmuir 2007, 23(9) , 5148-5153.
• Ishida, H.; Wu, T.; Yu, L. Sudden Acceleration of Crystal Growth of Nifedipine near Tg without and with Polyvinylpyrrolidone. J. Pharm. Sci. 2007, 96(5) , 1131-8.
• Tao, J.; Yu, L. Cross-Nucleation between D-Mannitol Polymorphs in Seeded Crystallization. Cryst. Growth & Design 2007, 7(12) , 2410-2414.
• Yu, L. Survival of the fittest polymorph: how fast nucleater can lose to fast grower. CrystEngComm, 2007, 9 (10) , 847 - 851. Invited Highlight.
• Sun, Y.; Xi, H.; Ediger, M. D.; Yu, L. Diffusionless Crystal Growth from Glass Has Precursor in Equilibrium Liquid. J. Phys. Chem. B 2008, 112(3) , 661-664.
• Sun, Y.; Xi, H.; Chen, S.; Ediger, M. D.; Yu, L. Crystallization near Glass Transition: Transition from Diffusion-Controlled to Diffusionless Crystal Growth Studied with Seven Polymorphs. J. Phys. Chem. B 2008, 112 , 5594-5601.
• Kearns, K. L.; Swallen, S. F.; Ediger, M. D.; Wu, T.; Sun, Y.; Yu, L. Hiking down the Energy Landscape: Progress Toward the Kauzmann Temperature via Vapor Deposition. J. Phys. Chem. B 2008, 112 , 4934-4942.
• Huang, J.; Stringfellow, T. C.; Yu, L. Glycine Exists Mainly as Monomers, Not Dimers, in Supersaturated Aqueous Solutions: Implications for Understanding Its Crystallization and Polymorphism. J. Am. Chem. Soc. 2008, web posting Sept 25.
• Zhu, L.; Wong, L.; Yu, L. Surface-Enhanced Crystallization of Amorphous Nifedipine. Molecular Pharmaceutics 2008, web posting Sept 23.