CAREER: Taming Hydrogen Bonding in Water

With the support of the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Professor Wenqi Liu of the University of South Florida will investigate molecular recognition in water mediated by hydrogen bonding through the design, synthesis, and binding studies of water-soluble receptors with hybrid functionalities. Biological receptors adeptly utilize hydrogen bonding for molecular recognition in water--a remarkable feat that synthetic receptors have struggled to emulate due to the effects of hydration. This research seeks to uncover molecular design principles that enable synthetic receptors to use hydrogen bonding effectively in water. Successful outcomes could pave the way for advancements in various fields, including medical diagnostics, the development of anti-infective agents, synthetic antibodies, and carbohydrate sensors. Moreover, water-functional anion receptors could revolutionize agricultural practices with precise fertilization and play a crucial role in environmental remediation as sensors and scavengers for pollutants and radioactive contaminants. The broader impact of the work includes inspiring students to explore science through hands-on experiments, expanding STEM education opportunities for students from underserved communities, and enhancing learning and research experiences with modern technologies and workshops on cutting-edge research skills. The Liu research group aims to develop general synthetic strategies for constructing water-soluble receptors featuring hydrogen bonding functionalities integrated with hydrophobic surfaces or electrostatic binding residues. These methodologies, which involve dynamic imine chemistry coupled with imine-to-amide oxidation reactions, yield high-performance hydrogen-bonding receptors and allow for the exploration of structures that are difficult to synthesize using conventional methods. The modularity of these methods facilitates a diverse examination of hydrophobic surfaces, charge densities, and spatial distributions of hydrogen bonding functionalities within these macrocycles and cages. This research will enhance our understanding of how hydrogen bonds can be utilized in synthetic receptors to mimic the efficiency of their biological counterparts in water, potentially leading to significant societal benefits in medicine, agriculture, and environmental protection. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.