Tonglei Li, Ph.D.

Our main research thrust stems from solid-state organic chemistry, with the long-term goal to understand molecular packing of organic crystals in order to predict and control crystal properties including polymorphism, growth morphology, dissolution, and solubility. The current focus is to use density functional theory (DFT) and quantum mechanical methods, in addition to a plethora of analytical methods, to study crystal structures of organic molecules. For this endeavor, We are supported by an NSF CAREER Award, titled Towards Fundamental Understanding and Rational Control of Crystal Growth. The project aims to investigate intermolecular interactions and the influence by solvents and additives in the crystal growth by exploring DFT concepts such as charge density, Fukui function, softness and hardness.

Computing (T. Li)

In addition to unveiling the connection between electronic properties and crystal packing, other synergetic efforts that are centered toward the general aim include:

• Understanding surface wettability with DFT concepts and contact angle measurement
• Developing an empirically augmented DFT method for calculating intermolecular interactions and lattice energies of organic crystals
• Investigating solid-state reactivity of organic crystals with DFT concepts
• Developing atomic force microscopy (AFM) methods for measuring surface energy
• Synthesizing structurally similar organic molecules and studying their crystal structures so as to understand the molecular structure-crystal packing relationship
• Studying polymorphism of organic crystals with DFT concepts, in particular, the Fukui function and local polarizability
• Examining the solvent-solute interaction with NMR and computational solvation models to discover how solvents affect the polymorphism

Analysis (C. Aubrey)

Through these ongoing efforts and by carrying out the NSF project, we are making meaningful contributions to solid-state organic chemistry. The uniqueness of our research lies in the application and development of electronic properties that may provide far-reaching insights beyond the paradigm in the research field. We envision the electronic structure of a crystal holds the key to solving many grand challenges such as polymorph prediction. By joining force with crystal engineering and instrumental analysis, our electronic studies will produce deep understandings and novel methods in crystal growth, helping advance both theoretical and practical fronts in organic solid-state materials.

An extension of our research in solid-state chemistry is development of nanocrystals for drug delivery of anticancer compounds. This effort is currently supported by a DOD Idea Award of medical research. The novelty of the concept is to integrate ligands or antibodies with drug substances without going through complicated bioconjugation chemistry. Instead, ligand substances are self-assembled with drug molecules through physical means. The novel delivery system is believed to permit the direct targeting of chemotherapy agents to cancer cells. The nanocrystals are produced through crystallization techniques, different from traditional attrition methods (milling, homogenization, etc.), allowing the production of hybrid nanosystems that are biocompatible, able to target cancerous tissues, and physically stable during formulation, storage, and circulation. Both in vitro and in vivo tests are under way.