Plenary Lecture

Dr. Chenfeng Ke, Washington Unviersity in St. Louis
Associate Professor of Chemistry

Hydrogen-bonded Crosslinked Organic Frameworks, Sheets, and Cages
Time: 11:05 a.m.

Developing porous organic materials shows excellent potential for molecular recognition, storage and separation, catalysis, and energy-related applications. However, achieving high crystallinity, chemical stability, and durability has remained challenging for state-of-the-art organic framework materials. We have developed a new family of porous organic materials chemically stable, single crystalline, and dynamic to guest sorption. This new family of porous materials brings de novo supramolecular design of adaptive sorption and separation features to porous organic materials. Their adjustable networks allow for highly selective and durable molecular/ionic adsorption and separation based on different substrate-framework interactions. In this talk, I will discuss the general design principle of hydrogen-bonded crosslinked organic frameworks (HCOFs), which first utilize hydrogen bonds to pre-organize molecular entities into porous single crystals, then introduce flexible crosslinkers to form stable covalent frameworks with high crystallinity. The synthesized HCOF-1 to HCOF-4 demonstrated superior iodine uptake capacities and visible crystal size expansions. Recently, we introduced HCOF-6 and HCOF-102-105. Upon the uptake of guest/solvent molecules, the hydrogen bonding joints of these HCOF were disrupted, allowing the crystal to expand rapidly to more than three times its original length. These guest-induced material size expansions and contractions were highly reversible. I will also update some of our recent progress on the development of wavy sheets, and porous organic cages utilizing unconventional C(sp3)-H•••O hydrogen bonds, enabling selective perchlorate binding in water.

Short Talks

Mohammad (Mo) Chaudhry, Merck & Co.,
Postdoctoral Fellow

Expanding Merck's structure elucidation capabilities with frameworks
Time: 11:40 a.m.

The stereoisomeric nature of active pharmaceutical ingredients (APIs) can profoundly influence their potency, effectiveness, biocompatibility, and potential side effects. For example, R-Thalidomide is a widely-used treatment for various types of cancer, while its S-isomer has been observed to cause birth defects, such as phocomelia, in developing fetuses. This unfortunate discovery led to a global crisis during the 1950s and 1960s. Consequently, there is a compelling need to accurately determine the absolute stereochemical configuration of APIs to adequately assess potential risks.
However, conventional methodologies for absolute stereochemical identification, such as the Mosher method relying on spectroscopic techniques, can be prone to unreliability and may result in misidentification of stereoisomers. In contrast, single-crystal X-ray diffraction has emerged as a powerful and arguably the most definitive tool for structure determination. In recent advancements, porous frameworks, including metal-organic frameworks (MOFs), have been explored for crystallizing liquids, gases, and amorphous solids to facilitate accurate structure determination. However, MOFs face specific challenges, such as incorrect guest/atom identification, partial occupancy of molecules, and the presence of substantial structural or positional disorder.
In this talk, we show our progress in employing hydrogen-bonded organic frameworks (HOFs) based on guanidinium-sulfonate (GS) for absolute structure determination.

Kennedy Borchardt-Setter, University of Wisconsin-Madison
Ph.D. Candidate, Yu Lab; Oral Formulation Sciences Co-Op at Merck & Co.,

Chiral Resolution by Crystallization
Time: 12:05 p.m.

Chirality is everywhere in nature. The natural amino acids are the L-form while the natural sugars are the D-form. When a drug interacts with a living system, a change of chirality can make a medicine into a toxin. Current methods for chiral resolution are often expensive and depend greatly on the type of molecule being studied, leaving a gap in industry to develop a more general and effective resolution method. Previous work has shown that crystallization of a racemic melt commonly crystallizes as a racemate, with spontaneous chiral resolution making up about 5% of products observed. This work discusses how, using computational methods, we can predict whether chiral separation by crystallization is possible in different systems. We then experimentally observed that seeding a melt of racemic arabitol, which has not been previously reported to resolve spontaneously, with its pure enantiomeric form leads to its enantiomeric separation. The results of these works and potential applications will be presented.