UW-Madison School of Pharmacy

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Lian Yu, PhD

Pharmaceutical Sciences and Chemistry




Background: We study solids of organic molecules. These soft materials are being explored for applications in pharmaceutical and electronic technologies, and exhibit properties and physical phenomena unknown for hard materials. In this laboratory, physical measurements and crystallization experiments are performed to understand the formation, properties, and transformation of molecular solids. Our major techniques are crystallography, calorimetry, spectroscopy, and microscopy. Three areas of current research are polymorphism, crystallization of organic glasses, and molecular motions in solids.

(1) Polymorphism of Organic Materials. Polymorphism, the ability of the same molecule to crystallize in different structures, is important in the manufacture of drugs and specialty chemicals because polymorphs have different properties. Our work aims to discover polymorphs and control crystallization in polymorphic systems. 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. Organic glasses are materials for organic electronics, bio-preservation, and delivery of poorly soluble drugs. Any amorphous material must be stable against crystallization because crystallization negates its advantages. We study how organic glasses crystallize. Despite their solidity, glasses can crystallize, sometimes surprisingly fast. We are investigating fast modes of crystal growth that emerge in organic liquids as they are cooled to become glasses. The phenomenon is unknown or uncommon for hard materials. 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 fast surface 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 control how fast physicochemical changes can occur. We are studying two types of molecular mobility in organic solids: surface diffusion and moisture diffusion. The method of surface grating decay is used to measure surface molecular mobility. This property is of interest because crystal growth can occur much faster at the surface than in the bulk of organic glasses. Raman microscopy is used to measure moisture diffusion. This property is important 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.

Professional Interests: Crystallization, polymorphism, amorphous solids, solid-state chemistry.


