We apply computational quantum chemistry tools to understand how Nature creates wide ranges of weak to strong hydrogen bonds needed to accomplish complex chemical tasks, and use this knowledge to develop useful hydrogen bond design principles for chemical applications. 

Hydrogen Bond – π-Conjugation Coupling
Nearly 100 years past the birth of hydrogen bond research, the prevailing view of a hydrogen bond continues to follow the Higgins (1919, unpublished), Latimer-Rodebush (1920), and Pauling (1939) dogma, that a hydrogen bond is the attractive force of an H atom between two atoms, and that its strength depends on the electronegativity of the heavy atoms involved. This perspective largely shapes the way how chemists teach and think about hydrogen bonds. Such views, however, also have limited the ways hydrogen bonds are being applied for many chemical transformations (from catalyzing reactions to building supramolecular structures). Many puzzling findings in nature and in synthetic hydrogen bonded scaffolds also cannot be explained by this traditional view. Even simple O–H...O hydrogen bonds can exhibit strengths ranging from 1-30 kcal/mol!

We are exploring ways to control hydrogen bonding interactions for many chemistry-related applications. Recently, we discovered that, beyond simple electrostatic interactions, the π-conjugation patterns of hydrogen bonded units may be intentionally designed to, flexibly and predictably, fine-tune hydrogen bond strengths (by an up to 80% change). E.g., Hydrogen bonds that polarize the π-electrons of hydrogen bonded substrates to increase cyclic 4n+2 π electron delocalization (enhanced aromatic character) are strengthened, while those that increase cyclic 4n π electron delocalization (enhanced antiaromatic character) are weakened. We are mapping out the many chemical possibilities (e.g., in catalysis, self-assembly, and molecular recognition) enabled by this unique connection.


Computational Enzyme Design
Enzymes can accelerate reactions by up to 1020 times in mild conditions, but the molecular details of how they catalyze reactions remains largely elusive. We are studying catalytic strategies adopted by natural enzymes and applying them to improve the designs of catalysts and artificial enzymes.
Our latest work reveals how enzymes might form short, strong, hydrogen bonds to catalyze reactions.