Radical Approaches to  Cross-Coupling and Late-Stage Modification of Biomolecules

 

Radical Approaches to  Cross-Coupling and Late-Stage Modification of Biomolecules

 

Date: 12^thJune, 2025 (Thursday)

Time: 11:30 am - 12:30 pm (HKT)

 

Venue: Lecture Theatre P3, Chong Yuet Ming Physics Building

 

Prof. Tianning DIAO

New York University

 

Nature utilizes base metals, such as nickel, within enzymatic cofactors to catalyze diverse transformations via radical intermediates. Inspired by nickel’s ability to mediate radical pathways, nickel-catalyzed cross-coupling reactions have emerged as sustainable and innovative synthetic methods with a broad scope of alkyl coupling partners. However, the mechanisms of these processes remain poorly understood. Our research program seeks to elucidate the role of redox-active ligands in enabling nickel catalysts to initiate radical formation, capture radical species, and direct bond formation with open-shell intermediates. The orthogonal reactivity of radicals toward polar functional groups in biomolecules presents opportunities for late-stage modification of non-canonical carbohydrates, molecules of significant interest in drug discovery and chemical biology research. Additionally, we have developed a photoactivatable bioconjugation method, TagC-RED, a retro-ene type sigmatropic rearrangement of diazonium compounds designed for cysteine-specific conjugation, activated by infrared light. TagC-RED is quantitative, rapid, and capable of penetrating biological tissues, making it suitable for intracellular labeling deep within mouse brains. This technology holds significant potential as a platform for chemical biology studies, including targeted protein labeling, real-time tracking of cellular processes, and the development of novel diagnostic and therapeutic tools.