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


  • PhD Physical Chemistry - Ohio State University
  • BS Chemistry - Peking University
Highlighted Publications:
  1. Huang, C.; Ruan, S.; Cai, T.; Yu, L. Fast Surface Diffusion and Crystallization of Amorphous Griseofulvin. Phys. Chem. B, in review.
  2. Zhu, M.; Yu, L. Isomerization energies of azopyridines. J. Therm. Anal. Calorimetry, in review.
  3. Chen, Yinsha Zhu, Me Laventure, Audrey; Lebel, Olivier; Ediger, Mark; Yu, Lian. Influence of Hydrogen Bonding on the Surface Diffusion of Molecular Glasses: Comparison of Three Triazines. J. Phys. Chem. B, in press. DOI:
  4. Zhu, M.; Yu, L. Polyamorphism of D-manntitol. J. Chem. Phys. 2017, accepted.
  5. Shi, C.; Teerakapibal, R.; Yu, Lia Zhang, G. Pair distribution functions of amorphous organic thin films from synchrotron X-ray scattering in transmission mode. IUCrJ 2017, 4, https://doi.org/10.1107/S2052252517009344.
  6. Cavallo, D.; Francesca Galli, F.; Yu, L.; Alfonso, G. C. Cross-nucleation between concomitantly crystallizing α- and γ-phases in polypivalolactone: secondary nucleation of one polymorph on another. Crystal Growth Design 2017, 17, 2639–2645.
  7. Gómez, J.; Gujral, A.; Huang, C.; Bishop, C.; Yu, L.; Ediger, M. D. Nematic-like stable glasses without equilibrium liquid crystal phases. J. Chem. Phys. 2017, 146, 54503.
  8. Gujral, A.; Gómez, J.; Jiang, J.; Huang, C.; O’Hara, K. A.; Toney, M. F.; Chabinyc, M. L.; Yu, L.; Ediger, M. D. Tunable smectic-like packing in vapor-deposited glasses of a liquid crystal. Chem. Mater. 2017, 29, 849–858.
  9. Huang, C.; Powell, C. T.; Sun, Y.; Cai, T.; Yu, L. Effect of Low-Concentration Polymers on Crystal Growth in Molecular Glasses: A Controlling Role for Polymer Segmental Mobility Relative to Host Dynamics. J. Phys. Chem. B 2017, 121, 1963−1971.
  10. Ruan, S.; Musumeci, D.; Zhang, W.; Gujral, A.; Ediger, M. D.; Yu, L. Surface Transport Mechanisms in Molecular Glasses Probed by the Exposure of Nano-particles. J. Chem. Phys. 2017, 146, 203324.
  11. Chen, Y.; Powell, C. T.; Yu, L. Tensile Fracture of Molecular Glasses Studied by Differential Scanning Calorimetry: Reduction of Heat Capacity by Lateral Constraint. J. Phys. Chem. B. 2017, 121, 444−449.
  12. Chen, Y.; Zhang, W.; Yu, L. Hydrogen Bonding Slows Down Surface Diffusion of Molecular Glasses. J. Phys. Chem. B. 2016, 120, 8007–8015.
  13. Yu, L. Surface Mobility of Molecular Glasses and Its Importance in Physical Stability. Adv. Drug Delivery Rev. 2016, 100, 3–9.
  14. Zhang, W.; Yu, L. Surface diffusion of polymer glasses. Macromolecules 2016, 49, 731–735.
  15. Powell, C. T.; Xi, H.; Sun, Y.; Gunn, E.; Chen, Y.; Ediger, M. D.; Yu, L. Fast Crystal Growth in o-Terphenyl Glasses: A Possible Role for Fracture and Surface Mobility. J. Phys. Chem. B. 2015, 119, 10124−10130.
  16. Zhu, M.; Wang, J.; Perepezko, J. H.; Yu, L. Possible existence of two amorphous phases of D-mannitol related by a first-order transition. J. Chem. Phys. 2015, 142, 244504-1 to -7.
  17. Zhang, W.; Brian, C. W.; Yu, L. Fast Surface Diffusion of Amorphous o-Terphenyl and its Competition with Viscous Flow in Surface Evolution. J. Phys. Chem. B. 2015, 119, 5071–5078.
  18. Hasebe, M.; Musumeci, D.; Yu, L. Fast Surface Crystallization of Molecular Glasses: Creation of Depletion Zones by Surface Diffusion and Crystallization Flux. J. Phys. Chem. B. 2015, 119, 3304-3311.
  19. Musumeci, D.; Powell, C. T.; Ediger, M. D.; Yu, L. Termination of Solid-State Crystal Growth in Molecular Glasses by Fluidity. J. Phys. Chem. Lett. 2014, 5, 1705−1710.
  20. Zhang, S.; Harasimowicz, M. T.; Yu, L. Co-Crystals of Nicotinamide and R-Mandelic Acid in Many Ratios with Anomalous Formation Properties. J. Am. Chem. Soc. 2013, 135, 18981−18989.
