Crystal packing of organic molecules is poorly understood; predicting likely crystal structures of a given compound is even more challenging. This research project, supported by the Solid State and Materials Chemistry (SSMC) program of the Division of Materials Research (DMR), is to study how organic molecules interact in the solid state so as to learn and build up the fundamental understanding that will lead to viable solutions for crystal structure prediction. In particular, the locality of intermolecular interactions, both strength and directionality, in organic crystals will be investigated within the framework of conceptual density functional theory by utilizing such concepts as softness, Fukui function, and crystallization force. Through calculation and analysis of electronic structures of molecules and their respective crystal structures, the project will seek and establish the underlying, inherent linkage between a molecule's structure and its interacting characteristics with other molecules in crystals. The influence of a molecule's conformation on its intermolecular spatial arrangement is further studied by electronic calculations and crystallization experiments. Upon successful completion of this research project, a methodological framework will be built for advancing into practical tools to understand crystallization and to predict crystal structures of organic compounds.
NON-TECHNICAL SUMMARY Fascination of organic crystals lies in the infinite periodicity and intriguing complexity in the three-dimensional structure that is interweaved by weak forces. Despite years of vigorous studies, the scientific efforts to predict crystal structures have proved to be primitive, powerless in most cases, and in the end, futile. This research project aims at bringing advanced computational methods into the field and developing novel approaches for predicting crystal structures that are built upon ingenious ways of analyzing electronic structures of molecules and crystals. Moreover, the research will shed light on fundamental mechanisms of crystal growth and offer insights for designing new materials including pharmaceuticals, fine chemicals, and nonlinear optical materials. The project will serve as an excellent educational platform for undergraduate and graduate students to master their problem-solving skills and become future leaders in the area of organic materials.
Looking at a crystal structure on a computer screen, we are often amazed and intrigued by how molecules arrange themselves in such a symmetric, beautiful tessellation! The strength and directionality of intermolecular interactions, governed by structural diversity and conformational flexibility of molecule, dictate crystal structure formation. Subtle shifts in molecular interactions occasionally results in polymorphs of the same compound, driven by changes in crystallization conditions during the self-assembly process. Understanding and thereby predicting molecular packing in the crystal not only satisfies our curiosity, but also enables us to create new structures and materials with novel properties. Predicting how molecules pack themselves into crystal structures has long been sought, but far from being realized. The doubt over the predictability of crystal structure remains lingering, in part because of the poor performance demonstrated energy models for calculating molecular crystals and in part due to the complexity and a humongous number of possible crystal structures to evaluate for a given organic molecule. After over a decade of various attempts, we still cannot see the silver lining with all the daring efforts. It is clear, though, that lacking the powder of prediction – a hallmark of a well-developed scientific field – solid-state organic chemistry has undoubtedly a tremendous gap to fill. The intellectual merit of our efforts lies in understanding and predicting molecular packing and crystal formation based on the chemical intuition of the molecule of interest. We examine intermolecular interaction potentials from the molecule’s electronic structure and quantify the locality of such potentials within the framework of conceptual density functional theory (CDFT). Our studies are driven by the HSAB (hard and soft acids and bases) principle that has guided organic chemistry over half of a century. Our results of calculating and analyzing electronic structures of various crystal structures demonstrate the potential of using the molecular information for predicting intermolecular interactions and spatial arrangement. Furthermore, our studies uncover the electronic origin of how the molecular conformation may influence the strength of intermolecular interactions, and vice versa. The broader impact of the project, therefore, is believed to advance the making of novel organic materials, including pharmaceuticals and fine chemicals. Recognizing the locality and regioselectivity of interacting potentials directly from the chemical information embodied in the molecule will enable the rational design of new forms and novel materials, such as cocrystals and higher-energy forms to achieve enhanced functionalities (e.g., greater bioavailability for active pharmaceutical ingredients).
