CAREER: Towards Fundamental Understanding and Rational Control of Crystal Growth

This project focuses on understanding the role played by solvents and additives in affecting growth morphology (or habit) and polymorphism of organic crystals with density functional theory (DFf) based concepts and Pearson's HSAB (hard and soft acids and bases) principle. The fact that a variety of polymorphs as well as morphology of organic or molecular crystals can be produced in different solvents with and without additives leads to our belief that solvent molecules should match crystal surfaces of a particular polymorph or morphology with respect to their electronic properties. A better match slows down more the growth rate of a matched crystal face, making it a major face. A better match may also "sculpt" a set of crystal faces that collectively result in a unique polymorphic structure, reaching a better balance between surface energy and internal energy. Using additives may alter the original match between solvent and crystal, causing the change in growth morphology or polymorphism. Thus, this project's goals are two-fold. The fIrst is to prove the hypothesis with DFT-based hardness and softness concepts and principles. The second is to further the proof by designing proper co-solvent systems with or without additives and testing the control for a particular morphology or polymorph of selected crystals in accordance to the matching principles developed. Capitalizing on our recent fmding of the face-integrated Fukui function, this work will develop face- and surface-integrated hardness and softness to extend the HSAB principle to crystal growth. SpecifIcally, the research aims to (1) identify the electronic matching between solvent molecules and surfaces of a particular morphology or polymorph with DFT-based concepts; (2) study how additive molecules affect surface electronic properties of a crystal system and thus influence crystal growth; and (3) engineer growth morphology and polymorphs by designing co-solvents and additives based on developed electronic matching principles. The distinctive feature of this project is the use of ab initio methods and conceptual DFT to uncover fundamental mechanisms of solvent-crystal and additive-crystal interactions and their impact on crystal growth. As the sea of electrons on various faces of a crystal couples with or responds to electronic perturbations due to contact of a solvent/ additive, the difference in responding sensitivities of the faces may be described by face-integrated Fukui function, softness and hardness. Applying these concepts to establish HSAB type matching principles between solvents/additives and crystals, this project will create a new paradigm to clarify the influence of solvents and additives at the electronic level. Results from this research will allow the rational design of novel co-solvent systems and additives so as to control growth morphology and polymorph formation of molecular crystals. The work will also lead to developing new prediction methods of morphology and polymorphism of organic crystals that consider solvent/ additive effects, advancing our current understandings of crystal growth of organics to the electronic level. The impact of integrated research and education initiatives is broad and far reaching. Not only will the research make a signifIcant contribution to organic solid-state chemistry and crystal engineering, but it will also shine a strong light in surface science, nanotechnology, biomineralization and the conceptual DFT itself. Novel architectures and desirable morphology/size of crystalline materials will be created because of the rational design of growth condition, resulting in new materials with attracting properties. Some applications may include enhancement of stability, solubility and manufacturability of drug materials, creation of nanocrystals for drug delivery and photonics, and study of crystal deposition diseases. Furthermore, the education plan will help build a stronger graduate program at the University by developing a pharmaceutical materials science course, and recruiting and mentoring graduate and undergraduate students working in the project growing crystals and conducting electronic calculations. It will also help the State to improve its education system by attracting and hosting middle- and highschool students, especially minorities, women and those from rural areas, and getting them interested in crystals and materials science. Dissemination of the research will be ensured by publishing the research in top journals, hosting a regional solid-state chemistry symposium, and presenting at national meetings.