  21. Powell, C. T.; Cai, T.; Hasebe, M.; Gunn, E. M.; Gao, P.; Zhang, G.; Gong, Y.; Yu, L. Low-Concentration Polymers Inhibit and Accelerate Crystal Growth in Organic Glasses in Correlation with Segmental Mobility. J. Phys. Chem. B 2013, 117, 10334−10341.
  22.  Zhu, L.; Brian, C.; Swallen, S. F.; Straus, P. T.; Ediger, M. D.; Yu, L. Surface Diffusion of an Organic Glass. Phys. Rev. Lett. 2011, 106, 256103-1 to 256103-4.
  23.  Sun, Y.; Zhu, L.; Kearns, K. L.; Ediger, M. D.; Yu, L. Glasses Crystallize Rapidly at Surfaces by Growing Crystals Upward. Proc. Natl. Acad. Sci. U. S. A. 2011, 108(15), 5990-5995.
  24. Zhu, L.; Cai, T.; Huang, J.; Stringfellow, T. C.; Wall, M.; Yu, L. Water Self Diffusion in Glassy and Liquid Maltose Measured by Raman Microscopy and NMR. J. Phys. Chem. B 2011, 115(19), 5849-5855.
  25. Yu, L. Polymorphism in Molecular Solids: An Extraordinary System of Red, Orange, and Yellow Crystals.  Acc. Chem. Res. 2010, 43, 1257-1266.  Cover article.
  26. Zhu, L.; Yu, L. Generality of Forming Stable Organic Glasses by Vapor Deposition.  Chem. Phys. Lett. 2010, 499, 62–65.
  27. Tao, J.; Sun, Y.; Zhang, G. G. D.; Yu, L. Solubility of Small-Molecule Crystals in Polymers: D-Mannitol in PVP, Indomethacin in PVP/VA, and Nifedipine in PVP/VA.  Pharm. Res. 2009, 26, 855 – 864.  No. 1 most viewed paper of Pharm. Res. online (7874 times by 28 March 2012; http://www.pharmagateway.net/MostViewedArticles.aspx?JournalID=11095).
  28. 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, 130, 13973-13980.
  29. 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.
  30. Ediger, M.; Harrowell, P.; Yu, L. Crystal Growth Kinetics Depend on Liquid Fragility.  J. Chem. Phys. 2008, 128, 034709/1-034709/6.
  31. Yu, L. Survival of the fittest polymorph: how fast nucleater can lose to fast grower.  CrystEngComm, 2007, 9, 847 – 851.  Invited Highlight.
  32. Wu, T.; Sun, Y.; Li, N.; de Villiers, M.; Yu, L. Inhibiting Surface Crystallization of Amorphous Indomethacin by Nanocoating.  Langmuir 2007, 23, 5148-5153.
  33. 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.
  34. 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.
  35. Wu, T.; Yu, L. Origin of Enhanced Crystal Growth Kinetics near Tg Probed with Indomethacin Polymorphs.  J. Phys. Chem. B 2006, 110, 15694-15699.
  36. Wu, T.; Yu, L. Surface Crystallization of Indomethacin below Tg.  Pharm. Res. 2006, 23, 2350-2355.
  37. Huang, J.; Yu, L. Effect of Molecular Chirality on Racemate Stability: α-Amino Acids with Non-polar R Groups.  J. Am. Chem. Soc. 2006, 128, 1873-1878.
  38. Yu, L.; Huang, J.; Jones, K. J. Measuring Free-Energy Difference between Crystal Polymorphs through Eutectic Melting.  J. Phys. Chem. B 2005, 109, 19915-19922.
  39. Yu, L. Nucleation of One Polymorph by Another. J. Am. Chem. Soc. 2003, 125, 6380-6381.  Featured in Chem. & Eng. News, 2003, 81(May 19), 36 and Science News 2004, 166, 113-128.
  40. Yu, L. Color Changes Caused by Conformational Polymorphism:  Optical-Crystallography, Single-Crystal Spectroscopy, and Computational Chemistry. J. Phys. Chem. A 2002, 106, 544-550.
  41. Mitchell, C. A.; Yu, L.; Ward, M. D. Selective Nucleation and Discovery of Organic Polymorphs through Epitaxy with Single Crystal Substrates.  J. Am. Chem. Soc. 2001, 123, 10830-10839.
  42. Yu, L. Amorphous Pharmaceuticals - Preparation, Characterization and Stabilization. Adv. Drug Delivery Rev. 2001 48, 27-42.
  43. Yu, L.; Stephenson, G. A.; Mitchell, C. A.; Bunnell, C. A.; Snorek, S. V.; Bowyer, J. J.; Borchardt, T. B.; Stowell, J. G.; Byrn, S. R. Thermochemistry and Conformational Polymorphism of a Hexamorphic Crystal System.  J. Am. Chem. Soc. 2000, 122, 585-591.
  44. Yu, L.  Inferring Thermodynamic Stability Relationship of Polymorphs from Melting Data.  J. Pharm. Sci. 1995, 84, 966.